Default Mode Network Aberrant Connectivity Associated with Neurological Soft Signs in Schizophrenia Patients and Unaffected Relatives.

PubMed

Galindo, Liliana; Bergé, Daniel; Murray, Graham K; Mané, Anna; Bulbena, Antonio; Pérez, Victor; Vilarroya, Oscar

2017-01-01

Brain connectivity and neurological soft signs (NSS) are reportedly abnormal in schizophrenia and unaffected relatives, suggesting they might be useful neurobiological markers of the illness. NSS are discrete sensorimotor impairments thought to correspond to deviant brain development. Although NSS support the hypothesis that schizophrenia involves disruption in functional circuits involving several hetero modal association areas, little is known about the relationship between NSS and brain connectivity. We explored functional connectivity abnormalities of the default mode network (DMN) related to NSS in schizophrenia. A cross-sectional study was performed with 27 patients diagnosed with schizophrenia, 23 unaffected relatives who were unrelated to the schizophrenia subjects included in the study, and 35 healthy controls. Subjects underwent magnetic resonance imaging scans including a functional resting-state acquisition and NSS evaluation. Seed-to-voxel and independent component analyses were used to study brain connectivity. NSS scores were significantly different between groups, ranging from a higher to lower scores for patients, unaffected relatives, and healthy controls, respectively (analysis of variance effect of group F  = 56.51, p  < 0.001). The connectivity analysis revealed significant hyperconnectivity in the fusiform gyrus, insular and dorsolateral prefrontal cortices, inferior and middle frontal gyri, middle and superior temporal gyri, and posterior cingulate cortex [minimum p-family wise error (FWE) < 0.05 for all clusters] in patients with schizophrenia as compared with in controls. Also, unaffected relatives showed hyperconnectivity in relation to controls in the supramarginal association and dorsal posterior cingulate cortices (p-FWE < 0.05 for all clusters) in patients with schizophrenia as compared with in controls. Also, unaffected relatives showed hyperconnectivity in relation to controls in the supramarginal association and dorsal posterior cingulate cortices (p-FWE = 0.001) and in the anterior prefrontal cortex (42 voxels, p-FWE = 0.047). A negative correlation was found between left caudate connectivity and NSS [p-FWE = 0.044, cluster size ( k ) = 110 voxels]. These findings support the theory of widespread abnormal connectivity in schizophrenia, reinforcing DMN hyperconnectivity and NSS as neurobiological markers of schizophrenia. The results also indicate the caudate nucleus as the gateway to the motor consequences of abnormal DMN connectivity.

Sporadic adult onset dystonia: sensory abnormalities as an endophenotype in unaffected relatives

PubMed Central

Walsh, Richard; O'Dwyer, John P; Sheikh, Ifthikar H; O'Riordan, Sean; Lynch, Tim; Hutchinson, Michael

2007-01-01

Background Most patients with adult onset primary torsion dystonia (AOPTD) have the sporadic form of the disease. They may however be the only manifesting family members of a poorly penetrant genetic disorder. Sensory changes, including structural abnormalities of the primary sensory cortex, are found in AOPTD. Spatial discrimination threshold (SDT), a measure of sensory cortical organisation, is abnormal in AOPTD and in unaffected relatives of patients with familial AOPTD. Our hypothesis was that abnormal SDTs might be found in unaffected relatives of patients with sporadic AOPTD. Methods SDTs were assessed at the index finger bilaterally by a grating orientation task. Normal age related SDTs were derived from 141 control subjects aged 20–64 years. SDTs were considered abnormal when greater than 2.5 SD above the control mean. In total, 105 of 171 (61%) eligible unaffected siblings and offspring of patients with cervical dystonia had SDT examined. Results Fourteen of 48 siblings (29%) and 10 of 57 (18%) offspring were found to have an abnormal SDT. Only five of the 20 patients examined had abnormal SDTs. In 11 of the 25 families, no abnormality was found in an unaffected relative. In the 14 families where at least one unaffected relative had an abnormal SDT, 14 of 37 siblings (38%) and 10 of 33 offspring (30%) had abnormal SDTs. Conclusion Sensory abnormalities found in unaffected relatives of patients with apparently sporadic AOPTD may be a surrogate marker for the carriage of an abnormal gene. PMID:17702779

Functional dysconnectivity of corticostriatal circuitry as a risk phenotype for psychosis.

PubMed

Fornito, Alex; Harrison, Ben J; Goodby, Emmeline; Dean, Anna; Ooi, Cinly; Nathan, Pradeep J; Lennox, Belinda R; Jones, Peter B; Suckling, John; Bullmore, Edward T

2013-11-01

Dysregulation of corticostriatal circuitry has long been thought to be critical in the etiology of psychotic disorders, although the differential roles played by dorsal and ventral systems in mediating risk for psychosis have been contentious. To use resting-state functional magnetic resonance imaging to characterize disease-related, risk-related, and symptom-related changes of corticostriatal functional circuitry in patients with first-episode psychosis and their unaffected first-degree relatives. This case-control cross-sectional study was conducted at a specialist early psychosis clinic, GlaxoSmithKline Clinical Unit, and magnetic resonance imaging facility. Nineteen patients with first-episode psychosis, 25 of their unaffected first-degree relatives, and 26 healthy control subjects were included in this study. Voxelwise statistical parametric maps testing differences in the strength of functional connectivity between 6 striatal seed regions of interest (3 caudate and 3 putamen) per hemisphere and all other brain regions. Disease-related changes, reflecting differences between patients and control subjects, involved widespread dysregulation of corticostriatal systems characterized most prominently by a dorsal-to-ventral gradient of hypoconnectivity to hyperconnectivity between striatal and prefrontal regions. A similar gradient was evident in comparisons between relatives and control subjects, identifying it as a genetically inherited risk phenotype. In patients, functional connectivity in risk-affected and disease-affected dorsal frontostriatal circuitry correlated with the severity of both positive and negative symptoms. First-episode psychosis is associated with pronounced dysregulation of corticostriatal systems, characterized most prominently by hypoconnectivity of dorsal and hyperconnectivity of ventral frontostriatal circuits. These changes correlate with symptom severity and are also apparent in unaffected first-degree relatives, suggesting that they represent a putative risk phenotype for psychotic illness.

Neurocognitive function in an extended Afrikaner-ancestry family with affective illness.

PubMed

Savitz, Jonathan; van der Merwe, Lize; Solms, Mark; Ramesar, Rajkumar

2007-03-01

To characterize the neuropsychological profile of an extended family with unipolar depression (UPD) and other forms of affective illness. We administered a battery of neuropsychological tasks measuring various aspects of executive function and visual and verbal memory to 49 individuals in 1 extended family. Six participants had 1 lifetime episode of major depression (MDE-S), 15 were diagnosed with recurrent major depression (MDE-R), 11 had another DSM-IV diagnosis and 17 subjects were unaffected. After controlling for multiple confounding factors, including mood and medication, the MDE-R sample made significantly more errors than unaffected relatives on the Stroop Task, a measure of cognitive control. There may be at least 1 subtype of UPD characterized by a state-independent deficit in cognitive control.

Scanning Electron Microscopic Hair Shaft Analysis in Ectodermal Dysplasia Syndromes.

PubMed

Hirano-Ali, Stefanie A; Reed, Ashley M; Rowan, Brandon J; Sorrells, Timothy; Williams, Judith V; Pariser, David M; Hood, Antoinette F; Salkey, Kimberly

2015-01-01

The objective of the current study was to catalog hair shaft abnormalities in individuals with ectodermal dysplasia (ED) syndromes using scanning electron microscopy (SEM) and to compare the findings with those in unaffected controls. This is the second of a two-part study, the first of which used light microscopy as the modality and was previously published. Scanning electron microscopy was performed in a blinded manner on hair shafts from 65 subjects with seven types of ED syndromes and 41 unaffected control subjects. Assessment was performed along the length of the shaft and in cross section. Hair donations were collected at the 28th Annual National Family Conference held by the National Foundation for Ectodermal Dysplasia. Control subjects were recruited from a private dermatology practice and an academic children's hospital outpatient dermatology clinic. SEM identified various pathologic hair shaft abnormalities in each type of ED and in control patients. When hairs with all types of ED were grouped together and compared with those of control patients, the difference in the presence of small diameter and shallow and deep grooves was statistically significant (p < 0.05). When the EDs were separated according to subtype, statistically significant findings were also seen. SEM is a possible adjuvant tool in the diagnosis of ED syndromes. There are significant differences, with high specificity, between the hairs of individuals with ED and those of control subjects and between subtypes. © 2015 Wiley Periodicals, Inc.

Familial Cerebral Cavernous Malformations Are Associated with Adrenal Calcifications on CT Scans: An Imaging Biomarker for a Hereditary Cerebrovascular Condition.

PubMed

Strickland, Corinne D; Eberhardt, Steven C; Bartlett, Mary R; Nelson, Jeffrey; Kim, Helen; Morrison, Leslie A; Hart, Blaine L

2017-08-01

Purpose To determine if adrenal calcifications seen at computed tomography (CT) are associated with familial cerebral cavernous malformations (fCCMs) in carriers of the CCM1 Common Hispanic Mutation. Materials and Methods This study was approved by the institutional review board. The authors retrospectively reviewed abdominal CT scans in 38 patients with fCCM, 38 unaffected age- and sex-matched control subjects, and 13 patients with sporadic, nonfamilial cerebral cavernous malformation (CCM). The size, number, and laterality of calcifications and the morphologic characteristics of the adrenal gland were recorded. Brain lesion count was recorded from brain magnetic resonance (MR) imaging in patients with fCCM. The prevalence of adrenal calcifications in patients with fCCM was compared with that in unaffected control subjects and those with sporadic CCM by using the Fisher exact test. Additional analyses were performed to determine whether age and brain lesion count were associated with adrenal findings in patients with fCCM. Results Small focal calcifications (SFCs) (≤5 mm) were seen in one or both adrenal glands in 19 of the 38 patients with fCCM (50%), compared with 0 of the 38 unaffected control subjects (P < .001) and 0 of the 13 subjects with sporadic CCM (P = .001). Adrenal calcifications in patients with fCCM were more frequently left sided, with 17 of 19 patients having more SFCs in the left adrenal gland than the right adrenal gland and 50 of the 61 observed SFCs (82%) found in the left adrenal gland. No subjects had SFCs on the right side only. In patients with fCCM, the presence of SFCs showed a positive correlation with age (P < .001) and number of brain lesions (P < .001). Conclusion Adrenal calcifications identified on CT scans are common in patients with fCCM and may be a clinically silent manifestation of disease. © RSNA, 2017.

Psychiatric comorbidities in adolescents with attention-deficit hyperactivity disorder and their siblings.

PubMed

Yang, Li-Kuang; Shang, Chi-Yung; Gau, Susan Shur-Fen

2011-05-01

Despite high psychiatric comorbidities in adolescents with clinical diagnosis of attention-deficit hyperactivity disorder (ADHD), little is known about psychiatric comorbidities in their siblings. We investigated the psychiatric comorbid conditions in adolescents with ADHD, their siblings, and healthy control subjects from their school. The sample included 136 adolescent probands with ADHD according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), diagnostic criteria; 136 siblings (47 affected and 89 unaffected) and 136 age- and sex-matched healthy school control subjects. All participants and their parents received the structured psychiatric interviews for current and lifetime DSM-IV psychiatric disorders of the participants. The rate of ADHD (34.6%) in the siblings of probands with ADHD was about 7 times higher than in the general population. Probands with ADHD were significantly more likely than unaffected siblings (OR 6.38; 95% CI 3.43 to 11.88) and healthy school control subjects (OR 9.60; 95% CI 5.31 to 17.34) to have a DSM-IV psychiatric disorder, including oppositional defiant disorder (ODD), conduct disorder (CD), tic disorders, major depressive disorder, specific phobia (more than control subjects only), nicotine use disorder, and sleep disorders. The affected siblings were significantly more likely than healthy school control subjects to have ODD, CD, specific phobia, and to have consumed alcohol (ORs ranging from 2.30 to 20.16). Our findings suggest that siblings of probands with ADHD have increased risks for ADHD and that the affected siblings have more psychiatric comorbidities than healthy school control subjects. It warrants early identification of ADHD symptoms and other psychiatric comorbid conditions as well in siblings of adolescents with ADHD.

Distinguishing Adolescents With ADHD From Their Unaffected Siblings and Healthy Comparison Subjects by Neural Activation Patterns During Response Inhibition.

PubMed

van Rooij, Daan; Hoekstra, Pieter J; Mennes, Maarten; von Rhein, Daniel; Thissen, Andrieke J A M; Heslenfeld, Dirk; Zwiers, Marcel P; Faraone, Stephen V; Oosterlaan, Jaap; Franke, Barbara; Rommelse, Nanda; Buitelaar, Jan K; Hartman, Catharina A

2015-07-01

Dysfunctional response inhibition is a key executive function impairment in attention deficit hyperactivity disorder (ADHD). Still, behavioral response inhibition measures do not consistently differentiate affected from unaffected individuals. The authors therefore investigated neural correlates of response inhibition and the familial nature of these neural correlates. Functional MRI measurements of neural activation during the stop-signal task and behavioral measures of response inhibition were obtained in adolescents and young adults with ADHD (N=185), their unaffected siblings (N=111), and healthy comparison subjects (N=124). Stop-signal task reaction times were longer and error rates were higher in participants with ADHD, but not in their unaffected siblings, while reaction time variability was higher in both groups than in comparison subjects. Relative to comparison subjects, participants with ADHD and unaffected siblings had neural hypoactivation in frontal-striatal and frontal-parietal networks, whereby activation in inferior frontal and temporal/parietal nodes in unaffected siblings was intermediate between levels of participants with ADHD and comparison subjects. Furthermore, neural activation in inferior frontal nodes correlated with stop-signal reaction times, and activation in both inferior frontal and temporal/parietal nodes correlated with ADHD severity. Neural activation alterations in ADHD are more robust than behavioral response inhibition deficits and explain variance in response inhibition and ADHD severity. Although only affected participants with ADHD have deficient response inhibition, hypoactivation in inferior frontal and temporal-parietal nodes in unaffected siblings supports the familial nature of the underlying neural process. Activation deficits in these nodes may be useful as endophenotypes that extend beyond the affected individuals in the family.

Subject Case in Children with SLI and Unaffected Controls: Evidence for the Agr/Tns Omission Model.

ERIC Educational Resources Information Center

Wexler, Kenneth; Rice, Mabel; Schutze, Carson T.

1998-01-01

Presents new evidence for the view that specific language impairment (SLI) involves a syntactic-feature deficit within non-evident grammar. The data involve morphological case and its interaction with verbal inflection. (Author/VWL)

Altered inhibition of negative emotions in subjects at family risk of major depressive disorder.

PubMed

Lisiecka, Danuta M; Carballedo, Angela; Fagan, Andrew J; Connolly, Gerald; Meaney, James; Frodl, Thomas

2012-02-01

Unaffected 1st degree relatives of patients with major depressive disorder (MDD) are more likely to develop MDD than healthy controls. The aim of our study was to establish neuronal correlates of familial susceptibility in the process of inhibition of emotional information. Unaffected 1st degree relatives of patients with MDD (N = 21) and matched healthy controls (N = 25) underwent a functional magnetic resonance imaging procedure with an inhibition task. Blood oxygenated level dependent signal was evaluated for the two groups during inhibition of positive, negative and neutral information. In a 2 × 3 ANOVA unaffected relatives of patients with MDD were compared to healthy controls, jointly and separately for all three levels of emotional valence of the information. The interaction between group and emotional valence of the inhibited information was significant, indicating "a negative neural drift" in unaffected relatives of patients with MDD. The unaffected relatives of patients with MDD displayed an increased activation during inhibiting of negative material in the right middle cingulate cortex and the left caudate nucleus (p < 0.05, family wise error corrected). There was no difference between the two groups in terms of inhibiting positive or neutral stimuli. Our findings provide the first evidence that unaffected relatives of patients with MDD differ from the standard population in terms of neural correlates of inhibition of negative emotional information. Overactivation of cingulate cortex and caudate nucleus may indicate a learnt strategy aimed at coping with increased susceptibility to negative information schemata and may have future consequences for therapy. Copyright © 2011 Elsevier Ltd. All rights reserved.

Neurocognitive function in an extended Afrikaner-ancestry family with affective illness

PubMed Central

Savitz, Jonathan; van der Merwe, Lize; Solms, Mark; Ramesar, Rajkumar

2007-01-01

Objective To characterize the neuropsychological profile of an extended family with unipolar depression (UPD) and other forms of affective illness. Method We administered a battery of neuropsychological tasks measuring various aspects of executive function and visual and verbal memory to 49 individuals in 1 extended family. Six participants had 1 lifetime episode of major depression (MDE-S), 15 were diagnosed with recurrent major depression (MDE-R), 11 had another DSM-IV diagnosis and 17 subjects were unaffected. Results After controlling for multiple confounding factors, including mood and medication, the MDE-R sample made significantly more errors than unaffected relatives on the Stroop Task, a measure of cognitive control. Conclusion There may be at least 1 subtype of UPD characterized by a state-independent deficit in cognitive control. PMID:17353940

Is there an association between advanced paternal age and endophenotype deficit levels in schizophrenia?

PubMed

Tsuang, Debby; Esterberg, Michelle; Braff, David; Calkins, Monica; Cadenhead, Kristin; Dobie, Dorcas; Freedman, Robert; Green, Michael F; Greenwood, Tiffany; Gur, Raquel; Gur, Ruben; Horan, William; Lazzeroni, Laura C; Light, Gregory A; Millard, Steven P; Olincy, Ann; Nuechterlein, Keith; Seidman, Larry; Siever, Larry; Silverman, Jeremy; Stone, William; Sprock, Joyce; Sugar, Catherine; Swerdlow, Neal; Tsuang, Ming; Turetsky, Bruce; Radant, Allen

2014-01-01

The children of older fathers have increased risks of developing schizophrenia spectrum disorders, and among those who develop these disorders, those with older fathers present with more severe clinical symptoms. However, the influence of advanced paternal age on other important domains related to schizophrenia, such as quantitative endophenotype deficit levels, remains unknown. This study investigated the associations between paternal age and level of endophenotypic impairment in a well-characterized family-based sample from the Consortium on the Genetics of Schizophrenia (COGS). All families included at least one affected subject and one unaffected sibling. Subjects met criteria for schizophrenia (probands; n = 293) or were unaffected first-degree siblings of those probands (n = 382). Paternal age at the time of subjects' birth was documented. Subjects completed a comprehensive clinical assessment and a battery of tests that measured 16 endophenotypes. After controlling for covariates, potential paternal age-endophenotype associations were analyzed using one model that included probands alone and a second model that included both probands and unaffected siblings. Endophenotype deficits in the Identical Pairs version of the 4-digit Continuous Performance Test and in the Penn Computerized Neurocognitive Battery verbal memory test showed significant associations with paternal age. However, after correcting for multiple comparisons, no endophenotype was significantly associated with paternal age. These findings suggest that factors other than advanced paternal age at birth may account for endophenotypic deficit levels in schizophrenia.

Locomotion in Stroke Subjects: Interactions between Unaffected and Affected Sides

ERIC Educational Resources Information Center

Kloter, Evelyne; Wirz, Markus; Dietz, Volker

2011-01-01

The aim of this study was to evaluate the sensorimotor interactions between unaffected and affected sides of post-stroke subjects during locomotion. In healthy subjects, stimulation of the tibial nerve during the mid-stance phase is followed by electromyography responses not only in the ipsilateral tibialis anterior, but also in the proximal arm…

Dominant-negative TLR5 polymorphism reduces adaptive immune response to flagellin and negatively associates with Crohn's disease.

PubMed

Gewirtz, Andrew T; Vijay-Kumar, Matam; Brant, Steven R; Duerr, Richard H; Nicolae, Dan L; Cho, Judy H

2006-06-01

Crohn's disease (CD) is associated with elevated adaptive immunity to commensal microbes, with flagellin being a dominant antigen. In light of heightened awareness of the importance of innate immunity in regulating adaptive immunity and ambiguity as to the role of CD-associated immune responses in CD pathophysiology, we sought to determine whether natural acquisition of immune responses to flagellin were regulated by the innate immune flagellin receptor toll-like receptor 5 (TLR5) and determine whether persons carrying a recently defined common dominant-negative TLR5 polymorphism (TLR5-stop) might be protected from developing CD. Carriage rates of a recently defined dominant-negative TLR5 polymorphism (TLR5-stop) and levels of serum immunoreactivity to bacterial products were measured in inflammatory bowel disease patients, first-degree relatives, and unrelated controls. We observed that, in healthy subjects, persons carrying TLR5-stop had significantly lower levels of flagellin-specific IgG and IgA but had similar levels of total and LPS-specific Ig. Moreover, we observed that, among Jewish subjects, the carriage rate of TLR5-stop (in heterozygous state) was significantly less in CD patients, but not ulcerative colitis (UC) patients, compared with unaffected relatives and unrelated controls (5.4, 0.9, 6.0, and 6.5% for unaffected relatives, CD, UC, and unrelated Jewish controls, respectively, n = 296, 215, 185, and 416, respectively; P = 0.037 by likelihood calculation for CD vs. controls), indicating that TLR5-stop can protect persons of Jewish ethnicity against CD. We did not observe a significant association of TLR5-stop with CD in a non-Jewish cohort (11.1, 10.4, and 11.7% for unaffected relatives, CD, and UC, respectively; n = 841, 543, and 300 for unaffected relatives, respectively). These results demonstrate that natural acquisition of immune responses to flagellin are regulated by TLR5 and suggest that immune responses to flagellin are not merely associated with CD but rather promote the pathogenic response.

Recovery in the Severely Impaired Arm Post-stroke after Mirror Therapy - a Randomized Controlled Study.

PubMed

Chan, Wing Chiu; Au-Yeung, Stephanie Suk Yin

2018-03-09

This study aimed to examine the effectiveness of mirror therapy (MT) on recovery in the severely impaired arm after stroke. Using single-blind randomized controlled design, patients with severely impaired arm within 1-month post-stroke were assigned to received MT (n=20) or control therapy (CT) (n=21), 30min. twice daily for 4 weeks in addition to conventional rehabilitation. During MT and CT, subjects practiced similar structured exercises in both arms, except that mirror reflection of the unaffected arm was the visual feedback for MT, but mirror was absent for CT so that subjects could watch both arms in exercise. Fugl-Meyer Assessment (FMA) and Wolf Motor Function Test (WMFT) were the outcome measurements. After the intervention, both MT and CT groups had significant arm recovery similarly in FMA (p=0.867), WMFT-Time (p=0.947) and WMFT-Functional Ability Scale (p=0.676). MT or CT which involved exercises concurrently for the paretic and unaffected arms during subacute stroke promoted similar motor recovery in the severely impaired arm.

Minor physical anomalies are more common among the first-degree unaffected relatives of schizophrenia patients - Results with the Méhes Scale.

PubMed

Hajnal, András; Csábi, Györgyi; Herold, Róbert; Jeges, Sára; Halmai, Tamás; Trixler, Dániel; Simon, Maria; Tóth, Ákos Levente; Tényi, Tamás

2016-03-30

Minor physical anomalies are external markers of abnormal brain development,so the more common appearance of these signs among the relatives of schizophrenia patients can confirm minor physical anomalies as intermediate phenotypes. The aim of the present study was to investigate the rate and topological profile of minor physical anomalies in the first-degree unaffected relatives of patients with schizophrenia compared to matched normal control subjects. Using a list of 57 minor physical anomalies (the Méhes Scale), 20 relatives of patients with the diagnosis of schizophrenia and as a comparison 20 matched normal control subjects were examined. Minor physical anomalies were more common in the head and mouth regions among the relatives of schizophrenia patients compared to normal controls. By the differentiation of minor malformations and phenogenetic variants, we have found that only phenogenetic variants were more common in the relatives of schizophrenia patients compared to the control group, however individual analyses showed, that one minor malformation (flat forehead) was more prevalent in the relative group. The results can promote the concept, that minor physical anomalies can be endophenotypic markers of the illness. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Homocysteine Level and Risk of Abdominal Aortic Aneurysm: A Meta-Analysis

PubMed Central

Cao, Hui; Hu, Xinhua; Zhang, Qiang; Li, Jun; Wang, Junpeng; Shao, Yang; Liu, Bing; Xin, Shijie

2014-01-01

Objectives Previous studies have reported inconsistent findings regarding the association between elevated plasma homocysteine (Hcy) levels and abdominal aortic aneurysm (AAA). We investigated this association between Hcy levels in patients with AAA and unaffected controls by conducting a meta-analysis and systematic review. Methods We conducted a systematic literature search (up to August 2013) of the PubMed database and Embase. We selected observational studies that evaluated Hcy levels in subjects with AAA compared to unaffected controls. Criteria for inclusion were the assessment of baseline Hcy and risk of AAA as an outcome. The results were presented as odd ratio (OR) and corresponding 95% confidence intervals (CI) comparing AAA patients to the control subjects. Results 7 studies with 6,445 participants were identified and analyzed. Overall, elevated plasma Hcy was associated with an increased risk of AAA (3.29; 95% CI 1.66–6.51). The pooled adjusted OR from a random effect model of only men participants in the AAA compared with the control group was 2.36 (95% CI 0.63–8.82). Conclusion This meta-analysis and systematic review suggested that Hcy significantly increased the risk of AAA. PMID:24465733

Computed tomography demonstrates abnormalities of contralateral ear in subjects with unilateral sensorineural hearing loss.

PubMed

Marcus, Sonya; Whitlow, Christopher T; Koonce, James; Zapadka, Michael E; Chen, Michael Y; Williams, Daniel W; Lewis, Meagan; Evans, Adele K

2014-02-01

Prior studies have associated gross inner ear abnormalities with pediatric sensorineural hearing loss (SNHL) using computed tomography (CT). No studies to date have specifically investigated morphologic inner ear abnormalities involving the contralateral unaffected ear in patients with unilateral SNHL. The purpose of this study is to evaluate contralateral inner ear structures of subjects with unilateral SNHL but no grossly abnormal findings on CT. IRB-approved retrospective analysis of pediatric temporal bone CT scans. 97 temporal bone CT scans, previously interpreted as "normal" based upon previously accepted guidelines by board certified neuroradiologists, were assessed using 12 measurements of the semicircular canals, cochlea and vestibule. The control-group consisted of 72 "normal" temporal bone CTs with underlying SNHL in the subject excluded. The study-group consisted of 25 normal-hearing contralateral temporal bones in subjects with unilateral SNHL. Multivariate analysis of covariance (MANCOVA) was then conducted to evaluate for differences between the study and control group. Cochlea basal turn lumen width was significantly greater in magnitude and central lucency of the lateral semicircular canal bony island was significantly lower in density for audiometrically normal ears of subjects with unilateral SNHL compared to controls. Abnormalities of the inner ear were present in the contralateral audiometrically normal ears of subjects with unilateral SNHL. These data suggest that patients with unilateral SNHL may have a more pervasive disease process that results in abnormalities of both ears. The findings of a cochlea basal turn lumen width disparity >5% from "normal" and/or a lateral semicircular canal bony island central lucency disparity of >5% from "normal" may indicate inherent risk to the contralateral unaffected ear in pediatric patients with unilateral sensorineural hearing loss. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Brain Volumetric Correlates of Autism Spectrum Disorder Symptoms in Attention Deficit/Hyperactivity Disorder

PubMed Central

O’Dwyer, Laurence; Tanner, Colby; van Dongen, Eelco V.; Greven, Corina U.; Bralten, Janita; Zwiers, Marcel P.; Franke, Barbara; Oosterlaan, Jaap; Heslenfeld, Dirk; Hoekstra, Pieter; Hartman, Catharina A.; Rommelse, Nanda; Buitelaar, Jan K.

2014-01-01

Autism spectrum disorder (ASD) symptoms frequently occur in subjects with attention deficit/hyperactivity disorder (ADHD). While there is evidence that both ADHD and ASD have differential structural correlates, no study to date has investigated these structural correlates within a framework that robustly accounts for the phenotypic overlap between the two disorders. The presence of ASD symptoms was measured by the parent-reported Children’s Social and Behavioural Questionnaire (CSBQ) in ADHD subjects (n = 180), their unaffected siblings (n = 118) and healthy controls (n = 146). ADHD symptoms were assessed by a structured interview (K-SADS-PL) and the Conners’ ADHD questionnaires. Whole brain T1-weighted MPRAGE images were acquired and the structural MRI correlates of ASD symptom scores were analysed by modelling ASD symptom scores against white matter (WM) and grey matter (GM) volumes using mixed effects models which controlled for ADHD symptom levels. ASD symptoms were significantly elevated in ADHD subjects relative to both controls and unaffected siblings. ASD scores were predicted by the interaction between WM and GM volumes. Increasing ASD score was associated with greater GM volume. Equivocal results from previous structural studies in ADHD and ASD may be due to the fact that comorbidity has not been taken into account in studies to date. The current findings stress the need to account for issues of ASD comorbidity in ADHD. PMID:24979066

A home-based program of transcutaneous electrical nerve stimulation and task-related trunk training improves trunk control in patients with stroke: a randomized controlled clinical trial.

PubMed

Chan, Bill K S; Ng, Shamay S M; Ng, Gabriel Y F

2015-01-01

Impaired trunk motor control is common after stroke. Combining transcutaneous electrical nerve stimulation (TENS) with task-related trunk training (TRTT) has been shown to enhance the recovery of lower limb motor function. This study investigated whether combining TENS with TRTT would enhance trunk control after stroke. Methods. Thirty-seven subjects with stroke were recruited into a randomized controlled clinical trial. Subjects were randomly assigned to any one of the three 6-week home-based training groups: (1) TENS + TRTT, (2) placebo TENS + TRTT, or (3) control without active training. The outcome measures included isometric peak trunk flexion torque and extension torque; forward seated and lateral seated reaching distance to the affected and unaffected side; and Trunk Impairment Scale (TIS) scores. All outcome measures were assessed at baseline, after 3 and 6 weeks of training, and 4 weeks after training ended at follow-up. Both the TENS + TRTT and the placebo-TENS + TRTT groups had significantly greater improvements in isometric peak trunk flexion torque and extension torque, lateral seated reaching distance to affected and unaffected side, and TIS score than the control group after 3 weeks of training. The TENS + TRTT group had significantly greater and earlier improvement in its mean TIS score than the other 2 groups. Home-based TRTT is effective for improving trunk muscle strength, sitting functional reach and trunk motor control after stroke in subjects without somatosensory deficits. The addition of TENS to the trunk augments the effectiveness of the exercise in terms of TIS scores within the first 3 weeks of training. © The Author(s) 2014.

Structural Network Disorganization in Subjects at Clinical High Risk for Psychosis.

PubMed

Schmidt, André; Crossley, Nicolas A; Harrisberger, Fabienne; Smieskova, Renata; Lenz, Claudia; Riecher-Rössler, Anita; Lang, Undine E; McGuire, Philip; Fusar-Poli, Paolo; Borgwardt, Stefan

2017-05-01

Previous network studies in chronic schizophrenia patients revealed impaired structural organization of the brain's rich-club members, a set of highly interconnected hub regions that play an important integrative role for global brain communication. Moreover, impaired rich-club connectivity has also been found in unaffected siblings of schizophrenia patients, suggesting that abnormal rich-club connectivity is related to familiar, possibly reflecting genetic, vulnerability for schizophrenia. However, no study has yet investigated whether structural rich-club organization is also impaired in individuals with a clinical risk syndrome for psychosis. Diffusion tensor imaging and probabilistic tractography was used to construct structural whole-brain networks in 24 healthy controls and 24 subjects with an at-risk mental state (ARMS). Graph theory was applied to quantify the structural rich-club organization and global network properties. ARMS subjects revealed a significantly altered structural rich-club organization compared with the control group. The disruption of rich-club organization was associated with the severity of negative psychotic symptoms and led to an elevated level of modularity in ARMS subjects. This study shows that abnormal structural rich-club organization is already evident in clinical high-risk subjects for psychosis and further demonstrates the impact of rich-club disorganization on global network communication. Together with previous evidence in chronic schizophrenia patients and unaffected siblings, our findings suggest that abnormal structural rich-club organization may reflect an endophenotypic marker of psychosis. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

A functional Magnetic Resonance Imaging study of neurohemodynamic abnormalities during emotion processing in subjects at high risk for schizophrenia

PubMed Central

Venkatasubramanian, Ganesan; Puthumana, Dawn Thomas K.; Jayakumar, Peruvumba N.; Gangadhar, B. N.

2010-01-01

Background: Emotion processing abnormalities are considered among the core deficits in schizophrenia. Subjects at high risk (HR) for schizophrenia also show these deficits. Structural neuroimaging studies examining unaffected relatives at high risk for schizophrenia have demonstrated neuroanatomical abnormalities involving neo-cortical and sub-cortical brain regions related to emotion processing. The brain functional correlates of emotion processing in these HR subjects in the context of ecologically valid, real-life dynamic images using functional Magnetic Resonance Imaging (fMRI) has not been examined previously. Aim: To examine the neurohemodynamic abnormalities during emotion processing in unaffected subjects at high risk for schizophrenia in comparison with age-, sex-, handedness- and education-matched healthy controls, using fMRI. Materials and Methods: HR subjects for schizophrenia (n=17) and matched healthy controls (n=16) were examined. The emotion processing of fearful facial expression was examined using a culturally appropriate and valid tool for Indian subjects. The fMRI was performed in a 1.5-T scanner during an implicit emotion processing paradigm. The fMRI analyses were performed using the Statistical Parametric Mapping 2 (SPM2) software. Results: HR subjects had significantly reduced brain activations in left insula, left medial frontal gyrus, left inferior frontal gyrus, right cingulate gyrus, right precentral gyrus and right inferior parietal lobule. Hypothesis-driven region-of-interest analysis revealed hypoactivation of right amygdala in HR subjects. Conclusions: Study findings suggest that neurohemodynamic abnormalities involving limbic and frontal cortices could be potential indicators for increased vulnerability toward schizophrenia. The clinical utility of these novel findings in predicting the development of psychosis needs to be evaluated. PMID:21267363

Familial aggregation of MATRICS Consensus Cognitive Battery scores in a large sample of outpatients with schizophrenia and their unaffected relatives.

PubMed

Mucci, A; Galderisi, S; Green, M F; Nuechterlein, K; Rucci, P; Gibertoni, D; Rossi, A; Rocca, P; Bertolino, A; Bucci, P; Hellemann, G; Spisto, M; Palumbo, D; Aguglia, E; Amodeo, G; Amore, M; Bellomo, A; Brugnoli, R; Carpiniello, B; Dell'Osso, L; Di Fabio, F; di Giannantonio, M; Di Lorenzo, G; Marchesi, C; Monteleone, P; Montemagni, C; Oldani, L; Romano, R; Roncone, R; Stratta, P; Tenconi, E; Vita, A; Zeppegno, P; Maj, M

2018-06-01

The increased use of the MATRICS Consensus Cognitive Battery (MCCB) to investigate cognitive dysfunctions in schizophrenia fostered interest in its sensitivity in the context of family studies. As various measures of the same cognitive domains may have different power to distinguish between unaffected relatives of patients and controls, the relative sensitivity of MCCB tests for relative-control differences has to be established. We compared MCCB scores of 852 outpatients with schizophrenia (SCZ) with those of 342 unaffected relatives (REL) and a normative Italian sample of 774 healthy subjects (HCS). We examined familial aggregation of cognitive impairment by investigating within-family prediction of MCCB scores based on probands' scores. Multivariate analysis of variance was used to analyze group differences in adjusted MCCB scores. Weighted least-squares analysis was used to investigate whether probands' MCCB scores predicted REL neurocognitive performance. SCZ were significantly impaired on all MCCB domains. REL had intermediate scores between SCZ and HCS, showing a similar pattern of impairment, except for social cognition. Proband's scores significantly predicted REL MCCB scores on all domains except for visual learning. In a large sample of stable patients with schizophrenia, living in the community, and in their unaffected relatives, MCCB demonstrated sensitivity to cognitive deficits in both groups. Our findings of significant within-family prediction of MCCB scores might reflect disease-related genetic or environmental factors.

Increased neural responses to reward in adolescents and young adults with attention-deficit/hyperactivity disorder and their unaffected siblings.

PubMed

von Rhein, Daniel; Cools, Roshan; Zwiers, Marcel P; van der Schaaf, Marieke; Franke, Barbara; Luman, Marjolein; Oosterlaan, Jaap; Heslenfeld, Dirk J; Hoekstra, Pieter J; Hartman, Catharina A; Faraone, Stephen V; van Rooij, Daan; van Dongen, Eelco V; Lojowska, Maria; Mennes, Maarten; Buitelaar, Jan

2015-05-01

Attention-deficit/hyperactivity disorder (ADHD) is a heritable neuropsychiatric disorder associated with abnormal reward processing. Limited and inconsistent data exist about the neural mechanisms underlying this abnormality. Furthermore, it is not known whether reward processing is abnormal in unaffected siblings of participants with ADHD. We used event-related functional magnetic resonance imaging (fMRI) to investigate brain responses during reward anticipation and receipt with an adapted monetary incentive delay task in a large sample of adolescents and young adults with ADHD (n = 150), their unaffected siblings (n = 92), and control participants (n = 108), all of the same age. Participants with ADHD showed, relative to control participants, increased responses in the anterior cingulate, anterior frontal cortex, and cerebellum during reward anticipation, and in the orbitofrontal, occipital cortex and ventral striatum. Responses of unaffected siblings were increased in these regions as well, except for the cerebellum during anticipation and ventral striatum during receipt. ADHD in adolescents and young adults is associated with enhanced neural responses in frontostriatal circuitry to anticipation and receipt of reward. The findings support models emphasizing aberrant reward processing in ADHD, and suggest that processing of reward is subject to familial influences. Future studies using standard monetary incentive delay task parameters are needed to replicate our findings. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Fronto-striatal Dysfunction During Reward Processing in Unaffected Siblings of Schizophrenia Patients

PubMed Central

de Leeuw, Max; Kahn, René S.; Vink, Matthijs

2015-01-01

Schizophrenia is a psychiatric disorder that is associated with impaired functioning of the fronto-striatal network, in particular during reward processing. However, it is unclear whether this dysfunction is related to the illness itself or whether it reflects a genetic vulnerability to develop schizophrenia. Here, we examined reward processing in unaffected siblings of schizophrenia patients using functional magnetic resonance imaging. Brain activity was measured during reward anticipation and reward outcome in 27 unaffected siblings of schizophrenia patients and 29 healthy volunteers using a modified monetary incentive delay task. Task performance was manipulated online so that all subjects won the same amount of money. Despite equal performance, siblings showed reduced activation in the ventral striatum, insula, and supplementary motor area (SMA) during reward anticipation compared to controls. Decreased ventral striatal activation in siblings was correlated with sub-clinical negative symptoms. During the outcome of reward, siblings showed increased activation in the ventral striatum and orbitofrontal cortex compared to controls. Our finding of decreased activity in the ventral striatum during reward anticipation and increased activity in this region during receiving reward may indicate impaired cue processing in siblings. This is consistent with the notion of dopamine dysfunction typically associated with schizophrenia. Since unaffected siblings share on average 50% of their genes with their ill relatives, these deficits may be related to the genetic vulnerability for schizophrenia. PMID:25368371

Development of an assist controller with robot suit HAL for hemiplegic patients using motion data on the unaffected side.

PubMed

Kawamoto, Hiroaki; Kandone, Hideki; Sakurai, Takeru; Ariyasu, Ryohei; Ueno, Yukiko; Eguchi, Kiyoshi; Sankai, Yoshiyuki

2014-01-01

Among several characteristics seen in gait of hemiplegic patients after stroke, symmetry is known to be an indicator of the degree of impairment of walking ability. This paper proposes a control method for a wearable type lower limb motion assist robot to realize spontaneous symmetric gait for these individuals. This control method stores the motion of the unaffected limb during swing and then provides motion support on the affected limb during the subsequent swing using the stored pattern to realize symmetric gait based on spontaneous limb swing. This method is implemented on the robot suit HAL (Hybrid Assistive Limbs). Clinical tests were conducted in order to assess the feasibility of the control method. Our case study involved participation of one chronic stroke patient who was not able to flex his right knee. As a result, the walking support for hemiplegic leg provided by the HAL improved the subject's gait symmetry. The feasibility study showed promising basis for the future clinical study.

Structural brain network analysis in families multiply affected with bipolar I disorder.

PubMed

Forde, Natalie J; O'Donoghue, Stefani; Scanlon, Cathy; Emsell, Louise; Chaddock, Chris; Leemans, Alexander; Jeurissen, Ben; Barker, Gareth J; Cannon, Dara M; Murray, Robin M; McDonald, Colm

2015-10-30

Disrupted structural connectivity is associated with psychiatric illnesses including bipolar disorder (BP). Here we use structural brain network analysis to investigate connectivity abnormalities in multiply affected BP type I families, to assess the utility of dysconnectivity as a biomarker and its endophenotypic potential. Magnetic resonance diffusion images for 19 BP type I patients in remission, 21 of their first degree unaffected relatives, and 18 unrelated healthy controls underwent tractography. With the automated anatomical labelling atlas being used to define nodes, a connectivity matrix was generated for each subject. Network metrics were extracted with the Brain Connectivity Toolbox and then analysed for group differences, accounting for potential confounding effects of age, gender and familial association. Whole brain analysis revealed no differences between groups. Analysis of specific mainly frontal regions, previously implicated as potentially endophenotypic by functional magnetic resonance imaging analysis of the same cohort, revealed a significant effect of group in the right medial superior frontal gyrus and left middle frontal gyrus driven by reduced organisation in patients compared with controls. The organisation of whole brain networks of those affected with BP I does not differ from their unaffected relatives or healthy controls. In discreet frontal regions, however, anatomical connectivity is disrupted in patients but not in their unaffected relatives. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Atypical Activation during the Embedded Figures Task as a Functional Magnetic Resonance Imaging Endophenotype of Autism

ERIC Educational Resources Information Center

Spencer, Michael D.; Holt, Rosemary J.; Chura, Lindsay R.; Calder, Andrew J.; Suckling, John; Bullmore, Edward T.; Baron-Cohen, Simon

2012-01-01

Atypical activation during the Embedded Figures Task has been demonstrated in autism, but has not been investigated in siblings or related to measures of clinical severity. We identified atypical activation during the Embedded Figures Task in participants with autism and unaffected siblings compared with control subjects in a number of temporal…

A Shared Genetic Basis for Self-Limited Delayed Puberty and Idiopathic Hypogonadotropic Hypogonadism

PubMed Central

Zhu, Jia; Choa, Ruth E.-Y.; Guo, Michael H.; Plummer, Lacey; Buck, Cassandra; Palmert, Mark R.; Hirschhorn, Joel N.; Seminara, Stephanie B.

2015-01-01

Context: Delayed puberty (DP) is a common issue and, in the absence of an underlying condition, is typically self limited. Alhough DP seems to be heritable, no specific genetic cause for DP has yet been reported. In contrast, many genetic causes have been found for idiopathic hypogonadotropic hypogonadism (IHH), a rare disorder characterized by absent or stalled pubertal development. Objective: The objective of this retrospective study, conducted at academic medical centers, was to determine whether variants in IHH genes contribute to the pathogenesis of DP. Subjects and Outcome Measures: Potentially pathogenic variants in IHH genes were identified in two cohorts: 1) DP family members of an IHH proband previously found to have a variant in an IHH gene, with unaffected family members serving as controls, and 2) DP individuals with no family history of IHH, with ethnically matched control subjects drawn from the Exome Aggregation Consortium. Results: In pedigrees with an IHH proband, the proband's variant was shared by 53% (10/19) of DP family members vs 12% (4/33) of unaffected family members (P = .003). In DP subjects with no family history of IHH, 14% (8/56) had potentially pathogenic variants in IHH genes vs 5.6% (1 907/33 855) of controls (P = .01). Potentially pathogenic variants were found in multiple DP subjects for the genes IL17RD and TAC3. Conclusions: These findings suggest that variants in IHH genes can contribute to the pathogenesis of self-limited DP. Thus, at least in some cases, self-limited DP shares an underlying pathophysiology with IHH. PMID:25636053

Acute effects of whole-body vibration on the motor function of patients with stroke: a randomized clinical trial.

PubMed

Silva, Adriana Teresa; Dias, Miqueline Pivoto Faria; Calixto, Ruanito; Carone, Antonio Luis; Martinez, Beatriz Bertolaccini; Silva, Andreia Maria; Honorato, Donizeti Cesar

2014-04-01

The aim of this study was to investigate the acute effects of whole-body vibration on the motor function of patients with stroke. The present investigation was a randomized clinical trial studying 43 individuals with hemiparesis after stroke, with 33 subjects allocated to the intervention group and 10 subjects allocated to the control group. The intervention group was subjected to one session of vibration therapy (frequency of 50 Hz and amplitude of 2 mm) comprising four 1-min series with 1-min rest intervals between series in three body positions: bipedal stances with the knees flexed to 30 degrees and 90 degrees and a unipedal stance on the paretic limb. The analytical tests were as follows: simultaneous electromyography of the affected and unaffected tibialis anterior and rectus femoris muscles bilaterally in voluntary isometric contraction; the Six-Minute Walk Test; the Stair-Climb Test; and the Timed Get-Up-and-Go Test. The data were analyzed by independent and paired t tests and by analysis of covariance. There was no evidence of effects on the group and time interaction relative to variables affected side rectus femoris, unaffected side rectus femoris, affected side tibialis anterior, unaffected side tibialis anterior, and the Stair-Climb Test (P > 0.05). There was evidence of effects on the group interaction relative to variables Six-Minute Walk Test and Timed Get-Up-and-Go Test (P < 0.05). Whole-body vibration contributed little to improve the functional levels of stroke patients.

Is There an Association between Advanced Paternal Age and Endophenotype Deficit Levels in Schizophrenia?

PubMed Central

Tsuang, Debby; Esterberg, Michelle; Braff, David; Calkins, Monica; Cadenhead, Kristin; Dobie, Dorcas; Freedman, Robert; Green, Michael F.; Greenwood, Tiffany; Gur, Raquel; Gur, Ruben; Horan, William; Lazzeroni, Laura C.; Light, Gregory A.; Millard, Steven P.; Olincy, Ann; Nuechterlein, Keith; Seidman, Larry; Siever, Larry; Silverman, Jeremy; Stone, William; Sprock, Joyce; Sugar, Catherine; Swerdlow, Neal; Tsuang, Ming; Turetsky, Bruce; Radant, Allen

2014-01-01

The children of older fathers have increased risks of developing schizophrenia spectrum disorders, and among those who develop these disorders, those with older fathers present with more severe clinical symptoms. However, the influence of advanced paternal age on other important domains related to schizophrenia, such as quantitative endophenotype deficit levels, remains unknown. This study investigated the associations between paternal age and level of endophenotypic impairment in a well-characterized family-based sample from the Consortium on the Genetics of Schizophrenia (COGS). All families included at least one affected subject and one unaffected sibling. Subjects met criteria for schizophrenia (probands; n = 293) or were unaffected first-degree siblings of those probands (n = 382). Paternal age at the time of subjects’ birth was documented. Subjects completed a comprehensive clinical assessment and a battery of tests that measured 16 endophenotypes. After controlling for covariates, potential paternal age–endophenotype associations were analyzed using one model that included probands alone and a second model that included both probands and unaffected siblings. Endophenotype deficits in the Identical Pairs version of the 4-digit Continuous Performance Test and in the Penn Computerized Neurocognitive Battery verbal memory test showed significant associations with paternal age. However, after correcting for multiple comparisons, no endophenotype was significantly associated with paternal age. These findings suggest that factors other than advanced paternal age at birth may account for endophenotypic deficit levels in schizophrenia. PMID:24523888

Gray Matter Differences between Pediatric Obsessive-Compulsive Disorder Patients and High-Risk Siblings: A Preliminary Voxel-Based Morphometry Study

PubMed Central

Gilbert, Andrew R.; Keshavan, Matcheri S.; Diwadkar, Vaibhav; Nutche, Jeffrey; MacMaster, Frank; Easter, Phillip C.; Buhagiar, Christian J.; Rosenberg, David R.

2008-01-01

Neuroimaging studies have identified alterations in frontostriatal circuitry in OCD. Voxel-based morphometry (VBM) allows for the assessment of differences in gray matter density across the whole brain. VBM has not previously been used to examine regional gray matter density in pediatric OCD patients and the siblings of pediatric OCD patients. Volumetric magnetic resonance imaging (MRI) studies were conducted in 10 psychotropic-naïve pediatric patients with OCD, 10 unaffected siblings of pediatric patients with OCD, and 10 healthy controls. VBM analysis was conducted using SPM2. Statistical comparisons were performed with the general linear model, implementing small volume random field corrections for a priori regions of interest (anterior cingulate cortex or ACC, striatum and thalamus). VBM analysis revealed significantly lower gray matter density in OCD patients compared to healthy in the left ACC and bilateral medial superior frontal gyrus (SFG). Furthermore, a small volume correction was used to identify a significantly greater gray matter density in the right putamen in OCD patients as compared to unaffected siblings of OCD patients. These findings in patients, siblings, and healthy controls, although preliminary, suggest the presence of gray matter structural differences between affected subjects and healthy controls as well as between affected subjects and individuals at risk for OCD. PMID:18314272

Risk factors for suicide in Huntingtons disease: a retrospective case controlled study.

PubMed

Lipe, H; Schultz, A; Bird, T D

1993-12-15

We reviewed 11 instances of suicide in HD families to determine what clinical and social characteristics might alert health professionals to increased suicide potential. The subjects were eight males and one female affected with HD, one female at risk for HD, and one unaffected female spouse, ranging in age from 24 to 65 years. Six of the nine individuals with HD who committed suicide were single or divorced. Duration of HD symptoms ranged from 1 to 14 years. The single most important risk factor for suicide in HD was having no offspring. Other suicides in the family, being unmarried, having contact with others affected with HD, living alone, and depression slightly increased the risk of suicide. The suicide of an unaffected spouse and an individual at risk, but unaffected, emphasizes the heavy burden of HD on other family members. Recognition of these risk factors should allow health care providers to assist families coping with HD and presymptomatic diagnosis.

[Mutation analysis of FGFR3 gene in a family featuring hereditary dwarfism].

PubMed

Zhang, Qiong; Jiang, Hai-ou; Quan, Qing-li; Li, Jun; He, Ting; Huang, Xue-shuang

2011-12-01

To investigate the clinical symptoms and potential mutation in FGFR3 gene for a family featuring hereditary dwarfism in order to attain diagnosis and provide prenatal diagnosis. Five patients and two unaffected relatives from the family, in addition with 100 healthy controls, were recruited. Genome DNA was extracted. Exons 10 and 13 of the FGFR3 gene were amplified using polymerase chain reaction (PCR). PCR products were sequenced in both directions. All patients had similar features including short stature, short limbs, lumbar hyperlordosis but normal craniofacial features. A heterozygous mutation G1620T (N540K) was identified in the cDNA from all patients but not in the unaffected relatives and 100 control subjects. A heterozygous G380R mutation was excluded. The hereditary dwarfism featured by this family has been caused by hypochondroplasia (HCH) due to a N540K mutation in the FGFR3 gene.

Is impulsivity a common trait in bipolar and unipolar disorders?

PubMed

Henna, Elaine; Hatch, John P; Nicoletti, Mark; Swann, Alan C; Zunta-Soares, Giovana; Soares, Jair C

2013-03-01

  Impulsivity is increased in bipolar and unipolar disorders during episodes and is associated with substance abuse disorders and suicide risk. Impulsivity between episodes predisposes to relapses and poor therapeutic compliance. However, there is little information about impulsivity during euthymia in mood disorders. We sought to investigate trait impulsivity in euthymic bipolar and unipolar disorder patients, comparing them to healthy individuals and unaffected relatives of bipolar disorder patients.   Impulsivity was evaluated by the Barratt Impulsiveness Scale (BIS-11A) in 54 bipolar disorder patients, 25 unipolar disorder patients, 136 healthy volunteers, and 14 unaffected relatives. The BIS-11A mean scores for all four groups were compared through the Games-Howell test for all possible pairwise combinations. Additionally, we compared impulsivity in bipolar and unipolar disorder patients with and without a history of suicide attempt and substance abuse disorder.   Bipolar and unipolar disorder patients scored significantly higher than the healthy controls and unaffected relatives on all measures of the BIS-11A except for attentional impulsivity. On the attentional impulsivity measures there were no differences among the unaffected relatives and the bipolar and unipolar disorder groups, but all three of these groups scored higher than the healthy participant group. There was no difference in impulsivity between bipolar and unipolar disorder subjects with and without suicide attempt. However, impulsivity was higher among bipolar and unipolar disorder subjects with past substance use disorder compared to patients without such a history.   Questionnaire-measured impulsivity appears to be relatively independent of mood state in bipolar and unipolar disorder patients; it remains elevated in euthymia and is higher in individuals with past substance abuse. Elevated attentional and lower non-planning impulsivity in unaffected relatives of bipolar disorder patients distinguished them from healthy participants, suggesting that increased attentional impulsivity may predispose to development of affective disorders, while reduced attentional impulsivity may be protective. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Oxidative Burst of Circulating Neutrophils Following Traumatic Brain Injury in Human

PubMed Central

Liao, Yiliu; Liu, Peng; Guo, Fangyuan; Zhang, Zhi-Yuan; Zhang, Zhiren

2013-01-01

Besides secondary injury at the lesional site, Traumatic brain injury (TBI) can cause a systemic inflammatory response, which may cause damage to initially unaffected organs and potentially further exacerbate the original injury. Here we investigated plasma levels of important inflammatory mediators, oxidative activity of circulating leukocytes, particularly focusing on neutrophils, from TBI subjects and control subjects with general trauma from 6 hours to 2 weeks following injury, comparing with values from uninjured subjects. We observed increased plasma level of inflammatory cytokines/molecules TNF-α, IL-6 and CRP, dramatically increased circulating leukocyte counts and elevated expression of TNF-α and iNOS in circulating leukocytes from TBI patients, which suggests a systemic inflammatory response following TBI. Our data further showed increased free radical production in leukocyte homogenates and elevated expression of key oxidative enzymes iNOS, COX-2 and NADPH oxidase (gp91phox) in circulating leukocytes, indicating an intense induction of oxidative burst following TBI, which is significantly greater than that in control subjects with general trauma. Furthermore, flow cytometry assay proved neutrophils as the largest population in circulation after TBI and showed significantly up-regulated oxidative activity and suppressed phagocytosis rate for circulating neutrophils following brain trauma. It suggests that the highly activated neutrophils might play an important role in the secondary damage, even outside the injured brain. Taken together, the potent systemic inflammatory response induced by TBI, especially the intensively increase oxidative activity of circulating leukocytes, mainly neutrophils, may lead to a systemic damage, dysfunction/damage of bystander tissues/organs and even further exacerbate secondary local damage. Controlling these pathophysiological processes may be a promising therapeutic strategy and will protect unaffected organs and the injured brain from the secondary damage. PMID:23894384

Studies of Filipino patients with systemic lupus erythematosus: autoantibody profile of first-degree relatives.

PubMed

Navarra, S V; Ishimori, M I; Uy, E A; Hamijoyo, L; Sama, J; James, J A; Holers, V M; Weisman, M H

2011-04-01

This study surveyed the frequency of autoantibodies among un-affected first-degree relatives (FDRs) of Filipino systemic lupus erythematosus (SLE) patients compared with healthy un-related Filipino controls. The sensitivity, specificity and predictive value of the autoantibodies for SLE diagnosis were also assessed in this Filipino cohort. Filipino patients included in the University of Santo Tomas (UST) Lupus Database and un-affected FDRs were recruited. Healthy controls included those with no known personal or family history of autoimmune disease. The following autoantibodies were tested in all subjects: anti-nuclear antibody (ANA), anti-dsDNA, anti-Ro/SSA, anti-chromatin, anti-thyroid microsome, and anti-cardiolipin antibodies. Participants included 232 SLE patients, 546 FDRs, and 221 healthy controls. Median age of patients was 27 (range 8-66) years with median disease duration of 27.5 (range 1-292) months. Median age of FDRs was 42.0 (range 5-87) years. Compared with healthy controls, there were significantly more FDRs with positive ANA at titers 1 : 40 to 1 : 160 (p < 0.001) and 1 : 320 (p = 0.003), anti-Ro/SSA (4.94% versus 0.45%, p = 0.003), and anti-dsDNA ≥ 5.0 IU/ml (4.58% versus 1.36%, p = 0.031). ANA titer ≥1  :  160, anti-dsDNA, anti-Ro/SSA and anti-chromatin had the highest predictive value for SLE diagnosis. These findings reinforce the role of genetic influence in SLE risk among Filipinos, with a significant proportion of un-affected FDRs of SLE patients testing positive for autoantibodies compared with healthy Filipino controls. A longitudinal observational study in this same cohort will determine which proportion of these un-affected FDRs will evolve into clinical SLE disease in the future.

Visual suppression of the vestibulo-ocular reflex during space flight

NASA Technical Reports Server (NTRS)

Uri, John J.; Thornton, William E.; Moore, Thomas P.; Pool, Sam L.

1989-01-01

Visual suppression of the vestibulo-ocular reflex was studied in 16 subjects on 4 Space Shuttle missions. Eye movements were recorded by electro-oculography while subjects fixated a head mounted target during active sinusoidal head oscillation at 0.3 Hz. Adequacy of suppression was evaluated by the number of nystagmus beats, the mean amplitude of each beat, and the cumulative amplitude of nystagmus during two head oscillation cycles. Vestibulo-ocular reflex suppression was unaffected by space flight. Subjects with space motion sickness during flight had significantly more nystagmus beats than unaffected individuals. These susceptible subjects also tended to have more nystagmus beats before flight.

Patients with sacroiliac joint dysfunction exhibit altered movement strategies when performing a sit-to-stand task.

PubMed

Capobianco, Robyn A; Feeney, Daniel F; Jeffers, Jana R; Nelson-Wong, Erika; Morreale, Joseph; Grabowski, Alena M; Enoka, Roger M

2018-04-03

The ability to rise from a chair is a basic functional task that is frequently compromised in individuals diagnosed with orthopedic disorders in the low back and hip. There is no published literature that describes how this task is altered by sacroiliac joint dysfunction (SIJD). The objective of this study was to compare lower extremity biomechanics and the onset of muscle activity when rising from a chair in subjects with SIJD and in healthy persons. Six women with unilateral SIJD and six age-matched healthy controls performed a sit-to-stand task while we measured kinematics, kinetics, and muscle activity. Subjects stood up at a preferred speed from a seated position on an armless and backless adjustable stool. We measured kinematics with a 10-camera motion capture system, ground reaction forces for each leg with force plates, and muscle activity with surface electromyography. Joint angles and torques were calculated using inverse dynamics. Leg-loading rate was quantified as the average slope of vertical ground reaction (VGRF) force during the 500-millisecond interval preceding maximal knee extension. Between-leg differences in loading rates and peak VGRFs were significantly greater for the SIJD group than for the control group. Maximal hip angles were significantly less for the SIJD group (p=.001). Peak hip moment in the SIJD group was significantly greater in the unaffected leg (0.75±0.22 N⋅m/kg) than in the affected leg (0.47±0.29 N⋅m/kg, p=.005). There were no between-leg or between-group differences for peak knee or ankle moments. The onset of activity in the latissimus dorsi muscle on the affected side was delayed and the erector spinae muscles were activated earlier in the SIJD group than in the control group. Subjects with SIJD have a greater VGRF on the unaffected leg, generate a greater peak hip moment in the unaffected leg, use a smaller range of motion at the hip joint of the affected leg, and delay the onset of a key muscle on the affected side when rising from a seated position. Copyright © 2018 Elsevier Inc. All rights reserved.

Cortical reorganization associated lower extremity motor recovery as evidenced by functional MRI and diffusion tensor tractography in a stroke patient.

PubMed

Jang, Sung Ho; You, Sung H; Kwon, Yong-Hyun; Hallett, Mark; Lee, Mi Young; Ahn, Sang Ho

2005-01-01

Recovery mechanisms supporting upper extremity motor recovery following stroke are well established, but cortical mechanism associated with lower extremity motor recovery is unknown. The aim of this study was to assess cortical reorganization associated with lower extremity motor recovery in a hemiparetic patient. Six control subjects and a 17 year-old woman with left intracerebral hemorrhage due to an arterio-venous malformation rupture were evaluated. The motor function of the paretic (left) hip and knee had recovered slowly to the extent of her being able to overcome gravity for 10 months after the onset of stroke. However, her paretic upper extremity showed no significant motor recovery. Blood oxygenation level dependent (BOLD) functional MRI at 1.5 Tesla was used to determine the acutual location of cortical activation in the predefined regions of interest. Concurrently, Diffusion Tensor Imaging (DTI) in combination with a novel 3D-fiber reconstruction algorithm was utilized to investigate the pattern of the corticospinal pathway connectivity between the areas of the motor stream. All subjects' body parts were secured in the scanner and performed a sequential knee flexion-extension with a predetermined angle of 0-60 degrees at 0.5 Hz. Controls showed anticipated activation in the contralateral sensorimotor cortex (SM1) and the descending corticospinal fibers stemming from motor cortex. In contrast to control normal subjects, the stroke patient showed fMRI activation only in the unaffected (right) primary SM1 during either paretic or nonparetic knee movements. DTT fiber tracing data showed that the corticospinal tract fibers were found only in the unaffected hemisphere but not in the affected hemisphere. Our results indicate that an ipsilateral motor pathway from the unaffected (right) motor cortex to the paretic (right) leg was present in this patient. This study raises the potential that the contralesional (ipsilateral) SM1 is involved in cortical reorganization associated lower extremity motor recovery in stroke. This study is the first neuroimaging evidence that the combined fMRI and DTI fiber tracing can significantly expand the explanatory power of probing cortical reorganization underlying motor recovery mechanism in stroke.

A prospective study of autistic-like traits in unaffected siblings of probands with autism spectrum disorder.

PubMed

Georgiades, Stelios; Szatmari, Peter; Zwaigenbaum, Lonnie; Bryson, Susan; Brian, Jessica; Roberts, Wendy; Smith, Isabel; Vaillancourt, Tracy; Roncadin, Caroline; Garon, Nancy

2013-01-01

The presence of autistic-like traits in relatives of individuals with autism spectrum disorder (ASD) is well recognized, but, to our knowledge, the emergence of these traits early in development has not been studied. To prospectively investigate the emergence of autistic-like traits in unaffected (no ASD diagnosis) infant siblings of probands diagnosed as having ASD. Two groups of children unaffected with ASD were assessed prospectively-siblings of probands diagnosed as having ASD (high risk [HR]) and control subjects with no family history of ASD (low risk [LR]). Scores on a measure of autistic-like traits at 12 months of age were used in a cluster analysis of the entire sample. A prospective study of infant siblings of probands with ASD from 3 diagnostic centers in Canada. The study included 170 HR and 90 LR children, none of whom was diagnosed as having ASD at age 3 years. The Autism Observation Scale for Infants was used to measure autistic-like traits and derive clusters at 12 months of age. Clusters were compared on ASD symptoms, cognitive abilities, and social-emotional difficulties at age 3 years. Two clusters were identified. Cluster 1 (n = 37; 14.2% of total sample) had significantly higher levels of autistic-like traits compared with cluster 2. Within cluster 1, 33 children came from the siblings (19.4% of HR group) and only 4 came from the control subjects (4.5% of LR group). At age 3 years, children from cluster 1 had more social-communication impairment (effect size > 0.70; P < .001), lower cognitive abilities (effect size = -0.59; P < .005), and more internalizing problems (effect size = 0.55; P = .01). Compared with control subjects, HR siblings had a relative risk of 4.3 (95% CI,1.6-11.9) for membership in cluster 1. Study findings suggest the emergence of autistic-like traits resembling a broader autism phenotype by 12 months of age in approximately 19% of HR siblings who did not meet ASD diagnostic criteria at age 3 years.

Sensorimotor Control of Tracking Movements at Various Speeds for Stroke Patients as Well as Age-Matched and Young Healthy Subjects

PubMed Central

Ao, Di; Song, Rong; Tong, Kai-yu

2015-01-01

There are aging- and stroke-induced changes on sensorimotor control in daily activities, but their mechanisms have not been well investigated. This study explored speed-, aging-, and stroke-induced changes on sensorimotor control. Eleven stroke patients (affected sides and unaffected sides) and 20 control subjects (10 young and 10 age-matched individuals) were enrolled to perform elbow tracking tasks using sinusoidal trajectories, which included 6 target speeds (15.7, 31.4, 47.1, 62.8, 78.5, and 94.2 deg/s). The actual elbow angle was recorded and displayed on a screen as visual feedback, and three indicators, the root mean square error (RMSE), normalized integrated jerk (NIJ) and integral of the power spectrum density of normalized speed (IPNS), were used to investigate the strategy of sensorimotor control. Both NIJ and IPNS had significant differences among the four groups (P<0.01), and the values were ranked in the following order: young controls < age-matched controls

Cortical asymmetries in unaffected siblings of patients with obsessive-compulsive disorder.

PubMed

Peng, Ziwen; Li, Gang; Shi, Feng; Shi, Changzheng; Yang, Qiong; Chan, Raymond C K; Shen, Dinggang

2015-12-30

Obsessive-compulsive disorder (OCD) is considered to be associated with atypical brain asymmetry. However, no study has examined the asymmetry in OCD from the perspective of cortical morphometry. This study is aimed to describe the characteristics of cortical asymmetry in OCD patients, and to investigate whether these features exist in their unaffected siblings - a vital step in identifying putative endophenotypes for OCD. A total of 48 subjects (16 OCD patients, 16 unaffected siblings, and 16 matched controls) were recruited who had complete magnetic resonance imaging scans. Left-right hemispheric asymmetries of cortical thickness were measured using a surface-based threshold-free cluster enhancement method. OCD patients and siblings both showed leftward asymmetries of cortical thickness in the anterior cingulate cortex (ACC), which showed a significant positive correlation with compulsive subscale scores. In addition, siblings and healthy controls showed significantly decreased leftward asymmetries in the orbitofrontal cortex (OFC), and the decreased leftward bias in the OFC was accompanied by lower scales on the Yale-Brown Obsessive-Compulsive Scale. To sum up, leftward asymmetries of cortical thickness in the ACC may represent an endophenotype of increased hereditary risk for OCD, while decreased leftward asymmetries of cortical thickness in the OFC may represent a protective factor. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Cheiloscopy and dermatoglyphics as genetic markers in the transmission of cleft lip and palate: A case-control study.

PubMed

Saujanya, K; Prasad, M Ghanashyam; Sushma, B; Kumar, J Raghavendra; Reddy, Y S N; Niranjani, K

2016-01-01

Determining the relative risk of cleft lip and palate (CL[P]) on the basis of lip prints and dermatoglyphics as genetic background may be useful for genetic counseling, and the development of future preventive measures. (1) To analyze the various pattern types of lip prints and dermatoglyphics in parents of CL(P) children and to detect if any specific type can be contemplated as a genetic marker in the transmission of CL(P). (2) To compare these patterns with that of parents of unaffected children. 31 parents of children with CL(P) as a study group, and 31 parents of unaffected children as control group were included. Lip prints and finger prints were collected from all subjects and analysis of both patterns was carried out followed by a comparison of the patterns of unaffected parents with the controls statistically. Among the mothers of the study group, type O followed by type IIa lip patterns were found to be significantly higher in upper and lower lips, and in fathers type IIa followed by type O were significantly higher. In the control group, type IIb followed by type III were higher in both fathers and mothers. Dermatoglyphic analysis of palm and finger prints revealed no significant difference in the pattern types and total ridge counts, but the Atd angle asymmetry was found to be significant between study and control group. Types IIa and O lip patterns, asymmetry of Atd angles can be considered as genetic markers for the transmission of CL(P) deformity to offsprings.

RASopathies are associated with a distinct personality profile.

PubMed

Bizaoui, Varoona; Gage, Jessica; Brar, Rita; Rauen, Katherine A; Weiss, Lauren A

2018-06-01

Personality is a complex, yet partially heritable, trait. Although some Mendelian diseases like Williams-Beuren syndrome are associated with a particular personality profile, studies have failed to assign the personality features to a single gene or pathway. As a family of monogenic disorders caused by mutations in the Ras/MAPK pathway known to influence social behavior, RASopathies are likely to provide insight into the genetic basis of personality. Eighty subjects diagnosed with cardiofaciocutaneous syndrome, Costello syndrome, neurofibromatosis type 1, and Noonan syndrome were assessed using a parent-report BFQ-C (Big Five Questionnaire for Children) evaluating agreeableness, extraversion, conscientiousness, intellect/openness, and neuroticism, along with 55 unaffected sibling controls. A short questionnaire was added to assess sense of humor. RASopathy subjects and sibling controls were compared for individual components of personality, multidimensional personality profiles, and individual questions using Student tests, analysis of variance, and principal component analysis. RASopathy subjects were given lower scores on average compared to sibling controls in agreeableness, extraversion, conscientiousness, openness, and sense of humor, and similar scores in neuroticism. When comparing the multidimensional personality profile between groups, RASopathies showed a distinct profile from unaffected siblings, but no difference in this global profile was found within RASopathies, revealing a common profile for the Ras/MAPK-related disorders. In addition, several syndrome-specific strengths or weaknesses were observed in individual domains. We describe for the first time an association between a single pathway and a specific personality profile, providing a better understanding of the genetics underlying personality, and new tools for tailoring educational and behavioral approaches for individuals with RASopathies. © 2018 Wiley Periodicals, Inc.

Sporadic adult onset primary torsion dystonia is a genetic disorder by the temporal discrimination test.

PubMed

Kimmich, Okka; Bradley, David; Whelan, Robert; Mulrooney, Nicola; Reilly, Richard B; Hutchinson, Siobhan; O'Riordan, Sean; Hutchinson, Michael

2011-09-01

Adult-onset primary torsion dystonia is an autosomal dominant disorder with markedly reduced penetrance; patients with sporadic adult-onset primary torsion dystonia are much more prevalent than familial. The temporal discrimination threshold is the shortest time interval at which two stimuli are detected to be asynchronous and has been shown to be abnormal in adult-onset primary torsion dystonia. The aim was to determine the frequency of abnormal temporal discrimination thresholds in patients with sporadic adult-onset primary torsion dystonia and their first-degree relatives. We hypothesized that abnormal temporal discrimination thresholds in first relatives would be compatible with an autosomal dominant endophenotype. Temporal discrimination thresholds were examined in 61 control subjects (39 subjects <50 years of age; 22 subjects >50 years of age), 32 patients with sporadic adult-onset primary torsion dystonia (cervical dystonia n = 30, spasmodic dysphonia n = 1 and Meige's syndrome n = 1) and 73 unaffected first-degree relatives (36 siblings, 36 offspring and one parent) using visual and tactile stimuli. Z-scores were calculated for all subjects; a Z > 2.5 was considered abnormal. Abnormal temporal discrimination thresholds were found in 1/61 (2%) control subjects, 27/32 (84%) patients with adult-onset primary torsion dystonia and 32/73 (44%) unaffected relatives [siblings (20/36; 56%), offspring (11/36; 31%) and one parent]. When two or more relatives were tested in any one family, 22 of 24 families had at least one first-degree relative with an abnormal temporal discrimination threshold. The frequency of abnormal temporal discrimination thresholds in first-degree relatives of patients with sporadic adult-onset primary torsion dystonia is compatible with an autosomal dominant disorder and supports the hypothesis that apparently sporadic adult-onset primary torsion dystonia is genetic in origin.

Identification of genetic markers associated with Gilles de la Tourette syndrome in an Afrikaner population.

PubMed Central

Simonic, I; Gericke, G S; Ott, J; Weber, J L

1998-01-01

Because gene-mapping efforts, using large kindreds and parametric methods of analysis, for the neurologic disorder Tourette syndrome have failed, efforts are being redirected toward association studies in young, genetically isolated populations. The availability of dense marker maps makes it feasible to search for association throughout the entire genome. We report the results of such a genome scan using DNA samples from Tourette patients and unaffected control subjects from the South African Afrikaner population. To optimize mapping efficiency, we chose a two-step strategy. First, we screened pools of DNA samples from both affected and control individuals, using a dense collection of 1,167 short tandem-repeat polymorphisms distributed throughout the genome. Second, we typed those markers displaying evidence of allele frequency-distribution shifts, along with additional tightly linked markers, using DNA from each affected and unaffected individual. To reduce false positives, we tested two independent groups of case and control subjects. Strongest evidence for association (P values 10-2 to 10-5) were obtained for markers within chromosomal regions encompassing D2S1790 near the chromosome 2 centromere, D6S477 on distal 6p, D8S257 on 8q, D11S933 on 11q, D14S1003 on proximal 14q, D20S1085 on distal 20q, and D21S1252 on 21q. PMID:9718333

Identification of genetic markers associated with Gilles de la Tourette syndrome in an Afrikaner population.

PubMed

Simonic, I; Gericke, G S; Ott, J; Weber, J L

1998-09-01

Because gene-mapping efforts, using large kindreds and parametric methods of analysis, for the neurologic disorder Tourette syndrome have failed, efforts are being redirected toward association studies in young, genetically isolated populations. The availability of dense marker maps makes it feasible to search for association throughout the entire genome. We report the results of such a genome scan using DNA samples from Tourette patients and unaffected control subjects from the South African Afrikaner population. To optimize mapping efficiency, we chose a two-step strategy. First, we screened pools of DNA samples from both affected and control individuals, using a dense collection of 1,167 short tandem-repeat polymorphisms distributed throughout the genome. Second, we typed those markers displaying evidence of allele frequency-distribution shifts, along with additional tightly linked markers, using DNA from each affected and unaffected individual. To reduce false positives, we tested two independent groups of case and control subjects. Strongest evidence for association (P values 10-2 to 10-5) were obtained for markers within chromosomal regions encompassing D2S1790 near the chromosome 2 centromere, D6S477 on distal 6p, D8S257 on 8q, D11S933 on 11q, D14S1003 on proximal 14q, D20S1085 on distal 20q, and D21S1252 on 21q.

Retinal Nerve Fiber Layer and Peripapillary Choroidal Thicknesses in Non-Glaucomatous Unilateral Optic Atrophy Compared with Unilateral Advanced Pseudoexfoliative Glaucoma.

PubMed

Kucukevcilioglu, Murat; Ayyildiz, Onder; Aykas, Seckin; Gokce, Gokcen; Koylu, Mehmet Talay; Ozgonul, Cem; Ozge, Gokhan; Mumcuoglu, Tarkan; Yumusak, Erhan

2017-02-01

To investigate retinal nerve fiber layer thickness (RNFL-T) and peripapillary choroidal thickness (PC-T) in non-glaucomatous optic atrophy (OA) patients in comparison with unaffected and control eyes, furthermore, to compare thickness profiles with unilateral pseudoexfoliative advanced glaucoma. Thirty-three eyes with OA (Group A), 33 unaffected fellow eyes (Group B), 25 right eyes of 25 control subjects (Group C), and 15 eyes with advanced glaucoma (Group D) were enrolled. RNFL-T was measured in six regions by spectral-domain optical coherence tomography. Enhanced depth imaging optical coherence tomography was obtained to evaluate PC-T in corresponding regions. RNFL-T was significantly lower in Group A than in Groups B and C globally and at all peripapillary regions (all p < 0.001). P-CT in Group A was significantly lower globally (p = 0.03) and in three regions (temporal, p = 0.001; temporal-superior, p = 0.01; and nasal-inferior, p = 0.037) versus Group C. However, it was significantly thinner than in Group B in all regions (temporal, p = 0.02; temporal-superior, p = 0.013; nasal-superior, p = 0.044; nasal, p = 0.02; nasal-inferior, p < 0.001; and temporal-inferior, p < 0.001) and globally (p < 0.001). In Group A RNFL-T (thicker superiorly and inferiorly; thinner temporally and nasally) and PC-T (superior > temporal > nasal > inferior) profiles were almost identical to that in unaffected fellow eyes and control eyes. However, Group D showed different patterns with less regional differences in RNFL-T, and the greatest value of PC-T in nasal quadrant. Besides retinal nerve fiber layer thinning, non-glaucomatous OA is associated with choroidal thinning. The RNFL-T and PC-T profiles in advanced glaucoma eyes differed from the common patterns seen among OA eyes, unaffected fellow eyes, and control eyes.

Cleft lip with or without cleft palate and dermatoglyphic asymmetry: evaluation of a Chinese population.

PubMed

Neiswanger, K; Cooper, M E; Weinberg, S M; Flodman, P; Keglovits, A Bundens; Liu, Y; Hu, D N; Melnick, M; Spence, M A; Marazita, M L

2002-08-01

To determine if Chinese individuals with non syndromic cleft lip with or without cleft palate (CL/P) display more dermatoglyphic asymmetry than unaffected relatives or controls. Case-control study with two control groups (genetically related and unrelated). A total of 500 CL/P probands from Shanghai, China, 421 unaffected relatives, and 66 controls of Chinese heritage. Finger and palm prints were collected, and pattern frequencies, total ridge counts (TRC), and atd angles were calculated. Asymmetry scores between right and left hands were defined for each of the three dermatoglyphic measures. Probands' asymmetry scores were compared statistically with the scores of unaffected relatives and controls. In general, the probands' asymmetry scores for TRC and atd angle did not differ significantly from the scores of either unaffected relatives or controls. However, probands with a positive family history of clefting showed significantly more asymmetry in their pattern types than either probands without a family history, unaffected relatives or controls. These results suggest that a unique genetic mechanism of developmental instability may obtain in CL/P individuals with a positive family history of clefting.

Familial idiopathic pulmonary fibrosis. Evidence of lung inflammation in unaffected family members

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bitterman, P.B.; Rennard, S.I.; Keogh, B.A.

1986-05-22

We evaluated 17 clinically unaffected members of three families with an autosomal dominant form of idiopathic pulmonary fibrosis for evidence of alveolar inflammation. Each person in the study was examined by gallium-67 scanning for a general estimate of pulmonary inflammation, and by bronchoalveolar lavage for characterization of the types of recovered cells and their state of activation. Eight of the 17 subjects had evidence of alveolar inflammation on the lavage studies. Supporting data included increased numbers of neutrophils and activated macrophages that released one or more neutrophil chemoattractants, and growth factors for lung fibroblasts--findings similar to those observed in patientsmore » with overt idiopathic pulmonary fibrosis. Four of these eight also had a positive gallium scan; in all the other clinically unaffected subjects the scan was normal. During a follow-up of two to four years in seven of the eight subjects who had evidence of inflammation, no clinical evidence of pulmonary fibrosis has appeared. These results indicate that alveolar inflammation occurs in approximately half the clinically unaffected family members at risk of inheriting autosomal dominant idiopathic pulmonary fibrosis. Whether these persons with evidence of pulmonary inflammation but no fibrosis will proceed to have clinically evident pulmonary fibrosis is not yet known.« less

Voxel-based morphometry analysis reveals frontal brain differences in participants with ADHD and their unaffected siblings.

PubMed

Bralten, Janita; Greven, Corina U; Franke, Barbara; Mennes, Maarten; Zwiers, Marcel P; Rommelse, Nanda N J; Hartman, Catharina; van der Meer, Dennis; O'Dwyer, Laurence; Oosterlaan, Jaap; Hoekstra, Pieter J; Heslenfeld, Dirk; Arias-Vasquez, Alejandro; Buitelaar, Jan K

2016-06-01

Data on structural brain alterations in patients with attention-deficit/hyperactivity disorder (ADHD) have been inconsistent. Both ADHD and brain volumes have a strong genetic loading, but whether brain alterations in patients with ADHD are familial has been underexplored. We aimed to detect structural brain alterations in adolescents and young adults with ADHD compared with healthy controls. We examined whether these alterations were also found in their unaffected siblings, using a uniquely large sample. We performed voxel-based morphometry analyses on MRI scans of patients with ADHD, their unaffected siblings and typically developing controls. We identified brain areas that differed between participants with ADHD and controls and investigated whether these areas were different in unaffected siblings. Influences of medication use, age, sex and IQ were considered. Our sample included 307 patients with ADHD, 169 unaffected siblings and 196 typically developing controls (mean age 17.2 [range 8-30] yr). Compared with controls, participants with ADHD had significantly smaller grey matter volume in 5 clusters located in the precentral gyrus, medial and orbitofrontal cortex, and (para)cingulate cortices. Unaffected siblings showed intermediate volumes significantly different from controls in 4 of these clusters (all except the precentral gyrus). Medication use, age, sex and IQ did not have an undue influence on the results. Our sample was heterogeneous, most participants with ADHD were taking medication, and the comparison was cross-sectional. Brain areas involved in decision making, motivation, cognitive control and motor functioning were smaller in participants with ADHD than in controls. Investigation of unaffected siblings indicated familiality of 4 of the structural brain differences, supporting their potential in molecular genetic analyses in ADHD research.

Voxel-based morphometry analysis reveals frontal brain differences in participants with ADHD and their unaffected siblings

PubMed Central

Bralten, Janita; Greven, Corina U.; Franke, Barbara; Mennes, Maarten; Zwiers, Marcel P.; Rommelse, Nanda N.J.; Hartman, Catharina; van der Meer, Dennis; O’Dwyer, Laurence; Oosterlaan, Jaap; Hoekstra, Pieter J.; Heslenfeld, Dirk; Arias-Vasquez, Alejandro; Buitelaar, Jan K.

2016-01-01

Background Data on structural brain alterations in patients with attention-deficit/hyperactivity disorder (ADHD) have been inconsistent. Both ADHD and brain volumes have a strong genetic loading, but whether brain alterations in patients with ADHD are familial has been underexplored. We aimed to detect structural brain alterations in adolescents and young adults with ADHD compared with healthy controls. We examined whether these alterations were also found in their unaffected siblings, using a uniquely large sample. Methods We performed voxel-based morphometry analyses on MRI scans of patients with ADHD, their unaffected siblings and typically developing controls. We identified brain areas that differed between participants with ADHD and controls and investigated whether these areas were different in unaffected siblings. Influences of medication use, age, sex and IQ were considered. Results Our sample included 307 patients with ADHD, 169 unaffected siblings and 196 typically developing controls (mean age 17.2 [range 8–30] yr). Compared with controls, participants with ADHD had significantly smaller grey matter volume in 5 clusters located in the precentral gyrus, medial and orbitofrontal cortex, and (para)cingulate cortices. Unaffected siblings showed intermediate volumes significantly different from controls in 4 of these clusters (all except the precentral gyrus). Medication use, age, sex and IQ did not have an undue influence on the results. Limitations Our sample was heterogeneous, most participants with ADHD were taking medication, and the comparison was cross-sectional. Conclusion Brain areas involved in decision making, motivation, cognitive control and motor functioning were smaller in participants with ADHD than in controls. Investigation of unaffected siblings indicated familiality of 4 of the structural brain differences, supporting their potential in molecular genetic analyses in ADHD research. PMID:26679925

Impact of endothelin blockade on acute exercise-induced changes in blood flow and endothelial function in type 2 diabetes mellitus.

PubMed

Schreuder, Tim H A; van Lotringen, Jaap H; Hopman, Maria T E; Thijssen, Dick H J

2014-09-01

Positive vascular effects of exercise training are mediated by acute increases in blood flow. Type 2 diabetes patients show attenuated exercise-induced increases in blood flow, possibly mediated by the endothelin pathway, preventing an optimal stimulus for vascular adaptation. We examined the impact of endothelin receptor blockade (bosentan) on exercise-induced blood flow in the brachial artery and on pre- and postexercise endothelial function in type 2 diabetes patients (n = 9, 60 ± 7 years old) and control subjects (n = 10, 60 ± 5 years old). Subjects reported twice to the laboratory to perform hand-grip exercise in the presence of endothelin receptor blockade or placebo. We examined brachial artery endothelial function (via flow-mediated dilatation) before and after exercise, as well as blood flow during exercise. Endothelin receptor blockade resulted in a larger increase in blood flow during exercise in type 2 diabetes patients (P = 0.046), but not in control subjects (P = 0.309). Exercise increased shear rate across the exercise protocol, unaffected by endothelin receptor blockade. Exercise did not alter brachial artery diameter in either group, but endothelin receptor blockade resulted in a larger brachial artery diameter in type 2 diabetes patients (P = 0.033). Exercise significantly increased brachial artery flow-mediated dilatation in both groups, unaffected by endothelin receptor blockade. Endothelin receptor blockade increased exercise-induced brachial artery blood flow in type 2 diabetes patients, but not in control subjects. Despite this effect of endothelin receptor blockade on blood flow, we found no impact on baseline or post-exercise endothelial function in type 2 diabetes patients or control subjects, possibly related to normalization of the shear stimulus during exercise. The successful increase in blood flow during exercise in type 2 diabetes patients through endothelin receptor blockade may have beneficial effects in repeated exercise training. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

Evaluation of a collagenase generated osteoarthritis biomarker in the synovial fluid from elbow joints of dogs with medial coronoid disease and unaffected dogs.

PubMed

Prink, Adam; Hayashi, Kei; Kim, Sun-Young; Kim, James; Kapatkin, Amy

2010-01-01

To evaluate whether synovial fluid concentrations of an osteoarthritis biomarker in dysplastic canine elbows with medial coronoid disease (MCD) are elevated compared with unaffected elbows and to determine if these concentrations correlate to the degree of articular cartilage damage. Cross sectional clinical study. Dogs (n=19; 35 elbows) with MCD and dogs (8; 16 elbows) with unaffected elbows. Concentrations of a collagenase-generated cleavage neoepitope of type II collagen (Col2-3/4C(long mono), or C2C) in joint fluid from elbows were analyzed and compared between dogs with MCD and unaffected dogs. Correlation of C2C concentration with subjective grading of articular cartilage surface damage was also evaluated. Mean (+/-SD) C2C concentration from MCD dogs was significantly higher (112.3+/-24.8 ng/mL) than in unaffected dogs (76.1+/-16.9 ng/mL; P<.05). There was a moderate correlation between cartilage damage grade and increasing C2C concentrations (P<.05, r=0.62) C2C concentrations are elevated in the synovial fluid of dogs with MCD compared with unaffected elbows, and a moderate, significant correlation was identified between these concentrations and subjective grading of articular cartilage damage. This preliminary data suggest that C2C concentrations in synovial fluid may have potential as a biomarker for diagnosis of articular cartilage damage associated with MCD and as a means of objectively determining the degree of articular cartilage damage.

Theory of mind impairments in patients with first-episode schizophrenia and their unaffected siblings.

PubMed

Ho, Karen K Y; Lui, Simon S Y; Hung, Karen S Y; Wang, Yi; Li, Zhi; Cheung, Eric F C; Chan, Raymond C K

2015-08-01

Theory of mind (ToM) impairment has been consistently demonstrated in patients with schizophrenia, but whether ToM impairments exist in unaffected siblings of patients with schizophrenia remains unclear. Few studies have examined the affective and cognitive components of ToM in schizophrenia. This study aimed to examine whether ToM impairments exist in patients with first-episode schizophrenia and their unaffected siblings, and whether there is any dissociation between the affective and cognitive components of ToM. We adopted a family-based case-control design. Participants were 41 patients with first-episode schizophrenia, 43 unaffected siblings, and 42 healthy controls. The Yoni Task which measures the participants' ability to understand first- and second-order affective versus cognitive ToM and the Faux Pas Task which taps into integration of the affective and cognitive components of ToM were administered. Multivariate and univariate ANCOVAs were used to examine the group differences in ToM, while controlling for other neurocognitive functions. Compared with controls, patients with schizophrenia and their unaffected siblings performed poorer on the Faux Pas Task (p<0.001), with siblings having intermediate performance between patients and controls. Patients with schizophrenia performed worse than controls on second-order affective condition of the Yoni Task (p=0.004), but their unaffected siblings did not (p=0.063). We did not find any significant Group-by-Condition interaction in the Yoni Task (p=0.358). Patients with first-episode schizophrenia and their unaffected siblings exhibit ToM impairments, but no dissociation between affective and cognitive component of ToM was found. Our findings support the notion that ToM deficit may be a trait marker of schizophrenia. Copyright © 2014 Elsevier B.V. All rights reserved.

Tuberculin Skin-Test Reactions Are Unaffected by the Severity of Hyperendemic Intestinal Helminth Infections and Co-Infections

PubMed Central

Zevallos, Karine; Vergara, Katherine C.; Vergara, Antonio; Vidal, Carlos; Garcia, Hector H.; Evans, Carlton A.

2010-01-01

The tuberculin skin test (TST) quantifies cell-mediated immunity to tuberculosis antigens. Helminths suppress cell-mediated immunity, so we studied the effect of helminth infection and deworming on the TST in a randomized, double-blind, placebo-controlled study in an indigenous Amazon community (N = 195). Stool microscopy diagnosed helminths in 98% and co-infection with multiple species in 24% of study subjects. The TST was positive (≥ 10 mm) for 49%, and responses increased with age (P < 0.001), Bacille Calmette Guerin (BCG) vaccination (P = 0.01), and tuberculosis contact (P = 0.05). TST results had no association with helminth-egg concentrations, species, or co-infections (all P > 0.1). One month after deworming with albendazole (three daily 400-mg doses), helminths were reduced, but 63% remained infected with helminths. Albendazole did not cause a change in TST size (P = 0.8) or positivity (P = 0.9) relative to placebo. Thus, TST reactions were unaffected by albendazole therapy that partially cured intestinal helminth infections, and TST interpretation was unaffected by high-burden helminth infections and co-infection with multiple helminth species. PMID:20682875

Decreased regional activity of default-mode network in unaffected siblings of schizophrenia patients at rest.

PubMed

Guo, Wenbin; Su, Qinji; Yao, Dapeng; Jiang, Jiajing; Zhang, Jian; Zhang, Zhikun; Yu, Liuyu; Zhai, Jinguo; Xiao, Changqing

2014-04-01

Dysconnectivity hypothesis posits that abnormal resting-state connectivity within the default-mode network (DMN) acts as a key role in schizophrenia. However, little is known about the regional alterations of the DMN in unaffected siblings of schizophrenia patients. Unaffected siblings have a unique advantage in neuroimaging studies independent of clinical and treatment issues that complicate studies on patients themselves. In the present study, we used fractional amplitude of low-frequency fluctuation (fALFF) to investigate regional alterations of the DMN in unaffected siblings of schizophrenia patients at rest. Forty-six unaffected siblings of schizophrenia patients and 50 age-, sex-, and education-matched healthy controls underwent a resting-state functional magnetic resonance imaging (fMRI). The fALFF and independent component analysis (ICA) approaches were used to analyze the data. The unaffected siblings of schizophrenia patients had lower fALFF than the controls in the left inferior temporal gyrus (ITG). No significantly increased fALFF was found in any brain regions in the siblings compared to that in the controls. Further receiver operating characteristic (ROC) curve and support vector machine (SVM) analyses showed that the fALFF values of the left ITG could be utilized to separate the siblings from the controls. Our results first suggest that there is decreased regional activity of the DMN in unaffected siblings of schizophrenia patients, and provide a clue that decreased regional activity of the left ITG could be applied as a candidate biomarker to identify the siblings from the controls. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Choroidal thickness in traumatic optic neuropathy.

PubMed

Lee, Ju-Yeun; Eo, Doo-Ri; Park, Kyung-Ah; Oh, Sei Yeul

2017-12-01

To examine the choroidal thickness in patients with indirect traumatic optic neuropathy (TON) Methods: Patients with unilateral traumatic optic neuropathy over a period of 4 years were included in this study. Horizontal and vertical enhanced-depth imaging (EDI) from spectral-domain optical coherence tomography (SD-OCT) scans of the fovea were obtained in patients with unilateral TON within 2 weeks of injury. The main outcome measure was the choroidal thickness at nine locations. The choroidal thickness was compared between affected and unaffected eyes in the TON group, and the mean difference in the choroidal thickness in both eyes was compared between TON and control groups. A total of 16 patients and 20 control subjects were included. The choroidal thickness at horizontal, vertical and average subfoveal, inner temporal, and outer inferior locations was significantly thicker (13-23%) in affected eyes than in unaffected fellow eyes (p = 0.042, 0.046, 0.024, 0.013, 0.018, and 0.027, respectively). The mean difference value between choroidal thickness measurements in both eyes was significantly larger in the TON group than in the control group at the horizontal, vertical and average subfoveal, inner temporal, inner nasal, inner superior, inner inferior, and outer superior locations (p = 0.001, 0.011, <0.001, 0.001, 0.033, 0.014, 0.011, and 0.014, respectively). The choroidal thickness at subfoveal locations showed no statistical difference between TON and control eyes (p > 0.05). Eyes affected by TON showed a regionally thicker choroid than unaffected fellow eye. This thick choroid might be due to impaired blood circulation and vascular remodeling of the optic nerve head and choroid. These results help to better understand the pathophysiology of TON.

A Risk Score for Predicting Multiple Sclerosis.

PubMed

Dobson, Ruth; Ramagopalan, Sreeram; Topping, Joanne; Smith, Paul; Solanky, Bhavana; Schmierer, Klaus; Chard, Declan; Giovannoni, Gavin

2016-01-01

Multiple sclerosis (MS) develops as a result of environmental influences on the genetically susceptible. Siblings of people with MS have an increased risk of both MS and demonstrating asymptomatic changes in keeping with MS. We set out to develop an MS risk score integrating both genetic and environmental risk factors. We used this score to identify siblings at extremes of MS risk and attempted to validate the score using brain MRI. 78 probands with MS, 121 of their unaffected siblings and 103 healthy controls were studied. Personal history was taken, and serological and genetic analysis using the illumina immunochip was performed. Odds ratios for MS associated with each risk factor were derived from existing literature, and the log values of the odds ratios from each of the risk factors were combined in an additive model to provide an overall score. Scores were initially calculated using log odds ratio from the HLA-DRB1*1501 allele only, secondly using data from all MS-associated SNPs identified in the 2011 GWAS. Subjects with extreme risk scores underwent validation studies. MRI was performed on selected individuals. There was a significant difference in the both risk scores between people with MS, their unaffected siblings and healthy controls (p<0.0005). Unaffected siblings had a risk score intermediate to people with MS and controls (p<0.0005). The best performing risk score generated an AUC of 0.82 (95%CI 0.75-0.88). The risk score demonstrates an AUC on the threshold for clinical utility. Our score enables the identification of a high-risk sibling group to inform pre-symptomatic longitudinal studies.

Sensory Responsiveness in Siblings of Children with Autism Spectrum Disorders

PubMed Central

Hilton, Claudia L.; Babb-Keeble, Alison; Westover, Erin Eitzmann; Zhang, Yi; Adams, Claire; Collins, Diane M.; Karmarkar, Amol; Reistetter, Timothy A.; Constantino, John N.

2017-01-01

This study examined sensory responsiveness in unaffected siblings of children with autism spectrum disorder (ASD) and associations between sensory responsiveness and social severity. Sensory Profile Caregiver Questionnaires and Social Responsiveness Scales were completed by parents of 185 children between age 4 and 10.95 years. Significant differences were found between participants with ASD and controls, and between participants with ASD and unaffected siblings for all sensory quadrants and domains, but not between controls and unaffected siblings. Social responsiveness scores were significantly correlated with scores from most sensory profile categories. Sensory responsiveness as an endophenotype of ASD is not indicated from these findings; however, studies with larger numbers of unaffected siblings and controls are needed to confirm the null hypothesis. PMID:27704293

Sensory Responsiveness in Siblings of Children with Autism Spectrum Disorders.

PubMed

Hilton, Claudia L; Babb-Keeble, Alison; Westover, Erin Eitzmann; Zhang, Yi; Adams, Claire; Collins, Diane M; Karmarkar, Amol; Reistetter, Timothy A; Constantino, John N

2016-12-01

This study examined sensory responsiveness in unaffected siblings of children with autism spectrum disorder (ASD) and associations between sensory responsiveness and social severity. Sensory Profile Caregiver Questionnaires and Social Responsiveness Scales were completed by parents of 185 children between age 4 and 10.95 years. Significant differences were found between participants with ASD and controls, and between participants with ASD and unaffected siblings for all sensory quadrants and domains, but not between controls and unaffected siblings. Social responsiveness scores were significantly correlated with scores from most sensory profile categories. Sensory responsiveness as an endophenotype of ASD is not indicated from these findings; however, studies with larger numbers of unaffected siblings and controls are needed to confirm the null hypothesis.

Sex Differences in Familiality Effects on Neurocognitive Performance in Schizophrenia

PubMed Central

Calkins, Monica E.; Ray, Amrita; Gur, Ruben C.; Freedman, Robert; Green, Michael F.; Greenwood, Tiffany A.; Light, Gregory A.; Nuechterlein, Keith H.; Olincy, Ann; Radant, Allen D.; Seidman, Larry J.; Siever, Larry J.; Silverman, Jeremy M.; Stone, William S.; Sugar, Catherine; Swerdlow, Neal R.; Tsuang, Debby W.; Tsuang, Ming T.; Turetsky, Bruce I.; Braff, David L.; Lazzeroni, Laura C.; Gur, Raquel E.

2013-01-01

Background Numerous studies have documented that patients with schizophrenia show neurocognitive impairments, which are also heritable in schizophrenia families. In view of these findings, the current investigation tested the hypothesis that neurocognitive performance of schizophrenia probands can predict the neurocognitive performance of their unaffected family members. Methods Participants (n=1,967; schizophrenia=369; first-degree relatives=1,072; community comparison subjects=526) in the Consortium on the Genetics of Schizophrenia (COGS) were administered the Penn Computerized Neurocognitive Battery (CNB). Results Consistent with prior work, probands showed significant neurocognitive impairment, and neurocognitive ability was significantly heritable, across domains. On average, unaffected relatives did not differ from community comparison subjects in their neurocognitive performance. However, in 6 of 7 domains, probands’ score predicted the performance of their unaffected siblings. Male, but not female, probands’ performance was predictive of their unaffected relatives (siblings and mothers) performance, most consistently in face memory and spatial processing. Conclusions Using a novel approach in which individual probands are paired with their respective unaffected relatives within each family, we found that male probands’ performance predicted both sister and brother performance, an effect that was most powerfully observed for face memory and spatial processing. Results suggest that the familial transmission of sexually dimorphic neurocognitive domains, in which a particular sex tends to show a performance advantage over the other, may not itself be sex specific in schizophrenia families. PMID:23395246

Sex differences in familiality effects on neurocognitive performance in schizophrenia.

PubMed

Calkins, Monica E; Ray, Amrita; Gur, Ruben C; Freedman, Robert; Green, Michael F; Greenwood, Tiffany A; Light, Gregory A; Nuechterlein, Keith H; Olincy, Ann; Radant, Allen D; Seidman, Larry J; Siever, Larry J; Silverman, Jeremy M; Stone, William S; Sugar, Catherine; Swerdlow, Neal R; Tsuang, Debby W; Tsuang, Ming T; Turetsky, Bruce I; Braff, David L; Lazzeroni, Laura C; Gur, Raquel E

2013-05-15

Numerous studies have documented that patients with schizophrenia show neurocognitive impairments, which are also heritable in schizophrenia families. In view of these findings, the current investigation tested the hypothesis that neurocognitive performance of schizophrenia probands can predict the neurocognitive performance of their unaffected family members. Participants (n=1967; schizophrenia=369; first-degree relatives=1072; community comparison subjects=526) in the Consortium on the Genetics of Schizophrenia were administered the Penn Computerized Neurocognitive Battery. Consistent with prior work, probands showed significant neurocognitive impairment, and neurocognitive ability was significantly heritable across domains. On average, unaffected relatives did not differ from community comparison subjects in their neurocognitive performance. However, in six of seven domains, proband scores predicted the performance of their unaffected siblings. Male, but not female, proband performance was predictive of their unaffected relatives' (siblings and mothers) performance, most consistently in face memory and spatial processing. Using a novel approach in which individual probands are paired with their respective unaffected relatives within each family, we found that male proband performance predicted both sister and brother performance, an effect that was most powerfully observed for face memory and spatial processing. Results suggest that the familial transmission of sexually dimorphic neurocognitive domains, in which a particular sex tends to show a performance advantage over the other, may not itself be sex specific in schizophrenia families. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Contribution of olivofloccular circuitry developmental defects to atypical gaze in autism

PubMed Central

Wegiel, Jerzy; Kuchna, Izabela; Nowicki, Krzysztof; Imaki, Humi; Wegiel, Jarek; Ma, Shuang Yong; Azmitia, Efrain C.; Banerjee, Probal; Flory, Michael; Cohen, Ira L.; London, Eric; Brown, W. Ted; Hare, Carolyn Komich; Wisniewski, Thomas

2014-01-01

Individuals with autism demonstrate atypical gaze, impairments in smooth pursuit, altered movement perception and deficits in facial perception. The olivofloccular neuronal circuit is a major contributor to eye movement control. This study of the cerebellum in 12 autistic and 10 control subjects revealed dysplastic changes in the flocculus of eight autistic (67%) and two control (20%) subjects. Defects of the oculomotor system, including avoidance of eye contact and poor or no eye contact, were reported in 88% of autistic subjects with postmortem-detected floccular dysplasia. Focal disorganization of the flocculus cytoarchitecture with deficit, altered morphology, and spatial disorientation of Purkinje cells (PCs); deficit and abnormalities of granule, basket, stellate and unipolar brush cells; and structural defects and abnormal orientation of Bergmann glia are indicators of profound disruption of flocculus circuitry in a dysplastic area. The average volume of PCs was 26% less in the dysplastic region than in the unaffected region of the flocculus (p<0.01) in autistic subjects. Moreover, the average volume of PCs in the entire cerebellum was 25% less in the autistic subjects than in the control subjects (p<0.001). Findings from this study and a parallel study of the inferior olive (IO) suggest that focal floccular dysplasia combined with IO neurons and PC developmental defects may contribute to oculomotor system dysfunction and atypical gaze in autistic subjects. PMID:23558308

Choroidal thickness in Chinese patients with non-arteritic anterior ischemic optic neuropathy.

PubMed

Jiang, Libin; Chen, Lanlan; Qiu, Xiujuan; Jiang, Ran; Wang, Yaxing; Xu, Liang; Lai, Timothy Y Y

2016-08-31

Non-arteritic anterior ischemic optic neuropathy (NA-AION) is one of the most common types of ischemic optic neuropathy. Several recent studies suggested that abnormalities of choroidal thickness might be associated with NA-AION. The main objective of this case-control study was to evaluate whether choroidal thickness is an ocular risk factor for the development of NA-AION by evaluating the peripapillary and subfoveal choroidal thicknesses in affected Chinese patients. Forty-four Chinese patients with unilateral NA-AION were recruited and compared with 60 eyes of 60 normal age and refractive-error matched control subjects. Peripapillary and subfoveal choroidal thicknesses were measured by enhanced depth imaging optical coherence tomography. Choroidal thicknesses of eyes with NA-AION and unaffected fellow eyes were compared with normal controls. Choroidal thicknesses of NA-AION eyes with or without optic disc edema were also compared. The correlation between choroidal thickness and retinal nerve fiber layer (RNFL) thickness, logMAR best-corrected visual acuity (BCVA), and the mean deviation (MD) of Humphrey static perimetry in NA-AION eyes were analyzed. The peripapillary choroidal thicknesses at the nasal, nasal inferior and temporal inferior segments in NA-AION eyes with optic disc edema were significantly thicker compared with that of normal subjects (P < 0.05). There was no significant difference in the choroidal thicknesses between the unaffected fellow eyes of NA-AION patients and normal eyes of healthy controls; or between the NA-AION eyes with resolved optic disc edema and normal eyes (all P > 0.05). No significant correlation between choroidal thickness and RNFL thickness, logMAR BCVA and perimetry MD was found in eyes affected by NA-AION (all P > 0.05). Increase in peripapillary choroid thickness in some segments was found in NA-ION eyes with optic disc edema. However, our findings do not support the hypothesis that choroidal thickness is abnormal in Chinese patients with NA-AION compared with normal subjects with similar age and refractive error status.

Exercise-induced muscle fatigue in the unaffected knee joint and its influence on postural control and lower limb kinematics in stroke patients.

PubMed

Park, Sun Wook; Son, Sung Min; Lee, Na Kyung

2017-05-01

This study aimed to investigate the effects of exercise-induced muscle fatigue in the unaffected knee joint on postural control and kinematic changes in stroke patients. Forty participants (20 stroke patients, 20 age-matched healthy participants) were recruited. To induce fatigue, maximum voluntary isometric contractions were performed in the unaffected knee joint in a Leg Extension Rehab exercise machine using the pneumatic resistance. We measured static and dynamic balance and lower-limb kinematics during gait. Changes in postural control parameters anteroposterior sway speed and total center of pressure distance differed significantly between the stroke and control groups. In addition, changes in gait kinematic parameters knee and ankle angles of initial contact differed significantly between stroke (paretic and non-paretic) and control groups. Muscle fatigue in the unaffected knee and ankle impaired postural control and debilitates kinematic movement of ipsilateral and contralateral lower limbs, and may place the fatigued stroke patients at greater risk for falls.

Relation between adolescent idiopathic scoliosis and morphologic somatotypes.

PubMed

LeBlanc, R; Labelle, H; Rivard, C H; Poitras, B

1997-11-01

A prospective and controlled comparative study. To verify the difference in morphologic appearance between a group of adolescents with progressive adolescent idiopathic scoliosis and a control group of normal adolescents. In a previous retrospective study, the possibility of a relation between progressive adolescent idiopathic scoliosis and specific morphotypes was demonstrated. Fifty-two adolescent girls with progressive adolescent idiopathic scoliosis were compared with an age-matched control group of 62 unaffected girls using a classification technique based on morphologic somatotypes. Morphotypes were evaluated with standardized pre-established criteria based on Sheldon's technique. Patients with progressive adolescent idiopathic scoliosis showed significantly less mesomorphism (mean value of 0.88 +/- 0.51) than control girls (mean value of 1.72 +/- 0.52). Adolescent girls with progressive adolescent idiopathic scoliosis have a morphologic somatotype that is different from the normal adolescent population. Subjects with progressive adolescent idiopathic scoliosis are significantly less mesomorphic than control girls. This observation may be of value as a predictive factor for early identification of subjects with adolescent idiopathic scoliosis at greater risk of progression.

Motor co-activation in siblings of patients with juvenile myoclonic epilepsy: an imaging endophenotype?

PubMed Central

Wandschneider, Britta; Centeno, Maria; Vollmar, Christian; Symms, Mark; Thompson, Pamela J.; Duncan, John S.

2014-01-01

Juvenile myoclonic epilepsy is a heritable idiopathic generalized epilepsy syndrome, characterized by myoclonic jerks and frequently triggered by cognitive effort. Impairment of frontal lobe cognitive functions has been reported in patients with juvenile myoclonic epilepsy and their unaffected siblings. In a recent functional magnetic resonance imaging study we reported abnormal co-activation of the motor cortex and increased functional connectivity between the motor system and prefrontal cognitive networks during a working memory paradigm, providing an underlying mechanism for cognitively triggered jerks. In this study, we used the same task in 15 unaffected siblings (10 female; age range 18–65 years, median 40) of 11 of those patients with juvenile myoclonic epilepsy (six female; age range 22–54 years, median 35) and compared functional magnetic resonance imaging activations with 20 age- and gender-matched healthy control subjects (12 female; age range 23–46 years, median 30.5). Unaffected siblings showed abnormal primary motor cortex and supplementary motor area co-activation with increasing cognitive load, as well as increased task-related functional connectivity between motor and prefrontal cognitive networks, with a similar pattern to patients (P < 0.001 uncorrected; 20-voxel threshold extent). This finding in unaffected siblings suggests that altered motor system activation and functional connectivity is not medication- or seizure-related, but represents a potential underlying mechanism for impairment of frontal lobe functions in both patients and siblings, and so constitutes an endophenotype of juvenile myoclonic epilepsy. PMID:25001494

Neural activation patterns during response inhibition distinguish adolescents with ADHD, their unaffected siblings, and healthy controls

PubMed Central

van Rooij, Daan; Hoekstra, Pieter J.; Mennes, Maarten; von Rhein, Daniel; Thissen, Andrieke J.A.M.; Heslenfeld, Dirk; Zwiers, Marcel P.; Faraone, Stephen V.; Oosterlaan, Jaap; Franke, Barbara; Rommelse, Nanda; Buitelaar, Jan K.; Hartman, Catharina A.

2015-01-01

Objective Impaired response inhibition is a key executive function deficit of attention-deficit/hyperactivity disorder (ADHD). Still, behavioral response inhibition measures do not consistently differentiate individuals with ADHD from unaffected individuals. We therefore investigated the neural correlates of response inhibition as well as the familial nature of these neural correlates. Methods fMRI measurements of neural activation during the stop-signal task along with behavioral measures of response inhibition were obtained in adolescents and young adults with ADHD (N=185), their unaffected siblings (N=111), and healthy controls (N=124). Results Stop-signal reaction times were longer in participants with ADHD, but not in their unaffected siblings, while reaction time variability and error rates were higher in both groups than in controls. Neural hypoactivation was observed in frontal-striatal and frontal-parietal networks of participants with ADHD and unaffected siblings compared to controls, whereby activation in inferior frontal and temporal/parietal nodes in unaffected siblings was intermediate between that of participants with ADHD and controls. Furthermore, neural activation in inferior frontal nodes correlated with stop-signal reaction times, and activation in both inferior frontal and temporal/parietal nodes correlated with ADHD severity. Conclusions Neural activation alterations in ADHD are more robust than behavioral response inhibition deficits and explain variance in response inhibition and ADHD severity. Although only affected participants with ADHD have deficient response inhibition, hypoactivation in inferior frontal and temporal-parietal nodes in unaffected siblings support the familial nature of the underlying neural process. Hypoactivation in these nodes may be useful as endophenotypes that extend beyond the affected individuals in the family. PMID:25615565

Intradermal capsaicin as a neuropathic pain model in patients with unilateral sciatica

PubMed Central

Aykanat, Verna; Gentgall, Melanie; Briggs, Nancy; Williams, Desmond; Yap, Sharon; Rolan, Paul

2012-01-01

AIM This study compared the responses between patients with unilateral sciatica and pain-free volunteers following administration of intradermal capsaicin. METHODS Fourteen patients with unilateral sciatica and 12 pain-free volunteers received one injection per hour over 4 h of 1 µg and 10 µg capsaicin, into each calf. For each dose, spontaneous pain (10 cm VAS), area of flare (cm2) and the sum of allodynia and hyperalgesia radii across eight axes (cm) were recorded pre-injection and at 5, 15, 30, 45 and 60 min post injection. RESULTS Sciatica subjects experienced higher spontaneous pain and hyperalgesia responses in both legs compared with pain-free volunteers. The largest mean difference in spontaneous pain was 2.8 cm (95% CI 1.6, 3.9) at 5 min in the unaffected leg following 10 µg. The largest mean difference in hyperalgesia was 19.7 cm (95% CI 12.4, 27.0) at 60 min in the unaffected leg following 10 µg. Allodynia was greater in patients than in controls with the largest mean difference of 2.9 cm (95% CI 1, 4.8) at 5 min following 10 µg in the affected leg. Allodynia was also higher in the affected leg compared with the unaffected leg in sciatica patients with the highest mean difference of 3.0 cm (95% CI 1.2, 4.7) at 5 min following 10 µg. CONCLUSIONS The responses to intradermal capsaicin are quantitatively and qualitatively different in unilateral sciatica patients compared with pain-free controls. PMID:21740458

Gait post-stroke: Pathophysiology and rehabilitation strategies.

PubMed

Beyaert, C; Vasa, R; Frykberg, G E

2015-11-01

We reviewed neural control and biomechanical description of gait in both non-disabled and post-stroke subjects. In addition, we reviewed most of the gait rehabilitation strategies currently in use or in development and observed their principles in relation to recent pathophysiology of post-stroke gait. In both non-disabled and post-stroke subjects, motor control is organized on a task-oriented basis using a common set of a few muscle modules to simultaneously achieve body support, balance control, and forward progression during gait. Hemiparesis following stroke is due to disruption of descending neural pathways, usually with no direct lesion of the brainstem and cerebellar structures involved in motor automatic processes. Post-stroke, improvements of motor activities including standing and locomotion are variable but are typically characterized by a common postural behaviour which involves the unaffected side more for body support and balance control, likely in response to initial muscle weakness of the affected side. Various rehabilitation strategies are regularly used or in development, targeting muscle activity, postural and gait tasks, using more or less high-technology equipment. Reduced walking speed often improves with time and with various rehabilitation strategies, but asymmetric postural behaviour during standing and walking is often reinforced, maintained, or only transitorily decreased. This asymmetric compensatory postural behaviour appears to be robust, driven by support and balance tasks maintaining the predominant use of the unaffected side over the initially impaired affected side. Based on these elements, stroke rehabilitation including affected muscle strengthening and often stretching would first need to correct the postural asymmetric pattern by exploiting postural automatic processes in various particular motor tasks secondarily beneficial to gait. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

ACSS2 gene variant associated with cleft lip and palate in two independent Hispanic populations.

PubMed

Dodhia, Sonam; Celis, Katrina; Aylward, Alana; Cai, Yi; Fontana, Maria E; Trespalacios, Alberto; Hoffman, David C; Alfonso, Henry Ostos; Eisig, Sidney B; Su, Gloria H; Chung, Wendy K; Haddad, Joseph

2017-10-01

A candidate variant (p.Val496Ala) of the ACSS2 gene (T > C missense, rs59088485 variant at chr20: bp37 33509608) was previously found to consistently segregate with nonsyndromic cleft lip and/or palate (NSCLP) in three Honduran families. Objectives of this study were 1) to investigate the frequency of this ACSS2 variant in Honduran unrelated NSCLP patients and unrelated unaffected controls and 2) to investigate the frequency of this variant in Colombian unrelated affected NSCLP patients and unrelated unaffected controls. Case-control studies. Sanger sequencing of 99 unrelated Honduran NSCLP patients and 215 unrelated unaffected controls for the p.Val496Ala ACSS2 variant was used to determine the carrier frequency in NSCLP patients and controls. Sanger sequencing of 230 unrelated Colombian NSCLP patients and 146 unrelated unaffected controls for the p.Val496Ala ACSS2 variant was used to determine the carrier frequency in NSCLP patients and controls. In the Honduran population, the odds ratio of having NSCLP among carriers of the p.Val496Ala ACSS2 variant was 4.0 (P = .03), with a carrier frequency of seven of 99 (7.1%) in unrelated affected and four of 215 (1.9%) in unrelated unaffected individuals. In the Colombian population, the odds ratio of having NSCLP among carriers of the p.Val496Ala ACSS2 variant was 2.6 (P = .04), with a carrier frequency of 23 of 230 (10.0%) in unrelated affected and six of 146 (4.1%) in unrelated unaffected individuals. These findings support the role of ACSS2 in NSCLP in two independent Hispanic populations from Honduras and Colombia. NA Laryngoscope, 127:E336-E339, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Brain bioenergetics and redox state measured by 31P magnetic resonance spectroscopy in unaffected siblings of patients with psychotic disorders.

PubMed

Chouinard, Virginie-Anne; Kim, Sang-Young; Valeri, Linda; Yuksel, Cagri; Ryan, Kyle P; Chouinard, Guy; Cohen, Bruce M; Du, Fei; Öngür, Dost

2017-09-01

Brain bioenergetic anomalies and redox dysregulation have been implicated in the pathophysiology of psychotic disorders. The present study examined brain energy-related metabolites and the balance between nicotinamide adenine dinucleotide metabolites (oxidized NAD+ and reduced NADH) using 31 P-magnetic resonance spectroscopy ( 31 P-MRS) in unaffected siblings, compared to first episode psychosis (FEP) patients and healthy controls. 21 unaffected siblings, 32 FEP patients (including schizophrenia spectrum and affective psychoses), and 21 controls underwent 31 P-MRS in the frontal lobe (6×6×4cm 3 ) on a 4T MR scanner, using custom-designed dual-tuned surface coil with outer volume suppression. Brain parenchymal pH and steady-state metabolite ratios of high energy phosphate compounds were measured. NAD+ and NADH levels were determined using a 31 P-MRS fitting algorithm. 13 unaffected sibling-patient pairs were related; other patients and siblings were unrelated. ANCOVA analyses were used to examine 31 P-MRS measures, with age and gender as covariates. The phosphocreatine/adenosine triphosphate ratio was significantly reduced in both unaffected siblings and FEP patients, compared to controls. NAD+/NADH ratio was significantly reduced in patients compared to siblings and controls, with siblings showing a reduction in NAD+/NADH compared to controls that was not statistically significant. Compared to patients and controls, siblings showed significantly reduced levels of NAD+. Siblings did not differ from patients or controls on brain pH. Our results indicate that unaffected siblings show some, but not all the same abnormalities in brain energy metabolites and redox state as FEP patients. Thus, 31 P-MRS studies may identify factors related both to risk and expression of psychosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Subjective and objective screening tests for hydroxychloroquine toxicity.

PubMed

Cukras, Catherine; Huynh, Nancy; Vitale, Susan; Wong, Wai T; Ferris, Fredrick L; Sieving, Paul A

2015-02-01

To compare subjective and objective clinical tests used in the screening for hydroxychloroquine retinal toxicity to multifocal electroretinography (mfERG) reference testing. Prospective, single-center, case control study. Fifty-seven patients with a previous or current history of hydroxychloroquine treatment of more than 5 years' duration. Participants were evaluated with a detailed medical history, dilated ophthalmologic examination, color fundus photography, fundus autofluorescence (FAF) imaging, spectral-domain (SD) optical coherence tomography (OCT), automated visual field testing (10-2 visual field mean deviation [VFMD]), and mfERG testing. We used mfERG test parameters as a gold standard to divide participants into 2 groups: those affected by hydroxychloroquine-induced retinal toxicity and those unaffected. We assessed the association of various imaging and psychophysical variables in the affected versus the unaffected group. Fifty-seven study participants (91.2% female; mean age, 55.7±10.4 years; mean duration of hydroxychloroquine treatment, 15.0±7.5 years) were divided into affected (n = 19) and unaffected (n = 38) groups based on mfERG criteria. Mean age and duration of hydroxychloroquine treatment did not differ statistically between groups. Mean OCT retinal thickness measurements in all 9 macular subfields were significantly lower (<40 μm) in the affected group (P < 0.01 for all comparisons) compared with those in the unaffected group. Mean VFMD was 11 dB lower in the affected group (P < 0.0001). Clinical features indicative of retinal toxicity were scored for the 2 groups and were detected in 68.4% versus 0.0% using color fundus photographs, 73.3% versus 9.1% using FAF images, and 84.2% versus 0.0% on the scoring for the perifoveal loss of the photoreceptor ellipsoid zone on SD-OCT for affected and unaffected participants, respectively. Using a polynomial modeling approach, OCT inner ring retinal thickness measurements and Humphrey 10-2 VFMD were identified as the variables associated most strongly with the presence of hydroxychloroquine as defined by mfERG testing. Optical coherence tomography retinal thickness and 10-2 VFMD are objective measures demonstrating clinically useful sensitivity and specificity for the detection of hydroxychloroquine toxicity as identified by mfERG, and thus may be suitable surrogate tests. Published by Elsevier Inc.

Interval Timing Deficits Assessed by Time Reproduction Dual Tasks as Cognitive Endophenotypes for Attention-Deficit/Hyperactivity Disorder

PubMed Central

Hwang-Gu, Shoou-Lian; Gau, Susan Shur-Fen

2015-01-01

The literature has suggested timing processing as a potential endophenotype for attention deficit/hyperactivity disorder (ADHD); however, whether the subjective internal clock speed presented by verbal estimation and limited attention capacity presented by time reproduction could be endophenotypes for ADHD is still unknown. We assessed 223 youths with DSM-IV ADHD (age range: 10-17 years), 105 unaffected siblings, and 84 typically developing (TD) youths using psychiatric interviews, intelligence tests, verbal estimation and time reproduction tasks (single task and simple and difficult dual tasks) at 5-second, 12-second, and 17-second intervals. We found that youths with ADHD tended to overestimate time in verbal estimation more than their unaffected siblings and TD youths, implying that fast subjective internal clock speed might be a characteristic of ADHD, rather than an endophenotype for ADHD. Youths with ADHD and their unaffected siblings were less precise in time reproduction dual tasks than TD youths. The magnitude of estimated errors in time reproduction was greater in youths with ADHD and their unaffected siblings than in TD youths, with an increased time interval at the 17-second interval and with increased task demands on both simple and difficult dual tasks versus the single task. Increased impaired time reproduction in dual tasks with increased intervals and task demands were shown in youths with ADHD and their unaffected siblings, suggesting that time reproduction deficits explained by limited attention capacity might be a useful endophenotype of ADHD. PMID:25992899

Genome-wide Association Analysis of Psoriatic Arthritis and Cutaneous Psoriasis Reveals Differences in Their Genetic Architecture.

PubMed

Stuart, Philip E; Nair, Rajan P; Tsoi, Lam C; Tejasvi, Trilokraj; Das, Sayantan; Kang, Hyun Min; Ellinghaus, Eva; Chandran, Vinod; Callis-Duffin, Kristina; Ike, Robert; Li, Yanming; Wen, Xiaoquan; Enerbäck, Charlotta; Gudjonsson, Johann E; Kõks, Sulev; Kingo, Külli; Esko, Tõnu; Mrowietz, Ulrich; Reis, Andre; Wichmann, H Erich; Gieger, Christian; Hoffmann, Per; Nöthen, Markus M; Winkelmann, Juliane; Kunz, Manfred; Moreta, Elvia G; Mease, Philip J; Ritchlin, Christopher T; Bowcock, Anne M; Krueger, Gerald G; Lim, Henry W; Weidinger, Stephan; Weichenthal, Michael; Voorhees, John J; Rahman, Proton; Gregersen, Peter K; Franke, Andre; Gladman, Dafna D; Abecasis, Gonçalo R; Elder, James T

2015-12-03

Psoriasis vulgaris (PsV) is a common inflammatory and hyperproliferative skin disease. Up to 30% of people with PsV eventually develop psoriatic arthritis (PsA), an inflammatory musculoskeletal condition. To discern differences in genetic risk factors for PsA and cutaneous-only psoriasis (PsC), we carried out a genome-wide association study (GWAS) of 1,430 PsA case subjects and 1,417 unaffected control subjects. Meta-analysis of this study with three other GWASs and two targeted genotyping studies, encompassing a total of 9,293 PsV case subjects, 3,061 PsA case subjects, 3,110 PsC case subjects, and 13,670 unaffected control subjects of European descent, detected 10 regions associated with PsA and 11 with PsC at genome-wide (GW) significance. Several of these association signals (IFNLR1, IFIH1, NFKBIA for PsA; TNFRSF9, LCE3C/B, TRAF3IP2, IL23A, NFKBIA for PsC) have not previously achieved GW significance. After replication, we also identified a PsV-associated SNP near CDKAL1 (rs4712528, odds ratio [OR] = 1.16, p = 8.4 × 10(-11)). Among identified psoriasis risk variants, three were more strongly associated with PsC than PsA (rs12189871 near HLA-C, p = 5.0 × 10(-19); rs4908742 near TNFRSF9, p = 0.00020; rs10888503 near LCE3A, p = 0.0014), and two were more strongly associated with PsA than PsC (rs12044149 near IL23R, p = 0.00018; rs9321623 near TNFAIP3, p = 0.00022). The PsA-specific variants were independent of previously identified psoriasis variants near IL23R and TNFAIP3. We also found multiple independent susceptibility variants in the IL12B, NOS2, and IFIH1 regions. These results provide insights into the pathogenetic similarities and differences between PsC and PsA. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Peripheral blood gene expression signature differentiates children with autism from unaffected siblings

PubMed Central

Kong, SW; Shimizu-Motohashi, Y; Campbell, MG; Lee, IH; Collins, CD; Brewster, SJ; Holm, IA; Rappaport, L

2013-01-01

Autism spectrum disorder (ASD) is one of the most prevalent neurodevelopmental disorders with high heritability, yet a majority of genetic contribution to pathophysiology is not known. Siblings of individuals with ASD are at increased risk for ASD and autistic traits, but the genetic contribution for simplex families is estimated to be less when compared to multiplex families. To explore the genomic (dis-) similarity between proband and unaffected sibling in simplex families, we used genome-wide gene expression profiles of blood from 20 proband-unaffected sibling pairs and 18 unrelated control individuals. The global gene expression profiles of unaffected siblings were more similar to those from probands as they shared genetic and environmental background. One hundred eighty nine genes were significantly differentially expressed between proband-sib pairs (nominal p-value < 0.01) after controlling for age, sex, and family effects. Probands and siblings were distinguished into two groups by cluster analysis with these genes. Overall, unaffected siblings were equally distant from the centroid of probands and from that of unrelated controls with the differentially expressed genes. Interestingly, 5 of 20 siblings had gene expression profiles that were more similar to unrelated controls than to their matched probands. In summary, we found a set of genes that distinguished probands from the unaffected siblings, and a subgroup of unaffected siblings who were more similar to probands. The pathways that characterized probands compared to siblings using peripheral blood gene expression profiles were the up-regulation of ribosomal, spliceosomal, and mitochondrial pathways, and the down-regulation of neuroreceptor-ligand, immune response and calcium signaling pathways. Further integrative study with structural genetic variations such as de novo mutations, rare variants, and copy number variations would clarify whether these transcriptomic changes are structural or environmental in origin. PMID:23625158

Validity of the Addiction Severity Index (adapted version) in a Costa Rican population group.

PubMed

Sandí Esquivel, L E; Avila Corrales, K

1990-01-01

Until recently, no adapted and validated instrument was available for assessing the alcohol and drug problems of individuals in Costa Rica. This article reports the results of a study performed by Costa Rica's Institute on Alcoholism and Drug Dependence in order to test an adapted version of one such instrument, the Addiction Severity Index (ASI), in a Costa Rican setting. The instrument was used to interview 100 male subjects 18 to 64 years old (51 with diagnosed alcohol or drug problems and 49 controls). In general, the subjects with previously diagnosed alcohol or drug problems were assigned substantially higher scores. More specifically, statistical analysis indicated highly significant correlations (p less than 0.001) between the type of subject (test subject or control) and the likelihood that noteworthy problems would be found in the areas of alcohol use, family/social relations, work/finances, and psychological status. Overall, the study demonstrated that the instrument was capable of distinguishing between the affected and unaffected populations, and also of gauging the severity of the problems involved and the patients' treatment needs.

TMS measures of motor cortex function after stroke: A meta-analysis.

PubMed

McDonnell, Michelle N; Stinear, Cathy M

Transcranial magnetic stimulation (TMS) is commonly used to measure the effects of stroke on corticomotor excitability, intracortical function, and interhemispheric interactions. The interhemispheric inhibition model posits that recovery of motor function after stroke is linked to rebalancing of asymmetric interhemispheric inhibition and corticomotor excitability. This model forms the rationale for using neuromodulation techniques to suppress unaffected motor cortex excitability, and facilitate affected motor cortex excitability. However, the evidence base for using neuromodulation techniques to promote post-stroke motor recovery is inconclusive. The aim of this meta-analysis was to compare measures of corticomotor excitability, intracortical function, and interhemispheric inhibition, between the affected and unaffected hemispheres of people with stroke, and measures made in healthy adults. A literature search was conducted to identify studies that made TMS measures of the motor cortex in adult stroke patients. Two authors independently extracted data, and the quality of included studies was assessed. TMS measures were compared between the affected and unaffected hemispheres of stroke patients, between the affected hemisphere and healthy controls, and between the unaffected hemisphere and healthy controls. Analyses were carried out with data grouped according to the muscle from which responses were recorded, and separately according to time post-stroke (<3 months, and ≥6 months). Meta-analyses were carried out using a random effects model. There were 844 studies identified, and 112 studies included in the meta-analysis. Results were very similar across muscle groups. Affected hemisphere M1 excitability is lower than unaffected and healthy control M1 excitability after stroke. Affected hemisphere short interval intracortical inhibition (SICI) is lower than unaffected and healthy control SICI early after stroke, and not different in the chronic phase. There were no differences detected between the unaffected hemisphere and healthy controls. There were only seven studies of interhemispheric inhibition that could be included, with no clear effects of hemisphere or time post-stroke. The neurophysiological effects of stroke are primarily localised to the affected hemisphere, and there is no clear evidence for hyper-excitability of the unaffected hemisphere or imbalanced interhemispheric inhibition. This indicates that facilitating affected M1 excitability directly may be more beneficial than suppressing unaffected M1 excitability for promoting post-stroke recovery. Copyright © 2017 Elsevier Inc. All rights reserved.

School Functions in Unaffected Siblings of Youths with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Chien, Yi-Ling; Tu, En-Nien; Gau, Susan Shur-Fen

2017-01-01

This study investigated school functioning among unaffected siblings of youths with autistic spectrum disorder (ASD) and identified the correlates for school maladjustment. We recruited 66 youths with a clinical diagnosis of ASD, aged 8-19, their unaffected siblings and 132 typically developing controls (TD). We found that ASD youths had poorer…

Is inefficient cognitive processing in anorexia nervosa a familial trait? A neuropsychological pilot study of mothers of offspring with a diagnosis of anorexia nervosa.

PubMed

Lang, Katie; Treasure, Janet; Tchanturia, Kate

2016-06-01

Inefficient set shifting and poor global processing are thought to be possible traits in anorexia nervosa (AN). This study aimed to investigate the neuropsychological processing style of unaffected mothers of offspring with AN (unaffected AN mothers). The performance of 21 unaffected AN mothers were compared to 20 mothers of healthy control offspring on neuropsychological measures of set shifting (Wisconsin Card Sorting Test, WCST) and central coherence (Fragmented Pictures Task, FPT, and Rey Osterrieth Complex Figures Task, ROCFT). Associations between neuropsychological performance and clinical measures were examined in the unaffected AN mothers group. There were significant differences in perseverative errors on the WCST (P≤0.01), with the unaffected mothers displaying a more inflexible thinking style compared to the control group. There were also significant differences on the FPT (P ≤ 0.01) and the ROCFT (P ≤ 0.01), whereby unaffected AN mothers showed lower levels of global processing. The results of this study support the idea of the familial nature of cognitive styles in AN. The implications of these findings are discussed.

Delayed Development of Brain Connectivity in Adolescents With Schizophrenia and Their Unaffected Siblings.

PubMed

Zalesky, Andrew; Pantelis, Christos; Cropley, Vanessa; Fornito, Alex; Cocchi, Luca; McAdams, Harrison; Clasen, Liv; Greenstein, Deanna; Rapoport, Judith L; Gogtay, Nitin

2015-09-01

Abnormalities in structural brain connectivity have been observed in patients with schizophrenia. Mapping these abnormalities longitudinally and understanding their genetic risk via sibship studies will provide crucial insight into progressive developmental changes associated with schizophrenia. To identify corticocortical connections exhibiting an altered developmental trajectory in adolescents with childhood-onset schizophrenia (COS) and to determine whether similar alterations are found in patients' unaffected siblings. Using prospective structural brain magnetic resonance imaging, large-scale corticocortical connectivity was mapped from ages 12 to 24 years in 109 patients with COS (272 images), 86 of their unaffected siblings (184 images), and 102 healthy controls (262 images) over a 20-year period beginning January 1, 1991, through April 30, 2011, as part of the ongoing COS study at the National Institute of Mental Health. Structural connectivity between pairs of cortical regions was estimated using a validated technique based on across-subject covariation in magnetic resonance imaging-derived cortical thickness measurements. Compared with normally developing controls, significant left-hemisphere occipitotemporal deficits in cortical thickness correlations were found in patients with COS as well as their healthy siblings (P < .05). Deficits in siblings normalized by mid-adolescence, whereas patients with COS showed significantly longer maturational delays, with cortical thickness correlations between the left temporal lobe and left occipital cortex not showing evidence of development until early adulthood. The normalization of deficits with age in patients with COS correlated with improvement in symptoms. Compared with controls, left-hemisphere occipitotemporal thickness correlations in a subgroup of patients with high positive symptoms were significantly reduced from age 14 to 18 years (P < .05); however, other patients with low positive symptoms showed no significant deficits. Delayed maturation of occipitotemporal connectivity appears to be a trait marker in patients with COS, with a milder endophenotype in unaffected siblings associated with resilience to developing schizophrenia. These findings indicate genetically influenced and connection-specific developmental abnormalities in the schizophrenia connectome, and lead to the hypothesis that visual hallucinations in patients with COS may be because of delayed development of the inferior longitudinal fasciculus, a prominent occipitotemporal fiber.

Autonomic and subjective responsivity to emotional images in people with dissociative seizures.

PubMed

Pick, Susannah; Mellers, John D C; Goldstein, Laura H

2018-06-01

People with dissociative seizures (DS) report a range of difficulties in emotional functioning and exhibit altered responding to emotional facial expressions in experimental tasks. We extended this research by investigating subjective and autonomic reactivity (ratings of emotional valence, arousal and skin conductance responses [SCRs]) to general emotional images in 39 people with DS relative to 42 healthy control participants, whilst controlling for anxiety, depression, cognitive functioning and, where relevant, medication use. It was predicted that greater subjective negativity and arousal and increased SCRs in response to the affective pictures would be observed in the DS group. The DS group as a whole did not differ from controls in their subjective responses of valence and arousal. However, SCR amplitudes were greater in 'autonomic responders' with DS relative to 'autonomic responders' in the control group. A positive correlation was also observed between SCRs for highly arousing negative pictures and self-reported ictal autonomic arousal, in DS 'autonomic responders'. In the DS subgroup of autonomic 'non-responders', differences in subjective responses were observed for some conditions, compared to control 'non-responders'. The findings indicate unaffected subjective responses to emotional images in people with DS overall. However, within the group of people with DS, there may be subgroups characterized by differences in emotional responding. One subgroup (i.e., 'autonomic responders') exhibit heightened autonomic responses but intact subjective emotional experience, whilst another subgroup (i.e., 'autonomic non-responders') seem to experience greater subjective negativity and arousal for some emotional stimuli, despite less frequent autonomic reactions. The current results suggest that therapeutic interventions targeting awareness and regulation of physiological arousal and subjective emotional experience could be of value in some people with this disorder. © 2017 The Authors. Journal of Neuropsychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.

Reliability and Clinical Correlation of Transcranial Doppler Ultrasound in Sturge-Weber Syndrome.

PubMed

Offermann, Elizabeth A; Sreenivasan, Aditya; DeJong, M Robert; Lin, Doris D M; McCulloch, Charles E; Chung, Melissa G; Comi, Anne M

2017-09-01

The reproducibility of transcranial Doppler (TCD) ultrasound measurements in Sturge-Weber syndrome (SWS) and TCD's ability to predict neurological progression is unknown. In 14 individuals with SWS, TCD measured mean flow velocity, pulsatility index, peak systolic velocity, and end-diastolic velocity in the middle, posterior, and anterior cerebral arteries of the affected and unaffected hemisphere. TCD was performed either once (n = 5) or twice in one day (n = 9). We assessed the reproducibility of the measurements performed twice on the same day on subjects and compared the TCD measurements to previously published age-matched controls. Clinically obtained neuroimaging was scored for extent and severity of SWS brain involvement. Patients were prospectively assigned SWS neuroscores. Middle cerebral artery velocity (r = 0.79, P = 0.04, n = 7), posterior cerebral artery velocity (r = 0.90, P = 0.04, n = 5), and anterior cerebral artery pulsatility index (r = 0.82, P = 0.02, n = 7) were reproducible TCD measurements comparing same-day percent side-to-side differences. In subjects with SWS, affected and unaffected mean peak systolic velocity and end-diastolic velocity in the middle, posterior, and anterior cerebral arteries were globally lower compared with age-matched control subjects. Subjects with the lowest affected middle cerebral artery velocity had the greatest worsening in the total neurological score between time 1 and 2 (r = -0.73, P = 0.04, n = 8) and the most severe magnetic resonance imaging involvement of the affected frontal lobe (r = -0.82, P = 0.007, n = 9). TCD may be a reliable measure with potential clinical value, indicating that blood flow may be globally decreased in SWS patients with unilateral brain involvement. Copyright © 2017. Published by Elsevier Inc.

Using ipsilateral motor signals in the unaffected cerebral hemisphere as a signal platform for brain-computer interfaces in hemiplegic stroke survivors

NASA Astrophysics Data System (ADS)

Bundy, David T.; Wronkiewicz, Mark; Sharma, Mohit; Moran, Daniel W.; Corbetta, Maurizio; Leuthardt, Eric C.

2012-06-01

Brain-computer interface (BCI) systems have emerged as a method to restore function and enhance communication in motor impaired patients. To date, this has been applied primarily to patients who have a compromised motor outflow due to spinal cord dysfunction, but an intact and functioning cerebral cortex. The cortical physiology associated with movement of the contralateral limb has typically been the signal substrate that has been used as a control signal. While this is an ideal control platform in patients with an intact motor cortex, these signals are lost after a hemispheric stroke. Thus, a different control signal is needed that could provide control capability for a patient with a hemiparetic limb. Previous studies have shown that there is a distinct cortical physiology associated with ipsilateral, or same-sided, limb movements. Thus far, it was unknown whether stroke survivors could intentionally and effectively modulate this ipsilateral motor activity from their unaffected hemisphere. Therefore, this study seeks to evaluate whether stroke survivors could effectively utilize ipsilateral motor activity from their unaffected hemisphere to achieve this BCI control. To investigate this possibility, electroencephalographic (EEG) signals were recorded from four chronic hemispheric stroke patients as they performed (or attempted to perform) real and imagined hand tasks using either their affected or unaffected hand. Following performance of the screening task, the ability of patients to utilize a BCI system was investigated during on-line control of a one-dimensional control task. Significant ipsilateral motor signals (associated with movement intentions of the affected hand) in the unaffected hemisphere, which were found to be distinct from rest and contralateral signals, were identified and subsequently used for a simple online BCI control task. We demonstrate here for the first time that EEG signals from the unaffected hemisphere, associated with overt and imagined movements of the affected hand, can enable stroke survivors to control a one-dimensional computer cursor rapidly and accurately. This ipsilateral motor activity enabled users to achieve final target accuracies between 68% and 91% within 15 min. These findings suggest that ipsilateral motor activity from the unaffected hemisphere in stroke survivors could provide a physiological substrate for BCI operation that can be further developed as a long-term assistive device or potentially provide a novel tool for rehabilitation.

Dental Age Difference in Children with ADHD.

PubMed

Wadhwa, Puneet; Yu, Qingzhao; Zhu, Han; Townsend, Janice A

2018-01-01

The purpose of this study was to determine if changes in dental development are associated with Attention Deficit Hyperactivity Disorder (ADHD) or ADHD medications. This retrospective chart review evaluated the dental age of 128 patients between 6 and 16 years of age using the Demirjian method from the following two groups a) children with ADHD b) unaffected children. The ADHD group was further stratified into four groups according to the medication type. The impact of ADHD on dental age difference (the difference between dental age and chronologic age) was analyzed using T-test and the association between medication type and dental age difference was analyzed through one way ANOVA. The mean difference between estimated dental age and chronologic age (dental age difference) for all subjects was 0.80 years. There was no significant dental age difference in subjects with ADHD and the control group (0.78±1.28vs. 0.84 ±1.09 years respectively; P=0.75) and there was no significant difference in dental age difference and type of medication (P=0.84). No significant difference was found between children with ADHD and unaffected children with respect to dental age difference. No significant differences were found in dental age difference in the four medication groups.

Cooperative hand movements in post-stroke subjects: Neural reorganization.

PubMed

Schrafl-Altermatt, Miriam; Dietz, Volker

2016-01-01

Recent research indicates a task-specific neural coupling controlling cooperative hand movements reflected in bilateral electromyographic reflex responses in arm muscles following unilateral nerve stimulation. Reorganization of this mechanism was explored in post-stroke patients in this study. Electromyographic reflex responses in forearm muscles to unilateral electrical ulnar nerve stimulation were examined during cooperative and non-cooperative hand movements. Stimulation of the unaffected arm during cooperative hand movements led to electromyographic responses in bilateral forearm muscles, similar to those seen in healthy subjects, while stimulation of the affected side was followed only by ipsilateral responses. No contralateral reflex responses could be evoked in severely affected patients. The presence of contralateral responses correlated with the clinical motor impairment as assessed by the Fugl-Meyer test. The observations suggest that after stroke an impaired processing of afferent input from the affected side leads to a defective neural coupling and is associated with a greater involvement of fiber tracts from the unaffected hemisphere during cooperative hand movements. The mechanism of neural coupling underlying cooperative hand movements is shown to be defective in post-stroke patients. The neural re-organizations observed have consequences for the rehabilitation of hand function. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Evidence for disturbed insulin and growth hormone signaling as potential risk factors in the development of schizophrenia.

PubMed

van Beveren, N J M; Schwarz, E; Noll, R; Guest, P C; Meijer, C; de Haan, L; Bahn, S

2014-08-26

Molecular abnormalities in metabolic, hormonal and immune pathways are present in peripheral body fluids of a significant subgroup of schizophrenia patients. The authors have tested whether such disturbances also occur in psychiatrically ill and unaffected siblings of schizophrenia patients with the aim of identifying potential contributing factors to disease vulnerability. The subjects were recruited as part of the Genetic Risk and OUtcome of Psychosis (GROUP) study. The authors used multiplexed immunoassays to measure the levels of 184 molecules in serum from 112 schizophrenia patients, 133 siblings and 87 unrelated controls. Consistent with the findings of previous studies, serum from schizophrenia patients contained higher levels of insulin, C-peptide and proinsulin, decreased levels of growth hormone and altered concentrations of molecules involved in inflammation. In addition, significant differences were found in the levels of some of these proteins in siblings diagnosed with mood disorders (n=16) and in unaffected siblings (n=117). Most significantly, the insulin/growth hormone ratio was higher across all groups compared with the controls. Taken together, these findings suggest the presence of a molecular endophenotype involving disruption of insulin and growth factor signaling pathways as an increased risk factor for schizophrenia.

Electrophysiological correlates of motor conversion disorder.

PubMed

Liepert, Joachim; Hassa, Thomas; Tüscher, Oliver; Schmidt, Roger

2008-11-15

In patients with a functional (psychogenic) paresis, motor conduction tests are, by definition, normal. We investigated whether these patients exhibit an abnormal motor excitability. Four female patients with a functional paresis of the left upper extremity were studied using transcranial magnetic stimulation (TMS). We investigated motor thresholds, intracortical inhibition and intracortical facilitation at rest. Corticospinal excitability was evaluated by single pulse TMS during rest and during imagination of tonic index finger adductions. Data obtained from the affected first dorsal interosseous muscle were compared with the unaffected hand and with a healthy age-matched control group. Three patients demonstrated a flaccid paresis, one patient had a psychogenic dystonia. Motor thresholds, short interval intracortical inhibition and intracortical facilitation recorded from the affected side were normal. In healthy subjects, movement imagination produced an increase of corticospinal excitability. In the patients, motor imagery with the affected index finger resulted in a decrease of corticospinal excitability compared to rest, being significantly different from the unaffected side and from the control group. We suggest that suppression of corticospinal excitability during movement imagination is an electrophysiological correlate of the patients' inability to move voluntarily and provides some insight into the pathophysiology of this disorder.

[Identification of novel compound heterozygous mutations of USH2A gene in a family with Usher syndrome type II].

PubMed

Jiang, Haiou; Ge, Chuanqin; Wang, Yiwang; Tang, Genyun; Quan, Qingli

2015-06-01

To identify potential mutations in a Chinese family with Usher syndrome type II. Genomic DNA was obtained from two affected and four unaffected members of the family and subjected to amplification of the entire coding sequence and splicing sites of USH2A gene. Mutation detection was conducted by direct sequencing of the PCR products. A total of 100 normal unrelated individuals were used as controls. The patients were identified to be a compound heterozygote for two mutations: c.8272G>T (p.E2758X) in exon 42 from his mother and c.12376-12378ACT>TAA(p.T4126X) in exon 63 of the USH2A gene from his father. Both mutations were not found in either of the two unaffected family members or 100 unrelated controls, and had completely co-segregated with the disease phenotype in the family. Neither mutation has been reported in the HGMD database. The novel compound heterozygous mutations c.8272G>T and c.12376-12378ACT>TAA within the USH2A gene may be responsible for the disease. This result may provide new clues for molecular diagnosis of this disease.

Allogeneic Hematopoietic Cell Transplantation for Children with Sickle Cell Disease Is Beneficial and Cost-Effective: A Single-Center Analysis

PubMed Central

Arnold, Staci D.; Jin, Zhezhen; Sands, Stephen; Bhatia, Monica; Kung, Andrew L.; Satwani, Prakash

2017-01-01

Limited data exist regarding health care utilization (HCU) in patients receiving allogeneic hematopoietic cell transplantation (alloHCT) for sickle cell disease. Financial data from 2002 to 2011 were analyzed for 26 alloHCT patients and 48 control subjects (referred but without alloHCT). HCU of alloHCT was determined over 3 time periods: pre-alloHCT, during alloHCT (day 0 to day +365), and post-alloHCT. The median total cost per patient during the alloHCT year was $413,000 inpatient and $18,000 outpatient. Post-alloHCT HCU decreased when compared with pre-alloHCT and control subjects. The median cost of post-alloHCT outpatient visits per patient was significantly less when compared with pre-alloHCT (P = .044). The median cost of post-alloHCT inpatient visits per patient approached significance when compared with those pre-alloHCT (P = .079). Sixteen post-alloHCT patients, 19 control subjects, and 14 unaffected siblings were surveyed using Pediatric Quality of Life Inventory and EuroQOL questionnaires; however, the questionnaire scores across all 3 patient groups were not statistically significant (P = .2638). When adjusted for health-related quality of life, the analysis suggested alloHCT has a positive impact on health-related quality of life over control subjects. These pilot data support our hypothesis that alloHCT in children with sickle cell disease reduces HCU compared with control subjects without alloHCT. PMID:25615608

School Functions in Unaffected Siblings of Youths with Autism Spectrum Disorders.

PubMed

Chien, Yi-Ling; Tu, En-Nien; Gau, Susan Shur-Fen

2017-10-01

This study investigated school functioning among unaffected siblings of youths with autistic spectrum disorder (ASD) and identified the correlates for school maladjustment. We recruited 66 youths with a clinical diagnosis of ASD, aged 8-19, their unaffected siblings and 132 typically developing controls (TD). We found that ASD youths had poorer school functions than unaffected siblings and TD. Unaffected siblings had poorer attitude toward schoolwork and more severe behavioral problems at school than TD. Several associated factors for different scholastic functional domains (i.e., academic performance, attitude toward school work, social interactions, behavioral problems) in the siblings included IQ, autistic traits, inattention/oppositional symptoms, sibling relationships, etc. Our findings suggest the need of assessing school functions in unaffected siblings of ASD. Clinical trial registration identifier: NCT01582256.

Incidental brain MRI findings in an autism twin study.

PubMed

Monterrey, Julio C; Philips, Jennifer; Cleveland, Sue; Tanaka, Serena; Barnes, Patrick; Hallmayer, Joachim F; Reiss, Alan L; Lazzeroni, Laura C; Hardan, Antonio Y

2017-01-01

Brain magnetic resonance imaging (MRI) studies suggest the prevalence of asymptomatic "incidental" findings (IF) in autism spectrum disorder (ASD) is similar to that of neurotypically developing (NT) controls. However, given the causes of IF may include both genetic and environmental factors, a twin study would facilitate comparing brain IF between ASD and NT subjects. MRI scans were examined to assess the prevalence of brain IF in twin "case pairs" (at least one twin with diagnosis of ASD) and twin "control pairs" (NT). Fifty case pairs and thirty-two control pairs were analyzed. IF were found in 68% of subjects with ASD, 71% of unaffected ASD siblings, and in 58% of control subjects (P = 0.4). IF requiring clinical follow-up occurred more frequently in subjects with ASD compared to NT controls (17% vs. 5%, respectively; P = 0.02). The concordance rate of IF in twins was 83%. A mixed effects model found younger age, male sex, and "family environment" to be significantly associated with IF. There was no difference in the prevalence rate of IF between ASD subjects and NT controls. More IF required clinical follow-up in ASD subjects compared to NT controls. The prevalence rate of IF observed in this twin study was higher than rates previously reported in singleton studies. Our results suggest the shared environment of twins - perhaps in utero - increases the risk of brain IF. Brain MRI in the initial work-up of ASD may be indicated in twins, especially in males. Autism Res 2017, 10: 113-120. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Decreased resting-state interhemispheric functional connectivity in unaffected siblings of schizophrenia patients.

PubMed

Guo, Wenbin; Jiang, Jiajing; Xiao, Changqing; Zhang, Zhikun; Zhang, Jian; Yu, Liuyu; Liu, Jianrong; Liu, Guiying

2014-01-01

Neuroimaging studies in unaffected siblings of schizophrenia patients can provide clues to the pathophysiology for the development of schizophrenia. However, little is known about the alterations of the interhemispheric resting-state functional connectivity (FC) in siblings, although the dysconnectivity hypothesis is prevailing in schizophrenia for years. In the present study, we used a newly validated voxel-mirrored homotopic connectivity (VMHC) method to identify whether aberrant interhemispheric FC was present in unaffected siblings at increased risk of developing schizophrenia at rest. Forty-six unaffected siblings of schizophrenia patients and 50 age-, sex-, and education-matched healthy controls underwent a resting-state functional magnetic resonance imaging (fMRI). Automated VMHC was used to analyze the data. The sibling group had lower VMHC than the control group in the angular gyrus (AG) and the lingual gyrus/cerebellum lobule VI. No region exhibited higher VMHC in the sibling group than in the control group. There was no significant sex difference of the VMHC values between male siblings and female siblings or between male controls and female controls, although evidence has been accumulated that size and shape of the corpus callosum, and functional homotopy differ between men and women. Our results first suggest that interhemispheric resting-state FC of VMHC is disrupted in unaffected siblings of schizophrenia patients, and add a new clue of abnormal interhemispheric resting-state FC to the pathophysiology for the development of schizophrenia. Copyright © 2013 Elsevier B.V. All rights reserved.

White Matter Abnormalities in Autism and Unaffected Siblings.

PubMed

Jou, Roger J; Reed, Hannah E; Kaiser, Martha D; Voos, Avery C; Volkmar, Fred R; Pelphrey, Kevin A

2016-01-01

This study was conducted to identify a potential neuroendophenotype for autism using diffusion tensor imaging. Whole-brain, voxel-based analysis of fractional anisotropy was conducted in 50 children: 19 with autism, 20 unaffected siblings, and 11 controls. Relative to controls, participants with autism exhibited bilateral reductions in fractional anisotropy across association, commissure, and projection fibers. The most severely affected tracts included the uncinate fasciculus, forceps minor, and inferior fronto-occipital fasciculus. Unaffected siblings also exhibited reductions in fractional anisotropy, albeit less severe with fewer affected tracts, sparing the uncinate fasciculus and forceps minor. These results suggest the presence of a neuroendophenotype for autism.

Candidate Genes for Inherited Autism Susceptibility in the Lebanese Population.

PubMed

Kourtian, Silva; Soueid, Jihane; Makhoul, Nadine J; Guisso, Dikran Richard; Chahrour, Maria; Boustany, Rose-Mary N

2017-03-30

Autism spectrum disorder (ASD) is characterized by ritualistic-repetitive behaviors and impaired verbal/non-verbal communication. Many ASD susceptibility genes implicated in neuronal pathways/brain development have been identified. The Lebanese population is ideal for uncovering recessive genes because of shared ancestry and a high rate of consanguineous marriages. Aims here are to analyze for published ASD genes and uncover novel inherited ASD susceptibility genes specific to the Lebanese. We recruited 36 ASD families (ASD: 37, unaffected parents: 36, unaffected siblings: 33) and 100 unaffected Lebanese controls. Cytogenetics 2.7 M Microarrays/CytoScan™ HD arrays allowed mapping of homozygous regions of the genome. The CNTNAP2 gene was screened by Sanger sequencing. Homozygosity mapping uncovered DPP4, TRHR, and MLF1 as novel candidate susceptibility genes for ASD in the Lebanese. Sequencing of hot spot exons in CNTNAP2 led to discovery of a 5 bp insertion in 23/37 ASD patients. This mutation was present in unaffected family members and unaffected Lebanese controls. Although a slight increase in number was observed in ASD patients and family members compared to controls, there were no significant differences in allele frequencies between affecteds and controls (C/TTCTG: γ 2 value = 0.014; p = 0.904). The CNTNAP2 polymorphism identified in this population, hence, is not linked to the ASD phenotype.

Candidate Genes for Inherited Autism Susceptibility in the Lebanese Population

PubMed Central

Kourtian, Silva; Soueid, Jihane; Makhoul, Nadine J.; Guisso, Dikran Richard; Chahrour, Maria; Boustany, Rose-Mary N.

2017-01-01

Autism spectrum disorder (ASD) is characterized by ritualistic-repetitive behaviors and impaired verbal/non-verbal communication. Many ASD susceptibility genes implicated in neuronal pathways/brain development have been identified. The Lebanese population is ideal for uncovering recessive genes because of shared ancestry and a high rate of consanguineous marriages. Aims here are to analyze for published ASD genes and uncover novel inherited ASD susceptibility genes specific to the Lebanese. We recruited 36 ASD families (ASD: 37, unaffected parents: 36, unaffected siblings: 33) and 100 unaffected Lebanese controls. Cytogenetics 2.7 M Microarrays/CytoScan™ HD arrays allowed mapping of homozygous regions of the genome. The CNTNAP2 gene was screened by Sanger sequencing. Homozygosity mapping uncovered DPP4, TRHR, and MLF1 as novel candidate susceptibility genes for ASD in the Lebanese. Sequencing of hot spot exons in CNTNAP2 led to discovery of a 5 bp insertion in 23/37 ASD patients. This mutation was present in unaffected family members and unaffected Lebanese controls. Although a slight increase in number was observed in ASD patients and family members compared to controls, there were no significant differences in allele frequencies between affecteds and controls (C/TTCTG: γ2 value = 0.014; p = 0.904). The CNTNAP2 polymorphism identified in this population, hence, is not linked to the ASD phenotype. PMID:28358038

Psychiatric and autistic comorbidity in fragile X syndrome across ages.

PubMed

Gabis, Lidia V; Baruch, Yael Kesner; Jokel, Ariela; Raz, Raanan

2011-08-01

Fragile X syndrome is caused by CGG trinucleotide repeat expansion within the fragile X mental retardation 1 gene, when repeat number exceeds 200. The typical psychiatric profile of fragile X syndrome patients includes cognitive and behavioral deficits, psychiatric comorbidity, and autistic characteristics. Specific psychiatric features have not yet been clarified, specifically in relationship to age and genetic characteristics. The objective of this study was to characterize psychiatric comorbidities in subjects with fragile X syndrome at different ages. Subjects with fragile X syndrome and their unaffected siblings were recruited and their parents filled out functional-behavioral and psychiatric comorbidities questionnaires. Adolescents with fragile X syndrome showed decreased prevalence of functional-behavioral deficits. Incidence and severity of most psychiatric comorbidities were lower in older subjects. Incidence of generalized anxiety disorder increased with age in the fragile X syndrome group. The typical profile of patients with fragile X syndrome changes with age. Unaffected siblings exhibit anxiety and motor tics.

A comprehensive tractography study of patients with bipolar disorder and their unaffected siblings.

PubMed

Sprooten, Emma; Barrett, Jennifer; McKay, D Reese; Knowles, Emma E; Mathias, Samuel R; Winkler, Anderson M; Brumbaugh, Margaret S; Landau, Stefanie; Cyr, Lindsay; Kochunov, Peter; Glahn, David C

2016-10-01

Diffusion tensor imaging studies show reductions in fractional anisotropy (FA) in individuals with bipolar disorder and their unaffected siblings. However, the use of various analysis methods is an important source of between-study heterogeneity. Using tract-based spatial statistics, we previously demonstrated widespread FA reductions in patients and unaffected relatives. To better interpret the neuroanatomical pattern of this previous finding and to assess the influence of methodological heterogeneity, we here applied tractography to the same sample. Diffusion-weighted images were acquired for 96 patients, 69 unaffected siblings and 56 controls. We applied TRACULA, an extension of a global probabilistic tractography algorithm, to automatically segment 18 major fiber tracts. Average FA within each tract and at each cross-section along each tract was compared between groups. Patients had reduced FA compared to healthy controls and their unaffected siblings in general, and in particular in the parietal part of the superior longitudinal fasciculus. In unaffected siblings, FA was nominally reduced compared to controls in the corpus callosum. Point-wise analyses indicated that similar effects were present along extended sections, but with variable effect sizes. Current symptom severity negatively correlated with FA in several fronto-limbic association tracts. The differential sensitivity of analysis techniques likely explains between-study heterogeneity in anatomical localization of FA reductions. The present tractography analysis confirms the presence of overall FA reductions in patients with bipolar disorder, which are most pronounced in the superior longitudinal fasciculus. Unaffected siblings may display similar, albeit more subtle and anatomically restricted FA reductions. Hum Brain Mapp 37:3474-3485, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Community differentiation of the cutaneous microbiota in psoriasis.

PubMed

Alekseyenko, Alexander V; Perez-Perez, Guillermo I; De Souza, Aieska; Strober, Bruce; Gao, Zhan; Bihan, Monika; Li, Kelvin; Methé, Barbara A; Blaser, Martin J

2013-12-23

Psoriasis is a common chronic inflammatory disease of the skin. We sought to characterize and compare the cutaneous microbiota of psoriatic lesions (lesion group), unaffected contralateral skin from psoriatic patients (unaffected group), and similar skin loci in matched healthy controls (control group) in order to discern patterns that govern skin colonization and their relationship to clinical diagnosis. Using high-throughput 16S rRNA gene sequencing, we assayed the cutaneous bacterial communities of 51 matched triplets and characterized these samples using community data analysis techniques. Intragroup Unifrac β diversity revealed increasing diversity from control to unaffected to lesion specimens. Likewise, principal coordinates analysis (PCoA) revealed separation of the lesion samples from unaffected and control along the first axis, suggesting that psoriasis is a major contributor to the observed diversity. The taxonomic richness and evenness decreased in both lesion and unaffected communities compared to control. These differences are explained by the combined increased abundance of the four major skin-associated genera (Corynebacterium, Propionibacterium, Staphylococcus, and Streptococcus), which present a potentially useful predictor for clinical skin type. Psoriasis samples also showed significant univariate decreases in relative abundances and strong classification performance of Cupriavidus, Flavisolibacter, Methylobacterium, and Schlegelella genera versus controls. The cutaneous microbiota separated into two distinct clusters, which we call cutaneotypes: (1) Proteobacteria-associated microbiota, and (2) Firmicutes-associated and Actinobacteria-associated microbiota. Cutaneotype 2 is enriched in lesion specimens compared to control (odds ratio 3.52 (95% CI 1.44 to 8.98), P <0.01). Our results indicate that psoriasis induces physiological changes both at the lesion site and at the systemic level, which select for specific differential microbiota among the assayed clinical skin types. These differences in microbial community structure in psoriasis patients are potentially of pathophysiologic and diagnostic significance.

Resting-state cerebellar-cerebral networks are differently affected in first-episode, drug-naive schizophrenia patients and unaffected siblings.

PubMed

Guo, Wenbin; Liu, Feng; Chen, Jindong; Wu, Renrong; Zhang, Zhikun; Yu, Miaoyu; Xiao, Changqing; Zhao, Jingping

2015-11-26

Dysconnectivity hypothesis posits that schizophrenia is a disorder with dysconnectivity of the cortico-cerebellar-thalamic-cortical circuit (CCTCC). However, it remains unclear to the changes of the cerebral connectivity with the cerebellum in schizophrenia patients and unaffected siblings. Forty-nine patients with first-episode, drug-naive schizophrenia patients, 46 unaffected siblings of schizophrenia patients and 46 healthy controls participated in the study. Seed-based resting-state functional connectivity approach was employed to analyze the data. Compared with the controls, the patients and the siblings share increased default-mode network (DMN) seed - right Crus II connectivity. The patients have decreased right dorsal attention network (DAN) seed - bilateral cerebellum 4,5 connectivity relative to the controls. By contrast, the siblings exhibit increased FC between the right DAN seed and the right cerebellum 6 and right cerebellum 4,5 compared to the controls. No other abnormal connectivities (executive control network and salience network) are observed in the patients/siblings relative to the controls. There are no correlations between abnormal cerebellar-cerebral connectivities and clinical variables. Cerebellar-cerebral connectivity of brain networks within the cerebellum are differently affected in first-episode, drug-naive schizophrenia patients and unaffected siblings. Increased DMN connectivity with the cerebellum may serve as potential endophenotype for schizophrenia.

Resting-state cerebellar-cerebral networks are differently affected in first-episode, drug-naive schizophrenia patients and unaffected siblings

PubMed Central

Guo, Wenbin; Liu, Feng; Chen, Jindong; Wu, Renrong; Zhang, Zhikun; Yu, Miaoyu; Xiao, Changqing; Zhao, Jingping

2015-01-01

Dysconnectivity hypothesis posits that schizophrenia is a disorder with dysconnectivity of the cortico-cerebellar-thalamic-cortical circuit (CCTCC). However, it remains unclear to the changes of the cerebral connectivity with the cerebellum in schizophrenia patients and unaffected siblings. Forty-nine patients with first-episode, drug-naive schizophrenia patients, 46 unaffected siblings of schizophrenia patients and 46 healthy controls participated in the study. Seed-based resting-state functional connectivity approach was employed to analyze the data. Compared with the controls, the patients and the siblings share increased default-mode network (DMN) seed – right Crus II connectivity. The patients have decreased right dorsal attention network (DAN) seed – bilateral cerebellum 4,5 connectivity relative to the controls. By contrast, the siblings exhibit increased FC between the right DAN seed and the right cerebellum 6 and right cerebellum 4,5 compared to the controls. No other abnormal connectivities (executive control network and salience network) are observed in the patients/siblings relative to the controls. There are no correlations between abnormal cerebellar-cerebral connectivities and clinical variables. Cerebellar-cerebral connectivity of brain networks within the cerebellum are differently affected in first-episode, drug-naive schizophrenia patients and unaffected siblings. Increased DMN connectivity with the cerebellum may serve as potential endophenotype for schizophrenia. PMID:26608842

Enhanced ERPs to visual stimuli in unaffected male siblings of ASD children.

PubMed

Anzures, Gizelle; Goyet, Louise; Ganea, Natasa; Johnson, Mark H

2016-01-01

Autism spectrum disorders are characterized by deficits in social and communication abilities. While unaffected relatives lack severe deficits, milder impairments have been reported in some first-degree relatives. The present study sought to verify whether mild deficits in face perception are evident among the unaffected younger siblings of children with ASD. Children between 6-9 years of age completed a face-recognition task and a passive viewing ERP task with face and house stimuli. Sixteen children were typically developing with no family history of ASD, and 17 were unaffected children with an older sibling with ASD. Findings indicate that, while unaffected siblings are comparable to controls in their face-recognition abilities, unaffected male siblings in particular show relatively enhanced P100 and P100-N170 peak-to-peak amplitude responses to faces and houses. Enhanced ERPs among unaffected male siblings is discussed in relation to potential differences in neural network recruitment during visual and face processing.

Familiarity and recollection processes in patients with recent-onset schizophrenia and their unaffected parents.

PubMed

Lefèbvre, Andrée-Anne; Cellard, Caroline; Tremblay, Sébastien; Achim, Amélie; Rouleau, Nancie; Maziade, Michel; Roy, Marc-André

2010-01-30

Episodic memory deficits are present in patients with schizophrenia (SZ) and their unaffected relatives and could be considered as a cognitive indicator of genetic vulnerability to SZ. The present study, involving patients with SZ as well as their parents, used experimental tasks specifically designed to disentangle the contribution of familiarity and recollection processes to episodic memory. The performance of patients with SZ (n=26) and their unaffected parents (n=35) was compared with that of healthy control groups matched on socio-demographic variables (controls of patients, n=26; controls of parents, n=35) on two memory tasks assessing recollection and familiarity. The first task was designed to investigate item recognition and memory for item-spatial context associations whereas the second targeted item-item associations. The results revealed an overall episodic memory deficit in patients with SZ, encompassing both familiarity and recollection, while unaffected parents showed a dysfunction restricted to the recollection process. Our study highlights differences and similarities in the source of the episodic memory deficit found in patients with SZ and their unaffected parents, and it suggests that recollection could act as a cognitive endophenotype of SZ. The results also suggest that use of experimental tasks represents a promising method in the search of cognitive endophenotypes in SZ.

Abnormal frontoparietal synaptic gain mediating the P300 in patients with psychotic disorder and their unaffected relatives.

PubMed

Díez, Álvaro; Ranlund, Siri; Pinotsis, Dimitris; Calafato, Stella; Shaikh, Madiha; Hall, Mei-Hua; Walshe, Muriel; Nevado, Ángel; Friston, Karl J; Adams, Rick A; Bramon, Elvira

2017-06-01

The "dysconnection hypothesis" of psychosis suggests that a disruption of functional integration underlies cognitive deficits and clinical symptoms. Impairments in the P300 potential are well documented in psychosis. Intrinsic (self-)connectivity in a frontoparietal cortical hierarchy during a P300 experiment was investigated. Dynamic Causal Modeling was used to estimate how evoked activity results from the dynamics of coupled neural populations and how neural coupling changes with the experimental factors. Twenty-four patients with psychotic disorder, twenty-four unaffected relatives, and twenty-five controls underwent EEG recordings during an auditory oddball paradigm. Sixteen frontoparietal network models (including primary auditory, superior parietal, and superior frontal sources) were analyzed and an optimal model of neural coupling, explaining diagnosis and genetic risk effects, as well as their interactions with task condition were identified. The winning model included changes in connectivity at all three hierarchical levels. Patients showed decreased self-inhibition-that is, increased cortical excitability-in left superior frontal gyrus across task conditions, compared with unaffected participants. Relatives had similar increases in excitability in left superior frontal and right superior parietal sources, and a reversal of the normal synaptic gain changes in response to targets relative to standard tones. It was confirmed that both subjects with psychotic disorder and their relatives show a context-independent loss of synaptic gain control at the highest hierarchy levels. The relatives also showed abnormal gain modulation responses to task-relevant stimuli. These may be caused by NMDA-receptor and/or GABAergic pathologies that change the excitability of superficial pyramidal cells and may be a potential biological marker for psychosis. Hum Brain Mapp 38:3262-3276, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

UV-laser microdissection and mRNA expression analysis of individual neurons from postmortem Parkinson's disease brains.

PubMed

Gründemann, Jan; Schlaudraff, Falk; Liss, Birgit

2011-01-01

Cell specificity of gene expression analysis is essential to avoid tissue sample related artifacts, in particular when the relative number of target cells present in the compared tissues varies dramatically, e.g., when comparing dopamine neurons in midbrain tissues from control subjects with those from Parkinson's disease (PD) cases. Here, we describe a detailed protocol that combines contact-free UV-laser microdissection and quantitative PCR of reverse-transcribed RNA of individual neurons from postmortem human midbrain tissue from PD patients and unaffected controls. Among expression changes in a variety of dopamine neuron marker, maintenance, and cell-metabolism genes, we found that α-synuclein mRNA levels were significantly elevated in individual neuromelanin-positive dopamine midbrain neurons from PD brains when compared to those from matched controls.

Allogeneic Hematopoietic Cell Transplantation for Children with Sickle Cell Disease Is Beneficial and Cost-Effective: A Single-Center Analysis.

PubMed

Arnold, Staci D; Jin, Zhezhen; Sands, Stephen; Bhatia, Monica; Kung, Andrew L; Satwani, Prakash

2015-07-01

Limited data exist regarding health care utilization (HCU) in patients receiving allogeneic hematopoietic cell transplantation (alloHCT) for sickle cell disease. Financial data from 2002 to 2011 were analyzed for 26 alloHCT patients and 48 control subjects (referred but without alloHCT). HCU of alloHCT was determined over 3 time periods: pre-alloHCT, during alloHCT (day 0 to day +365), and post-alloHCT. The median total cost per patient during the alloHCT year was $413,000 inpatient and $18,000 outpatient. Post-alloHCT HCU decreased when compared with pre-alloHCT and control subjects. The median cost of post-alloHCT outpatient visits per patient was significantly less when compared with pre-alloHCT (P = .044). The median cost of post-alloHCT inpatient visits per patient approached significance when compared with those pre-alloHCT (P = .079). Sixteen post-alloHCT patients, 19 control subjects, and 14 unaffected siblings were surveyed using Pediatric Quality of Life Inventory and EuroQOL questionnaires; however, the questionnaire scores across all 3 patient groups were not statistically significant (P = .2638). When adjusted for health-related quality of life, the analysis suggested alloHCT has a positive impact on health-related quality of life over control subjects. These pilot data support our hypothesis that alloHCT in children with sickle cell disease reduces HCU compared with control subjects without alloHCT. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Effects of Anisometropic Amblyopia on Visuomotor Behavior, Part 2: Visually Guided Reaching

PubMed Central

Niechwiej-Szwedo, Ewa; Goltz, Herbert C.; Chandrakumar, Manokaraananthan; Hirji, Zahra; Crawford, J. Douglas; Wong, Agnes M. F.

2016-01-01

Purpose The effects of impaired spatiotemporal vision in amblyopia on visuomotor skills have rarely been explored in detail. The goal of this study was to examine the influences of amblyopia on visually guided reaching. Methods Fourteen patients with anisometropic amblyopia and 14 control subjects were recruited. Participants executed reach-to-touch movements toward targets presented randomly 5° or 10° to the left or right of central fixation in three viewing conditions: binocular, monocular amblyopic eye, and monocular fellow eye viewing (left and right monocular viewing for control subjects). Visual feedback of the target was removed on 50% of the trials at the initiation of reaching. Results Reaching accuracy was comparable between patients and control subjects during all three viewing conditions. Patients’ reaching responses were slightly less precise during amblyopic eye viewing, but their precision was normal during binocular or fellow eye viewing. Reaching reaction time was not affected by amblyopia. The duration of the acceleration phase was longer in patients than in control subjects under all viewing conditions, whereas the duration of the deceleration phase was unaffected. Peak acceleration and peak velocity were also reduced in patients. Conclusions Amblyopia affects both the programming and the execution of visually guided reaching. The increased duration of the acceleration phase, as well as the reduced peak acceleration and peak velocity, might reflect a strategy or adaptation of feedforward/feedback control of the visuomotor system to compensate for degraded spatiotemporal vision in amblyopia, allowing patients to optimize their reaching performance. PMID:21051723

Decreased Left Caudate Volume Is Associated with Increased Severity of Autistic-Like Symptoms in a Cohort of ADHD Patients and Their Unaffected Siblings

PubMed Central

O’Dwyer, Laurence; Tanner, Colby; van Dongen, Eelco V.; Greven, Corina U.; Bralten, Janita; Zwiers, Marcel P.; Franke, Barbara; Heslenfeld, Dirk; Oosterlaan, Jaap; Hoekstra, Pieter J.; Hartman, Catharina A.; Groen, Wouter; Rommelse, Nanda; Buitelaar, Jan K.

2016-01-01

Autism spectrum disorder (ASD) symptoms frequently occur in individuals with attention-deficit/hyperactivity disorder (ADHD). While there is evidence that both ADHD and ASD have differential structural brain correlates, knowledge of the structural brain profile of individuals with ADHD with raised ASD symptoms is limited. The presence of ASD-like symptoms was measured by the Children's Social Behavior Questionnaire (CSBQ) in a sample of typically developing controls (n = 154), participants with ADHD (n = 239), and their unaffected siblings (n = 144) between the ages of 8 and 29. Structural magnetic resonance imaging (MRI) correlates of ASD ratings were analysed by studying the relationship between ASD ratings and grey matter volumes using mixed effects models which controlled for ADHD symptom count and total brain volume. ASD ratings were significantly elevated in participants with ADHD relative to controls and unaffected siblings. For the entire group (participants with ADHD, unaffected siblings and TD controls), mixed effect models revealed that the left caudate nucleus volume was negatively correlated with ASD ratings (t = 2.83; P = 0.005). The current findings are consistent with the role of the caudate nucleus in executive function, including the selection of goals based on the evaluation of action outcomes and the use of social reward to update reward representations. There is a specific volumetric profile associated with subclinical ASD-like symptoms in participants with ADHD, unaffected siblings and controls with the caudate nucleus and globus pallidus being of critical importance in predicting the level of ASD-like symptoms in all three groups. PMID:27806078

Decreased Left Caudate Volume Is Associated with Increased Severity of Autistic-Like Symptoms in a Cohort of ADHD Patients and Their Unaffected Siblings.

PubMed

O'Dwyer, Laurence; Tanner, Colby; van Dongen, Eelco V; Greven, Corina U; Bralten, Janita; Zwiers, Marcel P; Franke, Barbara; Heslenfeld, Dirk; Oosterlaan, Jaap; Hoekstra, Pieter J; Hartman, Catharina A; Groen, Wouter; Rommelse, Nanda; Buitelaar, Jan K

2016-01-01

Autism spectrum disorder (ASD) symptoms frequently occur in individuals with attention-deficit/hyperactivity disorder (ADHD). While there is evidence that both ADHD and ASD have differential structural brain correlates, knowledge of the structural brain profile of individuals with ADHD with raised ASD symptoms is limited. The presence of ASD-like symptoms was measured by the Children's Social Behavior Questionnaire (CSBQ) in a sample of typically developing controls (n = 154), participants with ADHD (n = 239), and their unaffected siblings (n = 144) between the ages of 8 and 29. Structural magnetic resonance imaging (MRI) correlates of ASD ratings were analysed by studying the relationship between ASD ratings and grey matter volumes using mixed effects models which controlled for ADHD symptom count and total brain volume. ASD ratings were significantly elevated in participants with ADHD relative to controls and unaffected siblings. For the entire group (participants with ADHD, unaffected siblings and TD controls), mixed effect models revealed that the left caudate nucleus volume was negatively correlated with ASD ratings (t = 2.83; P = 0.005). The current findings are consistent with the role of the caudate nucleus in executive function, including the selection of goals based on the evaluation of action outcomes and the use of social reward to update reward representations. There is a specific volumetric profile associated with subclinical ASD-like symptoms in participants with ADHD, unaffected siblings and controls with the caudate nucleus and globus pallidus being of critical importance in predicting the level of ASD-like symptoms in all three groups.

Unique β-Glucuronidase Locus in Gut Microbiomes of Crohn's Disease Patients and Unaffected First-Degree Relatives.

PubMed

Gloux, Karine; Anba-Mondoloni, Jamila

2016-01-01

Crohn's disease, an incurable chronic inflammatory bowel disease, has been attributed to both genetic predisposition and environmental factors. A dysbiosis of the gut microbiota, observed in numerous patients but also in at least one hundred unaffected first-degree relatives, was proposed to have a causal role. Gut microbiota β-D-glucuronidases (EC 3.2.1.33) hydrolyse β-D-glucuronate from glucuronidated compounds. They include a GUS group, that is homologous to the Escherichia coli GusA, and a BG group, that is homologous to metagenomically identified H11G11 BG and has unidentified natural substrates. H11G11 BG is part of the functional core of the human gut microbiota whereas GusA, known to regenerate various toxic products, is variably found in human subjects. We investigated potential risk markers for Crohn's disease using DNA-sequence-based exploration of the β-D-glucuronidase loci (GUS or Firmicute H11G11-BG and the respective co-encoded glucuronide transporters). Crohn's disease-related microbiomes revealed a higher frequency of a C7D2 glucuronide transporter (12/13) compared to unrelated healthy subjects (8/32). This transporter was in synteny with the potential harmful GUS β-D-glucuronidase as only observed in a Eubacterium eligens plasmid. A conserved NH2-terminal sequence in the transporter (FGDFGND motif) was found in 83% of the disease-related subjects and only in 12% of controls. We propose a microbiota-pathology hypothesis in which the presence of this unique β-glucuronidase locus may contribute to an increase risk for Crohn's disease.

Quality of life of unaffected siblings of children with chronic neurological disorders.

PubMed

Rana, Pratyaksha; Mishra, Devendra

2015-06-01

To study quality of life (QoL) of the siblings of children with chronic neurological disorders. Between 1st August and 30th September, 2013, 50 children aged 12-18 y, whose child sibling was suffering from a chronic neurological disorder, were enrolled (Study group). Fifty age- and sex- matched siblings of apparently non-neurologically affected children were enrolled as controls (Control group). Those with more than one affected child or any affected adult in the family were excluded. QoL was assessed by a validated version of the WHOQOL-BREF in Hindi, and QoL was compared between cases and controls. The disorders in the index cases included cerebral palsy, 18 (15 with epilepsy); autism, 15; mental retardation, 12 and epilepsy, 5. The QoL in all domains was significantly poorer in the study group as compared to the controls. 64% study group children had insufficient knowledge about their sibling's condition. More than 1/4th study subjects faced difficulties in studies, play or work. There was no difference among the groups with regard to number of siblings who had 'dropped from the school'. The QoL of unaffected siblings of children with chronic neurological disorders was significantly impaired. Health-workers may consider including older siblings of neurologically affected children during family-counseling sessions, to provide information and suggest coping strategies. This intervention is likely to improve the functioning of the family unit as a whole.

Cortical mechanisms of mirror therapy after stroke.

PubMed

Rossiter, Holly E; Borrelli, Mimi R; Borchert, Robin J; Bradbury, David; Ward, Nick S

2015-06-01

Mirror therapy is a new form of stroke rehabilitation that uses the mirror reflection of the unaffected hand in place of the affected hand to augment movement training. The mechanism of mirror therapy is not known but is thought to involve changes in cerebral organization. We used magnetoencephalography (MEG) to measure changes in cortical activity during mirror training after stroke. In particular, we examined movement-related changes in the power of cortical oscillations in the beta (15-30 Hz) frequency range, known to be involved in movement. Ten stroke patients with upper limb paresis and 13 healthy controls were recorded using MEG while performing bimanual hand movements in 2 different conditions. In one, subjects looked directly at their affected hand (or dominant hand in controls), and in the other, they looked at a mirror reflection of their unaffected hand in place of their affected hand. The movement-related beta desynchronization was calculated in both primary motor cortices. Movement-related beta desynchronization was symmetrical during bilateral movement and unaltered by the mirror condition in controls. In the patients, movement-related beta desynchronization was generally smaller than in controls, but greater in contralesional compared to ipsilesional motor cortex. This initial asymmetry in movement-related beta desynchronization between hemispheres was made more symmetrical by the presence of the mirror. Mirror therapy could potentially aid stroke rehabilitation by normalizing an asymmetrical pattern of movement-related beta desynchronization in primary motor cortices during bilateral movement. © The Author(s) 2014.

Control of Angular Momentum during Walking in Children with Cerebral Palsy

ERIC Educational Resources Information Center

Bruijn, Sjoerd M.; Meyns, Pieter; Jonkers, Ilse; Kaat, Desloovere; Duysens, Jacques

2011-01-01

Children with hemiparetic Cerebral Palsy (CP) walk with marked asymmetries. For instance, we have recently shown that they have less arm swing on the affected side, and more arm swing at the unaffected side. Such an increase in arm swing at the unaffected side may be aimed at controlling total body angular momentum about the vertical axis,…

Reduced event-related low frequency EEG activity in patients with early onset schizophrenia and their unaffected siblings.

PubMed

Simmonite, Molly; Bates, Alan Thomas; Groom, Madeleine; Hollis, Chris; Liddle, Peter Francis

2015-04-30

Low-frequency oscillations in the electroencephalogram (EEG) have been found to be abnormal in patients with schizophrenia. It is unclear, however, whether these abnormalities are related to severity of illness or are a marker for risk. This study investigated total and evoked theta and delta activity in schizophrenia patients, unaffected siblings, and healthy controls (HCs). EEG data were recorded whilst 24 individuals with schizophrenia, 26 unaffected siblings of individuals with schizophrenia and 26 healthy control participants completed a Go/No-Go task. Event-related total activity and evoked theta and delta activity were calculated for correct hits (CH), failed inhibitions (FI) and correct inhibitions (CI) trials. Patients displayed significantly less total delta, evoked delta, total theta and evoked theta activity when compared with healthy controls. Unaffected siblings displayed abnormalities of evoked delta, but other measures were similar to those in control participants. The findings of this study add to evidence that abnormal low-frequency EEG oscillations contribute to impairments in information processing seen in schizophrenia. These findings also suggest abnormal evoked delta oscillations are associated with an increased familial risk of developing the disorder. Copyright © 2015. Published by Elsevier Ireland Ltd.

Childhood obsessive-compulsive traits in anorexia nervosa patients, their unaffected sisters and healthy controls: a retrospective study.

PubMed

Degortes, Daniela; Zanetti, Tatiana; Tenconi, Elena; Santonastaso, Paolo; Favaro, Angela

2014-07-01

Although there is evidence that childhood perfectionistic traits predate the onset of eating disorders, few studies to date have examined the prevalence and clinical correlates of these traits in patients with anorexia nervosa (AN) and their unaffected sisters. The aim of this work was to study the prevalence of childhood obsessive-compulsive traits in patients with lifetime AN, their unaffected sisters and healthy women. A total of 116 AN patients, 32 healthy sisters and 119 controls were assessed by the EATATE Interview to assess traits such as perfectionism, inflexibility, rule-bound traits, drive for order and symmetry, and excessive doubt and cautiousness. Both self-report and maternal reports were collected. AN patients reported more childhood obsessive-compulsive traits than their healthy sisters and controls. In contrast, no differences between healthy controls and unaffected sisters emerged. In patients with AN, a dose-response relationship was found between the number of childhood obsessive-compulsive traits and psychopathology, including body image distortion, thus indicating that these traits are an important feature to be considered in assessing and treating eating disorders. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.

Executive functions as endophenotypes in ADHD: evidence from the Cambridge Neuropsychological Test Battery (CANTAB).

PubMed

Gau, Susan Shur-Fen; Shang, Chi-Yung

2010-07-01

Little is known about executive functions among unaffected siblings of children with attention deficit/hyperactivity disorder (ADHD), and there is lack of such information from non-Western countries. We examined verbal and nonverbal executive functions in adolescents with ADHD, unaffected siblings and controls to test whether executive functions could be potential endophenotypes for ADHD. We assessed 279 adolescents (age range: 11-17 years) with a childhood diagnosis of DSM-IV ADHD, 136 biological siblings (108 unaffected, 79.4%), and 173 unaffected controls by using psychiatric interviews, the Wechsler Intelligence Scale for Children - 3rd edition (WISC-III), including digit spans, and the tasks involving executive functions of the Cambridge Neuropsychological Test Automated Battery (CANTAB): Intra-dimensional/Extra-dimensional Shifts (IED), Spatial Span (SSP), Spatial Working Memory (SWM), and Stockings of Cambridge (SOC). Compared with the controls, adolescents with ADHD and unaffected siblings had a significantly shorter backward digit span, more extra-dimensional shift errors in the IED, shorter spatial span length in the SSP, more total errors and poorer strategy use in the SWM, and fewer problems solved in the minimum number of moves and shorter initial thinking time in the SOC. The magnitudes of the differences in the SWM and SOC increased with increased task difficulties. In general, neither persistent ADHD nor comorbidity was associated with increased deficits in executive functions among adolescents with ADHD. The lack of much difference in executive dysfunctions between unaffected siblings and ADHD adolescents suggests that executive dysfunctions may be useful cognitive endophenotypes for ADHD genetic studies.

Effect of constrained weight shift on the static balance and muscle activation of stroke patients

PubMed Central

Kang, Kyung Woo; Kim, Kyoung; Lee, Na Kyung; Kwon, Jung Won; Son, Sung Min

2015-01-01

[Purpose] The purpose of this study was to evaluate the effects of constrained weight shift induced by shoe lift beneath the unaffected lower extremity, on balance functions and electromyography of the affected lower extremity of stroke patients. [Subjects and Methods] Twelve patients with unilateral stroke were recruited as volunteers for this study. The subjects were repeatedly measured in a randomized order under three conditions: no-shoe lift, and shoe lifts of 5 mm and 10 mm heights beneath the unaffected lower extremity. [Results] Standing with a 10 mm shoe lift for the unaffected lower extremity decreased the mean velocity of mediolateral sway compared to no-shoe lift. Regarding the velocity of anteroposterior sway, standing with 5 mm and 10 mm shoe lifts decreased the mean velocity of anteroposterior sway. The muscle activation of the affected lower extremity was not significantly different among the no-shoe lift, 5 mm shoe lift and 10 mm shoe lift conditions; however, the muscle activities of the rectus femoris, biceps femoris, tibialis anterior, and medial gastrocnemius of the affected lower extremity progressively improved with increasing height of the shoe lift. [Conclusion] A constrained weight shift to the affected side elicited by a shoe insole of 10 mm height on the unaffected side can improve the static standing balance of stroke patients, and it resulted in 14–24% increases in the muscle activities of the affected leg. PMID:25931729

Regional white matter abnormalities in drug-naive, first-episode schizophrenia patients and their healthy unaffected siblings.

PubMed

Lyu, Hailong; Hu, Maorong; Eyler, Lisa T; Jin, Hua; Wang, Juan; Ou, Jianjun; Guo, Xiaofeng; He, Zhong; Liu, Fang; Zhao, Jingping; Guo, Wenbin

2015-03-01

Shared neuropathological features between schizophrenia patients and their siblings may represent intermediate phenotypes of schizophrenia and can be used to investigate genetic susceptibility to the illness. This study aimed to discover regional white matter abnormalities in first-episode schizophrenia (FES) patients and their unaffected siblings compared to healthy subjects in the Chinese Han population using optimized Voxel-Based Morphometry (VBM). A total of 51 drug-naive, FES patients, 45 of their unaffected siblings and 59 healthy comparisons were studied with magnetic resonance imaging (MRI). FES patients exhibited significant regional white matter deficits in the left inferior frontal gyrus and left joint of external capsule and internal capsule compared with healthy subjects (corrected FDR, p<0.005). The sibling group also showed significant white matter deficits in these two regions compared with the healthy comparison group (uncorrected, p<0.001). White matter deficits with a less stringent threshold for significance in the left cerebellum anterior lobe, left middle frontal gyrus, left hippocampus, right anterior cingulate and right internal capsule were observed in patients compared to their siblings. Our findings extend those from previous VBM analyses showing that FES patients and their unaffected siblings may share white matter deficits in the left inferior frontal gyrus and the left joint of external capsule and internal capsule. These regional white matter deficits may be related to genetic factors related to schizophrenia susceptibility. © The Royal Australian and New Zealand College of Psychiatrists 2014.

Visual processing as a potential endophenotype in youths with attention-deficit/hyperactivity disorder: A sibling study design using the counting Stroop functional MRI.

PubMed

Fan, Li-Ying; Shang, Chi-Yung; Tseng, Wen-Yih Isaac; Gau, Susan Shur-Fen; Chou, Tai-Li

2018-05-10

Deficits in inhibitory control and visual processing are common in youths with attention-deficit/hyperactivity disorder (ADHD), but little is known about endophenotypes for unaffected siblings of youths with ADHD. This study aimed to investigate the potential endophenotypes of brain activation and performance in inhibitory control and visual processing among ADHD probands, their unaffected siblings, and neurotypical youths. We assessed 27 ADHD probands, 27 unaffected siblings, and 27 age-, gender-, and IQ-matched neurotypical youths using the counting Stroop functional magnetic resonance imaging and two tasks of the Cambridge Neuropsychological Test Automated Battery (CANTAB): rapid visual information processing (RVP) for inhibitory control and spatial span (SSP) for visual processing. ADHD probands showed greater activation than their unaffected siblings and neurotypical youths in the right inferior frontal gyrus (IFG) and anterior cingulate cortex. Increased activation in the right IFG was positively correlated with the mean latency of the RVP in ADHD probands. Moreover, ADHD probands and their unaffected siblings showed less activation in the left superior parietal lobule (SPL) than neurotypical youths. Increased activation in the left SPL was positively correlated with the spatial length of the SSP in neurotypical youths. Our findings suggest that less activation in the left SPL might be considered as a candidate imaging endophenotype for visual processing in ADHD. © 2018 Wiley Periodicals, Inc.

Soluble HLA-G in pregnancies complicated by autoimmune rheumatic diseases.

PubMed

Beneventi, Fausta; Badulli, Carla; Locatelli, Elena; Caporali, Roberto; Ramoni, Véronique; Cavagnoli, Chiara; Simonetta, Margherita; Garbin, Giulia; Tinelli, Carmine; Alpini, Claudia; Montecucco, CarloMaurizio; Martinetti, Miryam; Spinillo, Arsenio

2015-08-01

Autoimmune rheumatic diseases in pregnancies are associated with increased adverse obstetric outcomes. We compared maternal soluble human leucocyte antigen-G (sHLA-G) blood levels in subjects with a rheumatic disease preexisting pregnancy and unaffected controls. Third-trimester blood maternal sHLA-G concentrations were significantly higher in subjects with rheumatic diseases than in controls (mean 93.1ng/ml [SD 42.1] vs 58.1ng/ml [SD 96.3], p=0.003). Cord blood sHLA-G concentrations were significantly higher in rheumatic disease than in those born to control mothers (median 41.2ng/ml [IQR: 3.3-44.0] vs 17.9ng/ml [IQR: 17.2-88.1], p=0.007). A strict positive correlation (r=0.88, p<0.001) was found between the maternal and fetal titers of ANA autoantibodies as well as between maternal and fetal sHLAG circulating levels (r=0.58 and r=0.67, respectively, for controls and cases, p<0.001). Maternal s-HLA-G blood concentrations were significantly higher in subjects with rheumatic disease DEL/DEL homozygous for a polymorphism of the 3' untranslated regulatory region of HLA-G (HLA-G 14bp) than in the corresponding healthy controls (mean values 141.5ng/ml [SD: 166] vs 54.2ng/ml [SD: 35], p=0.009). Increasing maternal and cord blood levels of s-HLA-G concentrations among pregnant subjects with rheumatic diseases compared with controls suggest that autoimmune diseases prompt a maternal and fetal immune response that favors pregnancy immune tolerance. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Impaired strategic decision making in schizophrenia.

PubMed

Kim, Hyojin; Lee, Daeyeol; Shin, Young-Min; Chey, Jeanyung

2007-11-14

Adaptive decision making in dynamic social settings requires frequent re-evaluation of choice outcomes and revision of strategies. This requires an array of multiple cognitive abilities, such as working memory and response inhibition. Thus, the disruption of such abilities in schizophrenia can have significant implications for social dysfunctions in affected patients. In the present study, 20 schizophrenia patients and 20 control subjects completed two computerized binary decision-making tasks. In the first task, the participants played a competitive zero-sum game against a computer in which the predictable choice behavior was penalized and the optimal strategy was to choose the two targets stochastically. In the second task, the expected payoffs of the two targets were fixed and unaffected by the subject's choices, so the optimal strategy was to choose the target with the higher expected payoff exclusively. The schizophrenia patients earned significantly less money during the first task, even though their overall choice probabilities were not significantly different from the control subjects. This was mostly because patients were impaired in integrating the outcomes of their previous choices appropriately in order to maintain the optimal strategy. During the second task, the choices of patients and control subjects displayed more similar patterns. This study elucidated the specific components in strategic decision making that are impaired in schizophrenia. The deficit, which can be characterized as strategic stiffness, may have implications for the poor social adjustment in schizophrenia patients.

High Protein Intake Improves Insulin Sensitivity but Exacerbates Bone Resorption in Immobility (WISE Study)

NASA Technical Reports Server (NTRS)

Heer, Martina; Smith, Scott M.; Frings-Meuthen, Petra; Zwart, Sara R.; Baecker, Natalie

2012-01-01

Inactivity, like bed rest (BR), causes insulin resistance (IR) and bone loss even in healthy subjects. High protein intake seems to mitigate this IR but might exacerbate bone loss. We hypothesized that high protein intake (animal:vegetable protein ratio: 60:40), isocaloric, compared to the control group plus high potassium intake would prevent IR without affecting bone turnover. After a 20-day ambulatory adaptation to controlled confinement and diet, 16 women participated in a 60-day, 6 deg head-down-tilt BR and were assigned randomly to one of the two groups. Control subjects (CON, n=8) received 1g/kg body mass/d dietary protein. Nutrition subjects (NUT, n=8) received 1.45g/kg body mass/d dietary protein plus 7.2g branched chain amino acids per day during BR. All subjects received 1670 kcal/d. Bed rest decreased glucose disposal by 35% (p<0.05) in CON. Isocaloric high protein intake prevented insulin resistance, but exacerbated bed rest induced increase in bone resorption markers C-telopeptide (> 30%) and Ntelopeptide (>20%) (both: p<0.001). Bone formation markers were unaffected by high protein intake. We conclude from these results that high protein intake might positively affect glucose tolerance, but might also foster bone loss. Further long-duration studies are mandatory before high protein intake for diabetic patients, who have an increased fracture risk, might be recommended.

Moderators of neuropsychological mechanism in attention-deficit hyperactivity disorder.

PubMed

Nikolas, Molly A; Nigg, Joel T

2015-02-01

Neuropsychological measures have been proposed as both a way to tap mechanisms and as endophenotypes for child ADHD. However, substantial evidence supporting heterogeneity in neuropsychological performance among youth with ADHD as well as apparent effect differences by sex, age, and comorbidity have slowed progress. To address this, it is important to understand sibling effects in relation to these moderators. 461 youth ages 6-17 years (54.8 % male, including 251 youth with ADHD, 107 of their unaffected biological siblings, and 103 non-ADHD controls) completed diagnostic interviews and a theoretically informed battery of neuropsychological functioning. A structural equation model was used to consolidate neuropsychological domains. Group differences between unaffected siblings of youth with ADHD and controls across each domain were first examined as the primary endophenotype test for ADHD. Moderation of these effects was evaluated via investigation of interactions between diagnostic group and both proband and individual level characteristics, including sex, age, and comorbidity status. Unaffected siblings performed worse than control youth in the domains of inhibition, response time variability, and temporal information processing. Individual age moderated these effects, such that differences between controls and unaffected siblings were pronounced among younger children (ages 6-10 years) but absent among older youth (ages 11-17 years). Evidence for moderation of effects by proband sex and comorbidity status produced more variable and smaller effects. Results support the utility of inhibition, response time variability, and temporal processing as useful endophenotypes for ADHD in future genetic associations studies of the disorder, but suggest this value will vary by age among unaffected family members.

Intra-individual reaction time variability based on ex-Gaussian distribution as a potential endophenotype for attention-deficit/hyperactivity disorder.

PubMed

Lin, H-Y; Hwang-Gu, S-L; Gau, S S-F

2015-07-01

Intra-individual variability in reaction time (IIV-RT), defined by standard deviation of RT (RTSD), is considered as an endophenotype for attention-deficit/hyperactivity disorder (ADHD). Ex-Gaussian distributions of RT, rather than RTSD, could better characterize moment-to-moment fluctuations in neuropsychological performance. However, data of response variability based on ex-Gaussian parameters as an endophenotypic candidate for ADHD are lacking. We assessed 411 adolescents with clinically diagnosed ADHD based on the DSM-IV-TR criteria as probands, 138 unaffected siblings, and 138 healthy controls. The output parameters, mu, sigma, and tau, of an ex-Gaussian RT distribution were derived from the Conners' continuous performance test. Multi-level models controlling for sex, age, comorbidity, and use of methylphenidate were applied. Compared with unaffected siblings and controls, ADHD probands had elevated sigma value, omissions, commissions, and mean RT. Unaffected siblings formed an intermediate group in-between probands and controls in terms of tau value and RTSD. There was no between-group difference in mu value. Conforming to a context-dependent nature, unaffected siblings still had an intermediate tau value in-between probands and controls across different interstimulus intervals. Our findings suggest IIV-RT represented by tau may be a potential endophenotype for inquiry into genetic underpinnings of ADHD in the context of heterogeneity. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effect of chloroquine on insulin and glucose homoeostasis in normal subjects and patients with non-insulin-dependent diabetes mellitus.

PubMed Central

Smith, G D; Amos, T A; Mahler, R; Peters, T J

1987-01-01

Plasma glucose, insulin, and C peptide concentrations were determined after an oral glucose load in normal subjects and in a group of patients with non-insulin-dependent diabetes mellitus before and during a short course of treatment with chloroquine. In the control group there was a small but significant reduction in fasting blood glucose concentration but overall glucose tolerance and hormone concentrations were unaffected. In contrast, the patients with non-insulin-dependent diabetes mellitus showed a significant improvement in their glucose tolerance, which paralleled the severity of their diabetes. This response seems to reflect decreased degradation of insulin rather than increased pancreatic output. These observations suggest that treatment with chloroquine or suitable analogues may be a new approach to the management of diabetes. PMID:3103729

Failure to preserve beta-cell function with mycophenolate mofetil and daclizumab combined therapy in patients with new- onset type 1 diabetes.

PubMed

Gottlieb, Peter A; Quinlan, Scott; Krause-Steinrauf, Heidi; Greenbaum, Carla J; Wilson, Darrell M; Rodriguez, Henry; Schatz, Desmond A; Moran, Antoinette M; Lachin, John M; Skyler, Jay S

2010-04-01

This trial tested whether mycophenolate mofetil (MMF) alone or with daclizumab (DZB) could arrest the loss of insulin-producing beta-cells in subjects with new-onset type 1 diabetes. A multi-center, randomized, placebo-controlled, double-masked trial was initiated by Type 1 Diabetes TrialNet at 13 sites in North America and Europe. Subjects diagnosed with type 1 diabetes and with sufficient C-peptide within 3 months of diagnosis were randomized to either MMF alone, MMF plus DZB, or placebo, and then followed for 2 years. The primary outcome was the geometric mean area under the curve (AUC) C-peptide from the 2-h mixed meal tolerance test. One hundred and twenty-six subjects were randomized and treated during the trial. The geometric mean C-peptide AUC at 2 years was unaffected by MMF alone or MMF plus DZB versus placebo. Adverse events were more frequent in the active therapy groups relative to the control group, but not significantly. Neither MMF alone nor MMF in combination with DZB had an effect on the loss of C-peptide in subjects with new-onset type 1 diabetes. Higher doses or more targeted immunotherapies may be needed to affect the autoimmune process.

Failure to Preserve β-Cell Function With Mycophenolate Mofetil and Daclizumab Combined Therapy in Patients With New- Onset Type 1 Diabetes

PubMed Central

Gottlieb, Peter A.; Quinlan, Scott; Krause-Steinrauf, Heidi; Greenbaum, Carla J.; Wilson, Darrell M.; Rodriguez, Henry; Schatz, Desmond A.; Moran, Antoinette M.; Lachin, John M.; Skyler, Jay S.

2010-01-01

OBJECTIVE This trial tested whether mycophenolate mofetil (MMF) alone or with daclizumab (DZB) could arrest the loss of insulin-producing β-cells in subjects with new-onset type 1 diabetes. RESEARCH DESIGN AND METHODS A multi-center, randomized, placebo-controlled, double-masked trial was initiated by Type 1 Diabetes TrialNet at 13 sites in North America and Europe. Subjects diagnosed with type 1 diabetes and with sufficient C-peptide within 3 months of diagnosis were randomized to either MMF alone, MMF plus DZB, or placebo, and then followed for 2 years. The primary outcome was the geometric mean area under the curve (AUC) C-peptide from the 2-h mixed meal tolerance test. RESULTS One hundred and twenty-six subjects were randomized and treated during the trial. The geometric mean C-peptide AUC at 2 years was unaffected by MMF alone or MMF plus DZB versus placebo. Adverse events were more frequent in the active therapy groups relative to the control group, but not significantly. CONCLUSIONS Neither MMF alone nor MMF in combination with DZB had an effect on the loss of C-peptide in subjects with new-onset type 1 diabetes. Higher doses or more targeted immunotherapies may be needed to affect the autoimmune process. PMID:20067954

Long-term maternal recall of obstetric complications in schizophrenia research.

PubMed

Walshe, Muriel; McDonald, Colm; Boydell, Jane; Zhao, Jing Hua; Kravariti, Eugenia; Touloupoulou, Timothea; Fearon, Paul; Bramon, Elvira; Murray, Robin M; Allin, Matthew

2011-05-30

Obstetric complications (OCs) are consistently implicated in the aetiology of schizophrenia. Information about OCs is often gathered retrospectively, from maternal interview. It has been suggested that mothers of people with schizophrenia may not be accurate in their recollection of obstetric events. We assessed the validity of long term maternal recall by comparing maternal ratings of OCs with those obtained from medical records in a sample of mothers of offspring affected and unaffected with psychotic illness. Obstetric records were retrieved for 30 subjects affected with psychosis and 40 of their unaffected relatives. The Lewis-Murray scale of OCs was completed by maternal interview for each subject blind to the obstetric records. There was substantial agreement between maternal recall and birth records for the summary score of "definite" OCs, birth weight, and most of the individual items rated, with the exception of antepartum haemorrhage. There were no significant differences in the validity of recall or in errors of commission by mothers for affected and unaffected offspring. These findings indicate that several complications of pregnancy and delivery are accurately recalled by mother's decades after they occurred. Furthermore, there is no indication that mothers are less accurate in recalling OCs for their affected offspring than their unaffected offspring. When comparing women with and without recall errors, we found those with recall errors to have significantly worse verbal memory than women without such errors. Assessing the cognition of participants in retrospective studies may allow future studies to increase the reliability of their data. Copyright © 2011 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leonard, C.M.; Hauser, P.; Weintraub, B.D.

Resistance to thyroid hormone (RTH) is an autosomal dominant disease caused by mutations in the human thyroid receptor beta gene on chromosome 3. Individuals with RTH have an increased incidence of attention deficit hyperactivity disorder (ADHD). The purpose of this study was to search for developmental brain malformations associated with RTH. Forty-three subjects (20 affected males [AM], 23 affected females [AF]) with resistance to thyroid hormone and 32 unaffected first degree relatives (18 unaffected males [UM], 14 unaffected females [UF]) underwent MRI brain scans with a volumetric acquisition that provided 90 contiguous 2 mm thick sagittal images. Films of sixmore » contiguous images beginning at a standard sagittal position lateral to the insula were analyzed by an investigator who was blind with respect to subject characteristics. The presence of extra or missing gyri in the parietal bank of the Sylvian fissure (multimodal association cortex) and multiple Heschl`s transverse gyri (primary auditory cortex) were noted. There was a significantly increased frequency of anomalous Sylvian fissures in the left hemisphere in males with RTH (AM: 70%; AF: 30%; UM: 28% UF: 28%). Also, there was an increased frequency of anomalous Sylvian fissures on the left combined with multiple Heschl`s gyri in either hemisphere in males with RTH (AM: 50%; AF: 9%; UM: 6%; UF: 0%). However, RTH subjects with anomalies did not have an increased frequency of ADHD as compared with RTH subjects with no anomalies. Abnormal thyroid hormone action in the male fetus early during brain development may be associated with grossly observable cerebral anomalies of the left hemisphere. The effects of mutations in the thyroid receptor beta gene provide a model system for studying the complex interaction of genetic and non-genetic factors on brain and behavioral development. 19 refs., 2 figs., 2 tabs.« less

Unique β-Glucuronidase Locus in Gut Microbiomes of Crohn’s Disease Patients and Unaffected First-Degree Relatives

PubMed Central

Gloux, Karine; Anba-Mondoloni, Jamila

2016-01-01

Crohn’s disease, an incurable chronic inflammatory bowel disease, has been attributed to both genetic predisposition and environmental factors. A dysbiosis of the gut microbiota, observed in numerous patients but also in at least one hundred unaffected first-degree relatives, was proposed to have a causal role. Gut microbiota β-D-glucuronidases (EC 3.2.1.33) hydrolyse β-D-glucuronate from glucuronidated compounds. They include a GUS group, that is homologous to the Escherichia coli GusA, and a BG group, that is homologous to metagenomically identified H11G11 BG and has unidentified natural substrates. H11G11 BG is part of the functional core of the human gut microbiota whereas GusA, known to regenerate various toxic products, is variably found in human subjects. We investigated potential risk markers for Crohn’s disease using DNA-sequence-based exploration of the β-D-glucuronidase loci (GUS or Firmicute H11G11-BG and the respective co-encoded glucuronide transporters). Crohn’s disease-related microbiomes revealed a higher frequency of a C7D2 glucuronide transporter (12/13) compared to unrelated healthy subjects (8/32). This transporter was in synteny with the potential harmful GUS β-D-glucuronidase as only observed in a Eubacterium eligens plasmid. A conserved NH2-terminal sequence in the transporter (FGDFGND motif) was found in 83% of the disease-related subjects and only in 12% of controls. We propose a microbiota-pathology hypothesis in which the presence of this unique β-glucuronidase locus may contribute to an increase risk for Crohn’s disease. PMID:26824357

Optimal plasma progranulin cutoff value for predicting null progranulin mutations in neurodegenerative diseases: a multicenter Italian study.

PubMed

Ghidoni, Roberta; Stoppani, Elena; Rossi, Giacomina; Piccoli, Elena; Albertini, Valentina; Paterlini, Anna; Glionna, Michela; Pegoiani, Eleonora; Agnati, Luigi F; Fenoglio, Chiara; Scarpini, Elio; Galimberti, Daniela; Morbin, Michela; Tagliavini, Fabrizio; Binetti, Giuliano; Benussi, Luisa

2012-01-01

Recently, attention was drawn to a role for progranulin in the central nervous system with the identification of mutations in the progranulin gene (GRN) as an important cause of frontotemporal lobar degeneration. GRN mutations are associated with a strong reduction of circulating progranulin and widely variable clinical phenotypes: thus, the dosage of plasma progranulin is a useful tool for a quick and inexpensive large-scale screening of carriers of GRN mutations. To establish the best cutoff threshold for normal versus abnormal levels of plasma progranulin. 309 cognitively healthy controls (25-87 years of age), 72 affected and unaffected GRN+ null mutation carriers (24-86 years of age), 3 affected GRN missense mutation carriers, 342 patients with neurodegenerative diseases and 293 subjects with mild cognitive impairment were enrolled at the Memory Clinic, IRCCS S. Giovanni di Dio-Fatebenefratelli, Brescia, Italy, and at the Alzheimer Unit, Ospedale Maggiore Policlinico and IRCCS Istituto Neurologico C. Besta, Milan, Italy. Plasma progranulin levels were measured using an ELISA kit (AdipoGen Inc., Seoul, Korea). Plasma progranulin did not correlate with age, gender or body mass index. We established a new plasma progranulin protein cutoff level of 61.55 ng/ml that identifies, with a specificity of 99.6% and a sensitivity of 95.8%, null mutation carriers among subjects attending to a memory clinic. Affected and unaffected GRN null mutation carriers did not differ in terms of circulating progranulin protein (p = 0.686). A significant disease anticipation was observed in GRN+ subjects with the lowest progranulin levels. We propose a new plasma progranulin protein cutoff level useful for clinical practice. Copyright © 2011 S. Karger AG, Basel.

Primary motor cortex contributes to the implementation of implicit value-based rules during motor decisions.

PubMed

Derosiere, Gerard; Zénon, Alexandre; Alamia, Andrea; Duque, Julie

2017-02-01

In the present study, we investigated the functional contribution of the human primary motor cortex (M1) to motor decisions. Continuous theta burst stimulation (cTBS) was used to alter M1 activity while participants performed a decision-making task in which the reward associated with the subjects' responses (right hand finger movements) depended on explicit and implicit value-based rules. Subjects performed the task over two consecutive days and cTBS occurred in the middle of Day 2, once the subjects were just about to implement implicit rules, in addition to the explicit instructions, to choose their responses, as evident in the control group (cTBS over the right somatosensory cortex). Interestingly, cTBS over the left M1 prevented subjects from implementing the implicit value-based rule while its implementation was enhanced in the group receiving cTBS over the right M1. Hence, cTBS had opposite effects depending on whether it was applied on the contralateral or ipsilateral M1. The use of the explicit value-based rule was unaffected by cTBS in the three groups of subject. Overall, the present study provides evidence for a functional contribution of M1 to the implementation of freshly acquired implicit rules, possibly through its involvement in a cortico-subcortical network controlling value-based motor decisions. Copyright © 2016 Elsevier Inc. All rights reserved.

Neurocognitive performance, psychopathology and social functioning in individuals at high risk for schizophrenia or psychotic bipolar disorder.

PubMed

Gkintoni, Evgenia; Pallis, Eleftherios G; Bitsios, Panos; Giakoumaki, Stella G

2017-01-15

Although cognitive deficits are consistent endophenotypes of schizophrenia and bipolar disorder, findings in psychotic bipolar disorder (BDP) are inconsistent. In this study we compared adult unaffected first-degree relatives of schizophrenia and BDP patients on cognition, psychopathology, social functioning and quality of life. Sixty-six unaffected first-degree relatives of schizophrenia patients (SUnR), 36 unaffected first-degree relatives of BDP patients (BDPUnR) and 102 controls participated in the study. Between-group differences were examined and Discriminant Function Analysis (DFA) predicted group membership. Visual memory, control inhibition, working memory, cognitive flexibility and abstract reasoning were linearly impaired in the relatives' groups. Poorer verbal fluency and processing speed were evident only in the SUnR group. The SUnR group had higher depressive and somatization symptoms while the BDPUnR group had higher anxiety and lower social functioning compared with the controls. Individuals with superior cognition were more likely to be classified as controls; those with higher social functioning, prolonged processing speed and lower anxiety were more likely to be classified as SUnR. The relatives' sample is quite heterogeneous; the effects of genetic or environmental risk-factors were not examined. Cognitive functions mediated by a fronto-parietal network, show linear impairments in unaffected relatives of BDP and schizophrenia patients; processing speed and verbal fluency impairments were evident only in schizophrenia relatives. Self-perceived symptomatology and social functioning also differ between schizophrenia and BDP relatives. The continuum seen in patients in several indices was also seen in the cognitive impairments in unaffected relatives of schizophrenia and BDP patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Gastrointestinal motility in space motion sickness

NASA Technical Reports Server (NTRS)

Thornton, William E.; Linder, Barry J.; Moore, Thomas P.; Pool, Sam L.

1987-01-01

Gastrointestinal symptoms in space motion sickness (SMS) are significantly different from those in ordinary motion sickness (MS). Recording and tabulation of sounds was the only technique that could be used as a measure of motility during spaceflight operations. There were 17 subjects, six unaffected by SMS, who made ambulatory recordings preflight and inflight. With one exception, all those affected had sharply reduced sounds, while those unaffected had increases or moderate reductions. The mechanism of vomiting in SMS appears to be secondary to this ileus, in contrast to vomiting in ordinary MS, where the emesis center is thought to be directly triggered by the vestibular system.

Acute and past subjective stress influence working memory and related neural substrates.

PubMed

Luettgau, Lennart; Schlagenhauf, Florian; Sjoerds, Zsuzsika

2018-05-28

Stress has been proposed to affect cognitive control capacities, including working memory (WM) maintenance. This effect may depend on variability in stress reactivity and past subjective stress. However, as most studies employed between-subjects designs, evidence for within-subject stress effects remains scarce. To understand the role of intra-individual stress effects on WM, we adopted a within-subject design to study how acute stress, variability in stress reactivity, and past subjective stress influence behavioral and neural WM mechanisms. Thirty-four healthy males performed a WM task during functional magnetic resonance imaging (fMRI) in a control versus acute stress condition following the Trier Social Stress Test, a validated psychosocial stressor method. We tested for stress effects on WM performance and related neural activation by associating them with individual acute stress responsivity and past subjective stress experience using retrospective self-report questionnaires. We found no evidence of an effect of acute stress or related stress-reactivity on intra-individual WM performance. However, past subjective stress negatively influenced acute stress-induced changes to WM. On the neural level, acute stress reduced WM-related activation in the dorsolateral prefrontal cortex (dlPFC). The observed negative influence of inter-individual variability in past subjective stress experience on changes in WM performance, suggests that past subjective stress might induce vulnerability for impairing effects of acute stress on cognitive functioning. Because acute stress reduced WM-related dlPFC activation while WM performance remained unaffected, acute stress might boost neural processing efficiency in this group of high performing healthy individuals. Our study suggests that measures of past subjective stress should be considered when studying and interpreting the effects of acute stress on cognition. Copyright © 2018. Published by Elsevier Ltd.

Amygdala Hyperactivation During Face Emotion Processing in Unaffected Youth at Risk for Bipolar Disorder

ERIC Educational Resources Information Center

Olsavsky, Aviva K.; Brotman, Melissa A.; Rutenberg, Julia G.; Muhrer, Eli J.; Deveney, Christen M.; Fromm, Stephen J.; Towbin, Kenneth; Pine, Daniel S.; Leibenluft, Ellen

2012-01-01

Objective: Youth at familial risk for bipolar disorder (BD) show deficits in face emotion processing, but the neural correlates of these deficits have not been examined. This preliminary study tests the hypothesis that, relative to healthy comparison (HC) subjects, both BD subjects and youth at risk for BD (i.e., those with a first-degree BD…

Safety of primed repetitive transcranial magnetic stimulation and modified constraint-induced movement therapy in a randomized controlled trial in pediatric hemiparesis

PubMed Central

Gillick, Bernadette; Krach, Linda E; Feyma, Tim; Rich, Tonya L; Moberg, Kelli; Menk, Jeremiah; Cassidy, Jessica; Kimberley, Teresa; Carey, James R

2014-01-01

Objective To investigate the safety of combining 6-Hz primed low-frequency repetitive transcranial magnetic stimulation (rTMS) intervention in the contralesional hemisphere with a modified constraint-induced movement therapy (mCIMT) program in children with congenital hemiparesis. Design Phase 1 randomized, double-blinded, placebo-controlled pretest/posttest trial. Setting University academic facility and a pediatric specialty hospital. Participants Nineteen subjects aged 8 to 17 years with congenital hemiparesis due to ischemic stroke or periventricular leukomalacia. No subject withdrew due to adverse events. All subjects included completed the study. Interventions Subjects were randomized to one of two groups: either rTMSreal with mCIMT (n = 10) or rTMSsham with mCIMT (n = 9). Main Outcome Measures Adverse events, physician assessment, ipsilateral hand function, stereognosis, cognitive function, subject report of symptoms assessment and subject questionnaire. Results No major adverse events occurred. Minor adverse events were found in both groups. The most common were headaches (real: 50%, sham: 89%, p=0.14) and cast irritation (real: 30%, sham: 44%, p = 0.65). No differences between groups in secondary cognitive and unaffected hand motor measures were found. Conclusions Primed rTMS can be used safely with mCIMT in congenital hemiparesis. We provide new information on the use of rTMS in combination with mCIMT in children. These findings could be useful in research and future clinical applications in advancing function in congenital hemiparesis. PMID:25283350

Safety of primed repetitive transcranial magnetic stimulation and modified constraint-induced movement therapy in a randomized controlled trial in pediatric hemiparesis.

PubMed

Gillick, Bernadette T; Krach, Linda E; Feyma, Tim; Rich, Tonya L; Moberg, Kelli; Menk, Jeremiah; Cassidy, Jessica; Kimberley, Teresa; Carey, James R

2015-04-01

To investigate the safety of combining a 6-Hz primed low-frequency repetitive transcranial magnetic stimulation (rTMS) intervention in the contralesional hemisphere with a modified constraint-induced movement therapy (mCIMT) program in children with congenital hemiparesis. Phase 1 randomized, double-blinded, placebo-controlled pretest/posttest trial. University academic facility and pediatric specialty hospital. Subjects (N = 19; age range, 8-17 y) with congenital hemiparesis caused by ischemic stroke or periventricular leukomalacia. No subject withdrew because of adverse events. All subjects included completed the study. Subjects were randomized to 1 of 2 groups: either real rTMS plus mCIMT (n = 10) or sham rTMS plus mCIMT (n = 9). Adverse events, physician assessment, ipsilateral hand function, stereognosis, cognitive function, subject report of symptoms assessment, and subject questionnaire. No major adverse events occurred. Minor adverse events were found in both groups. The most common events were headaches (real: 50%, sham: 89%; P = .14) and cast irritation (real: 30%, sham: 44%; P = .65). No differences between groups in secondary cognitive and unaffected hand motor measures were found. Primed rTMS can be used safely with mCIMT in congenital hemiparesis. We provide new information on the use of rTMS in combination with mCIMT in children. These findings could be useful in research and future clinical applications in advancing function in congenital hemiparesis. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Increased Cerebellar Functional Connectivity With the Default-Mode Network in Unaffected Siblings of Schizophrenia Patients at Rest

PubMed Central

Guo, Wenbin; Liu, Feng; Zhang, Zhikun; Liu, Guiying; Liu, Jianrong; Yu, Liuyu; Xiao, Changqing; Zhao, Jingping

2015-01-01

The default-mode network (DMN) is vital in the neurobiology of schizophrenia, and the cerebellum participates in the high-order cognitive network such as the DMN. However, the specific contribution of the cerebellum to the DMN abnormalities remains unclear in unaffected siblings of schizophrenia patients. Forty-six unaffected siblings of schizophrenia patients and 46 healthy controls were recruited for a resting-state scan. The images were analyzed using the functional connectivity (FC) method. The siblings showed significantly increased FCs between the left Crus I and the left superior medial prefrontal cortex (MPFC), as well as between the lobule IX and the bilateral MPFC (orbital part) and right superior MPFC compared with the controls. No significantly decreased FC was observed in the siblings relative to the controls. The analyses were replicated in 49 first-episode, drug-naive patients with schizophrenia, and the results showed that the siblings and the patients shared increased FCs between the left Crus I and the left superior MPFC, as well as between the lobule IX and the left MPFC (orbital part) compared with the controls. These findings suggest that increased cerebellar-DMN connectivities emerge earlier than illness onset, which highlight the contribution of the cerebellum to the DMN alterations in unaffected siblings. The shared increased cerebellar-DMN connectivities between the patients and the siblings may be used as candidate endophenotypes for schizophrenia. PMID:25956897

Sex-dependent effects of sleep deprivation on myocardial sensitivity to ischemic injury.

PubMed

Zoladz, Phillip R; Krivenko, Anna; Eisenmann, Eric D; Bui, Albert D; Seeley, Sarah L; Fry, Megan E; Johnson, Brandon L; Rorabaugh, Boyd R

2016-01-01

Sleep deprivation is associated with increased risk of myocardial infarction. However, it is unknown whether the effects of sleep deprivation are limited to increasing the likelihood of experiencing a myocardial infarction or if sleep deprivation also increases the extent of myocardial injury. In this study, rats were deprived of paradoxical sleep for 96 h using the platform-over-water method. Control rats were subjected to the same condition except the control platform was large enough for the rats to sleep. Hearts from sleep deprived and control rats were subjected to 20 min ischemia on a Langendorff isolated heart system. Infarct size and post ischemic recovery of contractile function were unaffected by sleep deprivation in male hearts. In contrast, hearts from sleep-deprived females exhibited significantly larger infarcts than hearts from control females. Post ischemic recovery of rate pressure product and + dP/dT were significantly attenuated by sleep deprivation in female hearts, and post ischemic recovery of end diastolic pressure was significantly elevated in hearts from sleep deprived females compared to control females, indicating that post ischemic recovery of both systolic and diastolic function were worsened by sleep deprivation. These data provide evidence that sleep deprivation increases the extent of ischemia-induced injury in a sex-dependent manner.

The relationship between speech recognition, behavioural listening effort, and subjective ratings.

PubMed

Picou, Erin M; Ricketts, Todd A

2018-06-01

The purpose of this study was to evaluate the reliability and validity of four subjective questions related to listening effort. A secondary purpose of this study was to evaluate the effects of hearing aid beamforming microphone arrays on word recognition and listening effort. Participants answered subjective questions immediately following testing in a dual-task paradigm with three microphone settings in a moderately reverberant laboratory environment in two noise configurations. Participants rated their: (1) mental work, (2) desire to improve the situation, (3) tiredness, and (4) desire to give up. Data were analysed using repeated measures and reliability analyses. Eighteen adults with symmetrical sensorineural hearing loss participated. Beamforming differentially affected word recognition and listening effort. Analysis revealed the same pattern of results for behavioural listening effort and subjective ratings of desire to improve the situation. Conversely, ratings of work revealed the same pattern of results as word recognition performance. Ratings of tiredness and desire to give up were unaffected by hearing aid microphone or noise configuration. Participant ratings of their desire to control the listening situation appear to reliable subjective indicators of listening effort that align with results from a behavioural measure of listening effort.

Executive Functions as Endophenotypes in ADHD: Evidence from the Cambridge Neuropsychological Test Battery (CANTAB)

ERIC Educational Resources Information Center

Gau, Susan Shur-Fen; Shang, Chi-Yung

2010-01-01

Background: Little is known about executive functions among unaffected siblings of children with attention deficit/hyperactivity disorder (ADHD), and there is lack of such information from non-Western countries. We examined verbal and nonverbal executive functions in adolescents with ADHD, unaffected siblings and controls to test whether executive…

Social Motor Coordination in Unaffected Relatives of Schizophrenia Patients: A Potential Intermediate Phenotype

PubMed Central

Del-Monte, Jonathan; Capdevielle, Delphine; Varlet, Manuel; Marin, Ludovic; Schmidt, Richard C.; Salesse, Robin N.; Bardy, Benoît G.; Boulenger, Jean Philippe; Gély-Nargeot, Marie Christine; Attal, Jérôme; Raffard, Stéphane

2013-01-01

Intermediate endophenotypes emerge as an important concept in the study of schizophrenia. Although research on phenotypes mainly investigated cognitive, metabolic or neurophysiological markers so far, some authors also examined the motor behavior anomalies as a potential trait-marker of the disease. However, no research has investigated social motor coordination despite the possible importance of its anomalies in schizophrenia. The aim of this study was thus to determine whether coordination modifications previously demonstrated in schizophrenia are trait-markers that might be associated with the risk for this pathology. Interpersonal motor coordination in 27 unaffected first-degree relatives of schizophrenia patients and 27 healthy controls was assessed using a hand-held pendulum task to examine the presence of interpersonal coordination impairments in individuals at risk for the disorder. Measures of neurologic soft signs, clinical variables and neurocognitive functions were collected to assess the cognitive and clinical correlates of social coordination impairments in at-risk relatives. After controlling for potential confounding variables, unaffected relatives of schizophrenia patients had impaired intentional interpersonal coordination compared to healthy controls while unintentional interpersonal coordination was preserved. More specifically, in intentional coordination, the unaffected relatives of schizophrenia patients exhibited coordination patterns that had greater variability and in which relatives did not lead the coordination. These results show that unaffected relatives of schizophrenia patients, like the patients themselves, also present deficits in intentional interpersonal coordination. For the first time, these results suggest that intentional interpersonal coordination impairments might be a potential motor intermediate endophenotype of schizophrenia opening new perspectives for early diagnosis. PMID:24106467

The familial basis of facial emotion recognition deficits in adolescents with conduct disorder and their unaffected relatives.

PubMed

Sully, K; Sonuga-Barke, E J S; Fairchild, G

2015-07-01

There is accumulating evidence of impairments in facial emotion recognition in adolescents with conduct disorder (CD). However, the majority of studies in this area have only been able to demonstrate an association, rather than a causal link, between emotion recognition deficits and CD. To move closer towards understanding the causal pathways linking emotion recognition problems with CD, we studied emotion recognition in the unaffected first-degree relatives of CD probands, as well as those with a diagnosis of CD. Using a family-based design, we investigated facial emotion recognition in probands with CD (n = 43), their unaffected relatives (n = 21), and healthy controls (n = 38). We used the Emotion Hexagon task, an alternative forced-choice task using morphed facial expressions depicting the six primary emotions, to assess facial emotion recognition accuracy. Relative to controls, the CD group showed impaired recognition of anger, fear, happiness, sadness and surprise (all p < 0.005). Similar to probands with CD, unaffected relatives showed deficits in anger and happiness recognition relative to controls (all p < 0.008), with a trend toward a deficit in fear recognition. There were no significant differences in performance between the CD probands and the unaffected relatives following correction for multiple comparisons. These results suggest that facial emotion recognition deficits are present in adolescents who are at increased familial risk for developing antisocial behaviour, as well as those who have already developed CD. Consequently, impaired emotion recognition appears to be a viable familial risk marker or candidate endophenotype for CD.

Serotonergic antidepressants decrease hedonic signals but leave learning signals in the nucleus accumbens unaffected.

PubMed

Graf, Heiko; Metzger, Coraline D; Walter, Martin; Abler, Birgit

2016-01-06

Investigating the effects of serotonergic antidepressants on neural correlates of visual erotic stimulation revealed decreased reactivity within the dopaminergic reward network along with decreased subjective sexual functioning compared with placebo. However, a global dampening of the reward system under serotonergic drugs is not intuitive considering clinical observations of their beneficial effects in the treatment of depression. Particularly, learning signals as coded in prediction error processing within the dopaminergic reward system can be assumed to be rather enhanced as antidepressant drugs have been demonstrated to facilitate the efficacy of psychotherapeutic interventions relying on learning processes. Within the same study sample, we now explored the effects of serotonergic and dopaminergic/noradrenergic antidepressants on prediction error signals compared with placebo by functional MRI. A total of 17 healthy male participants (mean age: 25.4 years) were investigated under the administration of paroxetine, bupropion and placebo for 7 days each within a randomized, double-blind, within-subject cross-over design. During functional MRI, we used an established monetary incentive task to explore neural prediction error signals within the bilateral nucleus accumbens as region of interest within the dopaminergic reward system. In contrast to diminished neural activations and subjective sexual functioning under the serotonergic agent paroxetine under visual erotic stimulation, we revealed unaffected or even enhanced neural prediction error processing within the nucleus accumbens under this antidepressant along with unaffected behavioural processing. Our study provides evidence that serotonergic antidepressants facilitate prediction error signalling and may support suggestions of beneficial effects of these agents on reinforced learning as an essential element in behavioural psychotherapy.

Absence of an association between insulin-dependent diabetes mellitus and developmental learning difficulties.

PubMed

Crawford, S G; Kaplan, B J; Field, L L

1995-01-01

For several years, investigators have been examining the relationship between learning difficulties and a variety of immunological disorders. Two recent studies by Hansen and colleagues reported a negative association between Type 1 diabetes and reading disabilities (dyslexia): subjects with Type 1 diabetes had a lower prevalence of dyslexia than their nondiabetic relatives. In order to control for the impact of environmental variables on learning, we investigated the relationship between Type 1 diabetes and learning problems in 27 sibling pairs, ranging in age from 6 to 20 years. One child in each pair had Type 1 diabetes, and the other child was the unaffected sibling closest in age. Children were assessed for cognitive skills, academic achievement in reading, mathematics, and written language, as well as for speech articulation and motor coordination. Other variables that were examined included handedness, behavioural variables, medical history, and pregnancy and birth complications. We found no significant differences between the 27 children with Type 1 diabetes and their unaffected siblings on any of the cognitive, academic achievement, or speech articulation measures. There were also no significant differences on handedness, behavioural variables, or health history.

Theory of mind network activity is altered in subjects with familial liability for schizophrenia

PubMed Central

Mohnke, Sebastian; Erk, Susanne; Schnell, Knut; Romanczuk-Seiferth, Nina; Schmierer, Phöbe; Romund, Lydia; Garbusow, Maria; Wackerhagen, Carolin; Ripke, Stephan; Grimm, Oliver; Haller, Leila; Witt, Stephanie H.; Degenhardt, Franziska; Tost, Heike; Heinz, Andreas; Meyer-Lindenberg, Andreas; Walter, Henrik

2016-01-01

As evidenced by a multitude of studies, abnormalities in Theory of Mind (ToM) and its neural processing might constitute an intermediate phenotype of schizophrenia. If so, neural alterations during ToM should be observable in unaffected relatives of patients as well, since they share a considerable amount of genetic risk. While behaviorally, impaired ToM function is confirmed meta-analytically in relatives, evidence on aberrant function of the neural ToM network is sparse and inconclusive. The present study therefore aimed to further explore the neural correlates of ToM in relatives of schizophrenia. About 297 controls and 63 unaffected first-degree relatives of patients with schizophrenia performed a ToM task during functional magnetic resonance imaging. Consistent with the literature relatives exhibited decreased activity of the medial prefrontal cortex. Additionally, increased recruitment of the right middle temporal gyrus and posterior cingulate cortex was found, which was related to subclinical paranoid symptoms in relatives. These results further support decreased medial prefrontal activation during ToM as an intermediate phenotype of genetic risk for schizophrenia. Enhanced recruitment of posterior ToM areas in relatives might indicate inefficiency mechanisms in the presence of genetic risk. PMID:26341902

Heritage characteristics reported by a group of African-Americans who exhibit the pigment dispersion syndrome: a case-control study.

PubMed

Roberts, D K; Ho, L A; Beedle, N L; Flynn, F M; Gable, E M

2000-11-01

To investigate the racial heritage of a group of African-Americans who exhibit the pigment dispersion syndrome (PDS). Ten unrelated African-American PDS patients (age range 13-59) from a primary eye care population in Chicago, Illinois, USA, were interviewed to determine their racial heritage. Since Caucasian and Native American heritage were commonly reported, 101 unaffected African-American control subjects (age range 18-55) were also interviewed to determine the reported frequency of these specific racial heritage characteristics. Some degree of Caucasian heritage was reported by 100% of the PDS subjects and by 46.5% of controls. Native American heritage was reported by 90% of the PDS subjects and by 71.3% of controls. Based on these data, the PDS subjects were significantly more likely to report Caucasian heritage (Fisher's exact test, P=0.001) but they were not significantly more likely to report Native American heritage (P=0.282). In addition, the PDS subjects were significantly more likely to report Caucasian heritage from both parents (P=0.024) and more likely to report a combination of both Caucasian and Native American heritage (P=0.0006) than corresponding controls. In general, the PDS subjects had 'light' or 'medium' complexions. Results from this analysis are consistent with the hypothesis that non-African heritage, particularly Caucasian, is likely to be prevalent in the background of African-Americans who exhibit PDS. It is suggested that non-African heritage may not only be important for the transference of PDS causing genes, but it may also influence factors such as degree of iris pigmentation and rigidity which could influence iris contour and the subsequent expression of PDS in those who are genetically predisposed. Further investigation is needed to study the factors that influence the expression and severity of PDS among African-Americans, a population which traditionally has been considered to be rarely affected by this condition.

Laser speckle flowgraphy for differentiating between nonarteritic ischemic optic neuropathy and anterior optic neuritis.

PubMed

Maekubo, Tomoyuki; Chuman, Hideki; Nao-I, Nobuhisa

2013-07-01

The aim of this study was to investigate the usefulness of laser speckle flowgraphy (LSFG) for the differentiation of acute nonarteritic ischemic optic neuropathy (NAION) from anterior optic neuritis (ON). To investigate blood flow in the optic disc under normal conditions, NAION, and anterior ON, we compared the tissue blood flow of the right eye with that of the left eye in the control group, and that of the affected eye with that of the unaffected eye in the NAION and anterior ON groups. In the normal control group, the tissue blood flow did not significantly differ between the right and left eyes. In the NAION group, all 6 patients had decreased optic disc blood flow in the NAION eye when compared with the unaffected eye. By contrast, in the anterior ON group, all 6 patients had increased optic disc blood flow in the anterior ON eye when compared with the unaffected eye. In the NAION group, the mean blur rate (MBR) of the affected eyes was 29.5 % lower than that of the unaffected eyes. In the anterior ON group, the MBR of the affected eyes was 15.9 % higher than that of the unaffected eyes. LSFG could be useful in differentiating between NAION and anterior ON. In addition, this imaging technique saves time and is noninvasive.

The face and its emotion: right N170 deficits in structural processing and early emotional discrimination in schizophrenic patients and relatives.

PubMed

Ibáñez, Agustín; Riveros, Rodrigo; Hurtado, Esteban; Gleichgerrcht, Ezequiel; Urquina, Hugo; Herrera, Eduar; Amoruso, Lucía; Reyes, Migdyrai Martin; Manes, Facundo

2012-01-30

Previous studies have reported facial emotion recognition impairments in schizophrenic patients, as well as abnormalities in the N170 component of the event-related potential. Current research on schizophrenia highlights the importance of complexly-inherited brain-based deficits. In order to examine the N170 markers of face structural and emotional processing, DSM-IV diagnosed schizophrenia probands (n=13), unaffected first-degree relatives from multiplex families (n=13), and control subjects (n=13) matched by age, gender and educational level, performed a categorization task which involved words and faces with positive and negative valence. The N170 component, while present in relatives and control subjects, was reduced in patients, not only for faces, but also for face-word differences, suggesting a deficit in structural processing of stimuli. Control subjects showed N170 modulation according to the valence of facial stimuli. However, this discrimination effect was found to be reduced both in patients and relatives. This is the first report showing N170 valence deficits in relatives. Our results suggest a generalized deficit affecting the structural encoding of faces in patients, as well as the emotion discrimination both in patients and relatives. Finally, these findings lend support to the notion that cortical markers of facial discrimination can be validly considered as vulnerability markers. © 2011 Elsevier Ireland Ltd. All rights reserved.

De novo mutations in the gene encoding the synaptic scaffolding protein SHANK3 in patients ascertained for schizophrenia

PubMed Central

Gauthier, Julie; Champagne, Nathalie; Lafrenière, Ronald G.; Xiong, Lan; Spiegelman, Dan; Brustein, Edna; Lapointe, Mathieu; Peng, Huashan; Côté, Mélanie; Noreau, Anne; Hamdan, Fadi F.; Addington, Anjené M.; Rapoport, Judith L.; DeLisi, Lynn E.; Krebs, Marie-Odile; Joober, Ridha; Fathalli, Ferid; Mouaffak, Fayçal; Haghighi, Ali P.; Néri, Christian; Dubé, Marie-Pierre; Samuels, Mark E.; Marineau, Claude; Stone, Eric A.; Awadalla, Philip; Barker, Philip A.; Carbonetto, Salvatore; Drapeau, Pierre; Rouleau, Guy A.

2010-01-01

Schizophrenia likely results from poorly understood genetic and environmental factors. We studied the gene encoding the synaptic protein SHANK3 in 285 controls and 185 schizophrenia patients with unaffected parents. Two de novo mutations (R1117X and R536W) were identified in two families, one being found in three affected brothers, suggesting germline mosaicism. Zebrafish and rat hippocampal neuron assays revealed behavior and differentiation defects resulting from the R1117X mutant. As mutations in SHANK3 were previously reported in autism, the occurrence of SHANK3 mutations in subjects with a schizophrenia phenotype suggests a molecular genetic link between these two neurodevelopmental disorders. PMID:20385823

Effects of low-frequency repetitive transcranial magnetic stimulation and neuromuscular electrical stimulation on upper extremity motor recovery in the early period after stroke: a preliminary study.

PubMed

Tosun, Aliye; Türe, Sabiha; Askin, Ayhan; Yardimci, Engin Ugur; Demirdal, Secil Umit; Kurt Incesu, Tülay; Tosun, Ozgur; Kocyigit, Hikmet; Akhan, Galip; Gelal, Fazıl Mustafa

2017-07-01

To assess the efficacy of inhibitory repetitive transcranial magnetic stimulation (rTMS) and neuromuscular electrical stimulation (NMES) on upper extremity motor function in patients with acute/subacute ischemic stroke. Twenty-five ischemic acute/subacute stroke subjects were enrolled in this randomized controlled trial. Experimental group 1 received low frequency (LF) rTMS to the primary motor cortex of the unaffected side + physical therapy (PT) including activities to improve strength, flexibility, transfers, posture, balance, coordination, and activities of daily living, mainly focusing on upper limb movements; experimental group 2 received the same protocol combined with NMES to hand extensor muscles; and the control group received only PT. Functional magnetic resonance imaging (fMRI) scan was used to evaluate the activation or inhibition of the affected and unaffected primary motor cortex. No adverse effect was reported. Most of the clinical outcome scores improved significantly in all groups, however no statistically significant difference was found between groups due to the small sample sizes. The highest percent improvement scores were observed in TMS + NMES group (varying between 48 and 99.3%) and the lowest scores in control group (varying between 13.1 and 28.1%). Hand motor recovery was significant in both experimental groups while it did not change in control group. Some motor cortex excitability changes were also observed in fMRI. LF-rTMS with or without NMES seems to facilitate the motor recovery in the paretic hand of patients with acute/subacute ischemic stroke. TMS or the combination of TMS + NMES may be a promising additional therapy in upper limb motor training. Further studies with larger numbers of patients are needed to establish their effectiveness in upper limb motor rehabilitation of stroke.

Changes in gut hormone levels and negative energy balance during aerobic exercise in obese young males.

PubMed

Ueda, Shin-ya; Yoshikawa, Takahiro; Katsura, Yoshihiro; Usui, Tatsuya; Nakao, Hayato; Fujimoto, Shigeo

2009-04-01

We examined whether changes in gut hormone levels due to a single bout of aerobic exercise differ between obese young males and normal controls, and attempted to determine the involvement of hormonal changes during exercise in the regulation of energy balance (EB) in these obese subjects. Seven obese and seven age-matched subjects of normal weight participated in exercise and rest sessions. Subjects consumed a standardized breakfast that was followed by constant cycling exercise at 50% VO(2max) or rest for 60 min. At lunch, a test meal was presented, and energy intake (EI) and relative energy intake (REI) were calculated. Blood samples were obtained at 30 min intervals during both sessions for measurement of glucose, insulin, glucagon, ghrelin, peptide YY (PYY), and glucagon-like peptide-1 (GLP-1). Plasma levels of PYY and GLP-1 were increased by exercise, whereas plasma ghrelin levels were unaffected by exercise. The areas under the curve (AUC) of the time courses of PYY and GLP-1 levels did not significantly differ between the two groups. In contrast, EI and REI were decreased by exercise in both groups, and energy deficit was significantly larger in obese subjects than in normal controls. The present findings suggest that short-term EB during a single exercise session might be regulated not by increased amounts of these gut hormones per se.

Impaired color naming of food and body shape words: weight phobia or distinct affective state?

PubMed

Green, M W; Elliman, N A; Rogers, P J; Welch, D A

1997-01-01

The current study investigated whether a concern with body shape and weight represents a distinct affective state, or whether it is better conceptualized as a highly specific form of anxiety. The color-naming performance of women with a high Drive for Thinness score was examined under three experimental conditions: when a photograph of chocolate was present, when actual chocolate was present, and a control condition. High Drive for Thinness subjects demonstrated relatively impaired color naming of body shape words in the picture condition, but not in the food or control conditions. Although there was a significant impairment in the color naming of food words, this was unaffected by condition or degree of Drive for Thinness. The results are interpreted as supporting an analogy between weight/body shape concerns and subclinical phobic anxiety.

Lack of serologic evidence to link IgA nephropathy with celiac disease or immune reactivity to gluten.

PubMed

Moeller, Sina; Canetta, Pietro A; Taylor, Annette K; Arguelles-Grande, Carolina; Snyder, Holly; Green, Peter H; Kiryluk, Krzysztof; Alaedini, Armin

2014-01-01

IgA nephropathy is the most common form of primary glomerulonephritis worldwide. Mucosal infections and food antigens, including wheat gluten, have been proposed as potential contributing environmental factors. Increased immune reactivity to gluten and/or association with celiac disease, an autoimmune disorder triggered by ingestion of gluten, have been reported in IgA nephropathy. However, studies are inconsistent about this association. We aimed to evaluate the proposed link between IgA nephropathy and celiac disease or immune reactivity to gluten by conducting a comprehensive analysis of associated serologic markers in cohorts of well-characterized patients and controls. Study participants included patients with biopsy-proven IgA nephropathy (n = 99), unaffected controls of similar age, gender, and race (n = 96), and patients with biopsy-proven celiac disease (n = 30). All serum specimens were tested for IgG and IgA antibodies to native gliadin and deamidated gliadin, as well as IgA antibody to transglutaminase 2 (TG2). Anti-TG2 antibody-positive nephropathy patients and unaffected controls were subsequently tested for IgA anti-endomysial antibody and genotyped for celiac disease-associated HLA-DQ2 and -DQ8 alleles. In comparison to unaffected controls, there was not a statistically significant increase in IgA or IgG antibody reactivity to gliadin in individuals with IgA nephropathy. In addition, the levels of celiac disease-specific serologic markers, i.e., antibodies to deamidated gliadin and TG2, did not differ between IgA nephropathy patients and unaffected controls. Results of the additional anti-endomysial antibody testing and HLA genotyping were corroborative. The data from this case-control study do not reveal any evidence to suggest a significant role for celiac disease or immune reactivity to gluten in IgA nephropathy.

Lack of Serologic Evidence to Link IgA Nephropathy with Celiac Disease or Immune Reactivity to Gluten

PubMed Central

Moeller, Sina; Canetta, Pietro A.; Taylor, Annette K.; Arguelles-Grande, Carolina; Snyder, Holly; Green, Peter H.; Kiryluk, Krzysztof; Alaedini, Armin

2014-01-01

IgA nephropathy is the most common form of primary glomerulonephritis worldwide. Mucosal infections and food antigens, including wheat gluten, have been proposed as potential contributing environmental factors. Increased immune reactivity to gluten and/or association with celiac disease, an autoimmune disorder triggered by ingestion of gluten, have been reported in IgA nephropathy. However, studies are inconsistent about this association. We aimed to evaluate the proposed link between IgA nephropathy and celiac disease or immune reactivity to gluten by conducting a comprehensive analysis of associated serologic markers in cohorts of well-characterized patients and controls. Study participants included patients with biopsy-proven IgA nephropathy (n = 99), unaffected controls of similar age, gender, and race (n = 96), and patients with biopsy-proven celiac disease (n = 30). All serum specimens were tested for IgG and IgA antibodies to native gliadin and deamidated gliadin, as well as IgA antibody to transglutaminase 2 (TG2). Anti-TG2 antibody-positive nephropathy patients and unaffected controls were subsequently tested for IgA anti-endomysial antibody and genotyped for celiac disease-associated HLA-DQ2 and -DQ8 alleles. In comparison to unaffected controls, there was not a statistically significant increase in IgA or IgG antibody reactivity to gliadin in individuals with IgA nephropathy. In addition, the levels of celiac disease-specific serologic markers, i.e., antibodies to deamidated gliadin and TG2, did not differ between IgA nephropathy patients and unaffected controls. Results of the additional anti-endomysial antibody testing and HLA genotyping were corroborative. The data from this case-control study do not reveal any evidence to suggest a significant role for celiac disease or immune reactivity to gluten in IgA nephropathy. PMID:24732864

Recommendations for measuring non-image-forming effects of light: A practical method to apply on cognitive impaired and unaffected participants.

PubMed

van Duijnhoven, J; Aarts, M P J; Aries, M B C; Böhmer, M N; Rosemann, A L P

2017-01-01

The non-image-forming effects of luminous radiation on people with intellectual disabilities or dementia received attention from researchers. Such studies, however, have generally been conducted using disparate methodologies which precludes generalization and reproducibility. The aim of this study was to determine the practical applicability of measurement devices for studies investigating non-image-forming effects of luminous radiation, specifically for people with intellectual disabilities or dementia. In three experiments, ten cognitive impaired people and thirty-nine unaffected subjects participated by wearing one or more portable devices. Six devices were assessed in total. Measurement data was accompanied with user experiences obtained from questionnaires, interviews and observations in order to assess the devices on practical and comfort issues. On average, the devices worn by the cognitive impaired subjects were not experienced as annoying or irritating. No significant differences are found between genders and for one of the portable devices significantly less annoyance was reported by the cognitive impaired participants compared to the unaffected group of participants. The three phases of the research process in towards measuring personal luminous exposures are: selection of the most suitable portable device, application of the assessment method, and the application of the device in the (pilot) study. However, the findings of this study suggest that inaccuracies potentially caused by practical and comfort issues associated with the portable devices need to be considered.

Normative data on phases of the Valsalva maneuver

NASA Technical Reports Server (NTRS)

Denq, J. C.; O'Brien, P. C.; Low, P. A.

1998-01-01

The phases of the Valsalva maneuver have well-known pathophysiology, and are used in the evaluation of adrenergic function. Because scant normative data is available, we have evaluated normative data for the Valsalva maneuver in control subjects. The patient, supine, performed the Valsalva maneuver maintaining an expiratory pressure of 40 mm Hg for 15 seconds. We reviewed 188 Valsalva maneuver recordings of normal control subjects, and recordings were excluded if two reproducible recordings were not obtained, or if expiratory pressure was <30 mm Hg or < 10 seconds. One hundred and three recordings were acceptable for analysis; 47 female and 56 male subjects, age in years (mean +/- SD) was 52.2+/-17.3 and 44.8+/-17.3, respectively. The association of expiratory pressure with age (P < 0.001) and gender ( P < 0.001) was complex, expressed as a parabola in both men and women, but resulted in phases I and III that were not significantly different. An increase in age resulted in a progressively more negative phase II_E (P < 0.05) and attenuation of phase II_L (P < 0.01). An increase in supine blood pressure resulted in a significantly more negative phase II_E (P < 0.001) and a lower phase IV. Phase IV is unaffected by age and gender.

The effect of presleep video-game playing on adolescent sleep.

PubMed

Weaver, Edward; Gradisar, Michael; Dohnt, Hayley; Lovato, Nicole; Douglas, Paul

2010-04-15

Video-game use before bedtime has been linked with poor sleep outcomes for adolescents; however, experimental evidence to support this link is sparse. The present study investigated the capacity of presleep video-game playing to extend sleep latency and reduce subjective feelings of sleepiness in adolescents. The arousing psychophysiologic mechanisms involved and the impact of presleep video-game playing on sleep architecture were also explored. Thirteen male adolescent "evening types" (mean age = 16.6 years, SD = 1.1) participated in a counterbalanced, within-subjects design with experimental (active video gaming) and control (passive DVD watching) conditions. The experiment was conducted in the Flinders University Sleep Research Laboratory. Relative to the control condition, presleep video-game playing increased sleep-onset latency (Z= 2.45, p= .01) and reduced subjective sleepiness (Z = 2.36, p = .02)-but only slightly. Video gaming was related to changes in cognitive alertness (as measured by a power: p < 0.01) but not physiologic arousal (as measured by heart rate: p > 0.05). Contrary to previous findings, sleep architecture was unaffected (both rapid eye movement and slow wave sleep: p > 0.05). Results suggest the direct effect of presleep video-game playing on adolescent sleep may be more modest than previously thought, suggesting that surveys linking stimulating presleep activities to poor sleep need substantiating with empirical evidence.

Abnormal tactile temporal discrimination in psychogenic dystonia.

PubMed

Morgante, F; Tinazzi, M; Squintani, G; Martino, D; Defazio, G; Romito, L; Albanese, A; Di Matteo, A; Quartarone, A; Girlanda, P; Fiorio, M; Berardelli, A

2011-09-20

Neurophysiologic studies demonstrated that patients with primary torsion dystonia (PTD) and with psychogenic dystonia (Psy-D) share similar abnormalities in the motor system. In this study, we evaluated somatosensory function in Psy-D by testing temporal discrimination threshold (TDT), and compared the results with those obtained in patients with PTD. TDT of tactile stimuli was assessed in 10 patients with Psy-D, 10 patients with PTD, and 16 control subjects. The 2 groups of patients were matched for age, gender, disease duration, and distribution of dystonia. Tactile stimuli consisted of pairs of non-noxious electrical shocks delivered to the right or left hand at interstimulus interval increasing from 0 to 400 msec, in 10-msec steps. TDT was defined as the value at which subjects recognized the 2 stimuli as asynchronous. TDT was higher in Psy-D and PTD compared to control subjects, for both the right and the left hand. In a subgroup of patients with unilateral dystonia (Psy-D = 4, PTD = 5), TDT did not differ between the affected and the unaffected side in both groups of patients. Disease duration was not correlated to the increased TDT value. Our study suggests an impaired processing of somatosensory inputs in both Psy-D and PTD. These abnormalities might represent a neurophysiological trait predisposing to develop a dystonic posture triggered by psychiatric and psychological factors.

Disturbed functional connectivity of cortical activation during semantic discrimination in patients with schizophrenia and subjects at genetic high-risk.

PubMed

Li, Xiaobo; Branch, Craig A; Nierenberg, Jay; Delisi, Lynn E

2010-03-01

Schizophrenia has a strong genetic component that is relevant to the understanding of the pathophysiology of the syndrome. Thus, recent investigations have shifted from studies of diagnosed patients with schizophrenia to examining their unaffected relatives. Previous studies found that during language processing, relatives thought to be at genetic high-risk for the disorder exhibit aberrant functional activation in regions of language processing, specifically in the left inferior frontal gyrus (Broca's area). However, functional connectivity among the regions involved in language pathways is not well understood. In this study, we examined the functional connectivity between a seed located in Broca's area and the remainder of the brain during a visual lexical decision task, in 20 schizophrenia patients, 21 subjects at genetic high risk for the disorder and 21 healthy controls. Both the high-risk subjects and patients showed significantly reduced activation correlations between seed and regions related to visual language processing. Compared to the high-risk subjects, the schizophrenia patients showed even fewer regions that were correlated with the seed regions. These results suggest that there is aberrant functional connectivity within cortical language circuitry in high-risk subjects and patients with schizophrenia. Broca's area, which is one of the important regions for language processing in healthy controls, had a significantly reduced role in the high-risk subjects and patients with schizophrenia. Our findings are consistent with the existence of an underlying biological disturbance that begins in genetically at risk individuals and progresses to a greater extent in those who eventually develop schizophrenia.

Women Are More Susceptible to Caries but Individuals Born with Clefts Are Not

PubMed Central

Jindal, Aditi; McMeans, Michelle; Narayanan, Somnya; Rose, Erin K.; Jain, Shilpa; Marazita, Mary L.; Menezes, Renato; Letra, Ariadne; Carvalho, Flavia M.; Brandon, Carla A.; Resick, Judith M.; Mereb, Juan C.; Poletta, Fernando A.; Lopez-Camelo, Jorge S.; Castilla, Eduardo E.; Orioli, Iêda M.; Vieira, Alexandre R.

2011-01-01

The identification of individuals at a higher risk of developing caries is of great interest. Isolated forms of cleft lip and palate are among the most common craniofacial congenital anomalies in humans. Historically, several reports suggest that individuals born with clefts have a higher risk for caries. Caries continues to be the most common infectious noncontagious disease worldwide and a great burden to any health system. The identification of individuals of higher susceptibility to caries is of great interest. In this paper, we assessed caries experience of 1,593 individuals from three distinct populations. The study included individuals born with clefts, their unaffected relatives, and unrelated unaffected controls that were recruited from areas with similar cultural pressures and limited access to dental care. DMFT/dmft scores were obtained, and caries experience rates were compared among the three groups in each geographic area. Individuals born with clefts did not present higher caries experience in comparison to their unaffected relatives or unrelated unaffected controls. Women tend to present higher caries rates in comparison to men. Our work provides strong evidence that individuals born with clefts are not at higher risk to caries; however, women tend to have more severe caries experience. PMID:21747859

Modification of hemiplegic compensatory gait pattern by symmetry-based motion controller of HAL.

PubMed

Kawamoto, Hiroaki; Kadone, Hideki; Sakurai, Takeru; Sankai, Yoshiyuki

2015-01-01

As one of several characteristics of hemiplegic patients after stroke, compensatory gait caused by affected limb is often seen. The purpose of this research is to apply a symmetry-based controller of a wearable type lower limb robot, Hybrid Assistive Limb (HAL) to hemiplegic patients with compensatory gait, and to investigate improvement of gait symmetry. The controller is designed respectively for swing phase and support phase according to characteristics of hemiplegic gait pattern. The controller during swing phase stores the motion of the unaffected limb and then provides motion support on the affected limb during the subsequent swing using the stored pattern to realize symmetric gait based on spontaneous limb swing. Moreover, the controller during support phase provides motion to extend hip and knee joints to support wearer's body. Clinical tests were conducted in order to assess the modification of gait symmetry. Our case study involved participation of one chronic stroke patient who performs abnormally-compensatory gait for both of the affected and unaffected limbs. As a result, the patient's gait symmetry was improved by providing motion support during the swing phase on the affected side and motion constraint during the support phase on the unaffected side. The study showed promising basis for the effectiveness of the controller for the future clinical study.

Autism traits in the RASopathies.

PubMed

Adviento, Brigid; Corbin, Iris L; Widjaja, Felicia; Desachy, Guillaume; Enrique, Nicole; Rosser, Tena; Risi, Susan; Marco, Elysa J; Hendren, Robert L; Bearden, Carrie E; Rauen, Katherine A; Weiss, Lauren A

2014-01-01

Mutations in Ras/mitogen-activated protein kinase (Ras/MAPK) pathway genes lead to a class of disorders known as RASopathies, including neurofibromatosis type 1 (NF1), Noonan syndrome (NS), Costello syndrome (CS), and cardio-facio-cutaneous syndrome (CFC). Previous work has suggested potential genetic and phenotypic overlap between dysregulation of Ras/MAPK signalling and autism spectrum disorders (ASD). Although the literature offers conflicting evidence for association of NF1 and autism, there has been no systematic evaluation of autism traits in the RASopathies as a class to support a role for germline Ras/MAPK activation in ASDs. We examined the association of autism traits with NF1, NS, CS and CFC, comparing affected probands with unaffected sibling controls and subjects with idiopathic ASDs using the qualitative Social Communication Questionnaire (SCQ) and the quantitative Social Responsiveness Scale (SRS). Each of the four major RASopathies showed evidence for increased qualitative and quantitative autism traits compared with sibling controls. Further, each RASopathy exhibited a distinct distribution of quantitative social impairment. Levels of social responsiveness show some evidence of correlation between sibling pairs, and autism-like impairment showed a male bias similar to idiopathic ASDs. Higher prevalence and severity of autism traits in RASopathies compared to unaffected siblings suggests that dysregulation of Ras/MAPK signalling during development may be implicated in ASD risk. Evidence for sex bias and potential sibling correlation suggests that autism traits in the RASopathies share characteristics with autism traits in the general population and clinical ASD population and can shed light on idiopathic ASDs.

Cognition in Huntington's disease in manifest, premanifest and converting gene carriers over ten years.

PubMed

Hart, Ellen P; Dumas, Eve M; Giltay, Erik J; Middelkoop, Huub A M; Roos, Raymund A C

2013-01-01

Cognitive decline in Huntington's disease (HD) remains an area of inconsistencies, especially far from disease onset. To clarify the course of cognition in premanifest HD. Twenty-six premanifest HD, 19 manifest HD, and 87 control subjects were followed for ten years, using an extensive cognitive battery. Differences in baseline levels and change over time, on four factors (motor speed, global cognition, executive functioning (EF), and memory) were examined, using multilevel regression analyses. Converters were additionally analysed as a separate group. Also, the influence of motor speed and predicted years to disease onset on the cognitive factors was studied. Manifest HD subjects showed lower baseline scores compared to controls on the motor speed (p=0.002), memory (p<0.001) and EF (p<0.001). They additionally deteriorated over the ten-year follow-up on memory (p=0.01). Converters deteriorated on EF (p=0.04). Further analyses of premanifest subjects 'far from and close to predicted onset' revealed lower baseline scores for the 'close' group on EF, as compared to controls (p=0.001). They also deteriorated on memory (p=0.01). Motor speed substantially mediated the results of the three cognitive factors; when added as covariate to the model several baseline and slope differences for the cognitive factors ceased to be significant. Memory and EF are highly sensitive for ascertaining deterioration in premanifest HD gene carriers, especially in subjects close to onset. Lack of deterioration for the subjects further away from onset suggests that both domains are largely unaffected in those far from onset. Also, motor influence on cognition is substantial and should be taken into account in cognitive HD research.

The Idiopathic Pulmonary Fibrosis Honeycomb Cyst Contains A Mucocilary Pseudostratified Epithelium

PubMed Central

Seibold, Max A.; Smith, Russell W.; Urbanek, Cydney; Groshong, Steve D.; Cosgrove, Gregory P.; Brown, Kevin K.; Schwarz, Marvin I.

2013-01-01

Background We previously identified a MUC5B gene promoter-variant that is a risk allele for sporadic and familial Idiopathic Pulmonary Fibrosis/Usual Interstitial Pneumonia (IPF/UIP). This allele was strongly associated with increased MUC5B gene expression in lung tissue from unaffected subjects. Despite the strong association of this airway epithelial marker with disease, little is known of mucin expressing structures or of airway involvement in IPF/UIP. Methods Immunofluorescence was used to subtype mucus cells according to MUC5B and MUC5AC expression and to identify ciliated, basal, and alveolar type II (ATII) cells in tissue sections from control and IPF/UIP subjects. Staining patterns were quantified for distal airways (Control and IPF/UIP) and in honeycomb cysts (HC). Results MUC5B-expressing cells (EC) were detected in the majority of control distal airways. MUC5AC-EC were identified in half of these airways and only in airways that contained MUC5B-EC. The frequency of MUC5B+ and MUC5AC+ distal airways was increased in IPF/UIP subjects. MUC5B-EC were the dominant mucus cell type in the HC epithelium. The distal airway epithelium from control and IPF/UIP subjects and HC was populated by basal and ciliated cells. Most honeycombing regions were distinct from ATII hyperplasic regions. ATII cells were undetectable in the overwhelming majority of HC. Conclusions The distal airway contains a pseudostratified mucocilary epithelium that is defined by basal epithelial cells and mucus cells that express MUC5B predominantly. These data suggest that the HC is derived from the distal airway. PMID:23527003

Visual field defects of the contralateral eye of non-arteritic ischemic anterior optic neuropathy: are they related to sleep apnea?

PubMed

Aptel, Florent; Aryal-Charles, Nischal; Tamisier, Renaud; Pépin, Jean-Louis; Lesoin, Antoine; Chiquet, Christophe

2017-06-01

To evaluate whether obstructive sleep apnea (OSA) is responsible for the visual field defects found in the fellow eyes of patients with non-arteritic ischemic optic neuropathy (NAION). Prospective cross-sectional study. The visual fields of the fellow eyes of NAION subjects with OSA were compared to the visual fields of control OSA patients matched for OSA severity. All patients underwent comprehensive ophthalmological and general examination including Humphrey 24.2 SITA-Standard visual field and polysomnography. Visual field defects were classified according the Ischemic Optic Neuropathy Decompression Trial (IONDT) classification. From a cohort of 78 consecutive subjects with NAION, 34 unaffected fellow eyes were compared to 34 control eyes of subjects matched for OSA severity (apnea-hypopnea index [AHI] 35.5 ± 11.6 vs 35.4 ± 9.4 events per hour, respectively, p = 0.63). After adjustment for age and body mass index, all visual field parameters were significantly different between the NAION fellow eyes and those of the control OSA groups, including mean deviation (-4.5 ± 3.7 vs -1.3 ± 1.8 dB, respectively, p < 0.05), visual field index (91.6 ± 10 vs 97.4 ± 3.5%, respectively, p = 0.002), pattern standard deviation (3.7 ± 2.3 vs 2.5 ± 2 dB, respectively, p = 0.015), and number of subjects with at least one defect on the IONDT classification (20 vs 10, respectively, p < 0.05). OSA alone does not explain the visual field defects frequently found in the fellow eyes of NAION patients.

Motor strategies and bilateral transfer in sensorimotor learning of patients with subacute stroke and healthy subjects. A randomized controlled trial.

PubMed

Iosa, M; Morone, G; Ragaglini, M R; Fusco, A; Paolucci, S

2013-06-01

Bilateral transfer, i.e. the capacity to transfer from one to the other hand a learned motor skill, may help the recovery of upper limb functions after stroke. To investigate the motor strategies at the basis of sensorimotor learning involved in bilateral transfer. Randomized controlled trial. Neurorehabilitation Hospital. Eighty right-handed participants (65 ± 13 years old): 40 patients with subacute stroke, 40 control healthy subjects. Subjects performed the 9 hole-peg-test twice in an order defined by random allocation: first with low and then with high skilled hand (LS-HS) or the reverse (HS-LS). Time spent to complete the test and filling sequence were recorded, together with maximum pinch force (assessed using a dynamometer), upper limb functioning (Motricity Index), spasticity (modified Ashworth Scale), limb dominance (Edinburgh Handeness Inventory). As expected, in patients, the performance was found related to the residual pinch force (P<0.001), upper limb motricity (P=0.006) and side of hemiparesis (P=0.016). The performances of all subjects improved more in HS-LS than in LS-HS subgroups (P=0.043). The strategy adopted in the first trial influenced the velocity in the second one (P=0.030). Bilateral transfer was observed from high to low skilled hand. Learning was not due to a mere sequence repetition, but on a strategy chosen on the basis of the previous performance. The affected hand of patients with subacute stroke may benefit from sensorimotor learning occurred with the un-affected hand.

Evidence that hippocampal-parahippocampal dysfunction is related to genetic risk for schizophrenia.

PubMed

Di Giorgio, A; Gelao, B; Caforio, G; Romano, R; Andriola, I; D'Ambrosio, E; Papazacharias, A; Elifani, F; Bianco, L Lo; Taurisano, P; Fazio, L; Popolizio, T; Blasi, G; Bertolino, A

2013-08-01

Abnormalities in hippocampal-parahippocampal (H-PH) function are prominent features of schizophrenia and have been associated with deficits in episodic memory. However, it remains unclear whether these abnormalities represent a phenotype related to genetic risk for schizophrenia or whether they are related to disease state. We investigated H-PH-mediated behavior and physiology, using blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI), during episodic memory in a sample of patients with schizophrenia, clinically unaffected siblings and healthy subjects. Patients with schizophrenia and unaffected siblings displayed abnormalities in episodic memory performance. During an fMRI memory encoding task, both patients and siblings demonstrated a similar pattern of reduced H-PH engagement compared with healthy subjects. Our findings suggest that the pathophysiological mechanism underlying the inability of patients with schizophrenia to properly engage the H-PH during episodic memory is related to genetic risk for the disorder. Therefore, H-PH dysfunction can be assumed as a schizophrenia susceptibility-related phenotype.

The role of the GABRA2 polymorphism in multiplex alcohol dependence families with minimal comorbidity: within-family association and linkage analyses.

PubMed

Matthews, Abigail G; Hoffman, Eric K; Zezza, Nicholas; Stiffler, Scott; Hill, Shirley Y

2007-09-01

The genes encoding the gamma-aminobutyric acid(A) (GABA(A)) receptor have been the focus of several recent studies investigating the genetic etiology of alcohol dependence. Analyses of multiplex families found a particular gene, GABRA2, to be highly associated with alcohol dependence, using within-family association tests and other methods. Results were confirmed in three case-control studies. The objective of this study was to investigate the GABRA2 gene in another collection of multiplex families. Analyses were based on phenotypic and genotypic data available for 330 individuals from 65 bigenerational pedigrees with a total of 232 alcohol-dependent subjects. A proband pair of same-sex siblings meeting Diagnostic and Statistical Manual of Mental Disorders, Third Edition, criteria for alcohol dependence was required for entry of a family into the study. One member of the proband pair was identified while in treatment for alcohol dependence. Linkage and association of GABRA2 and alcohol dependence were evaluated using SIBPAL (a nonparametric linkage package) and both the Pedigree Disequilibrium Test and the Family-Based Association Test, respectively. We find no evidence of a relationship between GABRA2 and alcohol dependence. Linkage analyses exhibited no linkage using affected/affected, affected/unaffected, and unaffected/unaffected sib pairs (all p's < .13). There was no evidence of a within-family association (all p's > .39). Comorbidity may explain why our results differ from those in the literature. The presence of primary drug dependence and/or other psychiatric disorders is minimal in our pedigrees, although several of the other previously published multiplex family analyses exhibit a greater degree of comorbidity.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hitomi, Toshiaki; Habu, Toshiyuki; Kobayashi, Hatasu

Highlights: •Overexpression of RNF213 R4810K inhibited cell proliferation. •Overexpression of RNF213 R4810K had the time of mitosis 4-fold and mitotic failure. •R4810K formed a complex with MAD2 more readily than wild-type. •iPSECs from the MMD patients had elevated mitotic failure compared from the control. •RNF213 R4810K induced mitotic abnormality and increased risk of aneuploidy. -- Abstract: Moyamoya disease (MMD) is a cerebrovascular disease characterized by occlusive lesions in the Circle of Willis. The RNF213 R4810K polymorphism increases susceptibility to MMD. In the present study, we characterized phenotypes caused by overexpression of RNF213 wild type and R4810K variant in the cellmore » cycle to investigate the mechanism of proliferation inhibition. Overexpression of RNF213 R4810K in HeLa cells inhibited cell proliferation and extended the time of mitosis 4-fold. Ablation of spindle checkpoint by depletion of mitotic arrest deficiency 2 (MAD2) did not shorten the time of mitosis. Mitotic morphology in HeLa cells revealed that MAD2 colocalized with RNF213 R4810K. Immunoprecipitation revealed an RNF213/MAD2 complex: R4810K formed a complex with MAD2 more readily than RNF213 wild-type. Desynchronized localization of MAD2 was observed more frequently during mitosis in fibroblasts from patients (n = 3, 61.0 ± 8.2%) compared with wild-type subjects (n = 6, 13.1 ± 7.7%; p < 0.01). Aneuploidy was observed more frequently in fibroblasts (p < 0.01) and induced pluripotent stem cells (iPSCs) (p < 0.03) from patients than from wild-type subjects. Vascular endothelial cells differentiated from iPSCs (iPSECs) of patients and an unaffected carrier had a longer time from prometaphase to metaphase than those from controls (p < 0.05). iPSECs from the patients and unaffected carrier had significantly increased mitotic failure rates compared with controls (p < 0.05). Thus, RNF213 R4810K induced mitotic abnormalities and increased risk of genomic instability.« less

Increased Cerebellar Functional Connectivity With the Default-Mode Network in Unaffected Siblings of Schizophrenia Patients at Rest.

PubMed

Guo, Wenbin; Liu, Feng; Zhang, Zhikun; Liu, Guiying; Liu, Jianrong; Yu, Liuyu; Xiao, Changqing; Zhao, Jingping

2015-11-01

The default-mode network (DMN) is vital in the neurobiology of schizophrenia, and the cerebellum participates in the high-order cognitive network such as the DMN. However, the specific contribution of the cerebellum to the DMN abnormalities remains unclear in unaffected siblings of schizophrenia patients. Forty-six unaffected siblings of schizophrenia patients and 46 healthy controls were recruited for a resting-state scan. The images were analyzed using the functional connectivity (FC) method. The siblings showed significantly increased FCs between the left Crus I and the left superior medial prefrontal cortex (MPFC), as well as between the lobule IX and the bilateral MPFC (orbital part) and right superior MPFC compared with the controls. No significantly decreased FC was observed in the siblings relative to the controls. The analyses were replicated in 49 first-episode, drug-naive patients with schizophrenia, and the results showed that the siblings and the patients shared increased FCs between the left Crus I and the left superior MPFC, as well as between the lobule IX and the left MPFC (orbital part) compared with the controls. These findings suggest that increased cerebellar-DMN connectivities emerge earlier than illness onset, which highlight the contribution of the cerebellum to the DMN alterations in unaffected siblings. The shared increased cerebellar-DMN connectivities between the patients and the siblings may be used as candidate endophenotypes for schizophrenia. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Isolation of sulfur reducing and oxidizing bacteria found in contaminated drywall.

PubMed

Hooper, Dennis G; Shane, John; Straus, David C; Kilburn, Kaye H; Bolton, Vincent; Sutton, John S; Guilford, Frederick T

2010-02-05

Drywall from China has been reported to release sulfur producing products which are corrosive to metals, result in noxious odors, and represent a significant health risk. It has been reported that these emissions produce medical symptoms such as respiratory or asthma type problems, sinusitis, gastrointestinal disorders, and vision problems in home owners and their household pets. We report here a method of identifying a causative agent for these emissions by sampling affected gypsum wallboard and subjecting those samples to Real Time Polymerase Chain Reaction [RT-PCR] studies. Specific DNA probes and primers have been designed and patented that detect a specific iron and sulfur reducing bacterium (i.e., Thiobacillus ferrooxidans). One hundred percent of affected drywall samples obtained from homes located in the southeastern United States tested positive for the presence of T. ferrooxidans. All negative controls consisting of unaffected wallboard and internal controls, Geotrichum sp., tested negative within our limits of detection.

Isolation of Sulfur Reducing and Oxidizing Bacteria Found in Contaminated Drywall

PubMed Central

Hooper, Dennis G.; Shane, John; Straus, David C.; Kilburn, Kaye H.; Bolton, Vincent; Sutton, John S.; Guilford, Frederick T.

2010-01-01

Drywall from China has been reported to release sulfur producing products which are corrosive to metals, result in noxious odors, and represent a significant health risk. It has been reported that these emissions produce medical symptoms such as respiratory or asthma type problems, sinusitis, gastrointestinal disorders, and vision problems in home owners and their household pets. We report here a method of identifying a causative agent for these emissions by sampling affected gypsum wallboard and subjecting those samples to Real Time Polymerase Chain Reaction [RT-PCR] studies. Specific DNA probes and primers have been designed and patented that detect a specific iron and sulfur reducing bacterium (i.e., Thiobacillus ferrooxidans). One hundred percent of affected drywall samples obtained from homes located in the southeastern United States tested positive for the presence of T. ferrooxidans. All negative controls consisting of unaffected wallboard and internal controls, Geotrichum sp., tested negative within our limits of detection. PMID:20386658

Process for treating weldments

DOEpatents

Malik, R.K.

The tensile ducttility and impact strength of weldments of nickel-based and stainless steel alloys are improved to that of the unaffected base metal by subjecting the weldments to an elevated temperature at an isostatic pressure for a period of time sufficient to render the material in the weld more homogeneous.

Impact of melanoma genetic test reporting on perceived control over melanoma prevention.

PubMed

Aspinwall, Lisa G; Stump, Tammy K; Taber, Jennifer M; Kohlmann, Wendy; Leaf, Samantha L; Leachman, Sancy A

2015-10-01

To determine whether receiving melanoma genetic test results undermines perceived control over melanoma prevention, control-related beliefs were examined among 60 adults from melanoma-prone families receiving CDKN2A/p16 test results (27 unaffected noncarriers, 15 unaffected carriers, 18 affected carriers; response rate at 2 years = 64.9 % of eligible respondents). Multilevel modeling of perceived control ratings over a 2-year period revealed significant variation in individual trajectories: most participants showed increases (45 %) or no change (38.3 %), while 16.7 % showed decreases. At the group level, noncarriers reported sustained increases through the 2-year follow-up (ps < .05); unaffected carriers reported significant short-term increases (ps < .05); and affected carriers reported no change. Participants in all groups continued to rate photoprotection as highly effective in reducing melanoma risk and reported decreased beliefs that carrying the p16 mutation would inevitably lead to the development of melanoma. Qualitative responses immediately following counseling and test reporting corroborated these findings, as 93 % indicated it was possible to either prevent (64.9 %) or decrease the likelihood (28.1 %) of future melanomas. Thus, genetic test reporting does not generally undermine perceived control over melanoma prevention, though variability in response to positive results warrants future study.

Using Brain Oscillations and Corticospinal Excitability to Understand and Predict Post-Stroke Motor Function

PubMed Central

Thibaut, Aurore; Simis, Marcel; Battistella, Linamara Rizzo; Fanciullacci, Chiara; Bertolucci, Federica; Huerta-Gutierrez, Rodrigo; Chisari, Carmelo; Fregni, Felipe

2017-01-01

What determines motor recovery in stroke is still unknown and finding markers that could predict and improve stroke recovery is a challenge. In this study, we aimed at understanding the neural mechanisms of motor function recovery after stroke using neurophysiological markers by means of cortical excitability (transcranial magnetic stimulation—TMS) and brain oscillations (electroencephalography—EEG). In this cross-sectional study, 55 subjects with chronic stroke (62 ± 14 yo, 17 women, 32 ± 42 months post-stroke) were recruited in two sites. We analyzed TMS measures (i.e., motor threshold—MT—of the affected and unaffected sides) and EEG variables (i.e., power spectrum in different frequency bands and different brain regions of the affected and unaffected hemispheres) and their correlation with motor impairment as measured by Fugl-Meyer. Multiple univariate and multivariate linear regression analyses were performed to identify the predictors of good motor function. A significant interaction effect of MT in the affected hemisphere and power in beta bandwidth over the central region for both affected and unaffected hemispheres was found. We identified that motor function positively correlates with beta rhythm over the central region of the unaffected hemisphere, while it negatively correlates with beta rhythm in the affected hemisphere. Our results suggest that cortical activity in the affected and unaffected hemisphere measured by EEG provides new insights on the association between high-frequency rhythms and motor impairment, highlighting the role of an excess of beta in the affected central cortical region in poor motor function in stroke recovery. PMID:28539912

Using Brain Oscillations and Corticospinal Excitability to Understand and Predict Post-Stroke Motor Function.

PubMed

Thibaut, Aurore; Simis, Marcel; Battistella, Linamara Rizzo; Fanciullacci, Chiara; Bertolucci, Federica; Huerta-Gutierrez, Rodrigo; Chisari, Carmelo; Fregni, Felipe

2017-01-01

What determines motor recovery in stroke is still unknown and finding markers that could predict and improve stroke recovery is a challenge. In this study, we aimed at understanding the neural mechanisms of motor function recovery after stroke using neurophysiological markers by means of cortical excitability (transcranial magnetic stimulation-TMS) and brain oscillations (electroencephalography-EEG). In this cross-sectional study, 55 subjects with chronic stroke (62 ± 14 yo, 17 women, 32 ± 42 months post-stroke) were recruited in two sites. We analyzed TMS measures (i.e., motor threshold-MT-of the affected and unaffected sides) and EEG variables (i.e., power spectrum in different frequency bands and different brain regions of the affected and unaffected hemispheres) and their correlation with motor impairment as measured by Fugl-Meyer. Multiple univariate and multivariate linear regression analyses were performed to identify the predictors of good motor function. A significant interaction effect of MT in the affected hemisphere and power in beta bandwidth over the central region for both affected and unaffected hemispheres was found. We identified that motor function positively correlates with beta rhythm over the central region of the unaffected hemisphere, while it negatively correlates with beta rhythm in the affected hemisphere. Our results suggest that cortical activity in the affected and unaffected hemisphere measured by EEG provides new insights on the association between high-frequency rhythms and motor impairment, highlighting the role of an excess of beta in the affected central cortical region in poor motor function in stroke recovery.

Effect of atropine and methylatropine on human vaginal blood flow, sexual arousal and climax.

PubMed

Wagner, G; Levin, R J

1980-05-01

No experimental data on the regulatory mechanism of the change in vaginal blood flow occurring at sexual arousal exist. Six women were in a controlled laboratory study given atropine 0.035 mg/kg intravenously. The basal vaginal blood flow was recorded by a heat probe kept at set temperature on the vaginal wall. During sexual stimulation the flow was increased as in women when no drugs are applied and orgasm was unaffected as well. The neurotransmitter has been supposed to be acetylcholine but the present experiments suggest that it is not an atropine sensitive traditional muscarinic transmission. Methylatropine was given in five subjects and neither in these cases any effect on the vaginal vascular response was observed.

Conservation and Divergence of Circadian Clock Operation in a Stress-Inducible Crassulacean Acid Metabolism Species Reveals Clock Compensation against Stress1

PubMed Central

Boxall, Susanna F.; Foster, Jonathan M.; Bohnert, Hans J.; Cushman, John C.; Nimmo, Hugh G.; Hartwell, James

2005-01-01

One of the best-characterized physiological rhythms in plants is the circadian rhythm of CO2 metabolism in Crassulacean acid metabolism (CAM) plants, which is the focus here. The central components of the plant circadian clock have been studied in detail only in Arabidopsis (Arabidopsis thaliana). Full-length cDNAs have been obtained encoding orthologs of CIRCADIAN CLOCK-ASSOCIATED1 (CCA1)/LATE ELONGATED HYPOCOTYL (LHY), TIMING OF CAB EXPRESSION1 (TOC1), EARLY FLOWERING4 (ELF4), ZEITLUPE (ZTL), FLAVIN-BINDING KELCH REPEAT F-BOX1 (FKF1), EARLY FLOWERING3 (ELF3), and a partial cDNA encoding GIGANTEA in the model stress-inducible CAM plant, Mesembryanthemum crystallinum (Common Ice Plant). TOC1 and LHY/CCA1 are under reciprocal circadian control in a manner similar to their regulation in Arabidopsis. ELF4, FKF1, ZTL, GIGANTEA, and ELF3 are under circadian control in C3 and CAM leaves. ELF4 transcripts peak in the evening and are unaffected by CAM induction. FKF1 shows an abrupt transcript peak 3 h before subjective dusk. ELF3 transcripts appear in the evening, consistent with their role in gating light input to the circadian clock. Intriguingly, ZTL transcripts do not oscillate in Arabidopsis, but do in M. crystallinum. The transcript abundance of the clock-associated genes in M. crystallinum is largely unaffected by development and salt stress, revealing compensation of the central circadian clock against development and abiotic stress in addition to the well-known temperature compensation. Importantly, the clock in M. crystallinum is very similar to that in Arabidopsis, indicating that such a clock could control CAM without requiring additional components of the central oscillator or a novel CAM oscillator. PMID:15734916

Effects of a powered ankle-foot prosthesis on kinetic loading of the unaffected leg during level-ground walking

PubMed Central

2013-01-01

Background People with a lower-extremity amputation that use conventional passive-elastic ankle-foot prostheses encounter a series of stress-related challenges during walking such as greater forces on their unaffected leg, and may thus be predisposed to secondary musculoskeletal injuries such as chronic joint disorders. Specifically, people with a unilateral transtibial amputation have an increased susceptibility to knee osteoarthritis, especially in their unaffected leg. Previous studies have hypothesized that the development of this disorder is linked to the abnormally high peak knee external adduction moments encountered during walking. An ankle-foot prosthesis that supplies biomimetic power could potentially mitigate the forces and knee adduction moments applied to the unaffected leg of a person with a transtibial amputation, which could, in turn, reduce the risk of knee osteoarthritis. We hypothesized that compared to using a passive-elastic prosthesis, people with a transtibial amputation using a powered ankle-foot prosthesis would have lower peak resultant ground reaction forces, peak external knee adduction moments, and corresponding loading rates applied to their unaffected leg during walking over a wide range of speeds. Methods We analyzed ground reaction forces and knee joint kinetics of the unaffected leg of seven participants with a unilateral transtibial amputation and seven age-, height- and weight-matched non-amputees during level-ground walking at 0.75, 1.00, 1.25, 1.50, and 1.75 m/s. Subjects with an amputation walked while using their own passive-elastic prosthesis and a powered ankle-foot prosthesis capable of providing net positive mechanical work and powered ankle plantar flexion during late stance. Results Use of the powered prosthesis significantly decreased unaffected leg peak resultant forces by 2-11% at 0.75-1.50 m/s, and first peak knee external adduction moments by 21 and 12% at 1.50 and 1.75 m/s, respectively. Loading rates were not significantly different between prosthetic feet. Conclusions Use of a biomimetic powered ankle-foot prosthesis decreased peak resultant force at slow and moderate speeds and knee external adduction moment at moderate and fast speeds on the unaffected leg of people with a transtibial amputation during level-ground walking. Thus, use of an ankle-foot prosthesis that provides net positive mechanical work could reduce the risk of comorbidities such as knee osteoarthritis. PMID:23758860

Utility of Cystatin C to monitor renal function in Duchenne muscular dystrophy

PubMed Central

Viollet, Laurence; Gailey, Susan; Thornton, David J.; Friedman, Neil R.; Flanigan, Kevin M.; Mahan, John D.; Mendell, Jerry R.

2009-01-01

Introduction: Creatinine as a marker of renal function has limited value in Duchenne muscular dystrophy (DMD) because of reduced muscle mass. Alternative methods of assessing renal function are sorely needed. Cystatin C, a nonglycosylated protein unaffected by muscle mass, is potentially an ideal biomarker of nephrotoxicity for this population but requires validation. Methods: 75 subjects were recruited: 35 DMD (mean age 10.8 ± 5.4 years, corticosteroids n = 19, ambulatory n = 26), 29 healthy controls, 10 with renal disease, and one DMD with renal failure. Results: Cystatin C levels in DMD were normal irrespective of age, ambulation or corticosteroid treatment. Serum cystatin C was 0.67 ± 0.11 mg/L compared to normal controls 0.69 ± 0.09. mg/L. In these same individuals serum creatinine was severely reduced (0.27 ± 0.12 mg/dL) versus normals (0.75 ± 0.15 mg/dL, p < 0.01). In one DMD subject in renal failure, cystatin C was elevated. Discussion: This study demonstrates the potential value of cystatin C as a biomarker for monitoring renal function in DMD. Its applicability extends to other neuromuscular diseases. PMID:19623638

Dissociation of functional and anatomical brain abnormalities in unaffected siblings of schizophrenia patients.

PubMed

Guo, Wenbin; Song, Yan; Liu, Feng; Zhang, Zhikun; Zhang, Jian; Yu, Miaoyu; Liu, Jianrong; Xiao, Changqing; Liu, Guiying; Zhao, Jingping

2015-05-01

Schizophrenia patients and their unaffected siblings share similar brain functional and structural abnormalities. However, no study is engaged to investigate whether and how functional abnormalities are related to structural abnormalities in unaffected siblings. This study was undertaken to examine the association between functional and anatomical abnormalities in unaffected siblings. Forty-six unaffected siblings of schizophrenia patients and 46 age-, sex-, and education-matched healthy controls underwent structural and resting-state functional magnetic resonance imaging scanning. Voxel-based morphometry (VBM), amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) were utilized to analyze imaging data. The VBM analysis showed gray matter volume decreases in the fronto-temporal regions (the left middle temporal gyrus and right inferior frontal gyrus, orbital part) and increases in basal ganglia system (the left putamen). Functional abnormalities measured by ALFF and fALFF mainly involved in the fronto-limbic-sensorimotor circuit (decreased ALFF in bilateral middle frontal gyrus and the right middle cingulate gyrus, and decreased fALFF in the right inferior frontal gyrus, orbital part; and increased ALFF in the left fusiform gyrus and left lingual gyrus, and increased fALFF in bilateral calcarine cortex). No significant correlation was found between functional and anatomical abnormalities in the sibling group. A dissociation pattern of brain regions with functional and anatomical abnormalities is observed in unaffected siblings. Our findings suggest that brain functional and anatomical abnormalities might be present independently in unaffected siblings of schizophrenia patients. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Cryohemolysis, erythrocyte osmotic fragility, and supplementary hematimetric indices in the diagnosis of hereditary spherocytosis.

PubMed

Emilse, Ledesma Achem Miryam; Cecilia, Haro; María, Terán Magdalena; Eugenia, Mónaco María; Alicia, Issé Blanca; Lazarte, Sandra Stella

2018-03-01

Hereditary spherocytosis (HS) is a chronic hemolytic anemia characterized by microspherocytes in the peripheral blood and increased erythrocyte osmotic fragility (EOF). This study evaluated the cryohemolysis test (CHT); initial hemolysis (IH); immediate and incubated hemolysis percentage in 5.5 g/L NaCl (H5.5); mean corpuscular hemoglobin concentration (MCHC); red blood cell distribution width (RDW); and Hb/MCHC, Hb/RDW, and MCHC/RDW ratios for the diagnosis of HS. Data from 13 patients with HS were evaluated at the Instituto de Bioquímica Aplicada and compared with data from 14 unaffected individuals and 11 patients with anemia due to another etiology. Total blood and reticulocyte counts, CHT, and immediate and incubated EOF were performed in all subjects; sensitivity, specificity, efficiency, and Youden index (YI) were calculated. Eight patients with HS had MCHC ≥345 g/L, 10 had RDW ≥14.5%, 12 had IH >5.0 g/L, 11 had immediate H5.5 ≥5%, and 13 had incubated H5.5 ≥50% (the cut-off value to consider HS). The efficiency and YI were: immediate H5.5 (0.94-0.85), incubated H5.5 (0.89-0.82), IH (0.89-0.78), MCHC (0.87-0.62), CHT (0.84-0.54), and Hb/MCHC (0.71-0.56), respectively. The calculated ratios could distinguish subjects with HS from unaffected individuals ( P <0.05), but not those with anemia of another etiology ( P >0.05). Although the CHT and supplementary hematimetric indexes were useful to differentiate individuals with SH from healthy controls, they cannot distinguish from anemias of other etiology. CHT and MCHC, in addition to EOF, are recommended for diagnosing HS patients because of their low cost and efficiency.

Examination of chromosome 7p22 candidate genes RBaK, PMS2 and GNA12 in familial hyperaldosteronism type II.

PubMed

Jeske, Y W A; So, A; Kelemen, L; Sukor, N; Willys, C; Bulmer, B; Gordon, R D; Duffy, D; Stowasser, M

2008-04-01

1. There are two types of familial hyperaldosteronism (FH): FH-I and FH-II. FH-I is caused by a hybrid CYP11B1/CYP11B2 gene mutation. The genetic cause of FH-II, which is more common, is unknown. Adrenal hyperplasia and adenomas are features. We previously reported linkage of FH-II to a approximately 5 Mb region on chromosome 7p22. We subsequently reported finding no causative mutations in the retinoblastoma-associated Kruppel-associated box gene (RBaK), a candidate at 7p22 involved in tumorigenesis and cell cycle control. 2. In the current study we investigated RBaK regulatory regions and two other candidate genes: postmeiotic segregation increased 2 (PMS2, involved in DNA mismatch repair and tumour predisposition) and guanine nucleotide-binding protein alpha-12 (GNA12, a transforming oncogene). 3. The GNA12 and PMS2 genes were examined in two affected (A1, A2) and two unaffected (U1, U2) subjects from a large 7p22-linked FH-II family (family 1). No mutations were found. 4. The RBaK and PMS2 distal promoters were sequenced to -2150 bp from the transcription start site for RBaK and-2800 bp for PMS2. Five unreported single nucleotide polymorphisms (SNPs) were found in subjects A1, A2 but not in U1 or U2; A(-2031 bp)T, T(-2030 bp)G, G(-834 bp)C, C(-821 bp)G in RBaK and A(-876 bp)G in PMS2. Additional affected and unaffected subjects from family 1 and from two other 7p22-linked FH-II families and 58 unrelated normotensive control subjects were genotyped for these SNPs. 5. The five novel SNPs were found to be present in a significant proportion of normotensive controls. The four RBaK promoter SNPs were found to be in linkage disequilibrium in the normal population. The RBaK promoter (-)2031T/2030G/834C/821T allele was found to be in linkage disequilibrium with the causative mutation in FH-II family 1, but not in families 2 and 3. The PMS2 promoter (-)876G allele was also found to be linked to affected phenotypes in family 1. 6. The RBaK and PMS2 promoter SNPs alter the binding sites for several transcription factors. Although present in the normal population, it is possible that the RBaK (-)2031T/2030G/834C/821T and PMS2 (-)876G alleles may have functional roles contributing to the FH-II phenotype in family 1.

Gene Expression Profiles from Disease Discordant Twins Suggest Shared Antiviral Pathways and Viral Exposures among Multiple Systemic Autoimmune Diseases.

PubMed

Gan, Lu; O'Hanlon, Terrance P; Lai, Zhennan; Fannin, Rick; Weller, Melodie L; Rider, Lisa G; Chiorini, John A; Miller, Frederick W

2015-01-01

Viral agents are of interest as possible autoimmune triggers due to prior reported associations and widely studied molecular mechanisms of antiviral immune responses in autoimmunity. Here we examined new viral candidates for the initiation and/or promotion of systemic autoimmune diseases (SAID), as well as possible related signaling pathways shared in the pathogenesis of those disorders. RNA isolated from peripheral blood samples from 33 twins discordant for SAID and 33 matched, unrelated healthy controls was analyzed using a custom viral-human gene microarray. Paired comparisons were made among three study groups-probands with SAID, their unaffected twins, and matched, unrelated healthy controls-using statistical and molecular pathway analyses. Probands and unaffected twins differed significantly in the expression of 537 human genes, and 107 of those were associated with viral infections. These 537 differentially expressed human genes participate in overlapping networks of several canonical, biologic pathways relating to antiviral responses and inflammation. Moreover, certain viral genes were expressed at higher levels in probands compared to either unaffected twins or unrelated, healthy controls. Interestingly, viral gene expression levels in unaffected twins appeared intermediate between those of probands and the matched, unrelated healthy controls. Of the viruses with overexpressed viral genes, herpes simplex virus-2 (HSV-2) was the only human viral pathogen identified using four distinct oligonucleotide probes corresponding to three HSV-2 genes associated with different stages of viral infection. Although the effects from immunosuppressive therapy on viral gene expression remain unclear, this exploratory study suggests a new approach to evaluate shared viral agents and antiviral immune responses that may be involved in the development of SAID.

Effect of Transcranial Direct Current Stimulation on Severely Affected Arm-Hand Motor Function in Patients After an Acute Ischemic Stroke: A Pilot Randomized Control Trial.

PubMed

Rabadi, Meheroz H; Aston, Christopher E

2017-10-01

The aim of this article was to determine whether cathodal transcranial direct current stimulation (c-tDCS) to unaffected primary motor cortex (PMC) plus conventional occupational therapy (OT) improves functional motor recovery of the affected arm hand in patients after an acute ischemic stroke compared with sham transcranial direct current stimulation plus conventional OT. In this prospective, randomized, double-blinded, sham-controlled trial of 16 severe, acute ischemic stroke patients with severe arm-hand weakness were randomly assigned to either experimental (c-tDCS plus OT; n = 8) or control (sham transcranial direct current stimulation plus OT; n = 8) groups. All patients received a standard 3-hr in-patient rehabilitation therapy, plus an additional ten 30-min sessions of tDCS. During each session, 1 mA of cathodal stimulation to the unaffected PMC is performed followed by the patient's scheduled OT. The primary outcome measure was change in Action Research Arm Test (ARAT) total and subscores on discharge. Application of c-tDCS to unaffected PMC resulted in a clinically relevant 10-point improvement in the affected arm-hand function based on ARAT total score compared with a 2-point improvement in the control group. Application of 30-min of c-tDCS to the unaffected PMC showed a 10-point improvement in the ARAT score. This corresponds to a large effect size in improvement of affected arm-hand function in patients with severe, acute ischemic stroke. Although not statistically significant, this suggests that larger studies, enrolling at least 25 patients in each group, and with a longer follow-up are warranted.

Neural processing of intentional biological motion in unaffected siblings of children with autism spectrum disorder: an fMRI study.

PubMed

Ahmed, Alex A; Vander Wyk, Brent C

2013-12-01

Despite often showing behaviorally typical levels of social cognitive ability, unaffected siblings of children with autism spectrum disorder have been found to show similar functional and morphological deficits within brain regions associated with social processing. They have also been reported to show increased activation to biological motion in these same regions, such as the posterior superior temporal sulcus (pSTS), relative to both children with autism and control children. It has been suggested that this increased activation may represent a compensatory reorganization of these regions as a result of the highly heritable genetic influence of autism. However, the response patterns of unaffected siblings in the domain of action perception are unstudied, and the phenomenon of compensatory activation has not yet been replicated. The present study used functional magnetic resonance imaging to determine the neural responses to intentional biological actions in 22 siblings of children with autism and 22 matched controls. The presented actions were either congruent or incongruent with the actor's emotional cue. Prior studies reported that typically developing children and adults, but not children with autism, show increased activation to incongruent actions (relative to congruent), within the pSTS and dorsolateral prefrontal cortex. We report that unaffected siblings did not show a compensatory response, or a preference for incongruent over congruent trials, in any brain region. Moreover, interaction analyses revealed a sub-region of the pSTS in which control children showed an incongruency preference to a significantly greater degree than siblings, which suggests a localized deficit in siblings. A sample of children with autism also did not show differential activation in the pSTS, providing further evidence that it is an area of selective disruption in children with autism and siblings. While reduced activation to both conditions was unique to the autism sample, lack of differentiation to incongruent and congruent intentional actions was common to both children with ASD and unaffected siblings. Copyright © 2013 Elsevier Inc. All rights reserved.

Amplitude and timing of somatosensory cortex activity in Task Specific Focal Hand Dystonia

PubMed Central

Dolberg, Rebecca; Hinkley, Leighton B. N.; Honma, Susanne; Zhu, Zhao; Findlay, Anne M.; Byl, Nancy N.; Nagarjan, Srikantan S.

2011-01-01

Objective Task-specific focal hand dystonia (tspFHD) is a movement disorder diagnosed in individuals performing repetitive hand behaviors. The extent to which processing anomalies in primary sensory cortex extend to other regions or across the two hemispheres is presently unclear. Methods In response to low/high rate and novel tactile stimuli on the affected and unaffected hands, magnetoencephalography (MEG) was used to elaborate activity timing and amplitude in the primary somatosensory (S1) and secondary somatosensory/parietal ventral (S2/PV) cortices. MEG and clinical performance measures were collected from thirteen patients and matched controls. Results Compared to controls, subjects with tspFHD had increased response amplitude in S2/PV bilaterally in response to high rate and novel stimuli. Subjects with tspFHD also showed increased response latency (low rate, novel) of the affected digits in contralateral S1. For high rate, subjects with tspFHD showed increased response latency in ipsilateral S1 and S2/PV bilaterally. Activation differences correlated with functional sensory deficits (predicting a latency shift in S1), motor speed and muscle strength. Conclusions There are objective differences in the amplitude and timing of activity for both hands across contralateral and ipsilateral somatosensory cortex in patients with tspFHD. Significance Knowledge of cortical processing abnormalities across S1 and S2/PV in dystonia should be applied towards the development of learning based sensorimotor interventions. PMID:21802357

GH Receptor Deficiency in Ecuadorian Adults Is Associated With Obesity and Enhanced Insulin Sensitivity

PubMed Central

Rosenbloom, Arlan L.; Balasubramanian, Priya; Teran, Enrique; Guevara-Aguirre, Marco; Guevara, Carolina; Procel, Patricio; Alfaras, Irene; De Cabo, Rafael; Di Biase, Stefano; Narvaez, Luis; Saavedra, Jannette

2015-01-01

Context: Ecuadorian subjects with GH receptor deficiency (GHRD) have not developed diabetes, despite obesity. Objective: We sought to determine the metabolic associations for this phenomenon. Design: Four studies were carried out: 1) glucose, lipid, adipocytokine concentrations; 2) metabolomics evaluation; 3) metabolic responses to a high-calorie meal; and 4) oral glucose tolerance tests. Setting: Clinical Research Institute in Quito, Ecuador. Subjects: Adults homozygous for the E180 splice mutation of the GH receptor (GHRD) were matched for age, gender, and body mass index with unaffected control relatives (C) as follows: study 1, 27 GHRD and 35 C; study 2, 10 GHRD and 10 C; study 3, seven GHRD and 11 C; and study 4, seven GHRD and seven C. Results: Although GHRD subjects had greater mean percentage body fat than controls, their fasting insulin, 2-hour blood glucose, and triglyceride levels were lower. The indicator of insulin sensitivity, homeostasis model of assessment 2%S, was greater (P < .0001), and the indicator of insulin resistance, homeostasis model of assessment 2-IR, was lower (P = .0025). Metabolomic differences between GHRD and control subjects were consistent with their differing insulin sensitivity, including postprandial decreases of branched-chain amino acids that were more pronounced in controls. High molecular weight and total adiponectin concentrations were greater in GHRD (P = .0004 and P = .0128, respectively), and leptin levels were lower (P = .02). Although approximately 65% the weight of controls, GHRD subjects consumed an identical high-calorie meal; nonetheless, their mean glucose concentrations were lower, with mean insulin levels one-third those of controls. Results of the 2-hour oral glucose tolerance test were similar. Main Outcome Measures: Measures of insulin sensitivity, adipocytokines, and energy metabolites. Conclusions: Without GH counter-regulation, GHRD is associated with insulin efficiency and obesity. Lower leptin levels, despite higher percentage body fat, suggest that obesity-associated leptin resistance is GH dependent. Elevated adiponectin levels not correlated with percentage body fat indicate that GH signaling is necessary for their typical suppression with obesity. PMID:25985182

Economic games on the internet: the effect of $1 stakes.

PubMed

Amir, Ofra; Rand, David G; Gal, Ya'akov Kobi

2012-01-01

Online labor markets such as Amazon Mechanical Turk (MTurk) offer an unprecedented opportunity to run economic game experiments quickly and inexpensively. Using Mturk, we recruited 756 subjects and examined their behavior in four canonical economic games, with two payoff conditions each: a stakes condition, in which subjects' earnings were based on the outcome of the game (maximum earnings of $1); and a no-stakes condition, in which subjects' earnings are unaffected by the outcome of the game. Our results demonstrate that economic game experiments run on MTurk are comparable to those run in laboratory settings, even when using very low stakes.

CHK2, A Candidate Prostate Cancer Susceptibility Gene

DTIC Science & Technology

2003-01-01

To identify prostate cancer susceptibility genes, we applied a mutation screening of candidate gene approach. We screened for mutations in CHEK2 , the...families, 400 sporadic cases, and 423 unaffected men as control. A total of 28 (4.8%) germline CHEK2 mutations were found among 578 patients and...additional 11 in 9 families. Sixteen of 18 unique CHEK2 mutations identified in this study were not detected among 423 unaffected men, suggesting a

Theory of mind in children with Neurofibromatosis Type 1.

PubMed

Payne, Jonathan M; Porter, Melanie; Pride, Natalie A; North, Kathryn N

2016-05-01

Neurofibromatosis Type I (NF1) is a single gene disorder associated with cognitive and behavioral deficits. While there is clear evidence for poorer social outcomes in NF1, the factors underlying reduced social function are not well understood. This study examined theory of mind (ToM) in children with NF1 and unaffected controls. ToM was assessed in children with NF1 (n = 26) and unaffected controls (n = 36) aged 4-12 years using a nonverbal picture sequencing task. The task assessed understanding of ToM (unrealized goals, false belief, pretence, intention), while controlling for social script knowledge and physical cause-and-effect reasoning. Children with NF1 made significantly more errors than unaffected controls on most ToM stories while demonstrating no difficulty sequencing physical cause-and-effect stories. Performance on the picture sequencing task was not related to lower intellectual function, symptoms of attention deficit-hyperactivity disorder (ADHD), or parent ratings of executive function. Results suggest a generalized ToM deficit in children with NF1 that appears to be independent of general cognitive abilities and ADHD symptoms. The study refines understanding of the clinical presentation of NF1 and identifies psychological constructs that may contribute to the higher prevalence of social dysfunction in children with NF1. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Diagnostic Value of Facial Nerve Antidromic Evoked Potential in Patients With Bell's Palsy: A Preliminary Study

PubMed Central

Lee, Ji Hoon; Kim, Sun Mi; Yang, Hea Eun; Lee, Jang Woo

2014-01-01

Objective To assess the practical diagnostic value of facial nerve antidromic evoked potential (FNAEP), we compared it with the diagnostic value of the electroneurography (ENoG) test in Bell's palsy. Methods In total, 20 patients with unilateral Bell's palsy were recruited. Between the 1st and 17th days after the onset of facial palsy, FNAEP and ENoG tests were conducted. The degeneration ratio and FNAEP latency difference between the affected and unaffected sides were calculated in all subjects. Results In all patients, FNAEP showed prolonged latencies on the affected side versus the unaffected side. The difference was statistically significant. In contrast, there was no significant difference between sides in the normal control group. In 8 of 20 patients, ENoG revealed a degeneration ratio less than 50%, but FNAEP show a difference of more than 0.295±0.599 ms, the average value of normal control group. This shows FNAEP could be a more sensitive test for Bell's palsy diagnosis than ENoG. In particular, in 10 patients tested within 7 days after onset, an abnormal ENoG finding was noted in only four of them, but FNAEP showed a significant latency difference in all patients at this early stage. Thus, FANEP was more sensitive in detecting facial nerve injury than the ENoG test (p=0.031). Conclusion FNAEP has some clinical value in the diagnosis of facial nerve degeneration. It is important that FNAEP be considered in patients with facial palsy at an early stage and integrated with other relevant tests. PMID:25024963

Impaired regulation of emotion: neural correlates of reappraisal and distraction in bipolar disorder and unaffected relatives

PubMed Central

Kanske, P; Schönfelder, S; Forneck, J; Wessa, M

2015-01-01

Deficient emotion regulation has been proposed as a crucial pathological mechanism in bipolar disorder (BD). We therefore investigated emotion regulation impairments in BD, the related neural underpinnings and their etiological relevance for the disorder. Twenty-two euthymic patients with bipolar-I disorder and 17 unaffected first-degree relatives of BD-I patients, as well as two groups of healthy gender-, age- and education-matched controls (N=22/17, respectively) were included. Participants underwent functional magnetic resonance imaging while applying two different emotion regulation techniques, reappraisal and distraction, when presented with emotional images. BD patients and relatives showed impaired downregulation of amygdala activity during reappraisal, but not during distraction, when compared with controls. This deficit was correlated with the habitual use of reappraisal. The negative connectivity of amygdala and orbitofrontal cortex (OFC) observed during reappraisal in controls was reversed in BD patients and relatives. There were no significant differences between BD patients and relatives. As being observed in BD patients and unaffected relatives, deficits in emotion regulation through reappraisal may represent heritable neurobiological abnormalities underlying BD. The neural mechanisms include impaired control of amygdala reactivity to emotional stimuli and dysfunctional connectivity of the amygdala to regulatory control regions in the OFC. These are, thus, important aspects of the neurobiological basis of increased vulnerability for BD. PMID:25603413

Theory-of-mind understanding and theory-of-mind use in unaffected first-degree relatives of schizophrenia and bipolar disorder.

PubMed

Wang, Yong-Guang; Roberts, David L; Liang, Yan; Shi, Jian-Fei; Wang, Kai

2015-12-15

We assessed theory of mind (ToM) in unaffected first-degree relatives (FDR) of patients with schizophrenia (SC) and bipolar disorder (BD) compared to healthy controls with a revised computerized referential communication task. Results showed that FDR of SC performed worse than FDR of BD and controls on a task requiring ToM-use, but not on a task requiring ToM-understanding. This indicates that deficient ToM-use, rather than ToM-understanding impairments, may represent a potential candidate endophenotype for schizophrenia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Developmentally stable whole-brain volume reductions and developmentally sensitive caudate and putamen volume alterations in those with attention-deficit/hyperactivity disorder and their unaffected siblings.

PubMed

Greven, Corina U; Bralten, Janita; Mennes, Maarten; O'Dwyer, Laurence; van Hulzen, Kimm J E; Rommelse, Nanda; Schweren, Lizanne J S; Hoekstra, Pieter J; Hartman, Catharina A; Heslenfeld, Dirk; Oosterlaan, Jaap; Faraone, Stephen V; Franke, Barbara; Zwiers, Marcel P; Arias-Vasquez, Alejandro; Buitelaar, Jan K

2015-05-01

Attention-deficit/hyperactivity disorder (ADHD) is a heritable neurodevelopmental disorder. It has been linked to reductions in total brain volume and subcortical abnormalities. However, owing to heterogeneity within and between studies and limited sample sizes, findings on the neuroanatomical substrates of ADHD have shown considerable variability. Moreover, it remains unclear whether neuroanatomical alterations linked to ADHD are also present in the unaffected siblings of those with ADHD. To examine whether ADHD is linked to alterations in whole-brain and subcortical volumes and to study familial underpinnings of brain volumetric alterations in ADHD. In this cross-sectional study, we included participants from the large and carefully phenotyped Dutch NeuroIMAGE sample (collected from September 2009-December 2012) consisting of 307 participants with ADHD, 169 of their unaffected siblings, and 196 typically developing control individuals (mean age, 17.21 years; age range, 8-30 years). Whole-brain volumes (total brain and gray and white matter volumes) and volumes of subcortical regions (nucleus accumbens, amygdala, caudate nucleus, globus pallidus, hippocampus, putamen, thalamus, and brainstem) were derived from structural magnetic resonance imaging scans using automated tissue segmentation. Regression analyses revealed that relative to control individuals, participants with ADHD had a 2.5% smaller total brain (β = -31.92; 95% CI, -52.69 to -11.16; P = .0027) and a 3% smaller total gray matter volume (β = -22.51; 95% CI, -35.07 to -9.96; P = .0005), while total white matter volume was unaltered (β = -10.10; 95% CI, -20.73 to 0.53; P = .06). Unaffected siblings had total brain and total gray matter volumes intermediate to participants with ADHD and control individuals. Significant age-by-diagnosis interactions showed that older age was linked to smaller caudate (P < .001) and putamen (P = .01) volumes (both corrected for total brain volume) in control individuals, whereas age was unrelated to these volumes in participants with ADHD and their unaffected siblings. Attention-deficit/hyperactivity disorder was not significantly related to the other subcortical volumes. Global differences in gray matter volume may be due to alterations in the general mechanisms underlying normal brain development in ADHD. The age-by-diagnosis interaction in the caudate and putamen supports the relevance of different brain developmental trajectories in participants with ADHD vs control individuals and supports the role of subcortical basal ganglia alterations in the pathophysiology of ADHD. Alterations in total gray matter and caudate and putamen volumes in unaffected siblings suggest that these volumes are linked to familial risk for ADHD.

Screen Color and Reading Performance on Closed-Circuit Television.

ERIC Educational Resources Information Center

Jacobs, R. J.

1990-01-01

To investigate whether screen color is an important variable in the prescription of closed circuit television (CCTV) systems, 16 adults with low vision were assessed on reading performance on white, green, and amber screens. When the screen luminance and contrast were equated for each CCTV, subjects' reading performance was unaffected by screen…

Interpersonal Attraction and Dependence as a Function of Self-Esteem.

ERIC Educational Resources Information Center

Fortin, Joseph A.; Sesi, Maher S.

This experiment tested the hypotheses that interpersonal dependence would be an inverse function of the individual's chronic and situational levels of self-esteem, and that interpersonal attraction would be an inverse function of the individual's induced/situational level of self-esteem, but would be unaffected by her chronic level. Subjects were…

14 CFR 125.173 - Fire detectors.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Fire detectors. 125.173 Section 125.173....173 Fire detectors. Fire detectors must be made and installed in a manner that assures their ability... subjected. Fire detectors must be unaffected by exposure to fumes, oil, water, or other fluids that may be...

14 CFR 125.173 - Fire detectors.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Fire detectors. 125.173 Section 125.173....173 Fire detectors. Fire detectors must be made and installed in a manner that assures their ability... subjected. Fire detectors must be unaffected by exposure to fumes, oil, water, or other fluids that may be...

14 CFR 125.173 - Fire detectors.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Fire detectors. 125.173 Section 125.173....173 Fire detectors. Fire detectors must be made and installed in a manner that assures their ability... subjected. Fire detectors must be unaffected by exposure to fumes, oil, water, or other fluids that may be...

14 CFR 125.173 - Fire detectors.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Fire detectors. 125.173 Section 125.173....173 Fire detectors. Fire detectors must be made and installed in a manner that assures their ability... subjected. Fire detectors must be unaffected by exposure to fumes, oil, water, or other fluids that may be...

14 CFR 125.173 - Fire detectors.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Fire detectors. 125.173 Section 125.173....173 Fire detectors. Fire detectors must be made and installed in a manner that assures their ability... subjected. Fire detectors must be unaffected by exposure to fumes, oil, water, or other fluids that may be...

Compensatory T-Cell Regulation in Unaffected Relatives of SLE Patients, and Opposite IL-2/CD25-Mediated Effects Suggested by Coreferentiality Modeling

PubMed Central

Fesel, Constantin; Barreto, Marta; Ferreira, Ricardo C.; Costa, Nuno; Venda, Lara L.; Pereira, Clara; Carvalho, Claudia; Morães-Fontes, Maria Francisca; Ferreira, Carlos M.; Vasconcelos, Carlos; Viana, João F.; Santos, Eugenia; Martins, Berta; Demengeot, Jocelyne; Vicente, Astrid M.

2012-01-01

In human systemic lupus erythematosus (SLE), diverse autoantibodies accumulate over years before disease manifestation. Unaffected relatives of SLE patients frequently share a sustained production of autoantibodies with indiscriminable specificity, usually without ever acquiring the disease. We studied relations of IgG autoantibody profiles and peripheral blood activated regulatory T-cells (aTregs), represented by CD4+CD25bright T-cells that were regularly 70–90% Foxp3+. We found consistent positive correlations of broad-range as well as specific SLE-associated IgG with aTreg frequencies within unaffected relatives, but not patients or unrelated controls. Our interpretation: unaffected relatives with shared genetic factors compensated pathogenic effects by aTregs engaged in parallel with the individual autoantibody production. To study this further, we applied a novel analytic approach named coreferentiality that tests the indirect relatedness of parameters in respect to multivariate phenotype data. Results show that independently of their direct correlation, aTreg frequencies and specific SLE-associated IgG were likely functionally related in unaffected relatives: they significantly parallelled each other in their relations to broad-range immunoblot autoantibody profiles. In unaffected relatives, we also found coreferential effects of genetic variation in the loci encoding IL-2 and CD25. A model of CD25 functional genetic effects constructed by coreferentiality maximization suggests that IL-2-CD25 interaction, likely stimulating aTregs in unaffected relatives, had an opposed effect in SLE patients, presumably triggering primarily T-effector cells in this group. Coreferentiality modeling as we do it here could also be useful in other contexts, particularly to explore combined functional genetic effects. PMID:22479496

Physiogenomic analysis of localized FMRI brain activity in schizophrenia.

PubMed

Windemuth, Andreas; Calhoun, Vince D; Pearlson, Godfrey D; Kocherla, Mohan; Jagannathan, Kanchana; Ruaño, Gualberto

2008-06-01

The search for genetic factors associated with disease is complicated by the complexity of the biological pathways linking genotype and phenotype. This analytical complexity is particularly concerning in diseases historically lacking reliable diagnostic biological markers, such as schizophrenia and other mental disorders. We investigate the use of functional magnetic resonance imaging (fMRI) as an intermediate phenotype (endophenotype) to identify physiogenomic associations to schizophrenia. We screened 99 subjects, 30 subjects diagnosed with schizophrenia, 13 unaffected relatives of schizophrenia patients, and 56 unrelated controls, for gene polymorphisms associated with fMRI activation patterns at two locations in temporal and frontal lobes previously implied in schizophrenia. A total of 22 single nucleotide polymorphisms (SNPs) in 15 genes from the dopamine and serotonin neurotransmission pathways were genotyped in all subjects. We identified three SNPs in genes that are significantly associated with fMRI activity. SNPs of the dopamine beta-hydroxylase (DBH) gene and of the dopamine receptor D4 (DRD4) were associated with activity in the temporal and frontal lobes, respectively. One SNP of serotonin-3A receptor (HTR3A) was associated with temporal lobe activity. The results of this study support the physiogenomic analysis of neuroimaging data to discover associations between genotype and disease-related phenotypes.

Can stroke patients use visual analogue scales?

PubMed

Price, C I; Curless, R H; Rodgers, H

1999-07-01

Visual analogue scales (VAS) have been used for the subjective measurement of mood, pain, and health status after stroke. In this study we investigated how stroke-related impairments could alter the ability of subjects to answer accurately. Consent was obtained from 96 subjects with a clinical stroke (mean age, 72.5 years; 50 men) and 48 control subjects without cerebrovascular disease (mean age, 71.5 years; 29 men). Patients with reduced conscious level or severe dysphasia were excluded. Subjects were asked to rate the tightness that they could feel on the (unaffected) upper arm after 3 low-pressure inflations with a standard sphygmomanometer cuff, which followed a predetermined sequence (20 mm Hg, 40 mm Hg, 0 mm Hg). Immediately after each change, they rated the perceived tightness on 5 scales presented in a random order: 4-point rating scale (none, mild, moderate, severe), 0 to 10 numerical rating scale, mechanical VAS, horizontal VAS, and vertical VAS. Standard tests recorded deficits in language, cognition, and visuospatial awareness. Inability to complete scales with the correct pattern was associated with any stroke (P<0.001). There was a significant association between success using scales and milder clinical stroke subtype (P<0.01). Within the stroke group, logistic regression analysis identified significant associations (P<0.05) between impairments (cognitive and visuospatial) and inability to complete individual scales correctly. Many patients after a stroke are unable to successfully complete self-report measurement scales, including VAS.

Coexposure to toluene and p-xylene in man: central nervous functions.

PubMed Central

Olson, B A; Gamberale, F; Iregren, A

1985-01-01

Sixteen men were studied in an exposure chamber to assess the effect of four hours' exposure to toluene (3.25 mmol/m3), xylene (2.84 mmol/m3), a mixture of toluene and xylene (2.20 + 0.94 mmol/m3), and a control condition. With the aid of microcomputers, subjects performed tests of simple reaction time, short term memory, and choice reaction time immediately after entering the chamber, after two, and after four hours' exposure. The results indicate that the performance on the tests was unaffected by exposure. In the light of this result the risk of an acute effect on central nervous functions after exposure for four hours at concentrations that do not exceed the Swedish threshold limit values was considered to be minimal. PMID:3970870

Prenatal and perinatal risk factors and the clinical implications on autism spectrum disorder.

PubMed

Chien, Yi-Ling; Chou, Miao-Chun; Chou, Wen-Jiun; Wu, Yu-Yu; Tsai, Wen-Che; Chiu, Yen-Nan; Gau, Susan Shur-Fen

2018-06-01

Prenatal and perinatal factors may increase the risk of autism spectrum disorder. However, little is known about whether unaffected siblings of probands with autism spectrum disorder also share the phenomenon and whether the prenatal/perinatal factors are related to the clinical severity of autistic symptoms. We compared the frequency of prenatal and perinatal factors among 323 probands with autism spectrum disorder (mean age ± standard deviation, 10.7 ± 3.5 years; males, 91.0%), 257 unaffected siblings (11.7 ± 4.5; 42.8%), and 1504 typically developing controls (8.9 ± 1.6 years; 53.1%); and investigated their effects on the severity of autistic symptoms. We found that probands with autism spectrum disorder and their unaffected siblings had more prenatal/perinatal events than typically developing controls with higher numbers of prenatal/perinatal factors in probands than in unaffected siblings. The prenatal/perinatal events were associated with greater stereotyped behaviors, social-emotional problems, socio-communication deficits, and overall severity. We also found that six prenatal/perinatal factors (i.e. preeclampsia, polyhydramnios, oligoamnios, placenta previa, umbilical cord knot, and gestational diabetes) were associated with the severity of autistic symptoms, particularly stereotyped behaviors and socio-communication deficits. Our findings suggest that prenatal and perinatal factors may potentially moderate the clinical expression of autism spectrum disorder. The underlying mechanism warrants further research.

An Odor-Specific Threshold Deficit Implicates Abnormal Intracellular Cyclic AMP Signaling in Schizophrenia

PubMed Central

Turetsky, Bruce I.; Moberg, Paul J.

2012-01-01

Objective Although olfactory deficits are common in schizophrenia, their underlying pathophysiology remains unknown. Recent evidence has suggested that cAMP signaling may be disrupted in schizophrenia. Since cAMP mediates signal transduction in olfactory receptor neurons, this could contribute to the etiology of observed olfactory deficits. This study was designed to test this hypothesis by determining odor detection threshold sensitivities to two odorants that differ in their relative activations of this intracellular cAMP signaling cascade. Method Thirty schizophrenia patients, 25 healthy comparison subjects, and 19 unaffected first-degree relatives of schizophrenia patients were studied. Odor detection threshold sensitivities were measured for the two odorants citralva and lyral. Although both have fruity/floral scents, citralva strongly activates adenylyl cyclase to increase cAMP levels, while lyral is a very weak activator of adenylyl cyclase. Results There was a significant group-by-odor interaction. Both schizophrenia patients and unaffected first-degree relatives were impaired in their ability to detect lyral versus citralva. Comparison subjects were equally sensitive to both odorants. This selective deficit could not be explained by differences in age, sex, smoking, clinical symptom profile, or medication use. Conclusions This study establishes the presence of an odor-specific hyposmia that may denote a disruption of cAMP-mediated signal transduction in schizophrenia. The presence of a parallel deficit in the patients’ unaffected first-degree relatives suggests that this deficit is genetically mediated. Although additional physiological studies are needed to confirm the underlying mechanism, these results offer strong inferential support for the hypothesis that cAMP signaling is dys-regulated in schizophrenia. PMID:19074977

An odor-specific threshold deficit implicates abnormal intracellular cyclic AMP signaling in schizophrenia.

PubMed

Turetsky, Bruce I; Moberg, Paul J

2009-02-01

Although olfactory deficits are common in schizophrenia, their underlying pathophysiology remains unknown. Recent evidence has suggested that cAMP signaling may be disrupted in schizophrenia. Since cAMP mediates signal transduction in olfactory receptor neurons, this could contribute to the etiology of observed olfactory deficits. This study was designed to test this hypothesis by determining odor detection threshold sensitivities to two odorants that differ in their relative activations of this intracellular cAMP signaling cascade. Thirty schizophrenia patients, 25 healthy comparison subjects, and 19 unaffected first-degree relatives of schizophrenia patients were studied. Odor detection threshold sensitivities were measured for the two odorants citralva and lyral. Although both have fruity/floral scents, citralva strongly activates adenylyl cyclase to increase cAMP levels, while lyral is a very weak activator of adenylyl cyclase. There was a significant group-by-odor interaction. Both schizophrenia patients and unaffected first-degree relatives were impaired in their ability to detect lyral versus citralva. Comparison subjects were equally sensitive to both odorants. This selective deficit could not be explained by differences in age, sex, smoking, clinical symptom profile, or medication use. This study establishes the presence of an odor-specific hyposmia that may denote a disruption of cAMP-mediated signal transduction in schizophrenia. The presence of a parallel deficit in the patients' unaffected first-degree relatives suggests that this deficit is genetically mediated. Although additional physiological studies are needed to confirm the underlying mechanism, these results offer strong inferential support for the hypothesis that cAMP signaling is dysregulated in schizophrenia.

The effect of acetaminophen (four grams a day for three consecutive days) on hepatic tests in alcoholic patients – a multicenter randomized study

PubMed Central

Kuffner, EK; Green, JL; Bogdan, GM; Knox, PC; Palmer, RB; Heard, K; Slattery, JT; Dart, RC

2007-01-01

Background Hepatic failure has been associated with reported therapeutic use of acetaminophen by alcoholic patients. The highest risk period for alcoholic patients is immediately after discontinuation of alcohol intake. This period exhibits the largest increase in CYP2E1 induction and lowest glutathione levels. Our hypothesis was that common liver tests would be unaffected by administration of the maximum recommended daily dosage of acetaminophen for 3 consecutive days to newly-abstinent alcoholic subjects. Methods Adult alcoholic subjects entering two alcohol detoxification centers were enrolled in a prospective double-blind, randomized, placebo-controlled trial. Subjects were randomized to acetaminophen, 4 g/day, or placebo for 3 consecutive days. The study had 95% probability of detecting a 15 IU/L difference in serum ALT. Results A total of 443 subjects were enrolled: 308 (258 completed) received acetaminophen and 135 subjects (114 completed) received placebo. Study groups did not differ in demographics, alcohol consumption, nutritional status or baseline laboratory assessments. The peak mean ALT activity was 57 ± 45 IU/L and 55 ± 48 IU/L in the acetaminophen and placebo groups, respectively. Subgroup analyses for subjects presenting with an elevated ALT, subjects fulfilling a diagnosis of alcoholic hepatitis and subjects attaining a peak ALT greater than 200 IU/L showed no statistical difference between the acetaminophen and control groups. The one participant developing an increased international normalized ratio was in the placebo group. Conclusion Alcoholic patients treated with the maximum recommended daily dose of acetaminophen for 3 consecutive days did not develop increases in serum transaminase or other measures of liver injury. Treatment of pain or fever for 3 days with acetaminophen appears safe in newly-abstinent alcoholic patients, such as those presenting for acute medical care. PMID:17537264

Three-dimensional movement analysis of handwriting in subjects with mild hemiparesis.

PubMed

Harada, Takako; Okajima, Yasutomo; Takahashi, Hidetoshi

2010-08-01

To investigate the effects of hemiparesis on handwriting using a 3-dimensional movement analyzer. Comparative case study. Ambulatory care clinic. Right-handed patients (n=25; mean age +/- SD, 62.3+/-10y) with mild right hemiparesis secondary to subcortical stroke, and age-matched (n=10; 65.6+/-13y) and age-unmatched (n=15; 32.4+/-10y) control subjects. Not applicable. Time required to write a Japanese character of 2 different sizes and average speed of handwriting at the pen tip. Average radii of tracks of the moving pen tip, metacarpal head of the index finger, and distal end of the forearm during writing. Correlation coefficients of the instantaneous speed-time graph of the pen tip with that of the index finger and with that of the distal forearm during writing. Time for writing with the hemiparetic right hand was longer than that with the unaffected left hand (P=.05 approximately .03), while it was shorter in healthy control subjects (P=.07 approximately .05). In contrast with the left-hand writing, the track radius of the pen tip of the right-hand writing in patients with hemiparesis with normal joint position sense was significantly larger than that of the finger or distal forearm (P=.01). The finding was the same as in the young and elderly control subjects. This right-left difference disappeared in the patients with hemiparesis with position sense impairment. The correlation coefficient of speed between the pen tip and the finger was larger in right-hand than left-hand writing in the control and sensory-normative patients with hemiparesis even though the difference was significant only in the healthy elderly subjects (P=.03). Irrespective of the right or left hand use, the correlation coefficient between the pen tip and the finger or distal forearm significantly increased as the character size increased (P=.03 approximately 6 x10(-6)) in all subjects and patients. However, this size-related difference was less significant in the patients with sensory impairment. The characteristics of handwriting movement by the dominant hand were preserved in patients with mild dominant-hand hemiparesis when joint position sense was normative but were lost in those with position sense impairment.

Differential effects of common variants in SCN2A on general cognitive ability, brain physiology, and messenger RNA expression in schizophrenia cases and control individuals.

PubMed

Dickinson, Dwight; Straub, Richard E; Trampush, Joey W; Gao, Yuan; Feng, Ningping; Xie, Bin; Shin, Joo Heon; Lim, Hun Ki; Ursini, Gianluca; Bigos, Kristin L; Kolachana, Bhaskar; Hashimoto, Ryota; Takeda, Masatoshi; Baum, Graham L; Rujescu, Dan; Callicott, Joseph H; Hyde, Thomas M; Berman, Karen F; Kleinman, Joel E; Weinberger, Daniel R

2014-06-01

One approach to understanding the genetic complexity of schizophrenia is to study associated behavioral and biological phenotypes that may be more directly linked to genetic variation. To identify single-nucleotide polymorphisms associated with general cognitive ability (g) in people with schizophrenia and control individuals. Genomewide association study, followed by analyses in unaffected siblings and independent schizophrenia samples, functional magnetic resonance imaging studies of brain physiology in vivo, and RNA sequencing in postmortem brain samples. The discovery cohort and unaffected siblings were participants in the National Institute of Mental Health Clinical Brain Disorders Branch schizophrenia genetics studies. Additional schizophrenia cohorts were from psychiatric treatment settings in the United States, Japan, and Germany. The discovery cohort comprised 339 with schizophrenia and 363 community control participants. Follow-up analyses studied 147 unaffected siblings of the schizophrenia cases and independent schizophrenia samples including a total of an additional 668 participants. Imaging analyses included 87 schizophrenia cases and 397 control individuals. Brain tissue samples were available for 64 cases and 61 control individuals. We studied genomewide association with g, by group, in the discovery cohort. We used selected genotypes to test specific associations in unaffected siblings and independent schizophrenia samples. Imaging analyses focused on activation in the prefrontal cortex during working memory. Brain tissue studies yielded messenger RNA expression levels for RefSeq transcripts. The schizophrenia discovery cohort showed genomewide-significant association of g with polymorphisms in sodium channel gene SCN2A, accounting for 10.4% of g variance (rs10174400, P = 9.27 × 10(-10)). Control individuals showed a trend for g/genotype association with reversed allelic directionality. The genotype-by-group interaction was also genomewide significant (P = 1.75 × 10(-9)). Siblings showed a genotype association with g parallel to the schizophrenia group and the same interaction pattern. Parallel, but weaker, associations with cognition were found in independent schizophrenia samples. Imaging analyses showed a similar pattern of genotype associations by group and genotype-by-group interaction. Sequencing of RNA in brain revealed reduced expression in 2 of 3 SCN2A alternative transcripts in the patient group, with genotype-by-group interaction, that again paralleled the cognition effects. The findings implicate SCN2A and sodium channel biology in cognitive impairment in schizophrenia cases and unaffected relatives and may facilitate development of cognition-enhancing treatments.

Enhanced perceived responsibility decreases metamemory but not memory accuracy in obsessive-compulsive disorder (OCD).

PubMed

Moritz, S; Wahl, K; Zurowski, B; Jelinek, L; Hand, I; Fricke, S

2007-09-01

Mixed findings have been obtained in prior research with respect to the presence and severity of memory and metamemory deficits in obsessive-compulsive disorder (OCD). We tested the hypothesis that experimentally induced increments of subjective responsibility would lead to a disproportionately strong decline of memory confidence and enhanced response latencies in OCD while leaving memory accuracy unaffected. Twenty-eight OCD patients and 28 healthy controls were presented a computerized memory test framed with two different scenarios. In the neutral scenario, the participant was requested to imagine purchasing 15 items from a do-it-yourself store. In the recognition phase, the 15 needed items were presented along with 15 distractor items. The participant was asked to decide whether items were on his or her shopping list or not, graded by subjective confidence. In the responsibility scenario, the general experimental setup was analogous except that the participant now had to envision that he or she was a helper in a region recently struck by an earthquake, dispatched to provide 15 urgently needed goods from a nearby town. In line with prior work by our group, samples did not differ in either condition on memory accuracy in a subsequent recognition task. As hypothesized, OCD participants were less certain in their responses for the high responsibility condition than controls. Whereas patients and controls did not differ in their subjective estimates for memorized items, patients expressed stronger doubt that their earthquake mission was successful. The findings indicate that low memory confidence in OCD may only be elicited in situations where perceived responsibility is high and that patients may share higher performance standards ("good is not good enough") than controls when perceived responsibility is inflated.

A novel missense mutation of the paired box 3 gene in a Turkish family with Waardenburg syndrome type 1

PubMed Central

Ozturk, A.Taylan; Adibelli, Hamit; Unal, Nurettin; Tukun, Ajlan

2013-01-01

Purpose Screening of mutations in the paired box 3 (PAX3) gene in three generations of a Turkish family with Waardenburg syndrome type 1 (WS1). Methods WS1 was diagnosed in a 13-month-old girl according to the WS Consortium criteria. Detailed family history of the proband revealed eight affected members in three generations. Routine clinical and audiological examination and ophthalmologic evaluation were performed on eight affected and five healthy members of the study family. Dystopia canthorum was detected in all affected patients; however, a brilliant blue iris was present in five patients who also had mild retinal hypopigmentation. Genomic DNA was extracted from the peripheral blood of affected and unaffected individuals in the family as well as 50 unrelated healthy volunteers. All coding exons and adjacent intronic regions of PAX3 were sequenced directly. Results A novel missense heterozygous c.788T>G mutation was identified in eight patients. This nucleotide alteration was not found in unaffected members of the study family or in the 50 unrelated control subjects. The mutation causes V263G amino-acid substitution in the homeodomain of the PAX3 protein, which represents the 45th residue of helix 3. Conclusions We identified a novel missense c.788T>G mutation in PAX3 in a family with Waardenburg syndrome with intrafamilial phenotypic heterogeneity. PMID:23378733

A novel missense mutation of the paired box 3 gene in a Turkish family with Waardenburg syndrome type 1.

PubMed

Hazan, Filiz; Ozturk, A Taylan; Adibelli, Hamit; Unal, Nurettin; Tukun, Ajlan

2013-01-01

Screening of mutations in the paired box 3 (PAX3) gene in three generations of a Turkish family with Waardenburg syndrome type 1 (WS1). WS1 was diagnosed in a 13-month-old girl according to the WS Consortium criteria. Detailed family history of the proband revealed eight affected members in three generations. Routine clinical and audiological examination and ophthalmologic evaluation were performed on eight affected and five healthy members of the study family. Dystopia canthorum was detected in all affected patients; however, a brilliant blue iris was present in five patients who also had mild retinal hypopigmentation. Genomic DNA was extracted from the peripheral blood of affected and unaffected individuals in the family as well as 50 unrelated healthy volunteers. All coding exons and adjacent intronic regions of PAX3 were sequenced directly. A novel missense heterozygous c.788T>G mutation was identified in eight patients. This nucleotide alteration was not found in unaffected members of the study family or in the 50 unrelated control subjects. The mutation causes V263G amino-acid substitution in the homeodomain of the PAX3 protein, which represents the 45(th) residue of helix 3. We identified a novel missense c.788T>G mutation in PAX3 in a family with Waardenburg syndrome with intrafamilial phenotypic heterogeneity.

Post-stroke aphasia recovery assessed with fMRI and a picture identification task

PubMed Central

Szaflarski, Jerzy P.; Eaton, Kenneth; Ball, Angel L.; Banks, Christi; Vannest, Jennifer; Allendorfer, Jane B.; Page, Stephen; Holland, Scott K.

2010-01-01

Background Stroke patients often display deficits in language function such as correctly naming objects. Our aim was to evaluate the reliability and the patterns of post-stroke language recovery using a picture identification task during fMRI at 4T. Material and Methods 4 healthy and 4 left MCA stroke subjects with chronic (>1 year) aphasia. Ten fMRI scans were performed for each subject over a 10-week period using a picture identification task. Active condition involved presenting subjects with a panel of 4 figures (e.g., drawings of 4 animals) every 6 seconds; subjects indicated which figure matched the written name in the center. Control condition was same/different judgment task of pairs of geometric figures (squares, octagons or combination) presented every 6 seconds. Thirty-second active/control blocks were repeated 5 times each; responses were recorded. Results Patients and controls exhibited similar demographic characteristics: age (46 vs. 53 years), personal handedness (EHI; 89 vs. 95), familial handedness (93 vs. 95) or years of education (14.3 vs. 14.8). For the active condition, controls performed better than patients (97.7% vs. 89.1%, p<0.001); performance was similar for the control condition (99.5% vs. 98.8%, p=0.23). During fMRI, controls exhibited bilateral, L>R positive blood oxygenation-level dependent (BOLD) activations in frontal and temporal language areas and symmetric retro-splenial and posterior cingulate areas and symmetric negative BOLD activations in bilateral fronto-temporal language networks. However, the patient group showed positive BOLD activations predominantly in peri-stroke areas and negative BOLD activations in the unaffected (right) hemisphere. Both the control and patient groups displayed high activation reliability (as measured by the ICC) in left frontal and temporal language areas, although the ICC in frontal regions of the patients was spread over a much larger peri-stroke area. Conclusion This study documents the utility of the picture identification task for post-stroke language recovery evaluation. Study data suggest that adult stroke patients utilize functional peri-stroke areas to perform language functions. PMID:20719532

Default network connectivity as a vulnerability marker for obsessive compulsive disorder.

PubMed

Peng, Z W; Xu, T; He, Q H; Shi, C Z; Wei, Z; Miao, G D; Jing, J; Lim, K O; Zuo, X N; Chan, R C K

2014-05-01

Aberrant functional connectivity within the default network is generally assumed to be involved in the pathophysiology of obsessive compulsive disorder (OCD); however, the genetic risk of default network connectivity in OCD remains largely unknown. Here, we systematically investigated default network connectivity in 15 OCD patients, 15 paired unaffected siblings and 28 healthy controls. We sought to examine the profiles of default network connectivity in OCD patients and their siblings, exploring the correlation between abnormal default network connectivity and genetic risk for this population. Compared with healthy controls, OCD patients exhibited reduced strength of default network functional connectivity with the posterior cingulate cortex (PCC), and increased functional connectivity in the right inferior frontal lobe, insula, superior parietal cortex and superior temporal cortex, while their unaffected first-degree siblings only showed reduced local connectivity in the PCC. These findings suggest that the disruptions of default network functional connectivity might be associated with family history of OCD. The decreased default network connectivity in both OCD patients and their unaffected siblings may serve as a potential marker of OCD.

Head Circumferences in Twins with and without Autism Spectrum Disorders

ERIC Educational Resources Information Center

Froehlich, Wendy; Cleveland, Sue; Torres, Andrea; Phillips, Jennifer; Cohen, Brianne; Torigoe, Tiffany; Miller, Janet; Fedele, Angie; Collins, Jack; Smith, Karen; Lotspeich, Linda; Croen, Lisa A.; Ozonoff, Sally; Lajonchere, Clara; Grether, Judith K.; Hallmayer, Joachim

2013-01-01

To determine the genetic relationship between head circumference (HC) and Autism Spectrum Disorders (ASDs). Twin pairs with at least one twin with an ASD were assessed. HCs in affected and unaffected individuals were compared, as were HC correlations in monozygotic and dizygotic pairs. 404 subjects, ages 4-18, were included. 20% of males and 27%…

The Impact of Acquaintance Rape Stories and Case-Specific Pretrial Publicity on Juror Decision Making.

ERIC Educational Resources Information Center

Mullin, Charles; And Others

1996-01-01

Reports on a trial simulation in which exposure to publicity regarding the defendant and general stories about acquaintance rape were manipulated; participants then viewed an enacted rape trial. Finds that male subjects exposed to predatory rape publicity were pro-defendant, whereas women were unaffected. Discusses male reaction to information…

Investigation of gender role behaviors in boys with hypospadias: comparative study with unaffected boys and girls.

PubMed

Sung, Ji Yean; Han, Sang Won; Chung, Kyong-Mee; Lee, Hyeyoung; Cho, Sang Hee

2014-10-01

The purpose of the study was (1) to investigate gender role behaviors of boys with hypospadias compared with groups of unaffected boys and girls using parental reports and direct observations; and (2) to directly observe effects of socialization (mothers' presence) on children's gender role behaviors. Ages of 19 children with hypospadias ranged from 3 to 7 years, and each of them were matched to controls of unaffected boys and girls by age. All the children participated with their mothers. Children's gender role behaviors and their mothers' behaviors were evaluated using an observation coding system. Mothers also completed questionnaires regarding their children's gender role behaviors. Results indicated no atypical gender role behavior for the boys with hypospadias and no direct effects of socialization on their gender role behaviors. However, differences were found in negative communicative behaviors between boys with hypospadias and unaffected boys, suggesting a possible role of socialization. © The Author 2014. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Structural and Diffusion Property Alterations in Unaffected Siblings of Patients with Obsessive-Compulsive Disorder

PubMed Central

Shi, Changzheng; Miao, Guodong; Yang, Qiong; Gao, Wei; Wolff, Jason J.; Chan, Raymond C. K.; Shen, Dinggang

2014-01-01

Disrupted white matter integrity and abnormal cortical thickness are widely reported in the pathophysiology of obsessive-compulsive disorder (OCD). However, the relationship between alterations in white matter connectivity and cortical thickness in OCD is unclear. In addition, the heritability of this relationship is poorly understood. To investigate the relationship of white matter microstructure with cortical thickness, we measure fractional anisotropy (FA) of white matter in 30 OCD patients, 19 unaffected siblings and 30 matched healthy controls. Then, we take those regions of significantly altered FA in OCD patients compared with healthy controls to perform fiber tracking. Next, we calculate the fiber quantity in the same tracts. Lastly, we compare cortical thickness in the target regions of those tracts. Patients with OCD exhibited decreased FA in cingulum, arcuate fibers near the superior parietal lobule, inferior longitudinal fasciculus near the right superior temporal gyrus and uncinate fasciculus. Siblings showed reduced FA in arcuate fibers near the superior parietal lobule and anterior limb of internal capsule. Significant reductions in both fiber quantities and cortical thickness in OCD patients and their unaffected siblings were also observed in the projected brain areas when using the arcuate fibers near the left superior parietal lobule as the starting points. Reduced FA in the left superior parietal lobule was observed not only in patients with OCD but also in their unaffected siblings. Originated from the superior parietal lobule, the number of fibers was also found to be decreased and the corresponding cortical regions were thinner relative to controls. The linkage between disrupted white matter integrity and the abnormal cortical thickness may be a vulnerability marker for OCD. PMID:24489665

Gene Expression Profiles from Disease Discordant Twins Suggest Shared Antiviral Pathways and Viral Exposures among Multiple Systemic Autoimmune Diseases

PubMed Central

Gan, Lu; O’Hanlon, Terrance P.; Lai, Zhennan; Fannin, Rick; Weller, Melodie L.; Rider, Lisa G.; Chiorini, John A.; Miller, Frederick W.

2015-01-01

Viral agents are of interest as possible autoimmune triggers due to prior reported associations and widely studied molecular mechanisms of antiviral immune responses in autoimmunity. Here we examined new viral candidates for the initiation and/or promotion of systemic autoimmune diseases (SAID), as well as possible related signaling pathways shared in the pathogenesis of those disorders. RNA isolated from peripheral blood samples from 33 twins discordant for SAID and 33 matched, unrelated healthy controls was analyzed using a custom viral-human gene microarray. Paired comparisons were made among three study groups—probands with SAID, their unaffected twins, and matched, unrelated healthy controls—using statistical and molecular pathway analyses. Probands and unaffected twins differed significantly in the expression of 537 human genes, and 107 of those were associated with viral infections. These 537 differentially expressed human genes participate in overlapping networks of several canonical, biologic pathways relating to antiviral responses and inflammation. Moreover, certain viral genes were expressed at higher levels in probands compared to either unaffected twins or unrelated, healthy controls. Interestingly, viral gene expression levels in unaffected twins appeared intermediate between those of probands and the matched, unrelated healthy controls. Of the viruses with overexpressed viral genes, herpes simplex virus-2 (HSV-2) was the only human viral pathogen identified using four distinct oligonucleotide probes corresponding to three HSV-2 genes associated with different stages of viral infection. Although the effects from immunosuppressive therapy on viral gene expression remain unclear, this exploratory study suggests a new approach to evaluate shared viral agents and antiviral immune responses that may be involved in the development of SAID. PMID:26556803

HIV and Child Mental Health: A Case-Control Study in Rwanda

PubMed Central

Scorza, Pamela; Kanyanganzi, Frederick; Fawzi, Mary C. Smith; Sezibera, Vincent; Cyamatare, Felix; Beardslee, William; Stulac, Sara; Bizimana, Justin I.; Stevenson, Anne; Kayiteshonga, Yvonne

2014-01-01

BACKGROUND: The global HIV/AIDS response has advanced in addressing the health and well-being of HIV-positive children. Although attention has been paid to children orphaned by parental AIDS, children who live with HIV-positive caregivers have received less attention. This study compares mental health problems and risk and protective factors in HIV-positive, HIV-affected (due to caregiver HIV), and HIV-unaffected children in Rwanda. METHODS: A case-control design assessed mental health, risk, and protective factors among 683 children aged 10 to 17 years at different levels of HIV exposure. A stratified random sampling strategy based on electronic medical records identified all known HIV-positive children in this age range in 2 districts in Rwanda. Lists of all same-age children in villages with an HIV-positive child were then collected and split by HIV status (HIV-positive, HIV-affected, and HIV-unaffected). One child was randomly sampled from the latter 2 groups to compare with each HIV-positive child per village. RESULTS: HIV-affected and HIV-positive children demonstrated higher levels of depression, anxiety, conduct problems, and functional impairment compared with HIV-unaffected children. HIV-affected children had significantly higher odds of depression (1.68: 95% confidence interval [CI] 1.15–2.44), anxiety (1.77: 95% CI 1.14–2.75), and conduct problems (1.59: 95% CI 1.04–2.45) compared with HIV-unaffected children, and rates of these mental health conditions were similar to HIV-positive children. These results remained significant after controlling for contextual variables. CONCLUSIONS: The mental health of HIV-affected children requires policy and programmatic responses comparable to HIV-positive children. PMID:25049342

The caries experience and behavior of dental patients with autism spectrum disorder.

PubMed

Loo, Cheen Y; Graham, Richard M; Hughes, Christopher V

2008-11-01

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. The authors conducted a study to evaluate the demographics, caries experience and behavior of patients with ASD and compare these characteristics with those of patients without ASD (unaffected patients). The authors reviewed patients' charts and identified a group of 395 patients with ASD and a group of 386 unaffected patients. They obtained the following patient data for analysis: primary diagnosis, age, sex, residence (home versus institution or group home), presence of seizure disorder, additional diagnosis (mental retardation, cerebral palsy, self-injurious behavior or pica), medications, caries prevalence, caries severity and behavior. The ASD group had a male:female ratio of 4:1, and patients had a diagnosis of autism, pervasive developmental disorder-not otherwise specified or Asperger syndrome. Sex distribution was equal in the unaffected group, which was younger and had a higher decayed, missing and filled teeth (DMFT) score than did the ASD group. When the authors controlled for age and sex, they noted a statistically significant association between ASD and dental caries prevalence. A significantly higher percentage of patients with ASD than unaffected patients were uncooperative and required dental treatment to take place under general anesthesia. Caries prevalence and severity in patients with ASD were not associated with institutionalization, presence of seizure disorder or additional diagnosis. People with ASD were more likely to be caries-free and had lower DMFT scores than did their unaffected peers. Significantly more patients with ASD than unaffected patients were uncooperative and required general anesthesia to undergo dental treatment.

Prevention of metabolic alterations caused by suspension hypokinesia in leg muscles of rats

NASA Technical Reports Server (NTRS)

Tischler, M. E.; Jaspers, S. R.; Fagan, J. M.

1983-01-01

Rats were subjected to tail-cast suspension hypokinesia for 6 days with one leg immobilized in dorsal flexion by casting. Control animals were also tail-casted. The soleus, gastrocnemius and plantaris muscles of uncasted hypokinetic legs were smaller than control muscles. Dorsal flexion prevented atrophy of these muscles and caused the soleus to hypertrophy. The anterior muscles were unaffected by hypokinesia. The smaller size of the soleus of the uncasted leg relative to the dorsal flexed and weight bearing limbs correlated with slower protein synthesis and faster proteolysis. The capacity of this muscle to synthesize glutamine (gln), which carries nitrogenous waste from muscle was also measured. Although tissue homogenates showed higher activities of gln synthetase, the rate of de novo synthesis was not altered in intact muscle but the tissue ratio of gln/glutamate was decreased. Glutamate and ATP were not limiting for gln synthesis, but availability of ammonia may be a limiting factor for this process in hypokinesia.

Structure and function of the abductors in patients with hip osteoarthritis: Systematic review and meta-analysis.

PubMed

Marshall, Amelia Rose; Noronha, Marcos de; Zacharias, Anita; Kapakoulakis, Theo; Green, Rodney

2016-04-27

Hip osteoarthritis (OA) is a major cause of morbidity. Rehabilitation for this population focuses on strengthening the hip muscles, particularly the abductors, however the deficit in function of these muscles is unclear. To review the evidence for the differences in structure and function of hip abductors (gluteus medius and minimus and tensor fascia lata) in hip OA. A systematic review was conducted using MEDLINE, AMED, CINAHL and SportDISCUS, from the earliest date to September 2013. Studies that compared hip OA patients with controls, or the unaffected contralateral hip were included. Studies needed to report data on an outcome related to gross gluteal muscle function. An initial yield of 141 studies was reduced to 22 after application of inclusion/exclusion criteria. Meta-analysis confirmed greater hip abductor strength in the control group (standardized mean difference = SMD -0.93, 95%CI -1.70 to -0.16) and the unaffected limb (SMD -0.26, 95%CI -0.48 to -0.04). Meta-analyses showed no differences in muscle size either between groups or limbs. Few electromyography studies have been reported and meta-analysis was not possible. Hip abductor strength is reduced in OA patients when compared to healthy controls and to the unaffected limb. Data on muscle size and activity is limited.

The role of injection cues in the production of the morphine preexposure effect in taste aversion learning.

PubMed

Davis, Catherine M; de Brugada, Isabel; Riley, Anthony L

2010-05-01

The attenuation of an LiCl-induced conditioned taste aversion (CTA) by LiCl preexposure is mediated primarily by associative blocking via injection-related cues. Given that preexposure to morphine attenuates morphine-induced CTAs, it was of interest to determine whether injection cues also mediate this effect. Certain morphine-induced behaviors such as analgesic tolerance are controlled associatively, via injection-related cues. Accordingly, animals in the present experiments were preexposed to morphine (or vehicle) every other day for five total exposures, followed by an extinction phase, in which the subjects were given saline injections (or no treatment) for 8 (Experiment 1) or 16 (Experiment 2) consecutive days. All of the animals then received five CTA trials with morphine (or vehicle). The morphine-preexposed animals in Experiment 1 displayed an attenuation of the morphine CTA that was unaffected by extinction saline injections, suggesting that blocking by injection cues during morphine preexposure does not mediate this effect. All of the morphine-preexposed subjects in Experiment 2 displayed a weakened preexposure effect, an effect inconsistent with a selective extinction of drug-associated stimuli. The attenuating effects of morphine preexposure in aversion learning are most likely controlled by nonassociative mechanisms, like drug tolerance.

Atypical activation during the Embedded Figures Task as a functional magnetic resonance imaging endophenotype of autism

PubMed Central

Holt, Rosemary J.; Chura, Lindsay R.; Calder, Andrew J.; Suckling, John; Bullmore, Edward T.; Baron-Cohen, Simon

2012-01-01

Atypical activation during the Embedded Figures Task has been demonstrated in autism, but has not been investigated in siblings or related to measures of clinical severity. We identified atypical activation during the Embedded Figures Task in participants with autism and unaffected siblings compared with control subjects in a number of temporal and frontal brain regions. Autism and sibling groups, however, did not differ in terms of activation during this task. This suggests that the pattern of atypical activation identified may represent a functional endophenotype of autism, related to familial risk for the condition shared between individuals with autism and their siblings. We also found that reduced activation in autism relative to control subjects in regions including associative visual and face processing areas was strongly correlated with the clinical severity of impairments in reciprocal social interaction. Behavioural performance was intact in autism and sibling groups. Results are discussed in terms of atypical information processing styles or of increased activation in temporal and frontal regions in autism and the broader phenotype. By separating the aspects of atypical activation as markers of familial risk for the condition from those that are autism-specific, our findings offer new insight into the factors that might cause the expression of autism in families, affecting some children but not others. PMID:23065480

Prenatal testosterone and theory of mind development: Findings from disorders of sex development.

PubMed

Khorashad, Behzad S; Khazai, Behnaz; Roshan, Ghasem M; Hiradfar, Mehran; Afkhamizadeh, Mozhgan; van de Grift, Tim C

2018-03-01

Women on average perform better than men on the "Reading the Mind in the Eyes" test (RMET) which is a measure of Theory of Mind (ToM). The aim of this study was to assess whether these sex differences are influenced by differences in prenatal testosterone levels through a study on individuals with Disorders of Sex Development and matched controls. ToM performance was examined using the RMET in female-assigned-at-birth individuals with increased prenatal testosterone exposure (Congenital Adrenal Hyperplasia (CAH) and 5-alpha Reductase type-2 Deficiency (5α-RD-2)), female-assigned-at-birth individuals with testosterone insensitivity (Complete Androgen Insensitivity Syndrome (CAIS)), and their age-matched unaffected male and female relatives. A total number of 158 individuals participated in the study; 19 with 5α-RD-2, 17 with CAH, 18 women with CAIS, 52 matched unaffected men and 52 matched unaffected women. All subgroups were around 20 years of age. Women with CAH scored significantly lower on RMET than control women and CAIS individuals. CAIS individuals scored significantly higher than control men and participants with 5α-RD. Statistically, CAIS individuals' performance on RMET was similar to control women's, women with CAH did not differ significantly from control men and 5α-RD-2 individuals scored significantly lower than control men. These results, which are in line with previous theories, illustrate that performance on the RMET, as an index of ToM, may be influenced by variations in prenatal androgens levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

Muscle coordination is habitual rather than optimal.

PubMed

de Rugy, Aymar; Loeb, Gerald E; Carroll, Timothy J

2012-05-23

When sharing load among multiple muscles, humans appear to select an optimal pattern of activation that minimizes costs such as the effort or variability of movement. How the nervous system achieves this behavior, however, is unknown. Here we show that contrary to predictions from optimal control theory, habitual muscle activation patterns are surprisingly robust to changes in limb biomechanics. We first developed a method to simulate joint forces in real time from electromyographic recordings of the wrist muscles. When the model was altered to simulate the effects of paralyzing a muscle, the subjects simply increased the recruitment of all muscles to accomplish the task, rather than recruiting only the useful muscles. When the model was altered to make the force output of one muscle unusually noisy, the subjects again persisted in recruiting all muscles rather than eliminating the noisy one. Such habitual coordination patterns were also unaffected by real modifications of biomechanics produced by selectively damaging a muscle without affecting sensory feedback. Subjects naturally use different patterns of muscle contraction to produce the same forces in different pronation-supination postures, but when the simulation was based on a posture different from the actual posture, the recruitment patterns tended to agree with the actual rather than the simulated posture. The results appear inconsistent with computation of motor programs by an optimal controller in the brain. Rather, the brain may learn and recall command programs that result in muscle coordination patterns generated by lower sensorimotor circuitry that are functionally "good-enough."

Amplitude and timing of somatosensory cortex activity in task-specific focal hand dystonia.

PubMed

Dolberg, Rebecca; Hinkley, Leighton B N; Honma, Susanne; Zhu, Zhao; Findlay, Anne M; Byl, Nancy N; Nagarajan, Srikantan S

2011-12-01

Task-specific focal hand dystonia (tspFHD) is a movement disorder diagnosed in individuals performing repetitive hand behaviors. The extent to which processing anomalies in primary sensory cortex extend to other regions or across the two hemispheres is presently unclear. In response to low/high rate and novel tactile stimuli on the affected and unaffected hands, magnetoencephalography (MEG) was used to elaborate activity timing and amplitude in the primary somatosensory (S1) and secondary somatosensory/parietal ventral (S2/PV) cortices. MEG and clinical performance measures were collected from 13 patients and matched controls. Compared to controls, subjects with tspFHD had increased response amplitude in S2/PV bilaterally in response to high rate and novel stimuli. Subjects with tspFHD also showed increased response latency (low rate, novel) of the affected digits in contralateral S1. For high rate, subjects with tspFHD showed increased response latency in ipsilateral S1 and S2/PV bilaterally. Activation differences correlated with functional sensory deficits (predicting a latency shift in S1), motor speed and muscle strength. There are objective differences in the amplitude and timing of activity for both hands across contralateral and ipsilateral somatosensory cortex in patients with tspFHD. Knowledge of cortical processing abnormalities across S1 and S2/PV in dystonia should be applied towards the development of learning-based sensorimotor interventions. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Dose-response study of N,N-dimethyltryptamine in humans. I. Neuroendocrine, autonomic, and cardiovascular effects.

PubMed

Strassman, R J; Qualls, C R

1994-02-01

To begin applying basic neuropharmacological hypotheses of hallucinogenic drug actions to humans, we generated dose-response data for intravenously administered dimethyltryptamine fumarate's (DMT) neuroendocrine, cardiovascular, autonomic, and subjective effects in a group of experienced hallucinogen users. Dimethyltryptamine, an endogenous mammalian hallucinogen and drug of abuse, was administered intravenously at 0.05, 0.1, 0.2, and 0.4 mg/kg to 11 experienced hallucinogen users, in a double-blind, saline placebo-controlled, randomized design. Treatments were separated by at least 1 week. Peak DMT blood levels and subjective effects were seen within 2 minutes after drug administration, and were negligible at 30 minutes. Dimethyltryptamine dose dependently elevated blood pressure, heart rate, pupil diameter, and rectal temperature, in addition to elevating blood concentrations of beta-endorphin, corticotropin, cortisol, and prolactin. Growth hormone blood levels rose equally in response to all doses of DMT, and melatonin levels were unaffected. Threshold doses for significant effects relative to placebo were also hallucinogenic (0.2 mg/kg and higher). Subjects with five or more exposures to 3,4-methylenedioxymethamphetamine demonstrated less robust pupil diameter effects than those with two or fewer exposures. Dimethyltryptamine can be administered safely to experienced hallucinogen users and dose-response data generated for several measures hypothesized under serotonergic modulatory control. Additional studies characterizing the specific mechanisms mediating DMT's biological effects may prove useful in psychopharmacological investigations of drug-induced and endogenous alterations in brain function.

Mental Fatigue and Physical and Cognitive Performance During a 2-Bout Exercise Test.

PubMed

Vrijkotte, Susan; Meeusen, Romain; Vandervaeren, Cloe; Buyse, Luk; Cutsem, Jeroen van; Pattyn, Nathalie; Roelands, Bart

2018-04-01

The 2-bout exercise protocol has been developed to diagnose nonfunctional overreaching and the "overtraining syndrome." It consists of 2 maximal exercise bouts separated by 4 hours. Mental fatigue negatively influences performance, but the effects of its occurrence during the 2-bout exercise protocol have never been investigated. The aim of this study was to examine whether mental fatigue (induced during the rest period) influences physical and cognitive performance during/after the second exercise bout of the 2-bout exercise protocol. Nine healthy, well-trained male cyclists participated in a single-blind, randomized, placebo-controlled crossover study. The intervention consisted of either 1.5-hour rest (control) or performing a computer-based Stroop task to induce mental fatigue. Cognitive (Eriksen Flanker task), physiological (lactate, maximum heart rate, and maximum wattage), and subjective data (mental fatigue-visual analog scale, Profile of Mood States, and rating of perceived exertion) were gathered. Ratings of fatigue, tension, and mental fatigue were affected in the mental fatigue condition (P < .05). Neither physiological nor cognitive differences were found between conditions. Ratings of mental fatigue were already affected after the first maximum exercise test (P < .05). Neither physical nor cognitive performance was affected by mental fatigue, but subjective ratings did reveal significant differences. It is recommended to exclude mentally challenging tasks during the 2-bout exercise protocol rest period to ascertain unaffected subjective test results. This study should be repeated in athletes diagnosed with nonfunctional overreaching/overtraining syndrome.

Attention-deficit/hyperactivity disorder (ADHD) and motor timing in adolescents and their parents: familial characteristics of reaction time variability vary with age.

PubMed

Thissen, Andrieke J A M; Luman, Marjolein; Hartman, Catharina; Hoekstra, Pieter; van Lieshout, Marloes; Franke, Barbara; Oosterlaan, Jaap; Rommelse, Nanda N J; Buitelaar, Jan K

2014-09-01

There is consistent evidence that attention-deficit/hyperactivity disorder (ADHD) is strongly related to impaired motor timing as reflected in decreased accuracy and increased reaction time variability (RTV). It is not known whether motor timing impairments are present in adolescents and adults with ADHD and their unaffected relatives to the same extent as has been reported in children, and whether ADHD and motor timing share familial underpinnings, as reflected in parent-offspring co-segregation and sibling cross-correlations. A total of 589 parents and 808 children/adolescents from families with ADHD and control families (parent/offspring average age: 48.6/17.3 years) were included. All participants were thoroughly assessed for ADHD and performed a 40-trial motor timing task (1-second interval production). Dependent neurocognitive measures included RT median (RTM: representing accuracy), RTV and ex-Gaussian component τ (τ: representing infrequent long response times). Generalized estimating equations were used for analyses. Unaffected children from families with ADHD had RTV (but not RTM or τ) scores in between those of affected and control children. However, during middle-to-late adolescence, unaffected offspring were not impaired compared to control offspring and differed from ADHD probands, whereas during late adolescence/early adulthood, all offspring groups performed equally. Affected and unaffected parents of families with ADHD showed increased RTV compared to controls, regardless of age (not significant after adjusting for IQ). There were indications for shared familiality between RTV and ADHD as reflected by sibling cross-correlations and between RTM and ADHD as reflected by sibling cross-correlations and a maternal parent-offspring relation (parent-of-origin effect). RTV and its familial characteristics are influenced by development during adolescence. Increased RTV in children with ADHD appears to reflect immaturities in their neurocognitive functioning. Maternal ADHD effects might be involved in transmission of RTM (not RTV), but overall RTM showed less compelling (familial) relationships with ADHD than RTV. Copyright © 2014. Published by Elsevier Inc.

Altered inhibition-related frontolimbic connectivity in obsessive-compulsive disorder.

PubMed

van Velzen, Laura S; de Wit, Stella J; Ćurĉić-Blake, Branislava; Cath, Daniëlle C; de Vries, Froukje E; Veltman, Dick J; van der Werf, Ysbrand D; van den Heuvel, Odile A

2015-10-01

Recent studies have shown that response inhibition is impaired in patients with obsessive-compulsive disorder and their unaffected siblings, suggesting that these deficits may be considered a cognitive endophenotype of obsessive-compulsive disorder. Structural and functional neural correlates of altered response inhibition have been identified in patients and siblings. This study aims to examine the functional integrity of the response inhibition network in patients with obsessive-compulsive disorder and their unaffected siblings. Forty-one unmedicated patients with obsessive-compulsive disorder, 17 of their unaffected siblings and 37 healthy controls performed a stop signal task during functional magnetic resonance imaging. Psycho-physiological interaction analysis was used to examine functional connectivity between the following regions of interest: the bilateral inferior frontal gyri, presupplementary motor area, subthalamic nuclei, inferior parietal lobes, anterior cingulate cortex, and amygdala. We then used dynamic causal modeling to investigate the directionality of the networks involved. Patients, and to a lesser extent also their unaffected siblings, show altered connectivity between the inferior frontal gyrus and the amygdala during response inhibition. The follow-up dynamic causal modeling suggests a bottom-up influence of the amygdala on the inferior frontal gyrus in healthy controls, whereas processing occurs top-down in patients with obsessive-compulsive, and in both directions in siblings. Our findings suggest that amygdala activation in obsessive-compulsive disorder interferes differently with the task-related recruitment of the inhibition network, underscoring the role of limbic disturbances in cognitive dysfunctions in obsessive-compulsive disorder. © 2015 Wiley Periodicals, Inc.

Radiographic Measurements of the Affected and Unaffected Feet in Patients with Unilateral Hallux Limitus A Case-Control Pilot Study.

PubMed

Knox, Andrew F; Bryant, Alan R

2016-05-01

Controversy exists regarding the structural and functional causes of hallux limitus, including metatarsus primus elevatus, a long first metatarsal, first-ray hypermobility, the shape of the first metatarsal head, and the presence of hallux interphalangeus. Some articles have reported on the radiographic evaluation of these measurements in feet affected by hallux limitus, but no study has directly compared the affected and unaffected feet in patients with unilateral hallux limitus. This case-control pilot study aimed to establish whether any such differences exist. Dorsoplantar and lateral weightbearing radiographs of both feet in 30 patients with unilateral hallux limitus were assessed for grade of disease, lateral intermetatarsal angle, metatarsal protrusion distance, plantar gapping at the first metatarsocuneiform joint, metatarsal head shape, and hallux abductus interphalangeus angle. Data analysis was performed using a statistical software program. Mean radiographic measurements for affected and unaffected feet demonstrated that metatarsus primus elevatus, a short first metatarsal, first-ray hypermobility, a flat metatarsal head shape, and hallux interphalangeus were prevalent in both feet. There was no statistically significant difference between feet for any of the radiographic parameters measured (Mann-Whitney U tests, independent-samples t tests, and Pearson χ(2) tests: P > .05). No significant differences exist in the presence of the structural risk factors examined between affected and unaffected feet in patients with unilateral hallux limitus. The influence of other intrinsic factors, including footedness and family history, should be investigated further.

Mnemonic strategies in older people: a comparison of errorless and errorful learning.

PubMed

Kessels, Roy P C; de Haan, Edward H F

2003-09-01

To compare the efficacy of errorless and errorful learning on memory performance in older people and young adults. Face-name association learning was examined in 18 older people and 16 young controls. Subjects were either prompted to guess the correct name during the presentation of photographs of unknown faces (errorful learning) or were instructed to study the face without guessing (errorless learning). The correct name was given after the presentation of each face in both task conditions. Uncued testing followed immediately after the two study phases and after a 10-minute delay. Older subjects had an overall lower memory performance and flatter learning curves compared to the young adults, regardless of task conditions. Also, errorless learning resulted in a higher accuracy than errorful learning, to an equal amount in both groups. Older people have difficulty in the encoding stages of face-name association learning, whereas retrieval is relatively unaffected. In addition, the prevention of errors occurring during learning results in a better memory performance, and is perhaps an effective strategy for coping with age-related memory decrement.

Olfactory mechanisms in the control of maternal aggression, appetite, and fearfulness: effects of lesions to olfactory receptors, mediodorsal thalamic nucleus, and insular prefrontal cortex.

PubMed

Ferreira, A; Dahlöf, L G; Hansen, S

1987-10-01

During lactation the female rat is hyperphagic, aggressive toward adult conspecifics, and less fearful than usual. In the first experiment the importance of olfactory receptors was investigated by surgically removing the olfactory epithelium of the nasal cavity. Mother rats subjected to this treatment consumed significantly less food and weighed less than sham-operated females. Moreover, experimental subjects displayed a dramatic decrease in maternal aggression. Fear behavior (sound-elicited freezing), on the other hand, was not affected by the lesions. The mediodorsal thalamic nucleus and the prefrontal insular cortex form part of the central olfactory system. The second experiment assessed the involvement of this olfactory-related thalamocortical system and the behavioral profile of mother rats. It was found that whereas the thalamic and cortical lesions left food intake and fear behavior unaffected, they significantly decreased the frequency with which the mother would attack an intruder male placed into her home cage. The sense of smell appears, according to the present experiments, to play a crucial role in maternal aggression.

Hypothalamic-Pituitary-Adrenal Axis Dysfunction and Illness Progression in Bipolar Disorder

PubMed Central

Vasconcelos-Moreno, Mirela Paiva; Gubert, Carolina; dos Santos, Bárbara Tietböhl Martins Quadros; Sartori, Juliana; Eisele, Bárbara; Ferrari, Pamela; Fijtman, Adam; Rüegg, Joëlle; Gassen, Nils Christian; Kapczinski, Flávio; Rein, Theo; Kauer-Sant’Anna, Márcia

2015-01-01

Background: Impaired stress resilience and a dysfunctional hypothalamic-pituitary-adrenal (HPA) axis are suggested to play key roles in the pathophysiology of illness progression in bipolar disorder (BD), but the mechanisms leading to this dysfunction have never been elucidated. This study aimed to examine HPA axis activity and underlying molecular mechanisms in patients with BD and unaffected siblings of BD patients. Methods: Twenty-four euthymic patients with BD, 18 siblings of BD patients, and 26 healthy controls were recruited for this study. All subjects underwent a dexamethasone suppression test followed by analyses associated with the HPA axis and the glucocorticoid receptor (GR). Results: Patients with BD, particularly those at a late stage of illness, presented increased salivary post-dexamethasone cortisol levels when compared to controls (p = 0.015). Accordingly, these patients presented reduced ex vivo GR responsiveness (p = 0.008) and increased basal protein levels of FK506-binding protein 51 (FKBP51, p = 0.012), a co-chaperone known to desensitize GR, in peripheral blood mononuclear cells. Moreover, BD patients presented increased methylation at the FK506-binding protein 5 (FKBP5) gene. BD siblings presented significantly lower FKBP51 protein levels than BD patients, even though no differences were found in FKBP5 basal mRNA levels. Conclusions: Our data suggest that the epigenetic modulation of the FKBP5 gene, along with increased FKBP51 levels, is associated with the GR hyporesponsiveness seen in BD patients. Our findings are consistent with the notion that unaffected first-degree relatives of BD patients share biological factors that influence the disorder, and that such changes are more pronounced in the late stages of the illness. PMID:25522387

Plasticity in cortical motor upper-limb representation following stroke and rehabilitation: two longitudinal multi-joint FMRI case-studies.

PubMed

Stark, A; Meiner, Z; Lefkovitz, R; Levin, N

2012-04-01

Motor dysfunction and recovery following stroke and rehabilitation are associated with primary motor cortex plasticity. To better track these effects we studied two patients with sub-acute sub-cortical stroke causing hemiparesis, who underwent an effective behavioral treatment termed Constraint Induced Movement Therapy (CIMT). The therapy involves 2 weeks of intensive motor training of the hemiparetic limb coupled with immobilization of the unaffected limb. The study included a longitudinal series of clinical evaluations and fMRI scans, before and after the treatment. The fMRI task included wrist, elbow, or ankle movements. Activity in the M1 upper-limb region of control subjects was stable, strictly contralateral, and similar in amplitude for elbow and wrist movements. These findings reflect the well-known contralateral motor control and support the idea of overlapping representations of adjacent joints in M1. In both patients, pre-CIMT activation patterns in M1 were tested twice and did not change significantly, were contralateral, and included elbow-wrist differences. Following CIMT, the clinical condition of both patients improved and three fMRI-explored prototypes were found: First, cluster position remained constant; Second, ipsilateral activity appeared in the unaffected hemispheres during hemiparetic movements; Third, patient-specific elbow-wrist inter and intra hemispheric differences were modified. All effects were long-lasting. We suggest that overlapping representations of adjacent joints contributed to the cortical plasticity observed following CIMT. Our findings should be confirmed by studying larger groups of homogeneous patients. Nevertheless, this study introduces multi-joint imaging studies and shows that it is both possible and valuable to carry it out in stroke patients.

Correlation of Leukocyte Telomere Length Measurement Methods in Patients with Dyskeratosis Congenita and in Their Unaffected Relatives.

PubMed

Khincha, Payal P; Dagnall, Casey L; Hicks, Belynda; Jones, Kristine; Aviv, Abraham; Kimura, Masayuki; Katki, Hormuzd; Aubert, Geraldine; Giri, Neelam; Alter, Blanche P; Savage, Sharon A; Gadalla, Shahinaz M

2017-08-13

Several methods have been employed to measure telomere length (TL) in human studies. It has been difficult to directly compare the results from these studies because of differences in the laboratory techniques and output parameters. We compared TL measurements (TLMs) by the three most commonly used methods, quantitative polymerase chain reaction (qPCR), flow cytometry with fluorescence in situ hybridization (flow FISH) and Southern blot, in a cohort of patients with the telomere biology disorder dyskeratosis congenita (DC) and in their unaffected relatives (controls). We observed a strong correlation between the Southern blot average TL and the flow FISH total lymphocyte TL in both the DC patients and their unaffected relatives ( R ² of 0.68 and 0.73, respectively). The correlation between the qPCR average TL and that of the Southern blot method was modest ( R ² of 0.54 in DC patients and of 0.43 in unaffected relatives). Similar results were noted when comparing the qPCR average TL and the flow FISH total lymphocyte TL ( R ² of 0.49 in DC patients and of 0.42 in unaffected relatives). In conclusion, the strengths of the correlations between the three widely used TL assays (qPCR, flow FISH, and Southern blot) were significantly different. Careful consideration is warranted when selecting the method of TL measurement for research and for clinical studies.

Contribution of classical and emerging risk factors to coronary artery disease in Asian Indians.

PubMed

Shanker, Jayashree; Kakkar, Vijay V

2016-07-01

The merits and demerits of classical risk factors in coronary artery disease (CAD) are widely debated. We analyzed the role of conventional (age, gender, diabetes, hypertension, smoking) and non-conventional risk factors (anthropometrics, fasting blood sugar, atherogenic index of plasma - AIP, family history) in Asian Indians with CAD. Out of 11,164 subjects (4855 affected, 6309 unaffected) enrolled in the Indian Atherosclerosis Research Study (IARS), 269 unaffected individuals with abnormal electrocardiogram and seven underage were excluded. Around 10,888 subjects along with two subsets, including 9888 individuals having family history information and 1616 individuals with intermediate Framingham risk score (FRS), were statistically analyzed using SPSS version 17.0 and R software. A combination of classical risk factors showed good discrimination between affected and unaffected individuals (C>0.85). Hypertension (OR 3.79) or male gender (OR 5.31) showed significant association with CAD when lipids were included or excluded from the predictive model, followed by age, diabetes and smoking. Hypertension and diabetes frequencies were higher in older patients (>55years) while smoking was more prevalent in younger patients (<55years). Family history and AIP provided a modest increase in C index over the classical factors (0.864 to 0.873), with 7.1% net reclassification in the intermediate FRS group. In CAD patients, 4% were classified as high risk by FRS, 52% were classified as having metabolic syndrome with revised criteria and over 90% had a high AIP score. Addition of AIP and family history to conventional risk factors improved risk discrimination in Asian Indians with CAD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Dentoalveolar growth inhibition induced by bone denudation on palates: a study of two isolated cleft palates with asymmetric scar tissue distribution.

PubMed

Ishikawa, H; Iwasaki, H; Tsukada, H; Chu, S; Nakamura, S; Yamamoto, K

1999-09-01

This report presents two cases of isolated cleft palate with asymmetric distribution of postsurgical scar tissue determined by laser Doppler flowmetry. To determine the effect of mucoperiosteal denudation of the bone on maxillary alveolar growth, the analysis of dentoalveolar structures compared the affected side to the unaffected side of each case. Two Japanese girls with isolated cleft palates were examined. Both subjects had undergone pushback operations (a modified version of the procedure of Wardill) for palatal repair at 18 months of age. Palatal blood flow was examined by laser Doppler flowmetry when the girls were 12 years old to determine the extent of postsurgical scar tissue over the denuded bone. To analyze the maxillary dentoalveolar structures three dimensionally, the whole surface of the upper dental cast was measured and recorded by an optical measuring device when the girls were 7 years old. Analysis via flowmetry showed that the palatal scar tissue area was limited to the anterior tooth region on the right (unaffected) side but extended posteriorly to the premolar region on the left (affected) side in both subjects. The two girls had similar dentoalveolar structures, with the dental and alveolar arches deflected lingually at the deciduous molar area on the affected side. There were no differences in the buccolingual inclination of deciduous molars or in the vertical growth of the alveolar processes between the affected and unaffected sides. In both girls, bone denudation in the premolar region appeared to result in less than 3 mm of displacement of the teeth palatally, with no change in lingual inclination. Any effects of scar tissue on the vertical development of the alveolus were not substantiated.

Reburn severity in managed and unmanaged vegetation in a large wildfire

PubMed Central

Thompson, Jonathan R.; Spies, Thomas A.; Ganio, Lisa M.

2007-01-01

Debate over the influence of postwildfire management on future fire severity is occurring in the absence of empirical studies. We used satellite data, government agency records, and aerial photography to examine a forest landscape in southwest Oregon that burned in 1987 and then was subject, in part, to salvage-logging and conifer planting before it reburned during the 2002 Biscuit Fire. Areas that burned severely in 1987 tended to reburn at high severity in 2002, after controlling for the influence of several topographical and biophysical covariates. Areas unaffected by the initial fire tended to burn at the lowest severities in 2002. Areas that were salvage-logged and planted after the initial fire burned more severely than comparable unmanaged areas, suggesting that fuel conditions in conifer plantations can increase fire severity despite removal of large woody fuels. PMID:17563370

Olfactory granule cell development in normal and hyperthyroid rats.

PubMed

Brunjes, P C; Schwark, H D; Greenough, W T

1982-10-01

Dendritic development was examined in olfactory bulbs of both normal 7-, 14-, 21- and 60-day-old rats and littermates treated on postnatal days 1-4 with 1 microgram/g body weight of L-thyroxine sodium. Tissue was processed via the Golgi-Cox technique and subjected to quantitative analyses of mitral and internal layer granule cell development. These populations of granule cells were selected because their pattern of late proliferation suggested potentially greater susceptibility to postnatal hormonal alterations. Although neonatal hyperthyroidism induces widespread acceleration of maturation, including precocious chemosensitivity, granule cell development was unaffected relative to littermate controls. Both normal and hyperthyroid groups exhibited an inverted U-shaped pattern of cellular development, with rapid dendritic dendritic growth and expansion occurring during the earliest ages tested, but with loss of processes and dendritic field size occurring after day 21.

Personality, depression, and premorbid lifestyle in twin pairs discordant for Parkinson's disease

PubMed Central

Heberlein, I.; Ludin, H.; Scholz, J.; Vieregge, P.

1998-01-01

Present personality traits (Freiburg personality inventory, FPI-R), depression (von Zerssen's depression scale), and self assessed state of health were evaluated in 15 twin pairs (six monozygotic and nine dizygotic; mean age 62.5 years) discordant for idiopathic Parkinson's disease and in 17 unrelated healthy control subjects. The twins had additional questionnaire based interviews on premorbid lifestyle.
For disability, twins with Parkinson's disease scored lower on FPI-R than controls in "achievement orientation" and "extraversion", higher in "inhibitedness", "somatic complaints", and "emotionality". They scored higher for depression and for state of health than unaffected twins and controls. For zygosity, monozygotic twins scored lower than dizygotic twins in "achievement orientation", "aggressiveness", and "strain". Monozygotic twins had less "achievement orientation" and "extraversion" and more "somatic complaints" than controls. Monozygotic twins had a lower within pair difference than dizygotic twins in "social orientation". During premorbid times the affected twin with later Parkinson's disease was estimated to have been "less often the leader" in the twin pair.
Although small in sample size, this twin study indicates a genetic impact for some personality features beyond the Parkinson's disease motor syndrome.

 PMID:9489545

Management and outcomes of neonates with down syndrome admitted to neonatal units.

PubMed

Mann, Jake P; Statnikov, Eugene; Modi, Neena; Johnson, Nik; Springett, Anna; Morris, Joan K

2016-06-01

Neonates with Down syndrome have an increased risk of being admitted to a neonatal unit compared with unaffected neonates. We aimed to estimate the proportion of neonates with Down syndrome admitted to a neonatal unit and compare their management and outcomes with other neonatal admissions. Case-control study of neonates born from 2009 to 2011 admitted to 122 NHS Neonatal Units in England using data from the National Down Syndrome Cytogenetic Register and the National Neonatal Research Database. For each neonate with Down syndrome, three neonates admitted to the same unit in the same month and born at the same gestation were identified. Forty-six percent of neonates with Down syndrome were admitted to a neonatal unit. Boys were more likely to be admitted than girls (odds ratio = 1.7; 95% confidence interval, 1.4-2.0). Neonates with Down syndrome required more intensive or high dependency care compared with unaffected neonates (37% vs. 27%. p < 0.01) and stayed in neonatal units for longer (11 days vs. 5 days, p < 0.01). A total of 31% of neonates with Down syndrome required respiratory support compared with 22% (p < 0.001) of unaffected neonates, and 11% were discharged requiring oxygen supplementation compared with 3% (p < 0.001) of unaffected neonates. A total of 3% of neonates with Down syndrome died in a neonatal unit compared with 1% (p = 0.01) of unaffected neonates. Neonates with Down syndrome are more likely than unaffected neonates to be admitted to a neonatal unit, have a prolonged stay, and be discharged home on supplemental oxygen. Birth Defects Research (Part A) 106:468-474, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Neurocognitive responses to a single session of static squats with whole body vibration.

PubMed

Amonette, William E; Boyle, Mandy; Psarakis, Maria B; Barker, Jennifer; Dupler, Terry L; Ott, Summer D

2015-01-01

The purpose of this study was to determine if the head accelerations using a common whole body vibration (WBV) exercise protocol acutely reduced neurocognition in healthy subjects. Second, we investigated differential responses to WBV plates with 2 different delivery mechanisms: vertical and rotational vibrations. Twelve healthy subjects (N = 12) volunteered and completed a baseline (BASE) neurocognitive assessment: the Immediate Postconcussion Assessment and Cognitive Test (ImPACT). Subjects then participated in 3 randomized exercise sessions separated by no more than 2 weeks. The exercise sessions consisted of five 2-minute sets of static hip-width stance squats, with the knees positioned at a 45° angle of flexion. The squats were performed with no vibration (control [CON]), with a vertically vibrating plate (vertical vibration [VV]), and with a rotational vibrating plate (rotational vibration [RV]) set to 30 Hz with 4 mm of peak-to-peak displacement. The ImPACT assessments were completed immediately after each exercise session and the composite score for 5 cognitive domains was analyzed: verbal memory, visual memory, visual motor speed, reaction time, and impulse control. Verbal memory scores were unaffected by exercise with or without vibration (p = 0.40). Likewise, visual memory was not different (p = 0.14) after CON, VV, or RV. Significant differences were detected for visual motor speed (p = 0.006); VV was elevated compared with BASE (p = 0.01). There were no significant differences (p = 0.26) in reaction time or impulse control (p = 0.16) after exercise with or without vibration. In healthy individuals, 10 minutes of 30 Hz, 4-mm peak-to-peak displacement vibration exposure with a 45° angle of knee flexion did not negatively affect neurocognition.

Effects of an isocaloric healthy Nordic diet on ambulatory blood pressure in metabolic syndrome: a randomized SYSDIET sub-study.

PubMed

Brader, L; Uusitupa, M; Dragsted, L O; Hermansen, K

2014-01-01

Dietary pattern is central in the prevention of hypertension and blood pressure (BP)-related diseases. A diet based on healthy Nordic foods may have a favourable impact on BP. The objective was to clarify whether a Nordic alternative for a healthy food pattern would have beneficial effects on ambulatory BP in subjects with metabolic syndrome (MetS). In total, 37 subjects were randomized to either a healthy Nordic diet or a control diet. A healthy Nordic diet embraced whole grains, rapeseed oil, berries, fruits, vegetables, fish, nuts and low-fat dairy products of Nordic origin. The mean nutrient intake in the Nordic countries formed the control diet, embracing wheat products, dairy fat-based spread and a lower intake of fruits, vegetables and fish. Diets were isoenergetic. Ambulatory BP was monitored and 24-h urine was collected before and after 12 weeks of intervention. After 12 weeks, ambulatory diastolic BP (-4.4 mm Hg; P=0.001) and mean arterial pressure (-4.2 mm Hg; P=0.006) were lowered by the healthy Nordic diet compared with the control diet, whereas changes in ambulatory systolic BP did not differ significantly between diets (-3.5 mm Hg; P=0.122). Heart rate tended to be lower in those on the healthy Nordic diet (P=0.057). Urinary sodium and potassium excretions were unaffected by diets and consequently not associated with the healthy Nordic diet-induced lowering of BP. Consumption of Nordic varieties of health-enhancing foods for 12 weeks decreased diastolic ambulatory BP and mean arterial pressure in subjects with features of MetS during weight-stable condition, suggesting beneficial effects of a healthy Nordic dietary pattern on ambulatory BP.

Defects of filaggrin-like proteins in both lesional and nonlesional atopic skin.

PubMed

Pellerin, Laurence; Henry, Julie; Hsu, Chiung-Yueh; Balica, Stéfana; Jean-Decoster, Catherine; Méchin, Marie-Claire; Hansmann, Britta; Rodriguez, Elke; Weindinger, Stefan; Schmitt, Anne-Marie; Serre, Guy; Paul, Carle; Simon, Michel

2013-04-01

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by a disturbed epidermal barrier. In a subset of patients, this is explained by nonsense mutations in the gene encoding filaggrin (FLG). We sought to evaluate the respective role of FLG mutations and proinflammatory cytokines and to assess the expression of FLG, hornerin (HRNR), and FLG2, 2 FLG-like proteins, which are involved in epidermal barrier functions, in normal skin and both lesional and nonlesional skin of patients with AD. An FLG-genotyped cohort of 73 adults with AD and 73 aged-matched control subjects was analyzed by using immunohistochemistry and immunoblotting. Normal primary human keratinocytes were differentiated in either the absence or presence of IL-4, IL-13, and IL-25. Compared with control subjects, FLG, HRNR, and FLG2 were detected at significantly lower levels in the skin of patients with AD, irrespective of their FLG genotype. The reduction was greater in lesional compared with nonlesional skin. In addition, the proFLG/FLG ratio was found to be higher in the skin of wild-type patients than in control subjects. Cytokine treatment of keratinocytes induced a dramatic reduction in FLG, FLG2, and HRNR expression both at the mRNA and protein levels. The stratum corneum of lesional but also clinically unaffected skin of adults with AD is abnormal, with reduced expression of FLG and FLG-like proteins. In addition to nonsense mutations, proinflammatory cytokines and some defects in the proFLG processing can contribute to the FLG downregulation. Our study suggests that skin inflammation reduces the expression of FLG-like proteins, contributing to the AD-related epidermal barrier dysfunction. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Autism-associated gene expression in peripheral leucocytes commonly observed between subjects with autism and healthy women having autistic children.

PubMed

Kuwano, Yuki; Kamio, Yoko; Kawai, Tomoko; Katsuura, Sakurako; Inada, Naoko; Takaki, Akiko; Rokutan, Kazuhito

2011-01-01

Autism spectrum disorder (ASD) is a severe neuropsychiatric disorder which has complex pathobiology with profound influences of genetic factors in its development. Although the numerous autism susceptible genes were identified, the etiology of autism is not fully explained. Using DNA microarray, we examined gene expression profiling in peripheral blood from 21 individuals in each of the four groups; young adults with ASD, age- and gender-matched healthy subjects (ASD control), healthy mothers having children with ASD (asdMO), and asdMO control. There was no blood relationship between ASD and asdMO. Comparing the ASD group with control, 19 genes were found to be significantly changed. These genes were mainly involved in cell morphology, cellular assembly and organization, and nerve system development and function. In addition, the asdMO group possessed a unique gene expression signature shown as significant alterations of protein synthesis despite of their nonautistic diagnostic status. Moreover, an ASD-associated gene expression signature was commonly observed in both individuals with ASD and asdMO. This unique gene expression profiling detected in peripheral leukocytes from affected subjects with ASD and unaffected mothers having ASD children suggest that a genetic predisposition to ASD may be detectable even in peripheral cells. Altered expression of several autism candidate genes such as FMR-1 and MECP2, could be detected in leukocytes. Taken together, these findings suggest that the ASD-associated genes identified in leukocytes are informative to explore the genetic, epigenetic, and environmental background of ASD and might become potential tools to assess the crucial factors related to the clinical onset of the disorder.

CHST6 mutations in North American subjects with macular corneal dystrophy: a comprehensive molecular genetic review.

PubMed

Klintworth, Gordon K; Smith, Clayton F; Bowling, Brandy L

2006-03-10

To evaluate mutations in the carbohydrate sulfotransferase-6 (CHST6) gene in American subjects with macular corneal dystrophy (MCD). We analyzed CHST6 in 57 patients from 31 families with MCD from the United States, 57 carriers (parents or children), and 27 unaffected blood relatives of affected subjects. We compared the observed nucleotide sequences with those found by numerous investigators in other populations with MCD and in controls. In 24 families, the corneal disorder could be explained by mutations in the coding region of CHST6 or in the region upstream of this gene in both the maternal and paternal chromosome. In most instances of MCD a homozygous or heterozygous missense mutation in exon 3 of CHST6 was found. Six cases resulted from a deletion upstream of CHST6. Nucleotide changes within the coding region of CHST6 are predicted to alter the encoded protein significantly within evolutionary conserved parts of the encoded sulfotransferase. Our findings support the hypothesis that CHST6 mutations are cardinal to the pathogenesis of MCD. Moreover, the observation that some cases of MCD cannot be explained by mutations in CHST6 suggests that MCD may result from other subtle changes in CHST6 or from genetic heterogeneity.

Physiogenomic Analysis of Localized fMRI Brain Activity in Schizophrenia

PubMed Central

Windemuth, Andreas; Calhoun, Vince D.; Pearlson, Godfrey D.; Kocherla, Mohan; Jagannathan, Kanchana; Ruaño, Gualberto

2009-01-01

The search for genetic factors associated with disease is complicated by the complexity of the biological pathways linking genotype and phenotype. This analytical complexity is particularly concerning in diseases historically lacking reliable diagnostic biological markers, such as schizophrenia and other mental disorders. We investigate the use of functional magnetic resonance imaging (fMRI) as an intermediate phenotype (endophenotype) to identify physiogenomic associations to schizophrenia. We screened 99 subjects, 30 subjects diagnosed with schizophrenia, 13 unaffected relatives of schizophrenia patients, and 56 unrelated controls, for gene polymorphisms associated with fMRI activation patterns at two locations in temporal and frontal lobes previously implied in schizophrenia. A total of 22 single nucleotide polymorphisms (SNPs) in 15 genes from the dopamine and serotonin neurotransmission pathways were genotyped in all subjects. We identified three SNPs in genes that are significantly associated with fMRI activity. SNPs of the dopamine beta-hydroxylase (DBH) gene and of the dopamine receptor D4 (DRD4) were associated with activity in the temporal and frontal lobes, respectively. One SNP of serotonin-3A receptor (HTR3A) was associated with temporal lobe activity. The results of this study support the physiogenomic analysis of neuroimaging data to discover associations between genotype and disease-related phenotypes. PMID:18330705

Impact of allergic rhinitis and its treatment on the pharmacokinetics of nasally administered fentanyl.

PubMed

Perelman, Michael; Fisher, Anthony N; Smith, Alan; Knight, Alastair

2013-05-01

Fentanyl pectin nasal spray (FPNS, Lazanda® in the US and PecFent® in Europe and Australia) is a novel analgesic approved for the management of breakthrough pain in cancer patients. Given that the fentanyl is nasally administered, it is important to understand whether concomitant allergic rhinitis, or its treatment with a vasoconstrictor, would affect its absorption and, potentially, its efficacy or safety. Subjects with a history of allergic rhinitis were screened to identify subjects who developed at least moderate rhinitis symptoms on exposure to pollen allergen (either ragweed or tree) in an environmental exposure chamber (EEC). These were entered into a randomized, three-way crossover study in which each subject received 100 μg of FPNS under three exposure conditions; Control (no rhinitis), Rhinitis (symptomatic without decongestant), Treated (symptomatic with concomitant oxymetazoline). Blood samples for fentanyl were collected over a 24-hour period. A total of 132 subjects was screened to identify 54 for inclusion in the study; 31 were evaluable for pharmacokinetics. Measures of fentanyl absorption (mean or median) were similar between Control and Rhinitis conditions: Cmax 453.0 vs. 467.8 pg/ml; AUCt 1,292.3 vs. 1,325.4 pg×h/ml, AUC0-∞ 1,430.6 vs. 1,387 pg×h/ml and tmax 20 vs. 17 minutes. When oxymetazoline was co-administered, overall fentanyl absorption was slightly reduced (AUC0-∞ 1,362.4 pg×h/ml); but, more clinically relevant were the delayed rate of absorption (tmax 53 minutes) and reduced Cmax (235.3 pg/ml). Patients treated with FPNS will be unaffected by the development of allergic rhinitis; but, if oxymetazoline is prescribed, the patient would benefit from added supervision when oxymetazoline is started and stopped.

Mother-Child Relationship in Youths with Attention-Deficit Hyperactivity Disorder and their Siblings.

PubMed

Chang, Jane Pei-Chen; Gau, Susan Shur-Fen

2017-07-01

Despite impaired mother-child interactions noted in youth with attention-deficit/hyperactivity disorder (ADHD), there is no such information for their siblings. This study aimed to test whether the affected and unaffected siblings, like youth with ADHD, also encountered impaired mothering and mother-child relationships as compared to typically developing youth (TD). The sample consisted of 122 probands (107 males, 87.7 %), aged 10-16, with DSM-IV ADHD, 44 affected (26 males, 59.1 %) and 78 unaffected (28 males, 35.9 %) siblings, and 122 TD youth. Both participants and their mothers received psychiatric interviews (K-SADS-E) about the participants and reported maternal parenting style, mother-child interactions and child behavioral problems at home. Based on both reports, probands with ADHD and affected siblings (only youth report) had more impaired relationships, more behavioral problems at home, and less perceived family support than unaffected siblings and TD youth. Probands with ADHD had higher maternal authoritarian control than unaffected siblings. The findings suggest that impaired mothering, mother-child interactions, and family support are related to the presence of ADHD diagnosis in both probands and their affected siblings.

Co-localisation of abnormal brain structure and function in specific language impairment

PubMed Central

Badcock, Nicholas A.; Bishop, Dorothy V.M.; Hardiman, Mervyn J.; Barry, Johanna G.; Watkins, Kate E.

2012-01-01

We assessed the relationship between brain structure and function in 10 individuals with specific language impairment (SLI), compared to six unaffected siblings, and 16 unrelated control participants with typical language. Voxel-based morphometry indicated that grey matter in the SLI group, relative to controls, was increased in the left inferior frontal cortex and decreased in the right caudate nucleus and superior temporal cortex bilaterally. The unaffected siblings also showed reduced grey matter in the caudate nucleus relative to controls. In an auditory covert naming task, the SLI group showed reduced activation in the left inferior frontal cortex, right putamen, and in the superior temporal cortex bilaterally. Despite spatially coincident structural and functional abnormalities in frontal and temporal areas, the relationships between structure and function in these regions were different. These findings suggest multiple structural and functional abnormalities in SLI that are differently associated with receptive and expressive language processing. PMID:22137677

Generation-V dual-Purkinje-image eyetracker

NASA Technical Reports Server (NTRS)

Crane, H. D.; Steele, C. M.

1985-01-01

Major advances characterize the Generation-V dual-Purkinje-image eyetracker compared with the Generation-III version previously described. These advances include a large reduction in size, major improvements in frequency response and noise level, automatic alignment to a subject, and automatic adjustment for different separation between the visual and optic axes, which can vary considerably from subject to subject. In a number of applications described in the paper, the eyetracker is coupled with other highly specialized optical devices. These applications include accurately stabilizing an image on a subject's retina; accurately simulating a visually dead retinal region (i.e., a scotoma) of arbitrary shape, size, and position; and, for clinical purposes, stabilizing the position of a laser coagulator beam on a patient's retina so that the point of contact is unaffected by the patient's own eye movements.

Thought Disorder in Schizophrenia and Bipolar Disorder Probands, Their Relatives, and Nonpsychiatric Controls

PubMed Central

Coleman, Michael J.; Ulgen, Ayse; Boling, Lenore; Cole, Jonathan O.; Johnson, Frederick V.; Lerbinger, Jan; Bodkin, J. Alexander; Holzman, Philip S.; Levy, Deborah L.

2017-01-01

Abstract Thought disorder (TD) has long been associated with schizophrenia (SZ) and is now widely recognized as a symptom of mania and other psychotic disorders as well. Previous studies have suggested that the TD found in the clinically unaffected relatives of SZ, schizoaffective and bipolar probands is qualitatively similar to that found in the probands themselves. Here, we examine which quantitative measures of TD optimize the distinction between patients with diagnoses of SZ and bipolar disorder with psychotic features (BP) from nonpsychiatric controls (NC) and from each other. In addition, we investigate whether these same TD measures also distinguish their respective clinically unaffected relatives (RelSZ, RelBP) from controls as well as from each other. We find that deviant verbalizations are significantly associated with SZ and are co-familial in clinically unaffected RelSZ, but are dissociated from, and are not co-familial for, BP disorder. In contrast, combinatory thinking was nonspecifically associated with psychosis, but did not aggregate in either group of relatives. These results provide further support for the usefulness of TD for identifying potential non-penetrant carriers of SZ-risk genes, in turn enhancing the power of genetic analyses. These findings also suggest that further refinement of the TD phenotype may be needed in order to be suitable for use in genetic studies of bipolar disorder. PMID:28338967

Cryohemolysis, erythrocyte osmotic fragility, and supplementary hematimetric indices in the diagnosis of hereditary spherocytosis

PubMed Central

Emilse, Ledesma Achem Miryam; Cecilia, Haro; María, Terán Magdalena; Eugenia, Mónaco María; Alicia, Issé Blanca

2018-01-01

Background Hereditary spherocytosis (HS) is a chronic hemolytic anemia characterized by microspherocytes in the peripheral blood and increased erythrocyte osmotic fragility (EOF). This study evaluated the cryohemolysis test (CHT); initial hemolysis (IH); immediate and incubated hemolysis percentage in 5.5 g/L NaCl (H5.5); mean corpuscular hemoglobin concentration (MCHC); red blood cell distribution width (RDW); and Hb/MCHC, Hb/RDW, and MCHC/RDW ratios for the diagnosis of HS. Methods Data from 13 patients with HS were evaluated at the Instituto de Bioquímica Aplicada and compared with data from 14 unaffected individuals and 11 patients with anemia due to another etiology. Total blood and reticulocyte counts, CHT, and immediate and incubated EOF were performed in all subjects; sensitivity, specificity, efficiency, and Youden index (YI) were calculated. Results Eight patients with HS had MCHC ≥345 g/L, 10 had RDW ≥14.5%, 12 had IH >5.0 g/L, 11 had immediate H5.5 ≥5%, and 13 had incubated H5.5 ≥50% (the cut-off value to consider HS). The efficiency and YI were: immediate H5.5 (0.94–0.85), incubated H5.5 (0.89–0.82), IH (0.89–0.78), MCHC (0.87–0.62), CHT (0.84–0.54), and Hb/MCHC (0.71–0.56), respectively. The calculated ratios could distinguish subjects with HS from unaffected individuals (P<0.05), but not those with anemia of another etiology (P>0.05). Conclusion Although the CHT and supplementary hematimetric indexes were useful to differentiate individuals with SH from healthy controls, they cannot distinguish from anemias of other etiology. CHT and MCHC, in addition to EOF, are recommended for diagnosing HS patients because of their low cost and efficiency. PMID:29662857

Electrodermal Recording and fMRI to Inform Sensorimotor Recovery in Stroke Patients

PubMed Central

MacIntosh, Bradley J.; McIlroy, William E.; Mraz, Richard; Staines, W. Richard; Black, Sandra E.; Graham, Simon J.

2016-01-01

Background Functional magnetic resonance imaging (fMRI) appears to be useful for investigating motor recovery after stroke. Some of the potential confounders of brain activation studies, however, could be mitigated through complementary physiological monitoring. Objective To investigate a sensorimotor fMRI battery that included simultaneous measurement of electrodermal activity in subjects with hemiparetic stroke to provide a measure related to the sense of effort during motor performance. Methods Bilateral hand and ankle tasks were performed by 6 patients with stroke (2 subacute, 4 chronic) during imaging with blood oxygen level-dependent (BOLD) fMRI using an event-related design. BOLD percent changes, peak activation, and laterality index values were calculated in the sensorimotor cortex. Electrodermal recordings were made concurrently and used as a regressor. Results Sensorimotor BOLD time series and percent change values provided evidence of an intact motor network in each of these well-recovered patients. During tasks involving the hemiparetic limb, electrodermal activity changes were variable in amplitude, and electrodermal activity time-series data showed significant correlations with fMRI in 3 of 6 patients. No such correlations were observed for control tasks involving the unaffected lower limb. Conclusions Electrodermal activity activation maps implicated the contralesional over the ipsilesional hemisphere, supporting the notion that stroke patients may require higher order motor processing to perform simple tasks. Electrodermal activity recordings may be useful as a physiological marker of differences in effort required during movements of a subject’s hemiparetic compared with the unaffected limb during fMRI studies. PMID:18784267

Suspected adverse reactions to oral administration of a praziquantel-pyrantel combination in captive cheetahs (Acinonyx jubatus).

PubMed

Whitehouse-Tedd, Katherine M; Smith, Liesl; Budd, Jane A; Lloyd, Christopher G

2017-11-15

OBJECTIVE To characterize adverse reactions to oral administration of a combination of praziquantel and pyrantel embonate or pyrantel pamoate, with or without oxantel embonate, in captive cheetahs (Acinonyx jubatus). DESIGN Retrospective case series and case-control study. ANIMALS 16 captive cheetahs with signs of adverse reaction to oral administration of praziquantel and pyrantel, with or without oxantel embonate (affected group), and 27 cheetahs without such reactions (unaffected group), all from 3 independent facilities. PROCEDURES Medical records and postmortem findings for affected cheetahs were reviewed and compared with those of unaffected animals. Anthelmintic doses administered, age, and sex of cheetahs were compared between groups. RESULTS 3 reactions in affected cheetahs were fatal, whereas the remainder ranged from mild to severe. Postmortem examination failed to reveal any disease processes or conditions to explain the deaths. No differences in anthelmintic dose were identified between affected and unaffected cheetahs for all facilities combined, and no correlation existed between dose and reaction severity. No association with sex was detected, but affected cheetahs were significantly younger than unaffected cheetahs. This difference was not significant after controlling for facility. CONCLUSIONS AND CLINICAL RELEVANCE Cheetahs were concluded to have had an adverse reaction to the praziquantel-pyrantel combination because of temporal proximity of onset of clinical signs to dose administration, similarity of signs to those reported for toxicosis in other species for these drugs, and a lack of other disease process or environmental explanatory factors. A highly cautious approach to the use of this drug combination is recommended for cheetahs.

Transcriptional profiling in facioscapulohumeral muscular dystrophy to identify candidate biomarkers

PubMed Central

Rahimov, Fedik; King, Oliver D.; Leung, Doris G.; Bibat, Genila M.; Emerson, Charles P.; Kunkel, Louis M.; Wagner, Kathryn R.

2012-01-01

Facioscapulohumeral muscular dystrophy (FSHD) is a progressive neuromuscular disorder caused by contractions of repetitive elements within the macrosatellite D4Z4 on chromosome 4q35. The pathophysiology of FSHD is unknown and, as a result, there is currently no effective treatment available for this disease. To better understand the pathophysiology of FSHD and develop mRNA-based biomarkers of affected muscles, we compared global analysis of gene expression in two distinct muscles obtained from a large number of FSHD subjects and their unaffected first-degree relatives. Gene expression in two muscle types was analyzed using GeneChip Gene 1.0 ST arrays: biceps, which typically shows an early and severe disease involvement; and deltoid, which is relatively uninvolved. For both muscle types, the expression differences were mild: using relaxed cutoffs for differential expression (fold change ≥1.2; nominal P value <0.01), we identified 191 and 110 genes differentially expressed between affected and control samples of biceps and deltoid muscle tissues, respectively, with 29 genes in common. Controlling for a false-discovery rate of <0.25 reduced the number of differentially expressed genes in biceps to 188 and in deltoid to 7. Expression levels of 15 genes altered in this study were used as a “molecular signature” in a validation study of an additional 26 subjects and predicted them as FSHD or control with 90% accuracy based on biceps and 80% accuracy based on deltoids. PMID:22988124

Thermal QST Phenotypes Associated with Response to Lumbar Epidural Steroid Injections: A Pilot Study.

PubMed

Maher, Dermot P; Ding, Weihua; Singh, Sarabdeep; Opalacz, Arissa; Fishman, Claire; Houghton, Mary; Ahmed, Shihab; Chen, Lucy; Mao, Jianren; Zhang, Yi

2017-08-01

Response to lumbar epidural steroid injection in lumbar radicular pain varies. The purpose of this study is to characterize the changes in quantitative sensory testing (QST) phenotypes of subjects and compare the QST characteristics in patients who do respond to treatment of radicular pain with a lumbar epidural steroid injection (ESI). Prospective, observational pilot study. Outpatient pain center. Twenty subjects with a lower extremity (LE) radicular pain who were scheduled to have an ESI were recruited. At the visit prior to and four weeks following an ESI, subjects underwent QST measurements of both the affected LE and the contralateral unaffected UE. Following an ESI, nine subjects reported a greater than 30% reduction in radicular pain and 11 reported a less than 30% reduction in radicular pain. Subjects who had less than 30% pain reduction response (nonresponders) to an ESI had increased pre-injection warm sensation threshold (37.30 °C, SD = 2.51 vs 40.39, SD = 3.36, P = 0.03) and heat pain threshold (47.22 °C, SD = 1.38, vs 48.83 °C, SD = 2.10, P = 0.04). Further, the nonresponders also showed increased pre-injection warm sensation threshold as measured in the difference of warm sensation detection threshold difference in the affected limb and the unaffected arm (2.68 °C, SD = 2.92 vs 5.67 °C, SD = 3.22, P  = 0.045). Other QST parameters were not affected. The results show that the nonresponders to ESIs have increased detection threshold to heat pain and warm sensation, suggesting that a preexisting dysfunction in the C fibers in this group of subjects who can be detected by QST. Such altered QST characteristics may prognosticate the response to ESIs. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Multisensory temporal function and EEG complexity in patients with epilepsy and psychogenic nonepileptic events.

PubMed

Noel, Jean-Paul; Kurela, LeAnne; Baum, Sarah H; Yu, Hong; Neimat, Joseph S; Gallagher, Martin J; Wallace, Mark

2017-05-01

Cognitive and perceptual comorbidities frequently accompany epilepsy and psychogenic nonepileptic events (PNEE). However, and despite the fact that perceptual function is built upon a multisensory foundation, little knowledge exists concerning multisensory function in these populations. Here, we characterized facets of multisensory processing abilities in patients with epilepsy and PNEE, and probed the relationship between individual resting-state EEG complexity and these psychophysical measures in each patient. We prospectively studied a cohort of patients with epilepsy (N=18) and PNEE (N=20) patients who were admitted to Vanderbilt's Epilepsy Monitoring Unit (EMU) and weaned off of anticonvulsant drugs. Unaffected age-matched persons staying with the patients in the EMU (N=15) were also recruited as controls. All participants performed two tests of multisensory function: an audio-visual simultaneity judgment and an audio-visual redundant target task. Further, in the cohort of patients with epilepsy and PNEE we quantified resting state EEG gamma power and complexity. Compared with both patients with epilepsy and control subjects, patients with PNEE exhibited significantly poorer acuity in audiovisual temporal function as evidenced in significantly larger temporal binding windows (i.e., they perceived larger stimulus asynchronies as being presented simultaneously). These differences appeared to be specific for temporal function, as there was no difference among the three groups in a non-temporally based measure of multisensory function - the redundant target task. Further, patients with PNEE exhibited more complex resting state EEG patterns as compared to their patients with epilepsy, and EEG complexity correlated with multisensory temporal performance on a subject-by-subject manner. Taken together, findings seem to indicate that patients with PNEE bind information from audition and vision over larger temporal intervals when compared with control subjects as well as patients with epilepsy. This difference in multisensory function appears to be specific to the temporal domain, and may be a contributing factor to the behavioral and perceptual alterations seen in this population. Published by Elsevier Inc.

A startling acoustic stimulus facilitates voluntary lower extremity movements and automatic postural responses in people with chronic stroke.

PubMed

Coppens, Milou J M; Roelofs, Jolanda M B; Donkers, Nicole A J; Nonnekes, Jorik; Geurts, Alexander C H; Weerdesteyn, Vivian

2018-05-14

A startling acoustic stimulus (SAS) involuntary releases prepared movements at accelerated latencies, known as the StartReact effect. Previous work has demonstrated intact StartReact in paretic upper extremity movements in people after stroke, suggesting preserved motor preparation. The question remains whether motor preparation of lower extremity movements is also unaffected after stroke. Here, we investigated StartReact effects on ballistic lower extremity movements and on automatic postural responses (APRs) following perturbations to standing balance. These APRs are particularly interesting as they are critical to prevent a fall following balance perturbations, but show substantial delays and poor muscle coordination after stroke. Twelve chronic stroke patients and 12 healthy controls performed voluntary ankle dorsiflexion movements in response to a visual stimulus, and responded to backward balance perturbations evoking APRs. Twenty-five percent of all trials contained a SAS (120 dB) simultaneously with the visual stimulus or balance perturbation. As expected, in the absence of a SAS muscle and movement onset latencies at the paretic side were delayed compared to the non-paretic leg and to controls. The SAS accelerated ankle dorsiflexion onsets in both the legs of the stroke subjects and in controls. Following perturbations, the SAS accelerated bilateral APR onsets not only in controls, but for the first time, we also demonstrated this effect in people after stroke. Moreover, APR inter- and intra-limb muscle coordination was rather weak in our stroke subjects, but substantially improved when the SAS was applied. These findings show preserved movement preparation, suggesting that there is residual (subcortical) capacity for motor recovery.

Metacognitive effects of initial question difficulty on subsequent memory performance.

PubMed

Pansky, Ainat; Goldsmith, Morris

2014-10-01

In two experiments, we examined whether relative retrieval fluency (the relative ease or difficulty of answering questions from memory) would be translated, via metacognitive monitoring and control processes, into an overt effect on the controlled behavior-that is, the decision whether to answer a question or abstain. Before answering a target set of multiple-choice general-knowledge questions (intermediate-difficulty questions in Exp. 1, deceptive questions in Exp. 2), the participants first answered either a set of difficult questions or a set of easy questions. For each question, they provided a forced-report answer, followed by a subjective assessment of the likelihood that their answer was correct (confidence) and by a free-report control decision-whether or not to report the answer for a potential monetary bonus (or penalty). The participants' ability to answer the target questions (forced-report proportion correct) was unaffected by the initial question difficulty. However, a predicted metacognitive contrast effect was observed: When the target questions were preceded by a set of difficult rather than easy questions, the participants were more confident in their answers to the target questions, and hence were more likely to report them, thus increasing the quantity of freely reported correct information. The option of free report was more beneficial after initial question difficulty than after initial question ease, in terms of both the gain in accuracy (Exp. 2) and a smaller cost in quantity (Exps. 1 and 2). These results demonstrate that changes in subjective experience can influence metacognitive monitoring and control, thereby affecting free-report memory performance independently of forced-report performance.

Altered Intrinsic Functional Brain Architecture in Children at Familial Risk of Major Depression.

PubMed

Chai, Xiaoqian J; Hirshfeld-Becker, Dina; Biederman, Joseph; Uchida, Mai; Doehrmann, Oliver; Leonard, Julia A; Salvatore, John; Kenworthy, Tara; Brown, Ariel; Kagan, Elana; de Los Angeles, Carlo; Gabrieli, John D E; Whitfield-Gabrieli, Susan

2016-12-01

Neuroimaging studies of patients with major depression have revealed abnormal intrinsic functional connectivity measured during the resting state in multiple distributed networks. However, it is unclear whether these findings reflect the state of major depression or reflect trait neurobiological underpinnings of risk for major depression. We compared resting-state functional connectivity, measured with functional magnetic resonance imaging, between unaffected children of parents who had documented histories of major depression (at-risk, n = 27; 8-14 years of age) and age-matched children of parents with no lifetime history of depression (control subjects, n = 16). At-risk children exhibited hyperconnectivity between the default mode network and subgenual anterior cingulate cortex/orbital frontal cortex, and the magnitude of connectivity positively correlated with individual symptom scores. At-risk children also exhibited 1) hypoconnectivity within the cognitive control network, which also lacked the typical anticorrelation with the default mode network; 2) hypoconnectivity between left dorsolateral prefrontal cortex and subgenual anterior cingulate cortex; and 3) hyperconnectivity between the right amygdala and right inferior frontal gyrus, a key region for top-down modulation of emotion. Classification between at-risk children and control subjects based on resting-state connectivity yielded high accuracy with high sensitivity and specificity that was superior to clinical rating scales. Children at familial risk for depression exhibited atypical functional connectivity in the default mode, cognitive control, and affective networks. Such task-independent functional brain measures of risk for depression in children could be used to promote early intervention to reduce the likelihood of developing depression. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

A novel missense mutation of NDP in a Chinese family with X-linked familial exudative vitreoretinopathy.

PubMed

Liu, Hong Yan; Huang, Jia; Wang, Rui Li; Wang, Yue; Guo, Liang Jie; Li, Tao; Wu, Dong; Wang, Hong Dan; Guo, Qian Nan; Dong, Dao Quan

2016-11-01

Familial exudative vitreoretinopathy (FEVR) is a hereditary ocular disorder characterized by a failure of peripheral retinal vascularization. In this report, we describe a novel missense mutation of the Norrie disease gene (NDP) in a Chinese family with X-linked FEVR. Ophthalmologic evaluation was performed on four male patients and seven unaffected individuals after informed consent was obtained. Venous blood was collected from the 11 members of this family, and genomic DNA was extracted using standard methods. The coding exons 2 and 3 and their corresponding exon-intron junctions of NDP were amplified by polymerase chain reaction and then subjected to direct DNA sequencing. A novel missense mutation (c.310A>C) in exon 3, leading to a lysine-to-glutamine substitution at position 104 (p.Lys104Gln), was identified in all four patients with X-linked FEVR. Three unaffected female individuals (III2, IV3, and IV11) were found to be carriers of the mutation. This mutation was not detected in other unaffected individuals. The mutation c.310A>C (p.Lys104Gln) in exon 3 of NDP is associated with FEVR in the studied family. This result further enriches the mutation spectrum of FEVR. Copyright © 2016. Published by Elsevier Taiwan LLC.

Computational Substrates of Social Norm Enforcement by Unaffected Third Parties

PubMed Central

Zhong, Songfa; Chark, Robin; Hsu, Ming; Chew, Soo Hong

2016-01-01

Enforcement of social norms by impartial bystanders in the human species reveals a possibly unique capacity to sense and to enforce norms from a third party perspective. Such behavior, however, cannot be accounted by current computational models based on an egocentric notion of norms. Here, using a combination of model-based fMRI and third party punishment games, we show that brain regions previously implicated in egocentric norm enforcement critically extend to the important case of norm enforcement by unaffected third parties. Specifically, we found that responses in the ACC and insula cortex were positively associated with detection of distributional inequity, while those in the anterior DLPFC were associated with assessment of intentionality to the violator. Moreover, during sanction decisions, the subjective value of sanctions modulated activity in both vmPFC and rTPJ. These results shed light on the neurocomputational underpinnings of third party punishment and evolutionary origin of human norm enforcement. PMID:26825438

The 1200 C cyclic oxidation behavior of two nickel-aluminum alloys (Ni3AL and NiAl) with additions of chromium, silicon, and titanium

NASA Technical Reports Server (NTRS)

Lowell, C. E.; Santoro, G. J.

1972-01-01

The alloys Ni3Al and NiAl with and without 1 and 3 atomic percent chromium, silicon, and titanium replacing the aluminum were cyclically oxidized at 1200 C for times to 200 hours, and the results were compared with those obtained with the alloy B-1900 subjected to the same oxidation process. The evaluation was based on metal recession, specific weight change, metallography, electron microprobe analysis, and X-ray diffraction. The oxidation resistance of Ni3Al was improved by Si, unaffected by Ti, and degraded by Cr. The oxidation resistance of NiAl was slightly improved by Ti, unaffected by Si, and degraded by Cr. The oxidation resistance of Ni3Al with 1 atomic percent Si was nearly equal to that of NiAl. Alloy B-1900 exhibited oxidation resistance comparable to that of Ni3Al + Cr compositions.

Atorvastatin Restores Endothelial Function in Normocholesterolemic Smokers Independent of Changes in Low-Density Lipoprotein

PubMed Central

Beckman, Joshua A.; Liao, James K.; Hurley, Shauna; Garrett, Leslie A.; Chui, Daoshan; Mitra, Debi; Creager, Mark A.

2009-01-01

Cigarette smoking impairs endothelial function. Hydroxymethylglutaryl (HMG) CoA reductase inhibitors (statins) may favorably affect endothelial function via nonlipid mechanisms. We tested the hypothesis that statins would improve endothelial function independent of changes in lipids in cigarette smokers. Twenty normocholesterolemic cigarette smokers and 20 matched healthy control subjects were randomized to atorvastatin 40 mg daily or placebo for 4 weeks, washed out for 4 weeks, and then crossed-over to the other treatment. Baseline low-density lipoprotein (LDL) levels were similar in smokers and healthy subjects, 103±22 versus 95±27 mg/dL, respectively (P=NS) and were reduced similarly in smokers and control subjects by atorvastatin, to 55±30 and 58±20 mg/dL, respectively (P=NS). Vascular ultrasonography was used to determine brachial artery, flow-mediated, endothelium-dependent, and nitroglycerin-mediated, endothelium-independent vasodilation. To elucidate potential molecular mechanisms that may account for changes in endothelial function, skin biopsy specimens were assayed for eNOS mRNA, eNOS activity, and nitrotyrosine. Endothelium-dependent vasodilation was less in smokers than nonsmoking control subjects during placebo treatment, 8.0±0.6% versus 12.1±1.1%, (P=0.003). Atorvastatin increased endothelium-dependent vasodilation in smokers to 10.5±1.3% (P=0.017 versus placebo) but did not change endothelium-dependent vasodilation in control subjects (to 11.0±0.8%, P=NS). Endothelium-independent vasodilation did not differ between groups during placebo treatment and was not significantly affected by atorvastatin. Multivariate analysis did not demonstrate any association between baseline lipid levels or the change in lipid levels and endothelium-dependent vasodilation. Cutaneous nitrotyrosine levels and skin microvessel eNOS mRNA, but not ENOS activity, were increased in smokers compared with controls but unaffected by atorvastatin treatment. Atorvastatin restores endothelium-dependent vasodilation in normocholesterolemic cigarette smokers independent of changes in lipids. These results are consistent with a lipid-independent vascular benefit of statins but could not be explained by changes in eNOS message and tissue oxidative stress. These findings implicate a potential role for statin therapy to restore endothelial function and thereby investigate vascular disease in cigarette smokers. PMID:15178637

The effect of lithium chloride on one-trial passive avoidance learning in rats.

PubMed Central

Johnson, F N

1976-01-01

1 Expression of a one-trial passive avoidance learning response in rats was examined following injections of lithium chloride or sodium chloride before and after initial training and before the first day of testing. Five tests were given at daily intervals, 24 h after training being the time of the first test. 2. Lithium given before the first day of testing impaired response expression on the first and all subsequent days of testing; the rate of extinction was unaffected. 3. Given both before and immediately after initial training, lithium impaired response expression on the first day of testing but slowed down the subsequent rate of extinction, leading eventually to improved performance on the fifth day, as compared with placebo-treated control subjects. 4. The results are interpreted in the light of the hypothesis that lithium impaired the central processing of sensory information. PMID:1252666

Dynamic stability of running: The effects of speed and leg amputations on the maximal Lyapunov exponent

DOE Office of Scientific and Technical Information (OSTI.GOV)

Look, Nicole; Arellano, Christopher J.; Grabowski, Alena M.

2013-12-15

In this paper, we study dynamic stability during running, focusing on the effects of speed, and the use of a leg prosthesis. We compute and compare the maximal Lyapunov exponents of kinematic time-series data from subjects with and without unilateral transtibial amputations running at a wide range of speeds. We find that the dynamics of the affected leg with the running-specific prosthesis are less stable than the dynamics of the unaffected leg and also less stable than the biological legs of the non-amputee runners. Surprisingly, we find that the center-of-mass dynamics of runners with two intact biological legs are slightlymore » less stable than those of runners with amputations. Our results suggest that while leg asymmetries may be associated with instability, runners may compensate for this effect by increased control of their center-of-mass dynamics.« less

The Effect of Presleep Video-Game Playing on Adolescent Sleep

PubMed Central

Weaver, Edward; Gradisar, Michael; Dohnt, Hayley; Lovato, Nicole; Douglas, Paul

2010-01-01

Study Objectives: Video-game use before bedtime has been linked with poor sleep outcomes for adolescents; however, experimental evidence to support this link is sparse. The present study investigated the capacity of presleep video-game playing to extend sleep latency and reduce subjective feelings of sleepiness in adolescents. The arousing psychophysiologic mechanisms involved and the impact of presleep video-game playing on sleep architecture were also explored. Method: Thirteen male adolescent “evening types” (mean age = 16.6 years, SD = 1.1) participated in a counterbalanced, within-subjects design with experimental (active video gaming) and control (passive DVD watching) conditions. The experiment was conducted in the Flinders University Sleep Research Laboratory. Results: Relative to the control condition, presleep video-game playing increased sleep-onset latency (Z = 2.45, p = 0.01) and reduced subjective sleepiness (Z = 2.36, p = 0.02)—but only slightly. Video gaming was related to changes in cognitive alertness (as measured by α power: p < 0.01) but not physiologic arousal (as measured by heart rate: p > 0.05). Contrary to previous findings, sleep architecture was unaffected (both rapid eye movement and slow wave sleep: p > 0.05). Conclusions: Results suggest the direct effect of presleep video-game playing on adolescent sleep may be more modest than previously thought, suggesting that surveys linking stimulating presleep activities to poor sleep need substantiating with empirical evidence. Citation: Weaver E; Gradisar M; Dohnt H; Lovato N; Douglas P. The effect of presleep video-game playing on adolescent sleep. J Clin Sleep Med 2010;6(2):184-189. PMID:20411697

Synergy effects of combined multichannel EMG-triggered electrical stimulation and mirror therapy in subacute stroke patients with severe or very severe arm/hand paresis.

PubMed

Schick, Thomas; Schlake, Hans-Peter; Kallusky, Juliane; Hohlfeld, Günter; Steinmetz, Maria; Tripp, Florian; Krakow, Karsten; Pinter, Michaela; Dohle, Christian

2017-01-01

Neurorehabilitation requires the development of severity-dependent and successful therapies for arm/hand rehabilitation in stroke patients. To evaluate the effectiveness of adding mirror therapy to bilateral EMG-triggered multi-channel electrostimulation for the treatment of severe arm/hand paresis in stroke patients. The subjects of this randomized, controlled, multicentre study were stroke patients who had suffered their first insult between 1 and 6 months before study start and had severe or very severe arm/hand paresis, as classified by Fugl-Meyer-Assessment. Subjects were randomly allocated to an intervention group (n = 16) or control group (n = 17). Both groups were treated for 3 weeks (5x week, 30 minutes) with bilateral EMG-triggered multi-channel electrostimulation. The intervention group additionally received mirror feedback of the unaffected limb. The primary outcome measure was motor recovery of the upper extremities, as measured by the Fugl-Meyer Assessment. The Intervention Group with very severe paresis had significantly better motor recovery in total Fugl-Meyer Assessment (p = 0.017) at a medium effect size (Cohen) of d = 0.7, due to a significant recovery of shoulder and elbow function (p = 0.003) in the Fugl-Meyer Assessment Part A subtest. For subjects with severe paresis, additional mirror therapy did not significantly influence outcome. Additional mirror therapy in combination with EMG-triggered multi-channel electrostimulation is therapeutically beneficial for post-acute stroke patients with very severe arm/hand paresis.

HIV and child mental health: a case-control study in Rwanda.

PubMed

Betancourt, Theresa; Scorza, Pamela; Kanyanganzi, Frederick; Fawzi, Mary C Smith; Sezibera, Vincent; Cyamatare, Felix; Beardslee, William; Stulac, Sara; Bizimana, Justin I; Stevenson, Anne; Kayiteshonga, Yvonne

2014-08-01

The global HIV/AIDS response has advanced in addressing the health and well-being of HIV-positive children. Although attention has been paid to children orphaned by parental AIDS, children who live with HIV-positive caregivers have received less attention. This study compares mental health problems and risk and protective factors in HIV-positive, HIV-affected (due to caregiver HIV), and HIV-unaffected children in Rwanda. A case-control design assessed mental health, risk, and protective factors among 683 children aged 10 to 17 years at different levels of HIV exposure. A stratified random sampling strategy based on electronic medical records identified all known HIV-positive children in this age range in 2 districts in Rwanda. Lists of all same-age children in villages with an HIV-positive child were then collected and split by HIV status (HIV-positive, HIV-affected, and HIV-unaffected). One child was randomly sampled from the latter 2 groups to compare with each HIV-positive child per village. HIV-affected and HIV-positive children demonstrated higher levels of depression, anxiety, conduct problems, and functional impairment compared with HIV-unaffected children. HIV-affected children had significantly higher odds of depression (1.68: 95% confidence interval [CI] 1.15-2.44), anxiety (1.77: 95% CI 1.14-2.75), and conduct problems (1.59: 95% CI 1.04-2.45) compared with HIV-unaffected children, and rates of these mental health conditions were similar to HIV-positive children. These results remained significant after controlling for contextual variables, there were no significant differences on mental health outcomes groups, reflecting a potential explanatory role of factors such as daily hardships, caregiver depression, and HIV-related stigma [corrected]. The mental health of HIV-affected children requires policy and programmatic responses comparable to HIV-positive children. Copyright © 2014 by the American Academy of Pediatrics.

Pancreatic beta-cell responses to GLP-1 after near-normalization of blood glucose in patients with type 2 diabetes.

PubMed

Asmar, Meena; Højberg, Patricia V; Deacon, Carolyn F; Hare, Kristine; Holst, Jens J; Madsbad, Sten

2010-02-25

This study investigated the effects of strict glycaemic control on beta-cell function in nine obese subjects with type 2 diabetes (T2DM), using graded glucose infusions together with infusions of saline or GLP-1 before (HbA(1)c: 8.0+/-0.4%) and after four weeks of near-normalization of blood glucose (BG) using insulin (mean diurnal BG: 6.4+/-0.3 mmol/l; HbA(1)c: 6.6+/-0.3%). Nine matched healthy subjects acted as controls. In controls, area-under-curve (AUC) for amylin, C-peptide and proinsulin were higher with GLP-1 than saline (P<0.001). The AUC amylin/C-peptide ratio was similar on both days, while AUC proinsulin/C-peptide ratio was higher with GLP-1 (P=0.02). In the patients, amylin, C-peptide and proinsulin AUCs were unaltered by near-normoglycaemia per se. Proinsulin responses to GLP-1 were unchanged, but amylin and C-peptide AUCs increased (P<0.05) after insulin treatment, and AUC amylin/C-peptide ratios rose to control levels. Near-normoglycaemia tended to reduce AUC proinsulin/C-peptide ratio, which was significant (P=0.04) with GLP-1, but still higher than with saline (P=0.004). In conclusion, amylin, C-peptide and proinsulin responses to glucose were unaffected by four weeks of near-normoglycaemia, whereas GLP-1 increased amylin and C-peptide secretion and amylin/C-peptide ratio. Near-normoglycaemia reduced proinsulin/C-peptide ratio during stimulation with GLP-1, suggesting that strict glycaemic control might ameliorate some of the disturbances in beta-cell function characterizing T2DM. Copyright 2010 Elsevier B.V. All rights reserved.

Prevalence of Extracranial Venous Narrowing on Magnetic Resonance Venography Is Similar in People With Multiple Sclerosis, Their Siblings, and Unrelated Healthy Controls: A Blinded, Case-Control Study.

PubMed

Martin, Nancy; Traboulsee, Anthony L; Machan, Lindsay; Klass, Darren; Ellchuk, Tasha; Zhao, Yinshan; Knox, Katherine B; Kopriva, David; Lala, Shantilal; Nickel, Darren; Otani, Robert; Perera, Warren R; Rauscher, Alexander; Sadovnick, A Dessa; Szkup, Peter; Li, David K

2017-05-01

The study sought to assess and compare the prevalence of narrowing of the major extracranial veins in subjects with multiple sclerosis and controls, and to assess the sensitivity and specificity of magnetic resonance venography (MRV) for describing extracranial venous narrowing as it applies to the chronic cerebrospinal venous insufficiency theory, using catheter venography (CV) as the gold standard. The jugular and azygos veins were assessed with time-of-flight MRV in this assessor-blinded, case-control study of subjects with multiple sclerosis, their unaffected siblings, and unrelated controls. The veins were evaluated by diameter and area, and compared with CV. Collateral vessels were also analyzed for maximal diameter, as a potential indicator of compensatory flow. A high prevalence of extracranial venous narrowing was demonstrated in all study groups, collectively up to 84% by diameter criteria and 90% by area, with no significant difference between the groups when assessed independently (P = .34 and .63, respectively). There was high interobserver variability in the reporting of vessel narrowing (kappa = 0.32), and poor vessel per vessel correlation between narrowing on MRV and CV (kappa = 0.064). Collateral neck veins demonstrated no convincing difference in maximum size or correlation with jugular narrowing. There is a high prevalence of narrowing of the major extracranial veins on MRV in all 3 study groups, with no significant difference between them. These findings do not support the chronic cerebrospinal venous insufficiency theory. Although MRV has shown a high sensitivity for identifying venous narrowing, time-of-flight imaging demonstrates poor interobserver agreement and poor specificity when compared with the gold standard CV. Copyright © 2016 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.

Familial mesial temporal lobe epilepsy and the borderland of déjà vu.

PubMed

Perucca, Piero; Crompton, Douglas E; Bellows, Susannah T; McIntosh, Anne M; Kalincik, Tomas; Newton, Mark R; Vajda, Frank J E; Scheffer, Ingrid E; Kwan, Patrick; O'Brien, Terence J; Tan, K Meng; Berkovic, Samuel F

2017-08-01

The cause of mesial temporal lobe epilepsy (MTLE) is often unknown. We ascertained to what extent newly diagnosed nonlesional MTLE actually represents familial MTLE (FMTLE). We identified all consecutive patients presenting to the Austin Health First Seizure Clinic with MTLE and normal magnetic resonance imaging (MRI) or MRI evidence of hippocampal sclerosis over a 10-year period. Patients' first-degree relatives and pairwise age- and sex-matched controls underwent a comprehensive epilepsy interview. Each interview transcript was reviewed independently by 2 epileptologists, blinded to relative or control status. Reviewers classified each subject as follows: epilepsy, specifying if MTLE; manifestations suspicious for epilepsy; or unaffected. Physiological déjà vu was noted. Forty-four patients were included. At the Clinic, MTLE had been recognized to be familial in 2 patients only. Among 242 subjects interviewed, MTLE was diagnosed in 9 of 121 relatives versus 0 of 121 controls (p = 0.008). All affected relatives had seizures with intense déjà vu and accompanying features; 6 relatives had not been previously diagnosed. Déjà vu experiences that were suspicious, but not diagnostic, of MTLE occurred in 6 additional relatives versus none of the controls (p = 0.04). Physiological déjà vu was common, and did not differ significantly between relatives and controls. After completing the relatives' interviews, FMTLE was diagnosed in 8 of 44 patients (18.2%). FMTLE accounts for almost one-fifth of newly diagnosed nonlesional MTLE, and it is largely unrecognized without direct questioning of relatives. Relatives of patients with MTLE may experience déjà vu phenomena that clinically lie in the "borderland" between epileptic seizures and physiological déjà vu. Ann Neurol 2017;82:166-176. © 2017 American Neurological Association.

Phenytoin-induced improvement in muscle cramping and insulin action in three patients with the syndrome of insulin resistance, acanthosis nigricans, and acral hypertrophy.

PubMed

Minaker, K L; Flier, J S; Landsberg, L; Young, J B; Moxley, R T; Kingston, W J; Meneilly, G S; Rowe, J W

1989-09-01

Phenytoin sodium has been used to treat muscle cramps of diverse causes, and is known to increase insulin sensitivity during long-term use. We have previously described a syndrome of insulin resistance, acanthosis nigricans, and acral hypertrophy with continual muscle cramping. The effect of 300 mg/d of phenytoin (Dilantin) on muscle cramping and carbohydrate economy was studied in three affected patients and four control subjects. Oral glucose tolerance tests, euglycemic insulin infusion studies, and monocyte insulin binding tests were conducted before and after phenytoin administration. All three patients had notable improvement in muscle cramps. In response to phenytoin, metabolic improvements were variable, with improvement characteristically better in patients with less severe baseline metabolic abnormalities. Patient 1, with the mildest degree of glucose intolerance, had decreased fasting insulin and blood glucose levels, improved glucose tolerance, and insulin-mediated glucose disposal, associated with an increase in monocyte insulin receptors. Patient 2 had reduced fasting plasma glucose and insulin levels and improved oral glucose tolerance, suggesting a beneficial effect on carbohydrate metabolism. Patient 3, with the most severely impaired carbohydrate economy, showed no metabolic improvement despite marked lessening of muscle pain. These clinical characteristics were unaffected in control subjects. We conclude that phenytoin is of value in the therapy of muscle cramps and glucose intolerance in patients with this syndrome.

Dipole source localization of event-related brain activity indicative of an early visual selective attention deficit in ADHD children.

PubMed

Jonkman, L M; Kenemans, J L; Kemner, C; Verbaten, M N; van Engeland, H

2004-07-01

This study was aimed at investigating whether attention-deficit hyperactivity disorder (ADHD) children suffer from specific early selective attention deficits in the visual modality with the aid of event-related brain potentials (ERPs). Furthermore, brain source localization was applied to identify brain areas underlying possible deficits in selective visual processing in ADHD children. A two-channel visual color selection task was administered to 18 ADHD and 18 control subjects in the age range of 7-13 years and ERP activity was derived from 30 electrodes. ADHD children exhibited lower perceptual sensitivity scores resulting in poorer target selection. The ERP data suggested an early selective-attention deficit as manifested in smaller frontal positive activity (frontal selection positivity; FSP) in ADHD children around 200 ms whereas later occipital and fronto-central negative activity (OSN and N2b; 200-400 ms latency) appeared to be unaffected. Source localization explained the FSP by posterior-medial equivalent dipoles in control subjects, which may reflect the contribution of numerous surrounding areas. ADHD children have problems with selective visual processing that might be caused by a specific early filtering deficit (absent FSP) occurring around 200 ms. The neural sources underlying these problems have to be further identified. Source localization also suggested abnormalities in the 200-400 ms time range, pertaining to the distribution of attention-modulated activity in lateral frontal areas.

Effects of wearing aircrew protective clothing on physiological and cognitive responses under various ambient conditions.

PubMed

Faerevik, Hilde; Reinertsen, Randi Eidsmo

2003-06-20

Heat stress can be a significant problem for pilots wearing protective clothing during flights, because they provide extra insulation which prevents evaporative heat loss. Heat stress can influence human cognitive activity, which might be critical in the flying situation, requiring efficient and error-free performance. This study investigated the effect of wearing protective clothing under various ambient conditions on physiological and cognitive performance. On several occasions, eight subjects were exposed for 3 h to three different environmental conditions; 0 degrees C at 80% RH, 23 degrees C at 63% RH and 40 degrees C at 19% RH. The subjects were equipped with thermistors, dressed as they normally do for flights (including helmet, two layers of underwear and an uninsulated survival suit). During three separate exposures the subjects carried out two cognitive performance tests (Vigilance test and DG test). Performance was scored as correct, incorrect, missed reaction and reaction time. Skin temperature, deep body temperature, heart rate, oxygen consumption, temperature and humidity inside the clothing, sweat loss, subjective sensation of temperature and thermal comfort were measured. Rises in rectal temperature, skin temperature, heart rate and body water loss indicated a high level of heat stress in the 40 degrees C ambient temperature condition in comparison with 0 degrees C and 23 degrees C. Performance of the DG test was unaffected by ambient temperature. However, the number of incorrect reactions in the Vigilance test was significantly higher at 40 degrees C than at 23 degrees C (p = 0.006) or 0 degrees C (p = 0.03). The effect on Vigilance performance correlated with changes in deep-body temperature, and this is in accordance with earlier studies that have demonstrated that cognitive performance is virtually unaffected unless environmental conditions are sufficient to change deep body temperature.

Two pedigrees of familial advanced sleep phase syndrome in Japan.

PubMed

Satoh, Kohtoku; Mishima, Kazuo; Inoue, Yuichi; Ebisawa, Takashi; Shimizu, Tetsuo

2003-06-15

To determine whether a known missense mutation (bp2106 A/G) in hPer2 (a human homolog of the Drosophila period gene) for familial advanced sleep phase syndrome in a Caucasian family is involved in Japanese familial advanced sleep phase syndrome pedigrees. We identified 2 new Japanese families with advanced sleep phase syndrome, and a systematic survey was carried out in 28 relatives of theses 2 families. A total of 9 affected subjects were identified. The affected members showed significantly strong morningness tendencies compared with the unaffected members in various circadian parameters including the Horne-Ostberg Morningness-Eveningness Questionnaire score (77.3 +/- 4.8 vs 57.5 +/- 7.6, p < 0.001), average sleep-onset time (20:45 +/- 75 min vs 23:16 +/- 64 min, p < 0.02), and average wake time (4:55 +/- 38 min vs 6:13 +/- 25 min, p < 0.01), as well as saliva dim-light melatonin-onset time (20:15 +/- 21 min vs 22:25 +/- 65 min, p < 0.02). DNA samples were obtained from 7 affected and 7 unaffected subjects. None of the tested subjects possessed the missense mutation (bp2106 A/G) in hPer2. Furthermore, there is no significant linkage between affected subjects with hPer2 region by 2-point mapping and by direct sequencing of 23 exons of hPer2. These findings support the notion of genetic heterogeneity of familial advanced sleep phase syndrome cases in humans. The search for more familial advanced sleep phase syndrome cases and for loci other than hPer2 are necessary to further examine the roles of circadian-related genes in genetically determined human circadian rhythm disorders.

Prevalence of bullying victimisation amongst first-episode psychosis patients and unaffected controls

PubMed Central

Trotta, Antonella; Di Forti, Marta; Mondelli, Valeria; Dazzan, Paola; Pariante, Carmine; David, Anthony; Mulè, Alice; Ferraro, Laura; Formica, Ivan; Murray, Robin M.; Fisher, Helen L.

2013-01-01

Background Despite increasing evidence suggesting that childhood maltreatment is significantly associated with psychosis, the specific role of bullying in the onset of psychotic disorders is still unclear. This study aimed to examine whether bullying was more prevalent amongst individuals presenting to services for the first time with a psychotic disorder than in unaffected community controls. Methods Data on exposure to bullying, psychotic symptoms, cannabis use and history of conduct disorder were collected cross-sectionally from 222 first-presentation psychosis cases and 215 geographically-matched controls. Bullying victimisation was assessed retrospectively as part of the Brief Life Events schedule. Logistic regression was used to examine associations between exposure to bullying and case-control status, while controlling for potential confounders. Results Psychosis cases were approximately twice as likely to report bullying victimisation when compared to controls. No significant interactions between bullying and either gender or cannabis use were found. Controls reporting being a victim of bullying were approximately twice as likely to also report at least one psychosis-like symptom. Conclusions Our results extend previous research by suggesting that bullying victimisation may contribute to vulnerability to develop a psychotic disorder in some individuals. PMID:23891482

Effect of DHEA on Bone in Young Adults

DTIC Science & Technology

1999-09-01

material from female subjects undergoing total hip replacement. Low-density mononuclear cells were isolated by centrifugation on Ficoll histopaque...affected genetic males that is similar to that of unaffected female animals (56). Another natural model is the case of a man with an estrogen receptor...transgenic estrogen receptor knockout mouse, has a BMD 20-25% that of normal mice (58). Similarly, male and female patients with aromatase deficiency have

Longitudinal Analysis of the Premature Infant Intestinal Microbiome Prior to Necrotizing Enterocolitis: A Case-Control Study

PubMed Central

Zhou, Yanjiao; Shan, Gururaj; Sodergren, Erica; Weinstock, George; Walker, W. Allan; Gregory, Katherine E.

2015-01-01

Necrotizing enterocolitis (NEC) is an inflammatory disease of the newborn bowel, primarily affecting premature infants. Early intestinal colonization has been implicated in the pathogenesis of NEC. The objective of this prospective case-control study was to evaluate differences in the intestinal microbiota between infants who developed NEC and unaffected controls prior to disease onset. We conducted longitudinal analysis of the 16S rRNA genes of 312 samples obtained from 12 NEC cases and 26 age-matched controls with a median frequency of 7 samples per subject and median sampling interval of 3 days. We found that the microbiome undergoes dynamic development during the first two months of life with day of life being the major factor contributing to the colonization process. Depending on when the infant was diagnosed with NEC (i.e. early vs. late onset), the pattern of microbial progression was different for cases and controls. The difference in the microbiota was most overt in early onset NEC cases and controls. In proximity to NEC onset, the abundances of Clostridium sensu stricto from Clostridia class were significantly higher in early onset NEC subjects comparing to controls. In late onset NEC, Escherichia/Shigella among Gammaproteobacteria, showed an increasing pattern prior to disease onset, and was significantly higher in cases than controls six days before NEC onset. Cronobacter from Gammaproteobacteria was also significantly higher in late onset NEC cases than controls 1-3 days prior to NEC onset. Thus, the specific infectious agent associated with NEC may vary by the age of infant at disease onset. We found that intravenously administered antibiotics may have an impact on the microbial diversity present in fecal material. Longitudinal analysis at multiple time points was an important strategy utilized in this study, allowing us to appreciate the dynamics of the premature infant intestinal microbiome while approaching NEC at various points. PMID:25741698

Skin Response to Delayed Hypersensitivity Testing in Persons With Unilateral Stroke-related Paresis: Implications for People With Spinal Cord Injury

PubMed Central

Trautner, Barbara W; Zimmermann, Kuno P; Squyres, Sara A; Darouiche, Rabih O

2007-01-01

Background: Vaccination rates among individuals with spinal cord injury (SCI) could be improved if it can be shown that vaccination performed on insensate areas is effective. This would eliminate the the risk of discomfort and soreness at the injection site. Objective: To determine whether immune responsiveness varies between areas with intact and impaired innervation in patients with stroke-related paresis. Design: Prospective trial in which each subject served as his or her own control. Setting: Rehabilitation wards and long-term care units at a Veterans Affairs Medical Center. Patients: Individuals with a history of cerebrovascular accident (CVA) affecting 1 side of the body. Methods: The Multitest cell-mediated immunity (CMI) and purified protein derivative (PPD) of tuberculin were administered intradermally to each arm of each subject. Main Outcome Measures: Total millimeters of induration in response to either test and positive vs negative responses to either test were compared between the 2 arms of each subject. Results: Response to delayed hypersensitivity testing did not differ between the arms affected and unaffected by CVA in each subject, and the time since CVA also did not affect the magnitude of the skin response. Conclusions: Skin testing for delayed hypersensitivity can be effectively administered in the paretic arms of persons who have experienced CVA. Although this study was performed in patients with stroke-related impairment, it has implications for vaccine administration in individuals with SCI-related neurologic deficits. PMID:17853658

Quantifying serum antibody in bird fanciers' hypersensitivity pneumonitis.

PubMed

McSharry, Charles; Dye, George M; Ismail, Tengku; Anderson, Kenneth; Spiers, Elizabeth M; Boyd, Gavin

2006-06-26

Detecting serum antibody against inhaled antigens is an important diagnostic adjunct for hypersensitivity pneumonitis (HP). We sought to validate a quantitative fluorimetric assay testing serum from bird fanciers. Antibody activity was assessed in bird fanciers and control subjects using various avian antigens and serological methods, and the titer was compared with symptoms of HP. IgG antibody against pigeon serum antigens, quantified by fluorimetry, provided a good discriminator of disease. Levels below 10 mg/L were insignificant, and increasing titers were associated with disease. The assay was unaffected by total IgG, autoantibodies and antibody to dietary hen's egg antigens. Antigens from pigeon serum seem sufficient to recognize immune sensitivity to most common pet avian species. Decreasing antibody titers confirmed antigen avoidance. Increasing antibody titer reflected the likelihood of HP, and decreasing titers confirmed antigen avoidance. Quantifying antibody was rapid and the increased sensitivity will improve the rate of false-negative reporting and obviate the need for invasive diagnostic procedures. Automated fluorimetry provides a method for the international standardization of HP serology thereby improving quality control and improving its suitability as a diagnostic adjunct.

Assessing the clinical significance of botanical supplementation on human cytochrome P450 3A activity: Comparison of a milk thistle and black cohosh product to rifampin and clarithromycin

PubMed Central

Gurley, Bill; Hubbard, Martha A.; Williams, D. Keith; Thaden, John; Tong, Yudong; Gentry, W. Brooks; Breen, Philip; Carrier, Danielle J.; Cheboyina, Shreekar

2007-01-01

Phytochemical-mediated modulation of cytochrome P450 enzymes (CYPs) may underlie many herb-drug interactions. This study’s purpose was to assess the effects of milk thistle and black cohosh supplementation on CYP3A activity and compare them to a clinically recognized inducer, rifampin, and inhibitor, clarithromycin. Healthy volunteers were randomly assigned to receive a standardized milk thistle (900 mg) or black cohosh (80 mg) supplement for 14 days. Subjects also received rifampin (600 mg) and clarithromycin (1000 mg) for 7 days as positive controls for CYP3A induction and inhibition, respectively. Midazolam was administered orally before and after each supplementation and control period. The effects of milk thistle, black cohosh, rifampin, and clarithromycin on midazolam pharmacokinetics were determined using noncompartmental techniques. Unlike those observed for rifampin and clarithromycin, midazolam pharmacokinetics were unaffected by milk thistle or black cohosh. Milk thistle and black cohosh appear to have no clinically relevant effect on CYP3A activity in vivo. PMID:16432272

Assessing the clinical significance of botanical supplementation on human cytochrome P450 3A activity: comparison of a milk thistle and black cohosh product to rifampin and clarithromycin.

PubMed

Gurley, Bill; Hubbard, Martha A; Williams, D Keith; Thaden, John; Tong, Yudong; Gentry, W Brooks; Breen, Philip; Carrier, Danielle J; Cheboyina, Shreekar

2006-02-01

Phytochemical-mediated modulation of cytochrome P450 enzymes (CYPs) may underlie many herb-drug interactions. This study's purpose was to assess the effects of milk thistle and black cohosh supplementation on CYP3A activity and compare them to a clinically recognized inducer, rifampin, and inhibitor, clarithromycin. Healthy volunteers were randomly assigned to receive a standardized milk thistle (900 mg) or black cohosh (80 mg) supplement for 14 days. Subjects also received rifampin (600 mg) and clarithromycin (1000 mg) for 7 days as positive controls for CYP3A induction and inhibition, respectively. Midazolam was administered orally before and after each supplementation and control period. The effects of milk thistle, black cohosh, rifampin, and clarithromycin on midazolam pharmacokinetics were determined using noncompartmental techniques. Unlike those observed for rifampin and clarithromycin, midazolam pharmacokinetics was unaffected by milk thistle or black cohosh. Milk thistle and black cohosh appear to have no clinically relevant effect on CYP3A activity in vivo.

Abnormally increased and incoherent resting-state activity is shared between patients with schizophrenia and their unaffected siblings.

PubMed

Liu, Chang; Xue, Zhimin; Palaniyappan, Lena; Zhou, Li; Liu, Haihong; Qi, Chang; Wu, Guowei; Mwansisya, Tumbwene E; Tao, Haojuan; Chen, Xudong; Huang, Xiaojun; Liu, Zhening; Pu, Weidan

2016-03-01

Several resting-state neuroimaging studies in schizophrenia indicate an excessive brain activity while others report an incoherent brain activity at rest. No direct evidence for the simultaneous presence of both excessive and incoherent brain activity has been established to date. Moreover, it is unclear whether unaffected siblings of schizophrenia patients who share half of the affected patient's genotype also exhibit the excessive and incoherent brain activity that may render them vulnerable to the development of schizophrenia. 27 pairs of schizophrenia patients and their unaffected siblings, as well as 27 healthy controls, were scanned using gradient-echo echo-planar imaging at rest. By using amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (Reho), we investigated the intensity and synchronization of local spontaneous neuronal activity in three groups. We observed that increased amplitude and reduced synchronization (coherence) of spontaneous neuronal activity were shared by patients and their unaffected siblings. The key brain regions with this abnormal neural pattern in both patients and siblings included the middle temporal, orbito-frontal, inferior occipital and fronto-insular gyrus. This abnormal neural pattern of excessive and incoherent neuronal activity shared by schizophrenia patients and their healthy siblings may improve our understanding of neuropathology and genetic predisposition in schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

Acute Knockdown of Uncoupling Protein-2 Increases Uncoupling via the Adenine Nucleotide Transporter and Decreases Oxidative Stress in Diabetic Kidneys

PubMed Central

Friederich-Persson, Malou; Aslam, Shakil; Nordquist, Lina; Welch, William J.; Wilcox, Christopher S.; Palm, Fredrik

2012-01-01

Increased O2 metabolism resulting in chronic hypoxia is common in models of endstage renal disease. Mitochondrial uncoupling increases O2 consumption but the ensuing reduction in mitochondrial membrane potential may limit excessive oxidative stress. The present study addressed the hypothesis that mitochondrial uncoupling regulates mitochondria function and oxidative stress in the diabetic kidney. Isolated mitochondria from kidney cortex of control and streptozotocin-induced diabetic rats were studied before and after siRNA knockdown of uncoupling protein-2 (UCP-2). Diabetes resulted in increased UCP-2 protein expression and UCP-2-mediated uncoupling, but normal mitochondria membrane potential. This uncoupling was inhibited by GDP, which also increased the membrane potential. siRNA reduced UCP-2 protein expression in controls and diabetics (−30–50%), but paradoxically further increased uncoupling and markedly reduced the membrane potential. This siRNA mediated uncoupling was unaffected by GDP but was blocked by ADP and carboxyatractylate (CAT). Mitochondria membrane potential after UCP-2 siRNA was unaffected by GDP but increased by CAT. This demonstrated that further increased mitochondria uncoupling after siRNA towards UCP-2 is mediated through the adenine nucleotide transporter (ANT). The increased oxidative stress in the diabetic kidney, manifested as increased thiobarbituric acids, was reduced by knocking down UCP-2 whereas whole-body oxidative stress, manifested as increased circulating malondialdehyde, remained unaffected. All parameters investigated were unaffected by scrambled siRNA. In conclusion, mitochondrial uncoupling via UCP-2 regulates mitochondria membrane potential in diabetes. However, blockade of the diabetes-induced upregulation of UCP- 2 results in excessive uncoupling and reduced oxidative stress in the kidney via activation of ANT. PMID:22768304

Twins discordant for myositis and systemic lupus erythematosus show markedly enriched autoantibodies in the affected twin supporting environmental influences in pathogenesis

PubMed Central

2014-01-01

Background Studies of twin pairs discordant for autoimmune conditions provide a unique opportunity to explore contributing factors triggered by complex gene-environment interactions. Methods In this cross-sectional study, thirty-one monozygotic or dizygotic twin pairs discordant for myositis or systemic lupus erythematosus (SLE), along with matched healthy controls were evaluated for antibodies against a panel of 21 autoantigens. Results Autoantibody profiling revealed that 42% of the affected twins showed significant seropositivity against autoantigens in the panel. In many of these affected twins, but none of healthy controls, there were high levels of autoantibodies detected against two or more autoantigens commonly seen in systemic autoimmune diseases including Ro52, Ro60, RNP-70 K and/or RNP-A. In contrast, only 10% (3/31) of the unaffected twins showed seropositivity and these immunoreactivities were against single autoantigens not seen in systemic autoimmune diseases. While no significant differences in autoantibodies were detected between the affected or unaffected twins against thyroid peroxidase, transglutaminase and several cytokines, 23% of the affected twins with myositis showed autoantibodies against the gastric ATPase. Analysis of the monozygotic twins separately also revealed a higher frequencies of autoantibodies in the affected twins compared to the unaffected twins (P = 0.046). Lastly, clinical analysis of both the affected monozygotic and dizygotic twins revealed that the autoantibody seropositive affected twins had a greater global disease activity score compared to seronegative affected twins (P = 0.019). Conclusion The findings of significantly more autoantibodies in the affected twins with myositis and SLE compared to the unaffected twins are consistent with potential non-genetic factors playing a role in autoantibody production and pathogenesis of these autoimmune disorders. PMID:24602337

Intracranial Fluid Redistribution During a Spaceflight Analog

NASA Technical Reports Server (NTRS)

Koppelmans, Vincent; Pasternak, Ofer; Bloomberg, Jacob J.; De Dios, Yiri E.; Wood, Scott J.; Riascos, Roy; Reuter-Lorenz, Patrica A.; Kofman, Igor S.; Mulavara, Ajitkumar P.; Seidler, Rachael D.

2017-01-01

The neural correlates of spaceflight-induced sensorimotor impairments are unknown. Head down-tilt bed rest (HDBR) serves as a microgravity analog because it mimics the headward fluid shift and limb unloading of spaceflight. We investigated focal brain white matter (WM) changes and fluid shifts during 70 days of 6 deg HDBR in 16 subjects who were assessed pre (2x), during (3x), and post-HDBR (2x). Changes over time were compared to those in control subjects (n=12) assessed four times over 90 days. Diffusion MRI was used to assess WM microstructure and fluid shifts. Free-Water Imaging, derived from diffusion MRI, was used to quantify the distribution of intracranial extracellular free water (FW). Additionally, we tested whether WM and FW changes correlated with changes in functional mobility and balance measures. HDBR resulted in FW increases in fronto-temporal regions and decreases in posterior-parietal regions that largely recovered by two weeks post-HDBR. WM microstructure was unaffected by HDBR. FW decreased in the post-central gyrus and precuneus. We previously reported that gray matter increases in these regions were associated with less HDBR-induced balance impairment, suggesting adaptive structural neuroplasticity. Future studies are warranted to determine causality and underlying mechanisms.

Abnormal reflex activation of hamstring muscles in dogs with cranial cruciate ligament rupture.

PubMed

Hayes, Graham M; Granger, Nicolas; Langley-Hobbs, Sorrel J; Jeffery, Nick D

2013-06-01

The mechanisms underlying cranial cruciate ligament rupture (CCLR) in dogs are poorly understood. In this study hamstring muscle reflexes in response to cranial tibial translation were analysed to determine whether these active stabilisers of the stifle joint are differently activated in dogs with CCLR compared to control dogs. In a prospective clinical study reflex muscle activity from the lateral and medial hamstring muscles (biceps femoris and semimembranosus) was recorded using surface electrodes in control dogs (n=21) and dogs with CCLR (n=22). These electromyographic recordings were analysed using an algorithm previously validated in humans. The hamstring reflex was reliably and reproducibly recorded in normal dogs. Both a short latency response (SLR, 17.6±2.1ms) and a medium latency response (MLR, 37.7±2.7ms) could be identified. In dogs with unilateral CCLR, the SLR and MLR were not significantly different between the affected and the unaffected limbs, but the MLR latency of both affected and unaffected limbs in CCLR dogs were significantly prolonged compared to controls. In conclusion, the hamstring reflex can be recorded in dogs and the MLR is prolonged in dogs with CCLR. Since both affected and unaffected limbs exhibit prolonged MLR, it is possible that abnormal hamstring reflex activation is a mechanism by which progressive CCL damage may occur. The methodology allows for further investigation of the relationship between neuromuscular imbalance and CCLR or limitations in functional recovery following surgical intervention. Copyright © 2012 Elsevier Ltd. All rights reserved.

The potential value of sibling controls compared with population controls for association studies of lifestyle-related risk factors: an example from the Breast Cancer Family Registry.

PubMed

Milne, Roger L; John, Esther M; Knight, Julia A; Dite, Gillian S; Southey, Melissa C; Giles, Graham G; Apicella, Carmel; West, Dee W; Andrulis, Irene L; Whittemore, Alice S; Hopper, John L

2011-10-01

A previous Australian population-based breast cancer case-control study found indirect evidence that control participation, although high, was not random. We hypothesized that unaffected sisters may provide a more appropriate comparison group than unrelated population controls. Three population-based case-control-family studies of breast cancer in women of white European origin were carried out by the Australian, Ontario and Northern California sites of the Breast Cancer Family Registry. We compared risk factors between 3643 cases, 2444 of their unaffected sisters and 2877 population controls and conducted separate case-control analyses based on population and sister controls using unconditional multivariable logistic regression. Compared with sister controls, population controls were more highly educated, had an earlier age at menarche, fewer births, their first birth at a later age and their last birth more recently. The established breast cancer associations detected using sister controls, but not detected using population controls, were decreasing risk with each of later age at menarche, more births, younger age at first birth and greater time since last birth. Since participation of population controls might be unintentionally related to some risk factors, we hypothesize that sister controls could provide more valid relative risk estimates and be recruited at lower cost. Given declining study participation by population controls, this contention is highly relevant to epidemiologic research.

Detectable reporter gene expression following transduction of adenovirus and adeno-associated virus serotype 2 vectors within full-thickness osteoarthritic and unaffected canine cartilage in vitro and unaffected guinea pig cartilage in vivo.

PubMed

Santangelo, Kelly S; Baker, Sarah A; Nuovo, Gerard; Dyce, Jonathan; Bartlett, Jeffrey S; Bertone, Alicia L

2010-02-01

This study quantified and compared the transduction efficiencies of adenoviral (Ad), Arg-Gly-Asp (RGD)-modified Ad, adeno-associated viral serotype 2 (AAV2), and self-complementary AAV2 (scAAV2) vectors within full-thickness osteoarthritic (OA) and unaffected canine cartilage explants in vitro. Intraarticular administration of Ad and scAAV2 vectors was performed to determine the ability of these vectors to transduce unaffected guinea pig cartilage in vivo. Following explant exposure to vector treatment or control, the onset and surface distribution of reporter gene expression was monitored daily with fluorescent microscopy. At termination, explants were divided: one half was digested for analysis using flow cytometry; the remaining portion was used for histology and immunohistochemistry (IHC). Intact articular joints were collected for real-time RT-PCR and IHC to detect reporter gene expression following injection of selected vectors. Ad vector transduced focal areas along the perimeters of explants; the remaining vectors transduced chondrocytes across 100% of the surface. Greater mean transduction efficiencies were found with both AAV2 vectors as compared to the Ad vector (p < or = 0.026). Ad and Ad-RGD vectors transduced only superficial chondrocytes of OA and unaffected cartilage. Uniform reporter gene expression from AAV2 and scAAV2 was detected in the tangential and transitional zones of OA cartilage, but not deeper zones. AAV2 and scAAV2 vectors achieved partial and full-thickness transduction of unaffected cartilage. In vivo work revealed that scAAV2 vector, but not Ad vector, transduced deeper zones of cartilage and menisci. This study demonstrates that AAV2 and scAAV2 are reliable vectors for use in cartilage in vitro and in vivo. (c) 2009 Orthopaedic Research Society.

Comparison of untreated adolescent idiopathic scoliosis with normal controls: a review and statistical analysis of the literature.

PubMed

Rushton, Paul R P; Grevitt, Michael P

2013-04-20

Review and statistical analysis of studies evaluating health-related quality of life (HRQOL) in adolescents with untreated adolescent idiopathic scoliosis (AIS) using Scoliosis Research Society (SRS) outcomes. To apply normative values and minimum clinical important differences for the SRS-22r to the literature. Identify whether the HRQOL of adolescents with untreated AIS differs from unaffected peers and whether any differences are clinically relevant. The effect of untreated AIS on adolescent HRQOL is uncertain. The lack of published normative values and minimum clinical important difference for the SRS-22r has so far hindered our interpretation of previous studies. The publication of this background data allows these studies to be re-examined. Using suitable inclusion criteria, a literature search identified studies examining HRQOL in untreated adolescents with AIS. Each cohort was analyzed individually. Statistically significant differences were identified by using 95% confidence intervals for the difference in SRS-22r domain mean scores between the cohorts with AIS and the published data for unaffected adolescents. If the lower bound of the confidence interval was greater than the minimum clinical important difference, the difference was considered clinically significant. Of the 21 included patient cohorts, 81% reported statistically worse pain than those unaffected. Yet in only 5% of cohorts was this difference clinically important. Of the 11 cohorts included examining patient self-image, 91% reported statistically worse scores than those unaffected. In 73% of cohorts this difference was clinically significant. Affected cohorts tended to score well in function/activity and mental health domains and differences from those unaffected rarely reached clinically significant values. Pain and self-image tend to be statistically lower among cohorts with AIS than those unaffected. The literature to date suggests that it is only self-image which consistently differs clinically. This should be considered when assessing the possible benefits of surgery.

Rapid growth rate results in remarkably hardened breast in broilers during the middle stage of rearing: A biochemical and histopathological study.

PubMed

Kawasaki, Takeshi; Iwasaki, Tomohito; Yamada, Michi; Yoshida, Takashi; Watanabe, Takafumi

2018-01-01

The high incidence of meat of impaired quality poses a serious problem in the poultry industry. In recent years, the incidence of the pectoralis major muscle that appeared pale colored, remarkably hardened, and exudative, called "wooden breast" or "woody breast" has increased in slaughter houses. In the present study, 19-day-old Ross 308 broiler chickens affected (n = 10) and unaffected (n = 10) with remarkably hardened breast were selected from a commercial broiler farm, and reared to 55 days of age under a controlled environment. Among the affected birds, 5 of 10 birds appeared exhausted with markedly suppressed weight gain and 4 of 10 birds died during the rearing period. In contrast, all unaffected birds survived and most gained weight. Four of 10 unaffected birds lost the ability of back-to-back wing contact by the late stage of rearing. The biochemical analysis of blood plasma samples of 20-day-old birds revealed that creatine kinase and L-aspartate aminotransferase values in most affected birds were higher than those in unaffected birds; however, these values in unaffected birds increased rapidly with lost wing contactability and increasing age. Postmortem examinations revealed that the mean diameter of myofibers in affected birds was smaller than that in unaffected birds. Moreover, symptoms of degenerative and regenerative muscles were observed in most birds in both groups. Among them, a decrease in, or defect of, the characteristic polygonal shape of myofibers was the most common change within the pectoralis major muscles in both groups. The present study demonstrated that broilers affected with remarkably hardened breast during the middle stage of rearing would have suppressed physical status and weight gain, or would die. It was suggested that rapid growth in broilers might be a cause of remarkably hardened breast.

Rapid growth rate results in remarkably hardened breast in broilers during the middle stage of rearing: A biochemical and histopathological study

PubMed Central

Iwasaki, Tomohito; Yamada, Michi; Yoshida, Takashi

2018-01-01

The high incidence of meat of impaired quality poses a serious problem in the poultry industry. In recent years, the incidence of the pectoralis major muscle that appeared pale colored, remarkably hardened, and exudative, called “wooden breast” or “woody breast” has increased in slaughter houses. In the present study, 19-day-old Ross 308 broiler chickens affected (n = 10) and unaffected (n = 10) with remarkably hardened breast were selected from a commercial broiler farm, and reared to 55 days of age under a controlled environment. Among the affected birds, 5 of 10 birds appeared exhausted with markedly suppressed weight gain and 4 of 10 birds died during the rearing period. In contrast, all unaffected birds survived and most gained weight. Four of 10 unaffected birds lost the ability of back-to-back wing contact by the late stage of rearing. The biochemical analysis of blood plasma samples of 20-day-old birds revealed that creatine kinase and L-aspartate aminotransferase values in most affected birds were higher than those in unaffected birds; however, these values in unaffected birds increased rapidly with lost wing contactability and increasing age. Postmortem examinations revealed that the mean diameter of myofibers in affected birds was smaller than that in unaffected birds. Moreover, symptoms of degenerative and regenerative muscles were observed in most birds in both groups. Among them, a decrease in, or defect of, the characteristic polygonal shape of myofibers was the most common change within the pectoralis major muscles in both groups. The present study demonstrated that broilers affected with remarkably hardened breast during the middle stage of rearing would have suppressed physical status and weight gain, or would die. It was suggested that rapid growth in broilers might be a cause of remarkably hardened breast. PMID:29474396

Left is where the L is right. Significantly delayed reaction time in limb laterality recognition in both CRPS and phantom limb pain patients.

PubMed

Reinersmann, Annika; Haarmeyer, Golo Sung; Blankenburg, Markus; Frettlöh, Jule; Krumova, Elena K; Ocklenburg, Sebastian; Maier, Christoph

2010-12-17

The body schema is based on an intact cortical body representation. Its disruption is indicated by delayed reaction times (RT) and high error rates when deciding on the laterality of a pictured hand in a limb laterality recognition task. Similarities in both cortical reorganisation and disrupted body schema have been found in two different unilateral pain syndromes, one with deafferentation (phantom limb pain, PLP) and one with pain-induced dysfunction (complex regional pain syndrome, CRPS). This study aims to compare the extent of impaired laterality recognition in these two groups. Performance on a test battery for attentional performance (TAP 2.0) and on a limb laterality recognition task was evaluated in CRPS (n=12), PLP (n=12) and healthy subjects (n=38). Differences between recognising affected and unaffected hands were analysed. CRPS patients and healthy subjects additionally completed a four-day training of limb laterality recognition. Reaction time was significantly delayed in both CRPS (2278±735.7ms) and PLP (2301.3±809.3ms) compared to healthy subjects (1826.5±517.0ms), despite normal TAP values in all groups. There were no differences between recognition of affected and unaffected hands in both patient groups. Both healthy subjects and CRPS patients improved during training, but RTs of CRPS patients (1874.5±613.3ms) remain slower (p<0.01) than those of healthy subjects (1280.6±343.2ms) after four-day training. Despite different pathomechanisms, the body schema is equally disrupted in PLP and CRPS patients, uninfluenced by attention and pain and cannot be fully reversed by training alone. This suggests the involvement of complex central nervous system mechanisms in the disruption of the body schema. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

D-tagatose is a bulk sweetener with zero energy determined in rats.

PubMed

Livesey, G; Brown, J C

1996-06-01

The ketohexose D-tagatose is readily oxidized but contributes poorly to lipid deposition. We therefore examined whether this sugar contributes to energy requirements by determining its net metabolizable energy value in rats. All substrate-induced energy losses from D-tagatose, with sucrose as reference standard, were determined as a single value accounting for the sum of the energy losses to feces, urine, gaseous hydrogen and methane and substrate-induced thermogenesis. A randomized parallel design involving two treatment periods (adaptation to D-tagatose and subsequent energy balance) and two control groups (to control for treatment effects in each period) was used. Rats consumed 1.8 g test carbohydrate daily as a supplement to a basal diet for a 40- or 41-d balance period after prior adaptation for 21 d. Growth, protein and lipid deposition were unaffected by supplementary gross energy intake from D-tagatose compared with an unsupplemented control, but sucrose significantly (P < 0.05) increased all three. Based on the changes induced in protein and fat gain during the balance period it was calculated that D-tagatose contributed -3 +/- 14% of its heat of combustion to net metabolizable energy, and therefore this ketohexose effectively has a zero energy value. D-Tagatose would potentially be helpful in body weight control, especially in diabetic subjects because of its antidiabetogenic effects.

Association of MEOX2 polymorphism with nonsyndromic cleft palate only in a Vietnamese population.

PubMed

Tran, Duy L; Imura, Hideto; Mori, Akihiro; Suzuki, Satoshi; Niimi, Teruyuki; Ono, Maya; Sakuma, Chisato; Nakahara, Shinichi; Nguyen, Tham T H; Pham, Phuong T; Hoang, Viet; Tran, Van T T; Nguyen, Minh D; Natsume, Nagato

2017-10-14

To evaluate the association between the single nucleotide polymorphism (SNP) rs227493 in the MEOX2 gene and nonsyndromic cleft palate only, this research was conducted as a case-control study by comparing a nonsyndromic cleft palate only group with an independent, healthy, and unaffected control group who were both examined by specialists. Based on clinical examination and medical records, we analyzed a total of 570 DNA samples, including 277 cases and 293 controls, which were extracted from dry blood spot samples collected from both the Odonto and Maxillofacial Hospital in Ho Chi Minh City and Nguyen Dinh Chieu Hospital in Ben Tre province, respectively. The standard procedures of genotyping the specific SNP (rs2237493) for MEOX2 were performed on a StepOne Realtime PCR system with TaqMan SNP Genotyping Assays. Significant statistical differences were observed in allelic frequencies (allele T and allele G) between the non-syndromic cleft palate only and control groups in female subjects, with an allelic odds ratio of 1.455 (95% confidence interval: 1.026-2.064) and P < 0.05. These study findings suggest that nonsyndromic isolated cleft palate might be influenced by variation of MEOX2, especially SNP rs2237493 in Vietnamese females. © 2017 Japanese Teratology Society.

Co-localisation of abnormal brain structure and function in specific language impairment.

PubMed

Badcock, Nicholas A; Bishop, Dorothy V M; Hardiman, Mervyn J; Barry, Johanna G; Watkins, Kate E

2012-03-01

We assessed the relationship between brain structure and function in 10 individuals with specific language impairment (SLI), compared to six unaffected siblings, and 16 unrelated control participants with typical language. Voxel-based morphometry indicated that grey matter in the SLI group, relative to controls, was increased in the left inferior frontal cortex and decreased in the right caudate nucleus and superior temporal cortex bilaterally. The unaffected siblings also showed reduced grey matter in the caudate nucleus relative to controls. In an auditory covert naming task, the SLI group showed reduced activation in the left inferior frontal cortex, right putamen, and in the superior temporal cortex bilaterally. Despite spatially coincident structural and functional abnormalities in frontal and temporal areas, the relationships between structure and function in these regions were different. These findings suggest multiple structural and functional abnormalities in SLI that are differently associated with receptive and expressive language processing. Copyright © 2011 Elsevier Inc. All rights reserved.

Introducing taxes, subsidies or both: the effects of various food pricing strategies in a web-based supermarket randomized trial.

PubMed

Waterlander, Wilma E; Steenhuis, Ingrid H M; de Boer, Michiel R; Schuit, Albertine J; Seidell, Jacob C

2012-05-01

Fiscal policies may form a solution in improving dietary intake. This study aimed to examine the effectiveness of varying taxing and subsiding schemes to stimulate healthier food purchases. A randomized controlled trial with three levels of price reduction on healthy foods (no; 25%; 50%)×three levels of price increase on unhealthy foods (5%; 10%; 25%) factorial design was used. 150 participants were randomized into one of nine conditions and were asked to purchase groceries at a web-based supermarket. Data were collected in the Netherlands in January-February 2010 and analyzed using analysis of covariance. Subjects receiving 50% discount purchased significantly more healthy foods than subjects receiving no (mean difference=6.62 items, p<0.01) or 25% discount (mean difference=4.87 items, p<0.05). Moreover, these subjects purchased more vegetables (mean difference=821 g;p<0.05 compared to no discount). However, participants with the highest discount also purchased significantly more calories. No significant effects of the price increases on unhealthy foods were found. Price decreases are effective in stimulating healthy food purchases, but the proportion of healthy foods remains unaffected. Price increases up to 25% on unhealthier products do not significantly affect food purchases. Future studies are important to validate these results in real supermarkets and across different countries. Copyright © 2012 Elsevier Inc. All rights reserved.

Survival features of EBV-stabilized cells from centenarians: morpho-functional and transcriptomic analyses.

PubMed

Matarrese, Paola; Tinari, Antonella; Ascione, Barbara; Gambardella, Lucrezia; Remondini, Daniel; Salvioli, Stefano; Tenedini, Elena; Tagliafico, Enrico; Franceschi, Claudio; Malorni, Walter

2012-12-01

In the present work, we analyzed the survival features of six different Epstein-Barr virus (EBV)-stabilized lymphoid cell lines obtained from adult subjects and from subjects of more than 95 years. For the first, we found that lymphoid B cells from centenarians were more resistant to apoptosis induction and displayed a more developed lysosomal compartment, the most critical component of phagic machinery, in comparison with lymphoid B cells from adult subjects. In addition, cells from centenarians were capable of engulfing and digesting other cells, i.e., their siblings (even entire cells), whereas lymphoid cells from "control samples", i.e., from adults, did not. This behavior was improved by nutrient deprivation but, strikingly, it was unaffected by the autophagy-modulating drug, rapamycin, an autophagy inducer, and 3-methyladenine, an autophagy inhibitor. Transcriptomic analyses indicated that: (1) aspartyl proteases, (2) cell surface molecules such as integrins and cadherins, and (3) some components of cytoskeletal network could contribute to establish this survival phenotype. Also, Kyoto Encyclopedia of Genes and Genomes pathways such as Wnt signaling pathway, an essential contributor to cell migration and actin cytoskeleton remodeling, appeared as prominent. Although we cannot rule out the possibility that EBV-immortalization could play a role, since we observed this phagic behavior in cells from centenarians but not in those from adults, we hypothesize that it may represent an important survival determinant in cells from centenarians.

Age and diagnostic performance of Alzheimer disease CSF biomarkers.

PubMed

Mattsson, N; Rosén, E; Hansson, O; Andreasen, N; Parnetti, L; Jonsson, M; Herukka, S-K; van der Flier, W M; Blankenstein, M A; Ewers, M; Rich, K; Kaiser, E; Verbeek, M M; Olde Rikkert, M; Tsolaki, M; Mulugeta, E; Aarsland, D; Visser, P J; Schröder, J; Marcusson, J; de Leon, M; Hampel, H; Scheltens, P; Wallin, A; Eriksdotter-Jönhagen, M; Minthon, L; Winblad, B; Blennow, K; Zetterberg, H

2012-02-14

Core CSF changes in Alzheimer disease (AD) are decreased amyloid β(1-42), increased total tau, and increased phospho-tau, probably indicating amyloid plaque accumulation, axonal degeneration, and tangle pathology, respectively. These biomarkers identify AD already at the predementia stage, but their diagnostic performance might be affected by age-dependent increase of AD-type brain pathology in cognitively unaffected elderly. We investigated effects of age on the diagnostic performance of CSF biomarkers in a uniquely large multicenter study population, including a cross-sectional cohort of 529 patients with AD dementia (median age 71, range 43-89 years) and 304 controls (67, 44-91 years), and a longitudinal cohort of 750 subjects without dementia with mild cognitive impairment (69, 43-89 years) followed for at least 2 years, or until dementia diagnosis. The specificities for subjects without AD and the areas under the receiver operating characteristics curves decreased with age. However, the positive predictive value for a combination of biomarkers remained stable, while the negative predictive value decreased only slightly in old subjects, as an effect of the high AD prevalence in older ages. Although the diagnostic accuracies for AD decreased with age, the predictive values for a combination of biomarkers remained essentially stable. The findings highlight biomarker variability across ages, but support the use of CSF biomarkers for AD even in older populations.

Age and diagnostic performance of Alzheimer disease CSF biomarkers

PubMed Central

Rosén, E.; Hansson, O.; Andreasen, N.; Parnetti, L.; Jonsson, M.; Herukka, S.-K.; van der Flier, W.M.; Blankenstein, M.A.; Ewers, M.; Rich, K.; Kaiser, E.; Verbeek, M.M.; Olde Rikkert, M.; Tsolaki, M.; Mulugeta, E.; Aarsland, D.; Visser, P.J.; Schröder, J.; Marcusson, J.; de Leon, M.; Hampel, H.; Scheltens, P.; Wallin, A.; Eriksdotter-Jönhagen, M.; Minthon, L.; Winblad, B.; Blennow, K.; Zetterberg, H.

2012-01-01

Objectives: Core CSF changes in Alzheimer disease (AD) are decreased amyloid β1–42, increased total tau, and increased phospho-tau, probably indicating amyloid plaque accumulation, axonal degeneration, and tangle pathology, respectively. These biomarkers identify AD already at the predementia stage, but their diagnostic performance might be affected by age-dependent increase of AD-type brain pathology in cognitively unaffected elderly. Methods: We investigated effects of age on the diagnostic performance of CSF biomarkers in a uniquely large multicenter study population, including a cross-sectional cohort of 529 patients with AD dementia (median age 71, range 43–89 years) and 304 controls (67, 44–91 years), and a longitudinal cohort of 750 subjects without dementia with mild cognitive impairment (69, 43–89 years) followed for at least 2 years, or until dementia diagnosis. Results: The specificities for subjects without AD and the areas under the receiver operating characteristics curves decreased with age. However, the positive predictive value for a combination of biomarkers remained stable, while the negative predictive value decreased only slightly in old subjects, as an effect of the high AD prevalence in older ages. Conclusion: Although the diagnostic accuracies for AD decreased with age, the predictive values for a combination of biomarkers remained essentially stable. The findings highlight biomarker variability across ages, but support the use of CSF biomarkers for AD even in older populations. PMID:22302554

Evidence that hidden hearing loss underlies amplitude modulation encoding deficits in individuals with and without tinnitus.

PubMed

Paul, Brandon T; Bruce, Ian C; Roberts, Larry E

2017-02-01

Damage to auditory nerve fibers that expresses with suprathreshold sounds but is hidden from the audiogram has been proposed to underlie deficits in temporal coding ability observed among individuals with otherwise normal hearing, and to be present in individuals experiencing chronic tinnitus with clinically normal audiograms. We tested whether these individuals may have hidden synaptic losses on auditory nerve fibers with low spontaneous rates of firing (low-SR fibers) that are important for coding suprathreshold sounds in noise while high-SR fibers determining threshold responses in quiet remain relatively unaffected. Tinnitus and control subjects were required to detect the presence of amplitude modulation (AM) in a 5 kHz, suprathreshold tone (a frequency in the tinnitus frequency region of the tinnitus subjects, whose audiometric thresholds were normal to 12 kHz). The AM tone was embedded within background noise intended to degrade the contribution of high-SR fibers, such that AM coding was preferentially reliant on low-SR fibers. We also recorded by electroencephalography the "envelope following response" (EFR, generated in the auditory midbrain) to a 5 kHz, 85 Hz AM tone presented in the same background noise, and also in quiet (both low-SR and high-SR fibers contributing to AM coding in the latter condition). Control subjects with EFRs that were comparatively resistant to the addition of background noise had better AM detection thresholds than controls whose EFRs were more affected by noise. Simulated auditory nerve responses to our stimulus conditions using a well-established peripheral model suggested that low-SR fibers were better preserved in the former cases. Tinnitus subjects had worse AM detection thresholds and reduced EFRs overall compared to controls. Simulated auditory nerve responses found that in addition to severe low-SR fiber loss, a degree of high-SR fiber loss that would not be expected to affect audiometric thresholds was needed to explain the results in tinnitus subjects. The results indicate that hidden hearing loss could be sufficient to account for impaired temporal coding in individuals with normal audiograms as well as for cases of tinnitus without audiometric hearing loss. Copyright © 2016 Elsevier B.V. All rights reserved.

Co-Localisation of Abnormal Brain Structure and Function in Specific Language Impairment

ERIC Educational Resources Information Center

Badcock, Nicholas A.; Bishop, Dorothy V. M.; Hardiman, Mervyn J.; Barry, Johanna G.; Watkins, Kate E.

2012-01-01

We assessed the relationship between brain structure and function in 10 individuals with specific language impairment (SLI), compared to six unaffected siblings, and 16 unrelated control participants with typical language. Voxel-based morphometry indicated that grey matter in the SLI group, relative to controls, was increased in the left inferior…

Elbow flexor and extensor muscle weakness in lateral epicondylalgia.

PubMed

Coombes, Brooke K; Bisset, Leanne; Vicenzino, Bill

2012-05-01

To evaluate whether deficits of elbow flexor and extensor muscle strength exist in lateral epicondylalgia (LE) in comparison with a healthy control population. Cross-sectional study. 150 participants with unilateral LE were compared with 54 healthy control participants. Maximal isometric elbow flexion and extension strength were measured bilaterally using a purpose-built standing frame such that gripping was avoided. The authors found significant side differences in elbow extensor (-6.54 N, 95% CI -11.43 to -1.65, p=0.008, standardised mean difference (SMD) -0.45) and flexor muscle strength (-11.26 N, 95% CI -19.59 to -2.94, p=0.009, SMD -0.46) between LE and control groups. Within the LE group, only elbow extensor muscle strength deficits between sides was significant (affected-unaffected: -2.94 N, 95% CI -5.44 to -0.44). Small significant deficits of elbow extensor and flexor muscle strength exist in the affected arm of unilateral LE in comparison with healthy controls. Notably, comparing elbow strength between the affected and unaffected sides in unilateral epicondylalgia is likely to underestimate these deficits. Trial Registration Australian New Zealand Clinical Trials Register ACTRN12609000051246.

Effect of a quality-controlled fermented nutraceutical on skin aging markers: An antioxidant-control, double-blind study

PubMed Central

BERTUCCELLI, GIUSEPPE; ZERBINATI, NICOLA; MARCELLINO, MASSIMILIANO; NANDA KUMAR, NAVALPUR SHANMUGAM; HE, FANG; TSEPAKOLENKO, VLADIMIR; CERVI, JOSEPH; LORENZETTI, ALDO; MAROTTA, FRANCESCO

2016-01-01

The aim of the present study was to determine whether oral supplementation with a fermented papaya preparation (FPP-treated group) or an antioxidant cocktail (antioxidant-control group, composed of 10 mg trans-resveratrol, 60 µg selenium, 10 mg vitamin E and 50 mg vitamin C) was able to improve the skin antioxidant capacity and the expression of key skin genes, while promoting skin antiaging effects. The study enrolled 60 healthy non-smoker males and females aged 40–65 years, all of whom showed clinical signs of skin aging. The subjects were randomly divided into two matched groups, and were administered FPP or antioxidant treatment of a 4.5 g/day sachet sublingually twice a day for 90 days in a double-blind fashion. The parameters investigated were: Skin surface, brown spots, skin evenness, skin moisturization, elasticity (face), redox balance, nitric oxide (NO) concentration, and the expression levels of key genes (outer forearm sample). As compared with the baseline (day 0) and antioxidant-control values, FPP-treated subjects showed a significant improvement in skin evenness, moisturization and elasticity. The two treatments improved the MDA and SOD skin concentrations, but only the FPP-treated group showed a higher SOD level and a significant NO increase, along with significant upregulation of acquaporin-3 and downregulation of the potentially pro-aging/carcinogenetic cyclophilin-A and CD147 genes (P<0.05). Progerin was unaffected in both treatment groups. In conclusion, these findings suggest that orally-administered FPP showed a consistent biological and gene-regulatory improvement in the skin, as was also demonstrated in previous experimental and clinical trials testing other tissues, while common oral antioxidants had only a minor effect. PMID:26998011

Effect of antioxidants on histamine receptor activation and sustained post-exercise vasodilatation in humans

PubMed Central

Romero, Steven A.; Ely, Matthew R.; Sieck, Dylan C.; Luttrell, Meredith J.; Buck, Tahisha M.; Kono, Jordan M.; Branscum, Adam J.; Halliwill, John R.

2015-01-01

An acute bout of aerobic exercise elicits a sustained post-exercise vasodilatation that is mediated by histamine H1 and H2 receptor activation. However, the upstream signaling pathway that leads to post-exercise histamine receptor activation is unknown. We tested the hypothesis that the potent antioxidant ascorbate would inhibit this histaminergic vasodilatation following exercise. Subjects performed 1 hr unilateral dynamic knee extension at 60% of peak power in three conditions: 1) control; 2) intravenous ascorbate infusion; and, 3) ascorbate infusion plus oral H1/H2 histamine receptor blockade. Femoral artery blood flow (Doppler ultrasound) was measured before exercise and for 2 hr post-exercise. Femoral vascular conductance was calculated as flow/pressure. Post-exercise vascular conductance was greater for control condition (3.4 ± 0.1 ml min−1 mmHg−1) compared with ascorbate (2.7 ± 0.1 ml min−1 mmHg−1, P < 0.05) and ascorbate plus H1/H2 blockade (2.8 ± 0.1 ml min−1 mmHg−1, P < 0.05), which did not differ from one another (P = 0.9). Because ascorbate may catalyze the degradation of histamine in vivo, we conducted a follow-up study where subjects performed exercise in two conditions: 1) control and 2) intravenous N-acetylcysteine infusion. Post-exercise vascular conductance was similar for control (4.0 ± 0.1 ml min−1 mmHg−1) and N-acetylcysteine conditions (4.0 ± 0.1 ml min−1 mmHg−1; P = 0.8). Thus, the results in study 1 were due to the degradation of histamine in skeletal muscle by ascorbate, since the histaminergic vasodilatation was unaffected by N-acetylcysteine. Taken together, exercise-induced oxidative stress does not appear to contribute to sustained post-exercise vasodilatation. PMID:25664905

Favorable effects of berry consumption on platelet function, blood pressure, and HDL cholesterol.

PubMed

Erlund, Iris; Koli, Raika; Alfthan, Georg; Marniemi, Jukka; Puukka, Pauli; Mustonen, Pirjo; Mattila, Pirjo; Jula, Antti

2008-02-01

Berries are a particularly rich source of polyphenols. They also contain other bioactive substances, such as vitamin C. Previous studies indicated that the consumption of polyphenol-rich foods (eg, cocoa, tea, and red wine) may induce beneficial changes in pathways related to cardiovascular health. Whether the consumption of berries has similar effects is unknown. We aimed to investigate the effects of berry consumption on hemostatic function, serum lipids, and blood pressure (BP). Middle-aged unmedicated subjects (n = 72) with cardiovascular risk factors consumed moderate amounts of berry or control products for 8 wk in a single-blind, randomized, placebo-controlled intervention trial. Berry consumption inhibited platelet function as measured with a platelet function analyzer (using collagen and ADP as platelet activator) [changes: 11% and -1.4% in the berry and control groups, respectively; P = 0.018, analysis of covariance (ANCOVA)]. Plasma biomarkers of platelet activation, coagulation, and fibrinolysis did not change during the intervention. Serum HDL-cholesterol concentrations increased significantly more (P = 0.006, ANCOVA) in the berry than in the control group (5.2% and 0.6%, respectively), but total cholesterol and triacylglycerol remained unchanged. Systolic BP decreased significantly (P = 0.050, ANCOVA); the decrease mostly occurred in subjects with high baseline BP (7.3 mm Hg in highest tertile; P = 0.024, ANCOVA). Polyphenol and vitamin C concentrations in plasma increased, whereas other nutritional biomarkers (ie, folate, tocopherols, sodium, and potassium) were unaffected. The consumption of moderate amounts of berries resulted in favorable changes in platelet function, HDL cholesterol, and BP. The results indicate that regular consumption of berries may play a role in the prevention of cardiovascular disease.

Different motor tasks impact differently on cognitive performance of older persons during dual task tests.

PubMed

Simoni, David; Rubbieri, Gaia; Baccini, Marco; Rinaldi, Lucio; Becheri, Dimitri; Forconi, Tatiana; Mossello, Enrico; Zanieri, Samanta; Marchionni, Niccolò; Di Bari, Mauro

2013-07-01

Dual task paradigm states that the introduction of a second task during a cognitive or motor performance results in a decreased performance in either task. Treadmill walk, often used in clinical applications of dual task testing, has never been compared to overground walk, to ascertain its susceptibility to interference from a second task. We compared the effects of overground and treadmill gait on dual task performance. Gait kinematic parameters and cognitive performance were obtained in 29 healthy older adults (mean age 75 years, 14 females) when they were walking freely on a sensorized carpet or during treadmill walking with an optoelectronic system, in single task or dual task conditions, using alternate repetition of letters as a cognitive verbal task. During overground walking, speed, cadence, step length stride length, and double support time (all with P value<0.001) and cognitive performance (number of correct words, P<0.001) decreased substantially from single to dual task testing. When subjects walked at a fixed speed on the treadmill, cadence decreased significantly (P=0.005), whereas cognitive performance remained unaffected. Both motor and cognitive performances decline during dual task testing with overground walking. Conversely, cognitive performance remains unaffected in dual task testing on the treadmill. In the light of current dual task paradigm, these findings may have relevant implication for our understanding of motor control, as they suggest that treadmill walk does not involve brain areas susceptible to interference from the introduction of a cognitive task. Copyright © 2013 Elsevier Ltd. All rights reserved.

Schizotypy and smooth pursuit eye movements as potential endophenotypes of obsessive-compulsive disorder.

PubMed

Bey, Katharina; Meyhöfer, Inga; Lennertz, Leonhard; Grützmann, Rosa; Heinzel, Stephan; Kaufmann, Christian; Klawohn, Julia; Riesel, Anja; Ettinger, Ulrich; Kathmann, Norbert; Wagner, Michael

2018-05-02

Patients with obsessive-compulsive disorder (OCD) show dysfunctions of the fronto-striatal circuitry, which imply corresponding oculomotor deficits including smooth pursuit eye movements (SPEM). However, evidence for a deficit in SPEM is inconclusive, with some studies reporting reduced velocity gain while others did not find any SPEM dysfunctions in OCD patients. Interestingly, psychosis-like traits have repeatedly been linked to both OCD and impaired SPEM. Here, we examined a large sample of n = 168 patients with OCD, n = 93 unaffected first-degree relatives and n = 171 healthy control subjects to investigate whether elevated levels of schizotypy and SPEM deficits represent potential endophenotypes of OCD. We applied a SPEM task with high demands on predictive pursuit that is more sensitive to assess executive dysfunctions than a standard task with continuous visual feedback, as episodes of target blanking put increased demands on basal ganglia and prefrontal involvement. Additionally, we examined the relation between schizotypy and SPEM performance in OCD patients and their relatives. Results indicate that OCD patients and unaffected relatives do not show deficient performance in either standard or predictive SPEM. Yet, both patients and relatives exhibited elevated levels of schizotypy, and schizotypy was significantly correlated with velocity gain during standard trials in unmedicated and depression-free OCD patients. These findings highlight the role of schizotypy as a candidate endophenotype of OCD and add to the growing evidence for predisposing personality traits in OCD. Furthermore, intact gain may represent a key characteristic that distinguishes the OCD and schizophrenia patient populations.

Parkinsonian motor impairment predicts personality domains related to genetic risk and treatment outcomes in schizophrenia

PubMed Central

Molina, Juan L; Calvó, María; Padilla, Eduardo; Balda, Mara; Alemán, Gabriela González; Florenzano, Néstor V; Guerrero, Gonzalo; Kamis, Danielle; Rangeon, Beatriz Molina; Bourdieu, Mercedes; Strejilevich, Sergio A; Conesa, Horacio A; Escobar, Javier I; Zwir, Igor; Cloninger, C Robert; de Erausquin, Gabriel A

2017-01-01

Identifying endophenotypes of schizophrenia is of critical importance and has profound implications on clinical practice. Here we propose an innovative approach to clarify the mechanims through which temperament and character deviance relates to risk for schizophrenia and predict long-term treatment outcomes. We recruited 61 antipsychotic naïve subjects with chronic schizophrenia, 99 unaffected relatives, and 68 healthy controls from rural communities in the Central Andes. Diagnosis was ascertained with the Schedules of Clinical Assessment in Neuropsychiatry; parkinsonian motor impairment was measured with the Unified Parkinson’s Disease Rating Scale; mesencephalic parenchyma was evaluated with transcranial ultrasound; and personality traits were assessed using the Temperament and Character Inventory. Ten-year outcome data was available for ~40% of the index cases. Patients with schizophrenia had higher harm avoidance and self-transcendence (ST), and lower reward dependence (RD), cooperativeness (CO), and self-directedness (SD). Unaffected relatives had higher ST and lower CO and SD. Parkinsonism reliably predicted RD, CO, and SD after correcting for age and sex. The average duration of untreated psychosis (DUP) was over 5 years. Further, SD was anticorrelated with DUP and antipsychotic dosing at follow-up. Baseline DUP was related to antipsychotic dose-years. Further, ‘explosive/borderline’, ‘methodical/obsessive’, and ‘disorganized/schizotypal’ personality profiles were associated with increased risk of schizophrenia. Parkinsonism predicts core personality features and treatment outcomes in schizophrenia. Our study suggests that RD, CO, and SD are endophenotypes of the disease that may, in part, be mediated by dopaminergic function. Further, SD is an important determinant of treatment course and outcome. PMID:28127577

Parkinsonian motor impairment predicts personality domains related to genetic risk and treatment outcomes in schizophrenia.

PubMed

Molina, Juan L; Calvó, María; Padilla, Eduardo; Balda, Mara; Alemán, Gabriela González; Florenzano, Néstor V; Guerrero, Gonzalo; Kamis, Danielle; Rangeon, Beatriz Molina; Bourdieu, Mercedes; Strejilevich, Sergio A; Conesa, Horacio A; Escobar, Javier I; Zwir, Igor; Cloninger, C Robert; de Erausquin, Gabriel A

2017-01-01

Identifying endophenotypes of schizophrenia is of critical importance and has profound implications on clinical practice. Here we propose an innovative approach to clarify the mechanims through which temperament and character deviance relates to risk for schizophrenia and predict long-term treatment outcomes. We recruited 61 antipsychotic naïve subjects with chronic schizophrenia, 99 unaffected relatives, and 68 healthy controls from rural communities in the Central Andes. Diagnosis was ascertained with the Schedules of Clinical Assessment in Neuropsychiatry; parkinsonian motor impairment was measured with the Unified Parkinson's Disease Rating Scale; mesencephalic parenchyma was evaluated with transcranial ultrasound; and personality traits were assessed using the Temperament and Character Inventory. Ten-year outcome data was available for ~40% of the index cases. Patients with schizophrenia had higher harm avoidance and self-transcendence (ST), and lower reward dependence (RD), cooperativeness (CO), and self-directedness (SD). Unaffected relatives had higher ST and lower CO and SD. Parkinsonism reliably predicted RD, CO, and SD after correcting for age and sex. The average duration of untreated psychosis (DUP) was over 5 years. Further, SD was anticorrelated with DUP and antipsychotic dosing at follow-up. Baseline DUP was related to antipsychotic dose-years. Further, 'explosive/borderline', 'methodical/obsessive', and 'disorganized/schizotypal' personality profiles were associated with increased risk of schizophrenia. Parkinsonism predicts core personality features and treatment outcomes in schizophrenia. Our study suggests that RD, CO, and SD are endophenotypes of the disease that may, in part, be mediated by dopaminergic function. Further, SD is an important determinant of treatment course and outcome.

Increased plasma chemokine levels in children with Prader-Willi syndrome.

PubMed

Butler, Merlin G; Hossain, Waheeda; Sulsona, Carlos; Driscoll, Daniel J; Manzardo, Ann M

2015-03-01

Prader-Willi syndrome (PWS) is caused by loss of paternally expressed genes from the 15q11-q13 region and reportedly rearranged as a cause of autism. Additionally, increased inflammatory markers and features of autism are reported in PWS. Cytokines encoded by genes involved with inflammation, cell proliferation, migration, and adhesion play a role in neurodevelopment and could be disturbed in PWS as abnormal plasma cytokine levels are reported in autism. We analyzed 41 plasma cytokines in a cohort of well-characterized children with PWS between 5 and 11 years of age and unaffected unrelated siblings using multiplex sandwich immunoassays with the Luminex magnetic-bead based platform. Data were analyzed using ANOVA testing for effects of diagnosis, gender, body mass index (BMI) and age on the 24 cytokines meeting laboratory criteria for inclusion. No significant effects were observed for age, gender or BMI. The log-transformed levels of the 24 analyzable cytokines were examined simultaneously using MANOVA adjusting for age and gender and a main effect of diagnosis was found (P-value <0.03). Four of 24 plasma cytokine levels (MCP1, MDC, Eotaxin, RANTES) were significantly higher in children with PWS compared with controls and classified as bioinflammatory chemokines supporting a disturbed immune response unrelated to obesity status. BMI was not statistically different in the two subject groups (PWS or unaffected unrelated siblings) and chemokine levels were not correlated with percentage of total body fat. Additional studies are required to identify whether possible early immunological disturbances and chemokine inflammatory processes found in PWS may contribute to neurodevelopment and behavioral features. © 2015 Wiley Periodicals, Inc.

Activated cranial cervical cord neurons affect left ventricular infarct size and the potential for sudden cardiac death

PubMed Central

Southerland, E. Marie; Gibbons, David D.; Smith, S. Brooks; Sipe, Adam; Williams, Carole Ann; Beaumont, Eric; Armour, J. Andrew; Foreman, Robert D.; Ardell, Jeffrey L.

2012-01-01

To evaluate whether cervical spinal neurons can influence cardiac indices and myocyte viability in the acutely ischemic heart, the hearts of anesthetized rabbits subjected to 30 min of LAD coronary arterial occlusion (CAO) were studied 3 hours after reperfusion. Control animals were compared to those exposed to pre-emptive high cervical cord stimulation (SCS; the dorsal aspect of the C1-C2 spinal cord was stimulated electrically at 50 Hz; 0.2 ms; 90% of motor threshold, starting 15 min prior to and continuing throughout CAO). Four groups of animals were so tested: 1) neuroaxis intact; 2) prior cervical vagotomy; 3) prior transection of the dorsal spinal columns at C6; and 4) following pharmacological treatment [muscarinic (atropine) or adrenergic (atenolol, prazosin or yohimbine) receptor blockade]. Infarct size (IS) was measured by tetrazolium, expressed as percentage of risk zone. C1-C2 SCS reduced acute ischemia induced IS by 43%, without changing the incidence of sudden cardiac death (SCD). While SCS-induced reduction in IS was unaffected by vagotomy, it was no longer evident following transection of C6 dorsal columns or atropinization. Beta-adrenoceptor blockade eliminated ischemia induced SCD, while alpha-receptor blockade doubled its incidence. During SCS, myocardial ischemia induced SCD was eliminated following vagotomy while remaining unaffected by atropinization. These data indicate that, in contrast to thoracic spinal neurons, i) cranial cervical spinal neurons affect both adrenergic and cholinergic motor outflows to the heart such that ii) their activation modifies ventricular infarct size and lethal arrhythmogenesis. PMID:22502863

Does abnormal interhemispheric inhibition play a role in mirror dystonia?

PubMed

Sattler, Virginie; Dickler, Maya; Michaud, Martin; Meunier, Sabine; Simonetta-Moreau, Marion

2014-05-01

The presence of mirror dystonia (dystonic movement induced by a specific task performed by the unaffected hand) in the dominant hand of writer's cramp patients when the nondominant hand is moved suggests an abnormal interaction between the 2 hemispheres. In this study we compare the level of interhemispheric inhibition (IHI) in 2 groups of patients with writer's cramp, one with the presence of a mirror dystonia and the other without as well as a control group. The level of bidirectional IHI was measured in wrist muscles with dual-site transcranial magnetic stimulation with a 10-millisecond (short IHI) and a 40-millisecond (long IHI) interstimulus interval during rest and while holding a pen in 9 patients with mirror dystonia 7 without mirror dystonia, and 13 controls. The group of patients without mirror dystonia did not differ from the controls in their IHI level. In contrast, IHI was significantly decreased in the group of patients with mirror dystonia in comparison with the group without mirror dystonia and the controls in both wrist muscles of both the dystonic and unaffected hand whatever the resting or active condition (P = 0.001). The decrease of IHI level in the group of patients with mirror dystonia was negatively correlated with the severity and the duration of the disease: the weaker the level of IHI, the more severe was the disease and the longer its duration. Interhemispheric inhibition disturbances are most likely involved in the occurrence of mirror dystonia. This bilateral deficient inhibition further suggests the involvement of the unaffected hemisphere in the pathophysiology of unilateral dystonia. © 2013 International Parkinson and Movement Disorder Society.

Familial liability to psychosis is a risk factor for multimorbidity in people with psychotic disorders and their unaffected siblings.

PubMed

Islam, M A; Khan, M F H; Quee, P J; Snieder, H; van den Heuvel, E R; Bruggeman, R; Alizadeh, B Z

2017-09-01

Multimorbidity may impose an overwhelming burden on patients with psychosis and is affected by gender and age. Our aim is to study the independent role of familial liability to psychosis as a risk factor for multimorbidity. We performed the study within the framework of the Genetic Risk and Outcome of Psychosis (GROUP) project. Overall, we compared 1024 psychotic patients, 994 unaffected siblings and 566 controls on the prevalence of 125 lifetime diseases, and 19 self-reported somatic complaints. Multimorbidity was defined as the presence of two or more complaints/diseases in the same individual. Generalized linear mixed model (GLMM) were used to investigate the effects of gender, age (adolescent, young, older) and familial liability (patients, siblings, controls) and their interactions on multimorbidity. Familial liability had a significant effect on multimorbidity of either complaints or diseases. Patients had a higher prevalence of multimorbidity of complaints compared to siblings (OR 2.20, 95% CI 1.79-2.69, P<0.001) and to controls (3.05, 2.35-3.96, P<0.001). In physical health multimorbidity, patients (OR 1.36, 95% CI 1.05-1.75, P=0.018), but not siblings, had significantly higher prevalence than controls. Similar finding were observed for multimorbidity of lifetime diseases, including psychiatric diseases. Significant results were observed for complaints and disease multimorbidity across gender and age groups. Multimorbidity is a common burden, significantly more prevalent in patients and their unaffected siblings. Familial liability to psychosis showed an independent effect on multimorbidity; gender and age are also important factors determining multimorbidity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Control networks in paediatric Tourette syndrome show immature and anomalous patterns of functional connectivity

PubMed Central

Fair, Damien A.; Dosenbach, Nico U. F.; Cohen, Alexander L.; Miezin, Francis M.; Petersen, Steven E.; Schlaggar, Bradley L.

2009-01-01

Tourette syndrome (TS) is a developmental disorder characterized by unwanted, repetitive behaviours that manifest as stereotyped movements and vocalizations called ‘tics’. Operating under the hypothesis that the brain's control systems may be impaired in TS, we measured resting-state functional connectivity MRI (rs-fcMRI) between 39 previously defined putative control regions in 33 adolescents with TS. We were particularly interested in the effect of TS on two of the brain's task control networks—a fronto-parietal network likely involved in more rapid, adaptive online control, and a cingulo-opercular network apparently important for set-maintenance. To examine the relative maturity of connections in the Tourette subjects, functional connections that changed significantly over typical development were examined. Age curves were created for each functional connection charting correlation coefficients over age for 210 healthy people aged 7–31 years, and the TS group correlation coefficients were compared to these curves. Many of these connections were significantly less ‘mature’ than expected in the TS group. This immaturity was true not only for functional connections that grow stronger with age, but also for those that diminish in strength with age. To explore other differences between Tourette and typically developing subjects further, we performed a second analysis in which the TS group was directly compared to an age-matched, movement-matched group of typically developing, unaffected adolescents. A number of functional connections were found to differ between the two groups. For these identified connections, a large number of connectional differences were found where the TS group value was out of range compared to typical developmental age curves. These anomalous connections were primarily found in the fronto-parietal network, thought to be important for online adaptive control. These results suggest that in adolescents with TS, immature functional connectivity is widespread, with additional, more profound deviation of connectivity in regions related to adaptive online control. PMID:18952678

Oculomotor Cognitive Control Abnormalities in Australian Rules Football Players with a History of Concussion.

PubMed

Clough, Meaghan; Mutimer, Steven; Wright, David K; Tsang, Adrian; Costello, Daniel M; Gardner, Andrew J; Stanwell, Peter; Mychasiuk, Richelle; Sun, Mujun; Brady, Rhys D; McDonald, Stuart J; Webster, Kyria M; Johnstone, Maddison R; Semple, Bridgette D; Agoston, Denes V; White, Owen B; Frayne, Richard; Fielding, Joanne; O'Brien, Terence J; Shultz, Sandy R

2018-03-01

This study used oculomotor, cognitive, and multi-modal magnetic resonance imaging (MRI) measures to assess for neurological abnormalities in current asymptomatic amateur Australian rules footballers (i.e., Australia's most participated collision sport) with a history of sports-related concussion (SRC). Participants were 15 male amateur Australian rules football players with a history of SRC greater than 6 months previously, and 15 sex-, age-, and education-matched athlete control subjects that had no history of neurotrauma or participation in collision sports. Participants completed a clinical interview, neuropsychological measures, and oculomotor measures of cognitive control. MRI investigation involved structural imaging, as well as diffusion tensor imaging and resting-state functional MRI sequences. Despite no group differences on conventional neuropsychological tests and multi-modal MRI measures, Australian rules football players with a history of SRC performed significantly worse on an oculomotor switch task: a measure of cognitive control that interleaves the response of looking towards a target (i.e., a prosaccade) with the response of looking away from a target (i.e., an antisaccade). Specifically, Australian footballers performed significantly shorter latency prosaccades and found changing from an antisaccade trial to a prosaccade trial (switch cost) significantly more difficult than control subjects. Poorer switch cost was related to poorer performance on a number of neuropsychological measures of inhibitory control. Further, when comparing performance on the cognitively more demanding switch task with performance on simpler, antisaccade/prosaccades tasks which require a single response, Australian footballers demonstrated a susceptibility to increased cognitive load, compared to the control group who were unaffected. These initial results suggest that current asymptomatic amateur Australian rules football players with a history of SRC may have persisting, subtle, cognitive changes, which are demonstrable on oculomotor cognitive measures. Future studies are required in order to further elucidate the full nature and clinical relevance of these findings.

Effects of Artificial Gravity and Bed Rest on Spatial Orientation and Balance Control

NASA Technical Reports Server (NTRS)

Paloski, William H.; Moore, S. T.; Feiveson, A. H.; Taylor, L. C.

2007-01-01

While the vestibular system should be well-adapted to bed rest (a condition it experiences approximately 8/24 hrs each day), questions remain regarding the degree to which repeated exposures to the unusual gravito-inertial force environment of a short-radius centrifuge might affect central processing of vestibular information used in spatial orientation and balance control. Should these functions be impaired by intermittent AG, its feasibility as a counter-measure would be diminished. We, therefore, examined the effects of AG on spatial orientation and balance control in 15 male volunteers before and after 21 days of 6 HDT bed rest (BR). Eight of the subjects were treated with daily 1hr AG exposures (2.5g at the feet; 1.0g at the heart) aboard a short radius (3m) centrifuge, while the other seven served as controls (C). Spatial orientation was assessed by measures of ocular counter-rolling (OCR; rotation of the eye about the line of sight, an otolith-mediated reflex) and subjective visual vertical (SVV; perception of the spatial upright). Both OCR and SVV measurements were made with the subject upright, lying on their left sides, and lying on their right sides. OCR was measured from binocular eye orientation recordings made while the subjects fixated for 10s on a point target directly in front of the face at a distance of 1 m. SVV was assessed by asking subjects (in the dark) to adjust to upright (using a handheld controller) the orientation of a luminous bar randomly perturbed (15) to either side of the vertical meridian. Balance control performance was assessed using a computerized dynamic posturography (CDP) protocol similar to that currently required for all returning crew members. During each session, the subjects completed a combination of trials of sensory organization test (SOT) 2 (eyes closed, fixed platform) and SOT 5 (eyes closed, sway-referenced platform) with and without static and dynamic pitch plane head movements (plus or minus 20 deg., dynamic paced by an audible tone at 0.33Hz). OCR and CDP performance were unaffected by BR and BR+AG; post-BR measures were unchanged from baseline for both AG and C groups. Similarly, BR did not affect SVV in the C group. However, BR+AG disrupted one measure of spatial orientation: SVV error was significantly increased on R+0 and R+1 following BR in the AG group. These results suggest a transient untoward effect on central vestibular processing may accompany repeated exposure to intermittent AG, a potential side-effect that should be studied more closely in future studies.

Abnormal functional motor lateralization in healthy siblings of patients with schizophrenia.

PubMed

Altamura, Mario; Fazio, Leonardo; De Salvia, Michela; Petito, Annamaria; Blasi, Giuseppe; Taurisano, Paolo; Romano, Raffaella; Gelao, Barbara; Bellomo, Antonello; Bertolino, Alessandro

2012-07-30

Earlier neuroimaging studies of motor function in schizophrenia have demonstrated reduced functional lateralization in the motor network during motor tasks. Here, we used event-related functional magnetic resonance imaging during a visually guided motor task in 18 clinically unaffected siblings of patients with schizophrenia and 24 matched controls to investigate if abnormal functional lateralization is related to genetic risk for this brain disorder. Whereas activity associated with motor task performance was mainly contralateral with only a marginal ipsilateral component in healthy participants, unaffected siblings had strong bilateral activity with significantly greater response in ipsilateral and contralateral premotor areas as well as in contralateral subcortical motor regions relative to controls. Reduced lateralization in siblings was also identified with a measure of laterality quotient. These findings suggest that abnormal functional lateralization of motor circuitry is related to genetic risk of schizophrenia. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Multisegment Foot Kinematic and Kinetic Compensations in Level and Uphill Walking Following Tibiotalar Arthrodesis.

PubMed

Bruening, Dustin A; Cooney, Timothy E; Ray, Matthew S; Daut, Gregory A; Cooney, Kevin M; Galey, Stephanie M

2016-10-01

Foot and ankle movement alterations following ankle arthrodesis are still not well understood, particularly those that might contribute to the documented increase in adjacent joint arthritis. Generalized tarsal hypermobility has long been postulated, but not confirmed in gait or functional movements. The purpose of this study was to more thoroughly evaluate compensation mechanisms used by arthrodesis patients during level and uphill gait through a variety of measurement modalities and a detailed breakdown of gait phases. Level ground and uphill gait of 14 unilateral tibiotalar arthrodesis patients and 14 matched controls was analyzed using motion capture, force, and pressure measurements in conjunction with a kinetic multisegment foot model. The affected limb exhibited several marked differences compared to the controls and to the unaffected limb. In loading response, ankle eversion was reduced but without a reduction in tibial rotation. During the second rocker, ankle dorsiflexion was reduced, yet was still considerable, suggesting compensatory talar articulation (subtalar and talonavicular) motion since no differences were seen at the midtarsal joint. Also during the second rocker, subjects abnormally internally rotated the tibia while moving their center of pressure laterally. Third rocker plantarflexion motion, moments, and powers were substantially reduced on the affected side and to a lesser extent on the unaffected side. Sagittal plane hypermobility is probable during the second rocker in the talar articulations following tibiotalar fusion, but is unlikely in other midfoot joints. The normal coupling between frontal plane hindfoot motion and tibial rotation in early and mid stance was also clearly disrupted. These alterations reflect a complex compensatory movement pattern that undoubtedly affects the function of arthrodesis patients, likely alters the arthrokinematics of the talar joints (which may be a mechanism for arthritis development), and should be considered in future arthrodesis as well as arthroplasty research. Level III, comparative study. © The Author(s) 2016.

Pathway-based outlier method reveals heterogeneous genomic structure of autism in blood transcriptome

PubMed Central

2013-01-01

Background Decades of research strongly suggest that the genetic etiology of autism spectrum disorders (ASDs) is heterogeneous. However, most published studies focus on group differences between cases and controls. In contrast, we hypothesized that the heterogeneity of the disorder could be characterized by identifying pathways for which individuals are outliers rather than pathways representative of shared group differences of the ASD diagnosis. Methods Two previously published blood gene expression data sets – the Translational Genetics Research Institute (TGen) dataset (70 cases and 60 unrelated controls) and the Simons Simplex Consortium (Simons) dataset (221 probands and 191 unaffected family members) – were analyzed. All individuals of each dataset were projected to biological pathways, and each sample’s Mahalanobis distance from a pooled centroid was calculated to compare the number of case and control outliers for each pathway. Results Analysis of a set of blood gene expression profiles from 70 ASD and 60 unrelated controls revealed three pathways whose outliers were significantly overrepresented in the ASD cases: neuron development including axonogenesis and neurite development (29% of ASD, 3% of control), nitric oxide signaling (29%, 3%), and skeletal development (27%, 3%). Overall, 50% of cases and 8% of controls were outliers in one of these three pathways, which could not be identified using group comparison or gene-level outlier methods. In an independently collected data set consisting of 221 ASD and 191 unaffected family members, outliers in the neurogenesis pathway were heavily biased towards cases (20.8% of ASD, 12.0% of control). Interestingly, neurogenesis outliers were more common among unaffected family members (Simons) than unrelated controls (TGen), but the statistical significance of this effect was marginal (Chi squared P < 0.09). Conclusions Unlike group difference approaches, our analysis identified the samples within the case and control groups that manifested each expression signal, and showed that outlier groups were distinct for each implicated pathway. Moreover, our results suggest that by seeking heterogeneity, pathway-based outlier analysis can reveal expression signals that are not apparent when considering only shared group differences. PMID:24063311

Temporal discrimination, a cervical dystonia endophenotype: penetrance and functional correlates.

PubMed

Kimmich, Okka; Molloy, Anna; Whelan, Robert; Williams, Laura; Bradley, David; Balsters, Joshua; Molloy, Fiona; Lynch, Tim; Healy, Daniel G; Walsh, Cathal; O'Riordan, Seán; Reilly, Richard B; Hutchinson, Michael

2014-05-01

The pathogenesis of adult-onset primary dystonia remains poorly understood. There is variable age-related and gender-related expression of the phenotype, the commonest of which is cervical dystonia. Endophenotypes may provide insight into underlying genetic and pathophysiological mechanisms of dystonia. The temporal discrimination threshold (TDT)-the shortest time interval at which two separate stimuli can be detected as being asynchronous-is abnormal both in patients with cervical dystonia and in their unaffected first-degree relatives. Functional magnetic resonance imaging (fMRI) studies have shown that putaminal activation positively correlates with the ease of temporal discrimination between two stimuli in healthy individuals. We hypothesized that abnormal temporal discrimination would exhibit similar age-related and gender-related penetrance as cervical dystonia and that unaffected relatives with an abnormal TDT would have reduced putaminal activation during a temporal discrimination task. TDTs were examined in a group of 192 healthy controls and in 158 unaffected first-degree relatives of 84 patients with cervical dystonia. In 24 unaffected first-degree relatives, fMRI scanning was performed during a temporal discrimination task. The prevalence of abnormal TDTs in unaffected female relatives reached 50% after age 48 years; whereas, in male relatives, penetrance of the endophenotype was reduced. By fMRI, relatives who had abnormal TDTs, compared with relatives who had normal TDTs, had significantly less activation in the putamina and in the middle frontal and precentral gyri. Only the degree of reduction of putaminal activity correlated significantly with worsening of temporal discrimination. These findings further support abnormal temporal discrimination as an endophenotype of cervical dystonia involving disordered basal ganglia circuits. © 2014 International Parkinson and Movement Disorder Society.

Physiological effects of hydrogen sulfide inhalation during exercise in healthy men.

PubMed

Bhambhani, Y; Singh, M

1991-11-01

Occupational exposure to hydrogen sulfide (H2S) is prevalent in a variety of industries. H2S when inhaled 1) is oxidized into a sulfate or a thiosulfate by oxygen bound to hemoglobin and 2) suppresses aerobic metabolism by inhibiting cytochrome oxidase (c and aa3) activity in the electron transport chain. The purpose of this study was to examine the acute effects of oral inhalation of H2S on the physiological responses during graded cycle exercise performed to exhaustion in healthy male subjects. Sixteen volunteers were randomly exposed to 0 (control), 0.5, 2.0, and 5.0 ppm H2S on four separate occasions. Compared with the control values, the results indicated that the heart rate and expired ventilation were unaffected as a result of the H2S exposures during submaximal and maximal exercise. The oxygen uptake had a tendency to increase, whereas carbon dioxide output had a tendency to decrease as a result of the H2S exposures, but only the 5.0 ppm exposure resulted in a significantly higher maximum oxygen uptake. Blood lactate concentrations increased significantly during submaximal and maximal exercise as a result of the 5.0 ppm exposure. Despite these large increases in lactate concentration, the maximal power output of the subjects was not significantly altered as a result of the 5.0 ppm H2S exposure. It was concluded that healthy young male subjects could safely exercise at their maximum metabolic rates while breathing 5.0 ppm H2S without experiencing a significant reduction in their maximum physical work capacity during short-term incremental exercise.

MRI assessment of cerebral oxygen metabolism in cocaine-addicted individuals: Hypoactivity and dose dependence

PubMed Central

Liu, Peiying; Lu, Hanzhang; Filbey, Francesca M.; Tamminga, Carol A.; Cao, Yan; Adinoff, Bryon

2014-01-01

Long-term cocaine use is known to negatively impact neural and cerebrovascular systems. However, the use of imaging markers to separately assess these parameters remains challenging. The primary reason is that most functional imaging markers such as cerebral blood flow, functional connectivity, and task-evoked functional MRI are known to reflect a complex interplay between neural and vascular components, thus the interpretation of the results is not straightforward. The goal of the present study is to examine neural-activity-specific changes in cocaine addiction, using cerebral metabolic rate of oxygen (CMRO2) as a surrogate marker of aggregated neural activity. We applied a recently developed CMRO2 technique in 13 cocaine-addicted subjects and 13 age and gender matched control subjects, and examined the impact of long-term cocaine use on CMRO2. Our results showed that CMRO2 in cocaine-addicted subjects (152±16 μmol/100g/min) is significantly lower (p=0.031) than that in controls (169±20 μmol/100g/min). Furthermore, the severity of this decreased metabolism is associated with lifetime cocaine use (p=0.05). Additionally, the CMRO2 reduction was accompanied by a trend of decrease in cerebral blood flow (p=0.058), but venous oxygenation was unaffected (p=0.96), which suggested that the CMRO2 change may be attributed to a vascular deficiency in chronic cocaine users. To our knowledge, this is the first study to measure CMRO2 in cocaine addicted individuals. Our findings suggest that CMRO2 may be a promising approach for assessing the long-term effects of cocaine use on the brain. PMID:24757009

A Multi-Cohort Study of ApoE ɛ4 and Amyloid-β Effects on the Hippocampus in Alzheimer’s Disease

PubMed Central

Khan, Wasim; Giampietro, Vincent; Banaschewski, Tobias; Barker, Gareth J.; Bokde, Arun L.W.; Büchel, Christian; Conrod, Patricia; Flor, Herta; Frouin, Vincent; Garavan, Hugh; Gowland, Penny; Heinz, Anreas; Ittermann, Bernd; Lemaître, Hervé; Nees, Frauke; Paus, Tomas; Pausova, Zdenka; Rietschel, Marcella; Smolka, Michael N.; Ströhle, Andreas; Gallinat, Jeurgen; Vellas, Bruno; Soininen, Hilkka; Kloszewska, Iwona; Tsolaki, Magda; Mecocci, Patrizia; Spenger, Christian; Villemagne, Victor L.; Masters, Colin L.; Muehlboeck, J-Sebastian; Bäckman, Lars; Fratiglioni, Laura; Kalpouzos, Grégoria; Wahlund, Lars-Olof; Schumann, Gunther; Lovestone, Simon; Williams, Steven C.R.; Westman, Eric; Simmons, Andrew

2017-01-01

The apolipoprotein E (APOE) gene has been consistently shown to modulate the risk of Alzheimer’s disease (AD). Here, using an AD and normal aging dataset primarily consisting of three AD multi-center studies (n = 1,781), we compared the effect of APOE and amyloid-β (Aβ) on baseline hippocampal volumes in AD patients, mild cognitive impairment (MCI) subjects, and healthy controls. A large sample of healthy adolescents (n = 1,387) was also used to compare hippocampal volumes between APOE groups. Subjects had undergone a magnetic resonance imaging (MRI) scan and APOE genotyping. Hippocampal volumes were processed using FreeSurfer. In the AD and normal aging dataset, hippocampal comparisons were performed in each APOE group and in ɛ4 carriers with positron emission tomography (PET) Aβ who were dichotomized (Aβ+/Aβ–) using previous cut-offs. We found a linear reduction in hippocampal volumes with ɛ4 carriers possessing the smallest volumes, ɛ3 carriers possessing intermediate volumes, and ɛ2 carriers possessing the largest volumes. Moreover, AD and MCI ɛ4 carriers possessed the smallest hippocampal volumes and control ɛ2 carriers possessed the largest hippocampal volumes. Subjects with both APOE ɛ4 and Aβ positivity had the lowest hippocampal volumes when compared to Aβ- ɛ4 carriers, suggesting a synergistic relationship between APOE ɛ4 and Aβ. However, we found no hippocampal volume differences between APOE groups in healthy 14-year-old adolescents. Our findings suggest that the strongest neuroanatomic effect of APOE ɛ4 on the hippocampus is observed in AD and groups most at risk of developing the disease, whereas hippocampi of old and young healthy individuals remain unaffected. PMID:28157104

Neuronal Antibody Biomarkers for Sydenham’s Chorea Identify a New Group of Children with Chronic Recurrent Episodic Acute Exacerbations of Tic and Obsessive Compulsive Symptoms Following a Streptococcal Infection

PubMed Central

Singer, Harvey S.; Mascaro-Blanco, Adda; Alvarez, Kathy; Morris-Berry, Christina; Kawikova, Ivana; Ben-Pazi, Hilla; Thompson, Carol B.; Ali, Syed F.; Kaplan, Edward L.; Cunningham, Madeleine W.

2015-01-01

Several autoantibodies (anti-dopamine 1 (D1R) and 2 (D2R) receptors, anti-tubulin, anti-lysoganglioside-GM1) and antibody-mediated activation of calcium calmodulin dependent protein kinase II (CaMKII) signaling activity are elevated in children with Sydenham’s chorea (SC). Recognizing proposed clinical and autoimmune similarities between SC and PANDAS (pediatric autoimmune neuropsychiatric disorder associated with a streptococcal infection), we sought to identify serial biomarker changes in a slightly different population. Antineuronal antibodies were measured in eight children (mean 11.3 years) with chronic, dramatic, recurrent tics and obsessive-compulsive disorder (OCD) associated with a group A β-hemolytic streptococcal (GABHS) respiratory tract infection, but differing because they lacked choreiform movements. Longitudinal serum samples in most subjects included two pre-exacerbation samples, Exac), one midst Exac (abrupt recurrence of tic/OCD; temporally association with a GABHS infection in six of eight subjects), and two post-Exac. Controls included four groups of unaffected children (n = 70; mean 10.8 years) obtained at four different institutions and published controls. Clinical exacerbations were not associated with a significant rise in antineuronal antibody titers. CaMKII activation was increased at the GABHS exacerbation point in 5/6 subjects, exceeded combined and published control’s 95th percentile at least once in 7/8 subjects, and median values were elevated at each time point. Anti-tubulin and anti-D2R titers did not differ from published or combined control group’s 95th percentile or median values. Differences in anti-lysoganglioside-GM1 and anti-D1R titers were dependent on the selected control. Variances in antibody titers and CaMKII activation were identified among the institutional control groups. Based on comparisons to published studies, results identify two groups of PANDAS: 1) a cohort, represented by this study, which lacks choreiform movements and elevated antibodies against D2R; 2) the originally reported group with choreiform movements and elevated anti-D2R antibodies, similar to SC. Increased antibody mediated CaMKII activation was found in both groups and requires further study as a potential biomarker. PMID:25793715

Computational substrates of social norm enforcement by unaffected third parties.

PubMed

Zhong, Songfa; Chark, Robin; Hsu, Ming; Chew, Soo Hong

2016-04-01

Enforcement of social norms by impartial bystanders in the human species reveals a possibly unique capacity to sense and to enforce norms from a third party perspective. Such behavior, however, cannot be accounted by current computational models based on an egocentric notion of norms. Here, using a combination of model-based fMRI and third party punishment games, we show that brain regions previously implicated in egocentric norm enforcement critically extend to the important case of norm enforcement by unaffected third parties. Specifically, we found that responses in the ACC and insula cortex were positively associated with detection of distributional inequity, while those in the anterior DLPFC were associated with assessment of intentionality to the violator. Moreover, during sanction decisions, the subjective value of sanctions modulated activity in both vmPFC and rTPJ. These results shed light on the neurocomputational underpinnings of third party punishment and evolutionary origin of human norm enforcement. Copyright © 2016 Elsevier Inc. All rights reserved.

Prevalence of syringomyelia in clinically unaffected Cavalier King Charles Spaniels in Germany (2006-2016).

PubMed

Schulze, Sabine; Refai, Miriam; Deutschland, Martin; Failing, Klaus; Schmidt, Martin

2018-06-01

The aim of the study was to investigate the prevalence of syringomyelia in clinically unaffected Cavalier King Charles Spaniels (CKCS) in Germany. From 2006 to 2016 a total of 339 asymptomatic CKCSs from all over Germany were included. Age ranged from 3 months to 11 years (mean 3.72 years ± 2.17 years). T1- and T2-weighted magnetic resonance images of the head and cervical spine were obtained. Overall, 163 out of 339 (48.1 %) CKCSs showed evidence of syringomyelia. The results (odds ratio of 1.27 per year; p < 0.0001) corroborate the findings of other studies, in which the risk of developing syringomyelia increases with age. In conclusion, around half of the dogs within the German CKCS population are affected by syringomyelia. The prevalence of syringomyelia of the German CKCS population is similar to that of the British CKCS population, which is subjected to breeding strategies on the basis of magnetic resonance imaging investigations. Schattauer GmbH.

α-Mangostin Disrupts the Development of Streptococcus mutans Biofilms and Facilitates Its Mechanical Removal

PubMed Central

Nguyen, Phuong Thi Mai; Falsetta, Megan L.; Hwang, Geelsu; Gonzalez-Begne, Mireya; Koo, Hyun

2014-01-01

α-Mangostin (αMG) has been reported to be an effective antimicrobial agent against planktonic cells of Streptococcus mutans, a biofilm-forming and acid-producing cariogenic organism. However, its anti-biofilm activity remains to be determined. We examined whether αMG, a xanthone purified from Garcinia mangostana L grown in Vietnam, disrupts the development, acidogenicity, and/or the mechanical stability of S. mutans biofilms. Treatment regimens simulating those experienced clinically (twice-daily, 60 s exposure each) were used to assess the bioactivity of αMG using a saliva-coated hydroxyapatite (sHA) biofilm model. Topical applications of early-formed biofilms with αMG (150 µM) effectively reduced further biomass accumulation and disrupted the 3D architecture of S. mutans biofilms. Biofilms treated with αMG had lower amounts of extracellular insoluble and intracellular iodophilic polysaccharides (30–45%) than those treated with vehicle control (P<0.05), while the number of viable bacterial counts was unaffected. Furthermore, αMG treatments significantly compromised the mechanical stability of the biofilm, facilitating its removal from the sHA surface when subjected to a constant shear stress of 0.809 N/m2 (>3-fold biofilm detachment from sHA vs. vehicle-treated biofilms; P<0.05). Moreover, acid production by S. mutans biofilms was disrupted following αMG treatments (vs. vehicle-control, P<0.05). The activity of enzymes associated with glucan synthesis, acid production, and acid tolerance (glucosyltransferases B and C, phosphotransferase-PTS system, and F1F0-ATPase) were significantly inhibited by αMG. The expression of manL, encoding a key component of the mannose PTS, and gtfB were slightly repressed by αMG treatment (P<0.05), while the expression of atpD (encoding F-ATPase) and gtfC genes was unaffected. Hence, this study reveals that brief exposures to αMG can disrupt the development and structural integrity of S. mutans biofilms, at least in part via inhibition of key enzymatic systems associated with exopolysaccharide synthesis and acidogenicity. αMG could be an effective anti-virulence additive for the control and/or removal of cariogenic biofilms. PMID:25350668

No impaired hemoglobin oxygenation in forearm muscles of patients with chronic CRPS-1.

PubMed

Brunnekreef, Jaap J J; Oosterhof, Jan; Wolff, André P; Crul, Ben J P; Wilder-Smith, Oliver H G; Oostendorp, Rob A B

2009-01-01

Physiotherapy is considered an important treatment option in patients with upper limb complex regional pain syndrome type-1 (CRPS-1). In case of chronic CRPS-1, exercise therapy of the affected limb forms an important part of the physiotherapeutic program. We investigated whether muscle loading in chronic CRPS-1 patients is associated with impairments in muscle circulation of the forearm of the affected limb. Thirty patients with chronic CRPS-1 unilaterally affecting their upper limbs, and 30 age-matched and sex-matched control participants were included in this study. Local muscle blood flow and hemoglobin oxygenation were measured by near infrared spectroscopy within the muscles of the forearm at rest, after 1-minute isometric handgrip exercises, and after arterial occlusion. Main outcome parameters were: local muscle blood flow, O2 consumption (mVO2), and postischemic reoxygenation (ReOx). We found no differences in baseline muscle blood flow, mVO2, and ReOx between the affected CRPS-1, unaffected CRPS-1, and control arms. After exercise, mVO2 of the affected CRPS-1 arms was not different from the clinically unaffected CRPS-1 arms. Furthermore, in comparison with the control arms, unaffected CRPS-1 arms showed no difference in mVO2 or ReOx. Muscle loading does not seems to be related to impairments in muscle oxygen uptake in forearm muscles of upper limbs affected by chronic CRPS-1. Our results suggest that exercise therapy can be safely used in physiotherapeutic training programs for chronic CRPS-1 of the upper limb.

Exploring the cognitive features in children with autism spectrum disorder, their co-twins, and typically developing children within a population-based sample.

PubMed

Brunsdon, Victoria E A; Colvert, Emma; Ames, Catherine; Garnett, Tracy; Gillan, Nicola; Hallett, Victoria; Lietz, Stephanie; Woodhouse, Emma; Bolton, Patrick; Happé, Francesca

2015-08-01

The behavioural symptoms of autism spectrum disorder (ASD) are thought to reflect underlying cognitive deficits/differences. The findings in the literature are somewhat mixed regarding the cognitive features of ASD. This study attempted to address this issue by investigating a range of cognitive deficits and the prevalence of multiple cognitive atypicalities in a large population-based sample comprising children with ASD, their unaffected co-twins, and typically developing comparison children. Participants included families from the Twins Early Development Study (TEDS) where one or both children met diagnostic criteria for ASD. Overall, 181 adolescents with a diagnosis of ASD and 73 unaffected co-twins were included, plus an additional 160 comparison control participants. An extensive cognitive battery was administered to measure IQ, central coherence, executive function, and theory of mind ability. Differences between groups (ASD, co-twin, control) are reported on tasks assessing theory of mind, executive function, and central coherence. The ASD group performed atypically in significantly more cognitive tasks than the unaffected co-twin and control groups. Nearly a third of the ASD group presented with multiple cognitive atypicalities. Multiple cognitive atypicalities appear to be a characteristic, but not universal feature, of ASD. Further work is needed to investigate whether specific cognitive atypicalities, either alone or together, are related to specific behaviours characteristic of ASD. © 2014 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.

Regional brain activity during early visual perception in unaffected siblings of schizophrenia patients.

PubMed

Lee, Junghee; Cohen, Mark S; Engel, Stephen A; Glahn, David; Nuechterlein, Keith H; Wynn, Jonathan K; Green, Michael F

2010-07-01

Visual masking paradigms assess the early part of visual information processing, which may reflect vulnerability measures for schizophrenia. We examined the neural substrates of visual backward performance in unaffected sibling of schizophrenia patients using functional magnetic resonance imaging (fMRI). Twenty-one unaffected siblings of schizophrenia patients and 19 healthy controls performed a backward masking task and three functional localizer tasks to identify three visual processing regions of interest (ROI): lateral occipital complex (LO), the motion-sensitive area, and retinotopic areas. In the masking task, we systematically manipulated stimulus onset asynchronies (SOAs). We analyzed fMRI data in two complementary ways: 1) an ROI approach for three visual areas, and 2) a whole-brain analysis. The groups did not differ in behavioral performance. For ROI analysis, both groups increased activation as SOAs increased in LO. Groups did not differ in activation levels of the three ROIs. For whole-brain analysis, controls increased activation as a function of SOAs, compared with siblings in several regions (i.e., anterior cingulate cortex, posterior cingulate cortex, inferior prefrontal cortex, inferior parietal lobule). The study found: 1) area LO showed sensitivity to the masking effect in both groups; 2) siblings did not differ from controls in activation of LO; and 3) groups differed significantly in several brain regions outside visual processing areas that have been related to attentional or re-entrant processes. These findings suggest that LO dysfunction may be a disease indicator rather than a risk indicator for schizophrenia. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

The rat suprachiasmatic nucleus: the master clock ticks at 30 Hz

PubMed Central

Tsuji, Takahiro; Tsuji, Chiharu; Ludwig, Mike

2016-01-01

Key points Light‐responsive neurones in the rat suprachiasmatic nucleus discharge with a harmonic distribution of interspike intervals, whereas unresponsive neurones seldom do.This harmonic patterning has a fundamental frequency of close to 30 Hz, and is the same in light‐on cells as in light‐off cells, and is unaffected by exposure to light.Light‐on cells are more active than light‐off cells in both subjective day and subjective night, and both light‐on cells and light‐off cells respond more strongly to changes in light intensity during the subjective night than during the subjective day.Paired recordings indicate that the discharge of adjacent light‐responsive cells is very tightly synchronized.The gap junction inhibitor carbenoxolone increases the spontaneous activity of suprachiasmatic nucleus neurones but does not block the harmonic discharge patterning. Abstract The suprachiasmatic nucleus (SCN) of the hypothalamus has an essential role in orchestrating circadian rhythms of behaviour and physiology. In the present study, we recorded from single SCN neurons in urethane‐anaesthetized rats, categorized them by the statistical features of their electrical activity and by their responses to light, and examined how activity in the light phase differs from activity in the dark phase. We classified cells as light‐on cells or light‐off cells according to how their firing rate changed in acute response to light, or as non‐responsive cells. In both sets of light‐responsive neurons, responses to light were stronger at subjective night than in subjective day. Neuronal firing patterns were analysed by constructing hazard functions from interspike interval data. For most light‐responsive cells, the hazard functions showed a multimodal distribution, with a harmonic sequence of modes, indicating that spike activity was driven by an oscillatory input with a fundamental frequency of close to 30 Hz; this harmonic pattern was rarely seen in non‐responsive SCN cells. The frequency of the rhythm was the same in light‐on cells as in light‐off cells, was the same in subjective day as at subjective night, and was unaffected by exposure to light. Paired recordings indicated that the discharge of adjacent light‐responsive neurons was very tightly synchronized, consistent with electrical coupling. PMID:27061101

Identification of novel mutations of the CHST6 gene in Vietnamese families affected with macular corneal dystrophy in two generations.

PubMed

Ha, Nguyen Thanh; Chau, Hoang Minh; Cung, Le Xuan; Thanh, Ton Kim; Fujiki, Keiko; Murakami, Akira; Hiratsuka, Yoshimune; Hasegawa, Nobuko; Kanai, Atsushi

2003-08-01

To report the clinical and genetic findings of Vietnamese families affected with macular corneal dystrophy (MCD) in 2 generations. Two families, including 7 patients and 3 unaffected members, were examined clinically. Blood samples were collected. Fifty normal Vietnamese individuals were used as controls. Genomic DNA was extracted from leukocytes. Analysis of the carbohydrate sulfotransferase (CHST6) gene was performed using polymerase chain reaction and direct sequencing. The typical form of MCD was recognized in family B, in which sequencing of CHST6 gene revealed an nt 1067-1068ins(GGCCGTG) mutation (frameshift after 125V) homozygously in MCD patients and heterozygously in the unaffected members. Family N also showed clinical features of MCD, moderate in the mother but severe in the affected son. Sequencing revealed a single heterozygous Arg211Gln in the mother, compound heterozygous Arg211Gln+ Gln82Stop in the affected son, and heterozygous Arg211Gln mutation in the unaffected members. The identified mutations in these pedigrees were excluded from normal controls. The novel frameshift and compound heterozygous mutations might be responsible for MCD in the families studied. The phenotypic variation between affected parents and offspring was unclear. In family N, severe MCD phenotype seen in the affected son may be due the fact that he had an early stop codon mutation (Gln82Stop).

Apolipoproteins C-II and C-III as nutritional markers unaffected by inflammation.

PubMed

Isshiki, Miwa; Hirayama, Satoshi; Ueno, Tsuyoshi; Ito, Masayuki; Furuta, Ayaka; Yano, Kouji; Yamatani, Kotoko; Sugihara, Masami; Idei, Mayumi; Miida, Takashi

2018-06-01

Rapid turnover proteins (RTPs), such as transthyretin (TTR), retinol binding protein (RBP), and transferrin (Tf), provide an accurate assessment of nutritional status but are susceptible to inflammation. Lipid-related markers, which have short half-lives in serum, may be better suited for nutritional assessment. We sought to identify sensitive nutritional markers unaffected by inflammation. Fasting serum samples were collected from 30 malnourished inpatients and 25 healthy volunteers. Malnourished inpatients were divided into 2 groups: a low-C-reactive protein (CRP) group (CRP < 20 mg/l, n = 15) and a high-CRP group (CRP ≥ 20 mg/l, n = 15). Lipid-related markers, traditional nutritional markers, RTPs, micronutrients, and ketone bodies were measured and compared among the groups. Apolipoprotein (Apo)C-II and ApoC-III concentrations were lower in malnourished inpatients than in the control group. There was no significant difference in ApoC-II and ApoC-III between the low- and high-CRP groups. Carnitine transporters and ketone bodies did not show a significant difference among the three groups. Albumin, TTR, RBP, and Tf concentrations were lowest in the high-CRP group, intermediate in the low-CRP group, and highest in the control group. These results indicate that ApoC-II and ApoC-III are appropriate nutritional biomarkers unaffected by inflammation. Copyright © 2018 Elsevier B.V. All rights reserved.

Identification and validation of mixed anxiety-depression.

PubMed

Hettema, J M; Aggen, S H; Kubarych, T S; Neale, M C; Kendler, K S

2015-10-01

Mixed anxiety-depression (MAD) has been under scrutiny to determine its potential place in psychiatric nosology. The current study sought to investigate its prevalence, clinical characteristics, course and potential validators. Restricted latent-class analyses were fit to 12-month self-reports of depression and anxiety symptom criteria in a large population-based sample of twins. Classes were examined across an array of relevant indicators (demographics, co-morbidity, adverse life events, clinical significance and twin concordance). Longitudinal analyses investigated the stability of, and transitions between, these classes for two time periods approximately 1.5 years apart. In all analyses, a class exhibiting levels of MAD symptomatology distinctly above the unaffected subjects yet having low prevalence of either major depression (MD) or generalized anxiety disorder (GAD) was identified. A restricted four-class model, constraining two classes to have no prior disorder history to distinguish residual or recurrent symptoms from new onsets in the last year, provided an interpretable classification: two groups with no prior history that were unaffected or had MAD and two with prior history having relatively low or high symptom levels. Prevalence of MAD was substantial (9-11%), and subjects with MAD differed quantitatively but not qualitatively from those with lifetime MD or GAD across the clinical validators examined. Our findings suggest that MAD is a commonly occurring, identifiable syndromal subtype that warrants further study and consideration for inclusion in future nosologic systems.

Gently restless: association of ADHD-like traits with response inhibition and interference control.

PubMed

Polner, Bertalan; Aichert, Désirée; Macare, Christine; Costa, Anna; Ettinger, Ulrich

2015-12-01

Impairment of inhibition-related functions is one of the most pronounced cognitive deficits found in attention-deficit/hyperactivity disorder (ADHD). Compelling evidence from studies of unaffected relatives of patients with ADHD and of ADHD-like traits in healthy subjects suggest the continuous distribution of ADHD symptoms in the population. A more subtle inhibitory deficit can also be found in healthy relatives of patients and in subjects with high ADHD-like traits. Here, we examined the relationship between inhibitory performance and ADHD-like traits, for the first time, in a large sample of healthy adults by applying multiple, widely used tests of inhibition-related functions. ADHD-like traits, in general, were independently predicted by Stroop interference score and, at trend level, by go/no-go commission error rate while controlling for socio-demographic factors, verbal intelligence and neuroticism. Additionally, higher inattentive traits were related to worse Stroop performance at trend level, and higher hyperactive/impulsive traits were significantly associated with more go/no-go commission errors. ADHD-like traits were strongly related to neuroticism. The study shows that individual differences in ADHD-like traits are related to variance in fundamental inhibition-related functions over and above effects of negative affect regulation, but the relationships tend to be small. The results suggest the quasi-dimensionality of ADHD and raise further questions about the relationship between genetic factors and the deficit of inhibition-related functions in the ADHD spectrum.

Asymmetric vestibular evoked myogenic potentials in unilateral Menière patients

PubMed Central

Wit, H. P.

2010-01-01

Vestibular evoked myogenic potentials (VEMPs) were measured in 22 unilateral Menière patients with monaural and binaural stimulation with 250 and 500 Hz tone bursts. For all measurement situations significantly lower VEMP amplitudes were on average measured at the affected side compared to the unaffected side. Unilateral Menière patients have, in contrast to normal subjects, asymmetric VEMPs, indicating a permanently affected vestibular (most likely otolith) system at the side of hearing loss. The diagnostic value of VEMP amplitude asymmetry measurement in individual patients is low, because of the large overlap of the VEMP amplitude asymmetry range for unilateral Menière patients with that for normal subjects. PMID:20665043

Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects.

PubMed

Hsia, Chien-Hsun; Shen, Ming-Ching; Lin, Jen-Shiou; Wen, Yao-Ke; Hwang, Kai-Lin; Cham, Thau-Ming; Yang, Nae-Cherng

2009-03-01

Nattokinase, a serine proteinase from Bacillus subtilis, is considered to be one of the most active functional ingredients found in natto. In this study, we hypothesized that nattokinase could reduce certain factors of blood clotting and lipids that are associated with an increase risk for cardiovascular disease (CVD). Thus, an open-label, self-controlled clinical trial was conducted on subjects of the following groups: healthy volunteers (Healthy Group), patients with cardiovascular risk factors (Cardiovascular Group), and patients undergoing dialysis (Dialysis Group). All subjects ingested 2 capsules of nattokinase (2000 fibrinolysis units per capsule) daily orally for 2 months. The laboratory measurements were performed on the screening visit and, subsequently, regularly after the initiation of the study. The intent-to-treat analysis was performed on all 45 enrolled subjects. By use of mixed model analysis, a significant time effect, but not group effect, was observed in the change from baseline of fibrinogen (P = .003), factor VII (P < .001), and factor VIII (P < .001), suggesting that the plasma levels of the 3 coagulation factors continuously declined during intake; also, the extents of decrease were similar between groups. After 2 months of administration, fibrinogen, factor VII, and factor VIII decreased 9%, 14%, and 17%, respectively, for the Healthy Group; 7%, 13%, and 19%, respectively, for the Cardiovascular Group; and 10%, 7%, and 19%, respectively, for the Dialysis Group, whereas blood lipids were unaffected by nattokinase. No significant changes of uric acid or notable adverse events were observed in any of the subjects. In summary, this study showed that oral administration of nattokinase could be considered as a CVD nutraceutical by decreasing plasma levels of fibrinogen, factor VII, and factor VIII.

Effects of affective picture viewing on postural control.

PubMed

Stins, John F; Beek, Peter J

2007-10-04

Emotion theory holds that unpleasant events prime withdrawal actions, whereas pleasant events prime approach actions. Recent studies have suggested that passive viewing of emotion eliciting images results in postural adjustments, which become manifest as changes in body center of pressure (COP) trajectories. From those studies it appears that posture is modulated most when viewing pictures with negative valence. The present experiment was conducted to test the hypothesis that pictures with negative valence have a greater impact on postural control than neutral or positive ones. Thirty-four healthy subjects passively viewed a series of emotion eliciting images, while standing either in a bipedal or unipedal stance on a force plate. The images were adopted from the International Affective Picture System (IAPS). We analysed mean and variability of the COP and the length of the associated sway path as a function of emotion. The mean position of the COP was unaffected by emotion, but unipedal stance resulted in overall greater body sway than bipedal stance. We found a modest effect of emotion on COP: viewing pictures of mutilation resulted in a smaller sway path, but only in unipedal stance. We obtained valence and arousal ratings of the images with an independent sample of viewers. These subjects rated the unpleasant images as significantly less pleasant than neutral images, and the pleasant images as significantly more pleasant than neutral images. However, the subjects rated the images as overall less pleasant and less arousing than viewers in a closely comparable American study, pointing to unknown differences in viewer characteristics. Overall, viewing emotion eliciting images had little effect on body sway. Our finding of a reduction in sway path length when viewing pictures of mutilation was indicative of a freezing strategy, i.e. fear bradycardia. The results are consistent with current knowledge about the neuroanatomical organization of the emotion system and the neural control of behavior.

Effects of affective picture viewing on postural control

PubMed Central

Stins, John F; Beek, Peter J

2007-01-01

Background Emotion theory holds that unpleasant events prime withdrawal actions, whereas pleasant events prime approach actions. Recent studies have suggested that passive viewing of emotion eliciting images results in postural adjustments, which become manifest as changes in body center of pressure (COP) trajectories. From those studies it appears that posture is modulated most when viewing pictures with negative valence. The present experiment was conducted to test the hypothesis that pictures with negative valence have a greater impact on postural control than neutral or positive ones. Thirty-four healthy subjects passively viewed a series of emotion eliciting images, while standing either in a bipedal or unipedal stance on a force plate. The images were adopted from the International Affective Picture System (IAPS). We analysed mean and variability of the COP and the length of the associated sway path as a function of emotion. Results The mean position of the COP was unaffected by emotion, but unipedal stance resulted in overall greater body sway than bipedal stance. We found a modest effect of emotion on COP: viewing pictures of mutilation resulted in a smaller sway path, but only in unipedal stance. We obtained valence and arousal ratings of the images with an independent sample of viewers. These subjects rated the unpleasant images as significantly less pleasant than neutral images, and the pleasant images as significantly more pleasant than neutral images. However, the subjects rated the images as overall less pleasant and less arousing than viewers in a closely comparable American study, pointing to unknown differences in viewer characteristics. Conclusion Overall, viewing emotion eliciting images had little effect on body sway. Our finding of a reduction in sway path length when viewing pictures of mutilation was indicative of a freezing strategy, i.e. fear bradycardia. The results are consistent with current knowledge about the neuroanatomical organization of the emotion system and the neural control of behavior. PMID:17916245

Substance use disorders in adolescents with attention deficit hyperactivity disorder: a 4-year follow-up study.

PubMed

Groenman, Annabeth P; Oosterlaan, Jaap; Rommelse, Nanda; Franke, Barbara; Roeyers, Herbert; Oades, Robert D; Sergeant, Joseph A; Buitelaar, Jan K; Faraone, Stephen V

2013-08-01

To examine the relationship between a childhood diagnosis of attention deficit hyperactivity disorder (ADHD) with or without oppositional defiant disorder (ODD)/conduct disorder (CD) and the development of later alcohol/drug use disorder [psychoactive substance use disorder (PSUD)] and nicotine dependence in a large European sample of ADHD probands, their siblings and healthy control subjects. Subjects (n = 1017) were participants in the Belgian, Dutch and German part of the International Multicenter ADHD Genetics (IMAGE) study. IMAGE families were identified through ADHD probands aged 5-17 years attending out-patient clinics, and control subjects from the same geographic areas. After a follow-up period (mean: 4.4 years) this subsample was re-assessed at a mean age of 16.4 years. PSUD and nicotine dependence were assessed using the Diagnostic Interview Schedule for Children, Alcohol Use Disorders Identification Test, Drug Abuse Screening Test and Fagerström test for Nicotine Dependence. The ADHD sample was at higher risk of developing PSUD [hazard ratio (HR) = 1.77, 95% confidence interval (CI) = 1.05-3.00] and nicotine dependence (HR = 8.61, 95% CI = 2.44-30.34) than healthy controls. The rates of these disorders were highest for ADHD youth who also had CD, but could not be accounted for by this comorbidity. We did not find an increased risk of developing PSUD (HR = 1.18, 95% CI = 0.62-2.27) or nicotine dependence (HR = 1.89, 95% CI = 0.46-7.77) among unaffected siblings of ADHD youth. A childhood diagnosis of attention deficit hyperactivity disorder is a risk factor for psychoactive substance use disorder and nicotine dependence in adolescence and comorbid conduct disorder, but not oppositional defiant disorder, further increases the risk of developing psychoactive substance use disorder and nicotine dependence. © 2013 Society for the Study of Addiction.

Concordance of Macular Pigment Measurement Using Customized Heterochromatic Flicker Photometry and Fundus Autofluorescence in Age-Related Macular Degeneration.

PubMed

Akuffo, Kwadwo Owusu; Beatty, Stephen; Stack, Jim; Peto, Tunde; Leung, Irene; Corcoran, Laura; Power, Rebecca; Nolan, John M

2015-12-01

We compared macular pigment (MP) measurements using customized heterochromatic flicker photometry (Macular Metrics Densitometer) and dual-wavelength fundus autofluorescence (Heidelberg Spectralis HRA + OCT MultiColor) in subjects with early age-related macular degeneration (AMD). Macular pigment was measured in 117 subjects with early AMD (age, 44-88 years) using the Densitometer and Spectralis, as part of the Central Retinal Enrichment Supplementation Trial (CREST; ISRCTN13894787). Baseline and 6-month study visits data were used for the analyses. Agreement was investigated at four different retinal eccentricities, graphically and using indices of agreement, including Pearson correlation coefficient (precision), accuracy coefficient, and concordance correlation coefficient (ccc). Agreement was poor between the Densitometer and Spectralis at all eccentricities, at baseline (e.g., at 0.25° eccentricity, accuracy = 0.63, precision = 0.35, ccc = 0.22) and at 6 months (e.g., at 0.25° eccentricity, accuracy = 0.52, precision = 0.43, ccc = 0.22). Agreement between the two devices was significantly greater for males at 0.5° and 1.0° of eccentricity. At all eccentricities, agreement was unaffected by cataract grade. In subjects with early AMD, MP measurements obtained using the Densitometer and Spectralis are not statistically comparable and should not be used interchangeably in either the clinical or research setting. Despite this lack of agreement, statistically significant increases in MP, following 6 months of supplementation with macular carotenoids, were detected with each device, confirming that these devices are capable of measuring change in MP within subjects over time. (http://www.controlled-trials.com number, ISRCTN13894787.).

Rhythmic crowd bobbing on a grandstand simulator

NASA Astrophysics Data System (ADS)

Comer, A. J.; Blakeborough, A.; Williams, M. S.

2013-01-01

It is widely accepted that concerted human activity such as bouncing or bobbing can excite cantilever grandstands. Crowd coordination can be unwitting and may be exacerbated by structural motion caused by resonant structural response. This is an area of uncertainty in the design and analysis of modern grandstands. This paper presents experimental measurement and analysis of rhythmic crowd bobbing loads obtained from tests on a grandstand simulator with two distinct support conditions; (a) rigid, and; (b) flexible. It was found that significant structural vibration at the bobbing frequency did not increase the effective bobbing load. Structural motion at the bobbing frequency caused a reduction in the dynamic load factor (DLF) at the frequency of the second harmonic while those at the first and third harmonics were unaffected. Two plausible reasons for this are: (a) the bobbing group were unable to supply significant energy to the system at the frequency of the second harmonic; (b) the bobbing group altered their bobbing style to reduce the response of the grandstand simulator. It was deduced that the bobbing group did not absorb energy from the dynamic system. Furthermore, dynamic load factors for groups of test subjects bobbing on a rigid structure were typically greater than those of synthesised groups derived from individuals bobbing alone, possibly due to group effects such as audio and visual stimuli from neighbouring test subjects. Last, the vibration levels experienced by the test subjects appear to be below levels likely to cause discomfort. This is to be expected as the test subjects were themselves controlling the magnitude and duration of vibration for the bobbing tests considered.

Serum preadipocyte factor-1 concentrations in females with obesity and type 2 diabetes mellitus: the influence of very low calorie diet, acute hyperinsulinemia, and fenofibrate treatment.

PubMed

Kavalkova, P; Touskova, V; Roubicek, T; Trachta, P; Urbanova, M; Drapalova, J; Haluzikova, D; Mraz, M; Novak, D; Matoulek, M; Lacinova, Z; Haluzik, M

2013-10-01

Appropriate differentiation capacity of adipose tissue significantly affects its ability to store lipids and to protect nonadipose tissues against lipid spillover and development of insulin resistance. Preadipocyte factor-1 (Pref-1) is an important negative regulator of preadipocyte differentiation. The aim of our study was to explore the changes in circulating Pref-1 concentrations in female subjects with obesity (OB) (n=19), females with obesity and type 2 diabetes mellitus (T2DM) (n=22), and sex- and age-matched healthy control subjects (C) (n=22), and to study its modulation by very low calorie diet (VLCD), acute hyperinsulinemia during isoglycemic-hyperinsulinemic clamp, and 3 months' treatment with PPAR-α agonist fenofibrate. At baseline, serum Pref-1 concentrations were significantly higher in patients with T2DM compared to control group, while only nonsignificant trend towards higher levels was observed in OB group. 3 weeks of VLCD decreased Pref-1 levels in both OB and T2DM group, whereas 3 months of fenofibrate treatment had no significant effect. Hyperinsulinemia during the clamp significantly suppressed Pref-1 levels in both C and T2DM subjects and this suppression was unaffected by fenofibrate treatment. In a combined population of all groups, circulating Pref-1 levels correlated positively with insulin, leptin and glucose levels and HOMA (homeostasis model assessment) index. We conclude that elevated Pref-1 concentrations in T2DM subjects may contribute to impaired adipose tissue differentiation capacity associated with insulin resistance in obese patients with T2DM. The decrease of Pref-1 levels after VLCD may be involved in the improvement of metabolic status and the amelioration of insulin resistance in T2DM patients. © Georg Thieme Verlag KG Stuttgart · New York.

Intrinsic Patterns of Human Activity

NASA Astrophysics Data System (ADS)

Hu, Kun; Ivanov, Plamen Ch.; Chen, Zhi; Hilton, Michael; Stanley, H. Eugene; Shea, Steven

2003-03-01

Activity is one of the defining features of life. Control of human activity is complex, being influenced by many factors both extrinsic and intrinsic to the body. The most obvious extrinsic factors that affect activity are the daily schedule of planned events, such as work and recreation, as well as reactions to unforeseen or random events. These extrinsic factors may account for the apparently random fluctuations in human motion observed over short time scales. The most obvious intrinsic factors are the body clocks including the circadian pacemaker that influences our sleep/wake cycle and ultradian oscillators with shorter time scales [2, 3]. These intrinsic rhythms may account for the underlying regularity in average activity level over longer periods of up to 24 h. Here we ask if the known extrinsic and intrinsic factors fully account for all complex features observed in recordings of human activity. To this end, we measure activity over two weeks from forearm motion in subjects undergoing their regular daily routine. Utilizing concepts from statistical physics, we demonstrate that during wakefulness human activity possesses previously unrecognized complex dynamic patterns. These patterns of activity are characterized by robust fractal and nonlinear dynamics including a universal probability distribution and long-range power-law correlations that are stable over a wide range of time scales (from minutes to hours). Surprisingly, we find that these dynamic patterns are unaffected by changes in the average activity level that occur within individual subjects throughout the day and on different days of the week, and between subjects. Moreover, we find that these patterns persist when the same subjects undergo time-isolation laboratory experiments designed to account for the phase of the circadian pacemaker, and control the known extrinsic factors by restricting behaviors and manipulating scheduled events including the sleep/wake cycle. We attribute these newly discovered patterns to a robust intrinsic multi-scale dynamic regulation of human activity that is independent of known extrinsic factors, and independent from the circadian and ultradian rhythms.

Spectrum of Dental Phenotypes in Nonsyndromic Orofacial Clefting.

PubMed

Howe, B J; Cooper, M E; Vieira, A R; Weinberg, S M; Resick, J M; Nidey, N L; Wehby, G L; Marazita, M L; Moreno Uribe, L M

2015-07-01

Children with oral clefts show a wide range of dental anomalies, adding complexity to understanding the phenotypic spectrum of orofacial clefting. The evidence is mixed, however, on whether the prevalence of dental anomalies is elevated in unaffected relatives and is mostly based on small samples. In the largest international cohort to date of children with nonsyndromic clefts, their relatives, and controls, this study characterizes the spectrum of cleft-related dental anomalies and evaluates whether families with clefting have a significantly higher risk for such anomalies compared with the general population. A total of 3,811 individuals were included: 660 cases with clefts, 1,922 unaffected relatives, and 1,229 controls. Dental anomalies were identified from in-person dental exams or intraoral photographs, and case-control differences were tested using χ(2) statistics. Cases had higher rates of dental anomalies in the maxillary arch than did controls for primary (21% vs. 4%, P = 3 × 10(-8)) and permanent dentitions (51% vs. 8%, P = 4 × 10(-62)) but not in the mandible. Dental anomalies were more prevalent in cleft lip with cleft palate than other cleft types. More anomalies were seen in the ipsilateral side of the cleft. Agenesis and tooth displacements were the most common dental anomalies found in case probands for primary and permanent dentitions. Compared with controls, unaffected siblings (10% vs. 2%, P = 0.003) and parents (13% vs. 7%, P = 0.001) showed a trend for increased anomalies of the maxillary permanent dentition. Yet, these differences were nonsignificant after multiple-testing correction, suggesting genetic heterogeneity in some families carrying susceptibility to both overt clefts and dental anomalies. Collectively, the findings suggest that most affected families do not have higher genetic risk for dental anomalies than the general population and that the higher prevalence of anomalies in cases is primarily a physical consequence of the cleft and surgical interventions. © International & American Associations for Dental Research 2015.

DNA Damage Observed in Unaffected Individuals with Family History of T2DM

NASA Astrophysics Data System (ADS)

Ramesh, Nikhila; Abilash, V. G.

2017-11-01

Diabetes has been documented to cause high levels of DNA fragmentation in some cases. As diabetes is inheritable and influenced by both genetic and environmental factors, an investigation into the genomic stability of individuals who are strongly at risk of inheriting diabetes was conducted by inducing oxidative stress, as DNA damage in unaffected individuals could be a sign of onset of the disease or the presence of genetic alterations that reduce cellular defences against reactive oxygen species. In this study, alkaline comet assay was performed on isolated human leukocytes to determine whether individuals with a family history of Type 2 Diabetes Mellitus (T2DM) are more prone to DNA damage under oxidative stress. Visual scoring of comets showed that these individuals have higher degree of DNA damage compared to a control individual with no family history of Type 2 Diabetes Mellitus. Further studies with large sample could determine the presence of disabled cellular defences against oxidative stress in unaffected individuals and intervention with antioxidants could prevent or manage Type 2 Diabetes Mellitus and its complications.

Amygdala abnormalities in first-degree relatives of individuals with schizophrenia unmasked by benzodiazepine challenge

PubMed Central

Wolf, Daniel H.; Satterthwaite, Theodore D.; Loughead, James; Pinkham, Amy; Overton, Eve; Elliott, Mark A.; Dent, Gersham W.; Smith, Mark A.; Gur, Ruben C.; Gur, Raquel E.

2014-01-01

Rationale Impaired emotion processing in schizophrenia predicts broader social dysfunction and has been related to negative symptom severity and amygdala dysfunction. Pharmacological modulation of emotion-processing deficits and related neural abnormalities may provide useful phenotypes for pathophysiological investigation. Objectives We used an acute benzodiazepine challenge to identify and modulate potential emotion-processing abnormalities in 20 unaffected first-degree relatives of individuals with schizophrenia, compared to 25 control subjects without a family history of psychosis. Methods An oral 1mg dose of the short-acting anxiolytic benzodiazepine alprazolam was administered in a balanced crossover placebo-controlled double-blind design, preceding identical 3T fMRI sessions approximately 1 week apart. Primary outcomes included fMRI activity in amygdala and related regions during two facial emotion-processing tasks: emotion identification and emotion memory. Results Family members exhibited abnormally strong alprazolam-induced reduction in amygdala and hippocampus activation during emotion identification, compared to equal reduction in both groups for the emotion memory task. Conclusions GABAergic modulation with alprazolam produced differential responses in family members vs. controls, perhaps by unmasking underlying amygdalar and/or GABAergic abnormalities. Such pharmacological fMRI paradigms could prove useful for developing drugs targeting specific neural circuits to treat or prevent schizophrenia. PMID:21603892

Fractal Dynamics of Heartbeat Interval Fluctuations in Health and Disease

NASA Astrophysics Data System (ADS)

Meyer, M.; Marconi, C.; Rahmel, A.; Grassi, B.; Ferretti, G.; Skinner, J. E.; Cerretelli, P.

The dynamics of heartbeat interval time series were studied by a modified random walk analysis recently introduced as Detrended Fluctuation Analysis. In this analysis, the intrinsic fractal long-range power-law correlation properties of beat-to-beat fluctuations generated by the dynamical system (i.e. cardiac rhythm generator), after decomposition from extrinsic uncorrelated sources, can be quantified by the scaling exponent which, in healthy subjects, is about 1.0. The finding of a scaling coefficient of 1.0, indicating scale-invariant long-range power-law correlations (1/ƒnoise) of heartbeat fluctuations, would reflect a genuinely self-similar fractal process that typically generates fluctuations on a wide range of time scales. Lack of a characteristic time scale suggests that the neuroautonomic system underlying the control of heart rate dynamics helps prevent excessive mode-locking (error tolerance) that would restrict its functional responsiveness (plasticity) to environmental stimuli. The 1/ƒ dynamics of heartbeat interval fluctuations are unaffected by exposure to chronic hypoxia suggesting that the neuroautonomic cardiac control system is preadapted to hypoxia. Functional (hypothermia, cardiac disease) and/or structural (cardiac transplantation, early cardiac development) inactivation of neuroautonomic control is associated with the breakdown or absence of fractal complexity reflected by anticorrelated random walk-like dynamics, indicating that in these conditions the heart is unadapted to its environment.

A comparison of skeletal maturation in patients with tooth agenesis and unaffected controls assessed by the cervical vertebral maturation (CVM) index.

PubMed

Casey, Christine; Gill, Daljit S; Jones, Steven P

2013-12-01

The aims of this study were to (1) investigate if there is a difference in skeletal maturation between tooth agenesis and control patients and (2) whether skeletal maturation is affected by the severity of tooth agenesis. The cervical vertebral maturation (CVM) index can be used to assess skeletal maturation. A retrospective cross-sectional study. Eastman Dental Hospital, London, UK. A total of 360 cephalograms of patients aged 9-17 years (164 males and 196 females) allocated to four subgroups (mild, moderate and severe tooth agenesis patients, and controls) were assessed retrospectively. There were 90 patients in each of the four subgroups. The skeletal maturation of each subject was assessed both quantitatively and qualitatively using the CVM index. All patients in the study were either currently receiving treatment or had been discharged from the hospital. There was no statistically significant relationship between skeletal maturation and the presence of tooth agenesis. Furthermore, there was no statistically significant relationship between the skeletal maturity of patients and different severities of tooth agenesis. The data obtained from this group of patients and using this measurement tool alone does not supply sufficient reason to reject the null hypothesis. However, it suggests that it is possible that no difference exists between the groups.

Electrophysiological assessment of the effects of obstructive sleep apnea on cognition.

PubMed

Gelir, Ethem; Başaran, Cenk; Bayrak, Sibel; Yağcıoğlu, Süha; Budak, Murat Timur; Fırat, Hikmet; Ungan, Pekcan

2014-01-01

We used electrophysiological measures to investigate the effects of obstructive sleep apnea on attention, learning, and memory. Thirty subjects (OSA group, n = 15, control group n = 15) participated in n-back tests, accompanied by P300 recordings, to investigate working memory and attention. The mirror-drawing test was used to study procedural memory, and the trail-making test (TMT) was used to evaluate divided attention and executive function. No significant group difference in reaction time was found in the 0-back and 1-back tests. In the 2-back test, reaction times of patients were longer than those of the control group. No P300 wave was obtained in the OSA group in any (0-, 1-, or 2-back) n-back test. In contrast, in the control group, significant P300 waves were recorded except for the 2-back test. The mirror-drawing scores were unaffected by sleep apnea. There was no difference between groups in the TMT-A test on any of the trials. Although no group difference was found in the first or second trials of the TMT-B test, OSA patients were less successful in learning on the third trial. According to our study results, OSA affects attention and executive function adversely however, we could not detect a significant effect on working or procedural memory.

A 3-year prospective study of the effects of adjuvant treatments on cognition in women with early stage breast cancer

PubMed Central

Jenkins, V; Shilling, V; Deutsch, G; Bloomfield, D; Morris, R; Allan, S; Bishop, H; Hodson, N; Mitra, S; Sadler, G; Shah, E; Stein, R; Whitehead, S; Winstanley, J

2006-01-01

The neuropsychological performance of 85 women with early stage breast cancer scheduled for chemotherapy, 43 women scheduled for endocrine therapy and/or radiotherapy and 49 healthy control subjects was assessed at baseline (T1), postchemotherapy (or 6 months) (T2) and at 18 months (T3). Repeated measures analysis found no significant interactions or main effect of group after controlling for age and intelligence. Using a calculation to examine performance at an individual level, reliable decline on multiple tasks was seen in 20% of chemotherapy patients, 26% of nonchemotherapy patients and 18% of controls at T2 (18%, 14 and 11%, respectively, at T3). Patients who had experienced a treatment-induced menopause were more likely to show reliable decline on multiple measures at T2 (OR=2.6, 95% confidence interval (CI) 0.823–8.266 P=0.086). Psychological distress, quality of life measures and self-reported cognitive failures did not impact on objective tests of cognitive function, but were significantly associated with each other. The results show that a few women experienced objective measurable change in their concentration and memory following standard adjuvant therapy, but the majority were either unaffected or even improve over time. PMID:16523200

Neurotoxic effects of n-hexane on the human central nervous system: evoked potential abnormalities in n-hexane polyneuropathy.

PubMed Central

Chang, Y C

1987-01-01

An outbreak of n-hexane polyneuropathy as a result of industrial exposure occurred in printing factories in Taipei area from December 1983 to February 1985. Multimodality evoked potentials study was performed on 22 of the polyneuropathy cases, five of the subclinical cases, and seven of the unaffected workers. The absolute and interpeak latencies of patterned visual evoked potential (pVEP) in both the polyneuropathy and subclinical groups were longer than in the normal controls. The pVEP interpeak amplitude was also decreased in the polyneuropathy cases. Brainstem auditory evoked potentials (BAEP), showed no difference of wave I latency between factory workers and normal controls, but prolongation of the wave I-V interpeak latencies was noted, corresponding with the severity of the polyneuropathy. In somatosensory evoked potentials (SEPs), both the absolute latencies and central conduction time (CCT) were longer in subclinical and polyneuropathy cases than in the unaffected workers and normal controls. From this evoked potentials study, chronic toxic effects of n-hexane on the central nervous system were shown. PMID:3031221

Aberrant leukocyte telomere length in Birdshot Uveitis.

PubMed

Vazirpanah, Nadia; Verhagen, Fleurieke H; Rothova, Anna; Missotten, Tom O A R; van Velthoven, Mirjam; Den Hollander, Anneke I; Hoyng, Carel B; Radstake, Timothy R D J; Broen, Jasper C A; Kuiper, Jonas J W

2017-01-01

Birdshot Uveitis (BU) is an archetypical chronic inflammatory eye disease, with poor visual prognosis, that provides an excellent model for studying chronic inflammation. BU typically affects patients in the fifth decade of life. This suggests that it may represent an age-related chronic inflammatory disease, which has been linked to increased erosion of telomere length of leukocytes. To study this in detail, we exploited a sensitive standardized quantitative real-time polymerase chain reaction to determine the peripheral blood leukocyte telomere length (LTL) in 91 genotyped Dutch BU patients and 150 unaffected Dutch controls. Although LTL erosion rates were very similar between BU patients and healthy controls, we observed that BU patients displayed longer LTL, with a median of log (LTL) = 4.87 (= 74131 base pair) compared to 4.31 (= 20417 base pair) in unaffected controls (P<0.0001). The cause underpinning the difference in LTL could not be explained by clinical parameters, immune cell-subtype distribution, nor genetic predisposition based upon the computed weighted genetic risk score of genotyped validated variants in TERC, TERT, NAF1, OBFC1 and RTEL1. These findings suggest that BU is accompanied by significantly longer LTL.

Predictive genetic testing for hereditary breast and ovarian cancer: psychological distress and illness representations 1 year following disclosure.

PubMed

Claes, E; Evers-Kiebooms, G; Denayer, L; Decruyenaere, M; Boogaerts, A; Philippe, K; Legius, E

2005-10-01

This prospective study evaluates emotional functioning and illness representations in 68 unaffected women (34 carriers/34 noncarriers) 1 year after predictive testing for BRCA1/2 mutations when offered within a multidisciplinary approach. Carriers had higher subjective risk perception of breast cancer than noncarriers. Carriers who did not have prophylactic oophorectomy had the highest risk perception of ovarian cancer. No differences were found between carriers and noncarriers regarding perceived seriousness and perceived control of breast and ovarian cancer. Mean levels of distress were within normal ranges. Only few women showed an overall pattern of clinically elevated distress. Cancer-specific distress and state-anxiety significantly decreased in noncarriers from pre- to posttest while general distress remained about the same. There were no significant changes in distress in the group of carriers except for ovarian cancer distress which significantly decreased from pre- to posttest. Our study did not reveal adverse effects of predictive testing when offered in the context of a multidisciplinary approach.

Reduction of conditioned pain modulation in humans by naltrexone: an exploratory study of the effects of pain catastrophizing

PubMed Central

Goodin, Burel; Kindler, Lindsay L.; Caudle, Robert M.; Edwards, Robert R.; Gravenstein, Nikolaus; Riley, Joseph L.; Fillingim, Roger B.

2013-01-01

The current study tested the hypothesis that conditioned pain modulation is mediated by the release of endogenous opioids with a placebo-controlled (sugar pill) study of naltrexone (50 mg) in 33 healthy volunteers over two counter-balanced sessions. Pain modulation consisted of rating of heat pain (palm) during concurrent cold water immersion (foot). Compared to baseline heat pain ratings, concurrent foot immersion lowered pain intensity ratings, which suggests an inhibitory effect, was reduced with naltrexone, suggesting at least partial dependence of inhibition on endogenous opioids. An exploratory analysis revealed that individual differences in catastrophizing moderated the effects of naltrexone; endogenous opioid blockade abolished modulation in subjects lower in catastrophizing while modulation was unaffected by naltrexone among high catastrophizers. The results suggest a role of endogenous opioids in endogenous analgesia, but hint that multiple systems might contribute to conditioned pain modulation, and that these systems might be differentially activated as a function of individual differences in responses to pain. PMID:22534819

The effect of benoxinate on the tear stability of Hong Kong-Chinese.

PubMed

Cho, P; Brown, B

1995-07-01

We conducted a series of experiments to examine the effect of local anaesthetic instillation on tear stability measurements. All experiments were conducted with the examiner masked with respect to treatments. We measured tear break-up time (TDUT) and non-invasive tear break-up time (NITBUT) 30s after instillation of benoxinate (0.4%) in a single masked experiment and found that NITBUT was significantly increased while TBUT was unaffected. In separate experiments tear stability was assessed 5 min after instillation of benoxinate and there was no significant effect on either TBUT or NITBUT measurements. In a control experiment to examine the effect of instilling a drop of liquid into the eye, neither TBUT nor NITBUT were affected 30s after the instillation of saline. No corneal staining was observed in any of the subjects after instillation of benoxinate. The results suggest that benoxinate does not affect the stability of the precorneal tear film, and that tear stability can be assessed after the instillation of unpreserved benoxinate.

Repetitive strain disorder: towards diagnostic criteria.

PubMed Central

Bird, H A; Hill, J

1992-01-01

Thirteen women (mean age 48.2 years; range 25-60 years) all of whom had developed musculoskeletal symptoms during employment in an industrial job with repetitive tasks were referred by their trade unions for adjudication on the cause of symptoms. One had rheumatoid arthritis. A study of the other 12 women provided an opportunity to document the natural history of repetitive strain disorder. Early symptoms of weakness were diffuse but were always relieved by rest. Several months later localisation of symptoms at a tendon, nerve, or enthesis could be predicted from the analysis of the action required in the particular repetitive task. Six of the 12 women required an operation several years later, thus providing histological confirmation of the presence of a lesion. Early loss of grip strength measured by a sphygmomanometer cuff compared with an unaffected control subject and improved by rest may be the most valuable sign in excluding compensation neurosis. The estimated prevalence of repetitive strain disorder defined by these strict criteria was at least 2% in conveyor belt workers. PMID:1417124

Novel mutations in the SOX10 gene in the first two Chinese cases of type IV Waardenburg syndrome.

PubMed

Jiang, Lu; Chen, Hongsheng; Jiang, Wen; Hu, Zhengmao; Mei, Lingyun; Xue, Jingjie; He, Chufeng; Liu, Yalan; Xia, Kun; Feng, Yong

2011-05-20

We analyzed the clinical features and family-related gene mutations for the first two Chinese cases of type IV Waardenburg syndrome (WS4). Two families were analyzed in this study. The analysis included a medical history, clinical analysis, a hearing test and a physical examination. In addition, the EDNRB, EDN3 and SOX10 genes were sequenced in order to identify the pathogenic mutation responsible for the WS4 observed in these patients. The two WS4 cases presented with high phenotypic variability. Two novel heterozygous mutations (c.254G>A and c.698-2A>T) in the SOX10 gene were detected. The mutations identified in the patients were not found in unaffected family members or in 200 unrelated control subjects. This is the first report of WS4 in Chinese patients. In addition, two novel mutations in SOX10 gene have been identified. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

Oculomotor function during space flight and susceptibility to space motion sickness

NASA Technical Reports Server (NTRS)

Thornton, William E.; Uri, John J.

1991-01-01

Horizontal vestibulo-ocular reflex (VOR) and saccadic eye movements (SEM) were studied in 18 subjects before and during five Space Shuttle missions to evaluate the effects of weightlessness and correlations between results and susceptibility to and actual presence of space motion sickness (SMS). Active sinusoidal head oscillation was the stimulus for VOR tests with vision (VVOR), with eyes shaded (VOR-ES), and VOR suppression (VOR-S). Eye movements were recorded by electrooculography and head position by a potentiometer. No pathological nystagmus or other abnormal eye movements were seen. No significant in-flight changes were seen in the gain, phase shift or waveform of VVOR, VOR-ES or VOR-S. Statistically significant increases in saccadic latency and decreases in saccadic velocity were seen, with no change in saccadic accuracy. Preflight differences between SMS susceptible and nonsusceptible subjects were noted only in VOR-S, with less complete suppression in susceptible subjects, a finding also seen in flight. During flight, VVOR gain was significantly increased in three nonaffected subjects. Saccades of SMS-affected subjects showed increased latency and velocity and decreased accuracy compared to saccades of unaffected subjects.

Factors influencing the latency of simple reaction time

PubMed Central

Woods, David L.; Wyma, John M.; Yund, E. William; Herron, Timothy J.; Reed, Bruce

2015-01-01

Simple reaction time (SRT), the minimal time needed to respond to a stimulus, is a basic measure of processing speed. SRTs were first measured by Francis Galton in the 19th century, who reported visual SRT latencies below 190 ms in young subjects. However, recent large-scale studies have reported substantially increased SRT latencies that differ markedly in different laboratories, in part due to timing delays introduced by the computer hardware and software used for SRT measurement. We developed a calibrated and temporally precise SRT test to analyze the factors that influence SRT latencies in a paradigm where visual stimuli were presented to the left or right hemifield at varying stimulus onset asynchronies (SOAs). Experiment 1 examined a community sample of 1469 subjects ranging in age from 18 to 65. Mean SRT latencies were short (231, 213 ms when corrected for hardware delays) and increased significantly with age (0.55 ms/year), but were unaffected by sex or education. As in previous studies, SRTs were prolonged at shorter SOAs and were slightly faster for stimuli presented in the visual field contralateral to the responding hand. Stimulus detection time (SDT) was estimated by subtracting movement initiation time, measured in a speeded finger tapping test, from SRTs. SDT latencies averaged 131 ms and were unaffected by age. Experiment 2 tested 189 subjects ranging in age from 18 to 82 years in a different laboratory using a larger range of SOAs. Both SRTs and SDTs were slightly prolonged (by 7 ms). SRT latencies increased with age while SDT latencies remained stable. Precise computer-based measurements of SRT latencies show that processing speed is as fast in contemporary populations as in the Victorian era, and that age-related increases in SRT latencies are due primarily to slowed motor output. PMID:25859198

Nonspherical femoral head shape (pistol grip deformity), neck shaft angle, and risk of hip osteoarthritis: a case-control study.

PubMed

Doherty, Michael; Courtney, Philip; Doherty, Sally; Jenkins, Wendy; Maciewicz, Rose A; Muir, Kenneth; Zhang, Weiya

2008-10-01

To determine whether 2-dimensional measures of femoral head shape and angle are associated with hip osteoarthritis (OA). We compared cases with symptomatic radiographic hip OA with asymptomatic controls with no radiographic hip OA. On anteroposterior pelvis radiographs, we measured "pistol grip deformity" for each hip (visually categorized as nonspherical, indeterminate, or spherical), the femoral head-to-femoral neck ratio as an interval measure of femoral head shape, and the femoral neck shaft angle. The relative risk of hip OA associated with each feature was estimated using odds ratios (ORs) and 95% confidence intervals (95% CIs), adjusted for possible confounders using a logistic regression model. Of 1,007 cases, 965 had definite radiographic hip OA; of 1,123 controls, 1,111 had no radiographic OA. The prevalence of pistol grip deformity in at least 1 hip was 3.61% in controls and 17.71% in cases (OR 6.95 [95% CI 4.64-10.41]), and the prevalence of abnormal femoral head-to-femoral neck ratio in at least 1 hip was 3.70% in controls and 24.27% in cases (OR 12.08 [95% CI 8.05-18.15]). The risk of hip OA increased as the femoral head-to-femoral neck ratio decreased (P for trend<0.001) and with each extreme of neck shaft angle (P<0.05). In cases with unilateral hip OA, the prevalence of abnormal femoral head-to-femoral neck ratio in the unaffected hip was 2 times greater than that in controls (OR 1.82 [95% CI 1.07-3.07]); in contrast, an abnormally low, but not abnormally high, neck shaft angle was more common in unaffected hips than in controls (OR 1.79 [95% CI 1.03-3.14]). Our findings indicate that pistol grip deformity is associated with hip OA. The increased prevalence of pistol grip deformity and an abnormally low neck shaft angle in unaffected hips of cases with unilateral OA suggests that they are risk factors for development of hip OA. However, both a nonspherical head shape and an increase in neck shaft angle may occur as a consequence of OA.

Changes in EEG spectral power on perception of neutral and emotional words in patients with schizophrenia, their relatives, and healthy subjects from the general population.

PubMed

Alfimova, M V; Uvarova, L G

2008-06-01

EEG correlates of impairments in the processing of emotiogenic information which might reflect a genetic predisposition to schizophrenia were sought by studying the dynamics of EEG rhythm powers on presentation of neutral and emotional words in 36 patients with schizophrenia, 50 of their unaffected first-degree relatives, and 47 healthy subjects without any inherited predisposition to psychoses. In controls, passive hearing of neutral words produced minimal changes in cortical rhythms, predominantly in the form of increases in the power levels of slow and fast waves, while perception of emotional words was accompanied by generalized reductions in the power of the alpha and beta(1) rhythms and regionally specific suppression of theta and beta(2) activity. Patients and their relatives demonstrated reductions in power of alpha and beta(1) activity, with an increase in delta power on hearing both groups of words. Thus, differences in responses to neutral and emotional words in patients and their relatives were weaker, because of increased reactions to neutral words. These results may identify EEG reflections of pathology of involuntary attention, which is familial and, evidently, inherited in nature. No reduction in reactions to emotiogenic stimuli was seen in patients' families.

Water-level representation by men and women as a function of rod-and-frame test proficiency and visual and postural information.

PubMed

Robert, M; Ohlmann, T

1994-01-01

In the water-level task, it has been repeatedly shown that, compared with men, women more often fail to represent the surface of a liquid as horizontal regardless of the tilt of the container. An attempt was made to reduce this robust gender gap through the manipulation of relevant upright references conveyed both by the position of the stimuli and the posture of the subject. It was reasoned that bringing the women to focus on such gravitational references through postural adjustment might help their performance equal that of men, thus shedding some light on the nature of the difficulty they experience in the standard setting. A lesser effect was anticipated among men. However, the results showed that, even after controlling for proficiency in the correlated visuospatial situation of the rod-and-frame test, the performance of men always surpassed that of women. Irrespective of gender, water-level representation on vertical sheets was unaffected by the subject's posture, whereas it improved when horizontal sheets were coupled with the most unstable posture. Whereas the persistence of the yet-unaccounted-for gender difference was underscored, the contributions of visual and postural cues issued at arm and full-body levels were discussed.

Intracranial Fluid Redistribution But No White Matter Microstructural Changes During a Spaceflight Analog.

PubMed

Koppelmans, Vincent; Pasternak, Ofer; Bloomberg, Jacob J; Dios, Yiri E De; Wood, Scott J; Riascos, Roy; Reuter-Lorenz, Patricia A; Kofman, Igor S; Mulavara, Ajitkumar P; Seidler, Rachael D

2017-06-09

The neural correlates of spaceflight-induced sensorimotor impairments are unknown. Head down-tilt bed rest (HDBR) serves as a microgravity analog because it mimics the headward fluid shift and axial body unloading of spaceflight. We investigated focal brain white matter (WM) changes and fluid shifts during 70 days of 6° HDBR in 16 subjects who were assessed pre (2x), during (3x), and post-HDBR (2x). Changes over time were compared to those in control subjects (n = 12) assessed four times over 90 days. Diffusion MRI was used to assess WM microstructure and fluid shifts. Free-Water Imaging was used to quantify distribution of intracranial extracellular free water (FW). Additionally, we tested whether WM and FW changes correlated with changes in functional mobility and balance measures. HDBR resulted in FW increases in fronto-temporal regions and decreases in posterior-parietal regions that largely recovered by two weeks post-HDBR. WM microstructure was unaffected by HDBR. FW decreases in the post-central gyrus and precuneus correlated negatively with balance changes. We previously reported that gray matter increases in these regions were associated with less HDBR-induced balance impairment, suggesting adaptive structural neuroplasticity. Future studies are warranted to determine causality and underlying mechanisms.

High-Resolution Imaging of the Optic Nerve and Retina in Optic Nerve Hypoplasia

PubMed Central

Pilat, Anastasia; Sibley, Daniel; McLean, Rebecca J.; Proudlock, Frank A.; Gottlob, Irene

2015-01-01

Purpose To investigate the optic nerve and macular morphology in patients with optic nerve hypoplasia (ONH) using spectral-domain optical coherence tomography (SD OCT). Design Prospective, cross-sectional, observational study. Subjects A total of 16 participants with ONH (10 female and 6 male; mean age, 17.2 years; 6 bilateral involvement) and 32 gender-, age-, ethnicity-, and refraction-matched healthy controls. Methods High-resolution SD OCT (Copernicus [Optopol Technology S.A., Zawiercie, Poland], 3 μm resolution) and handheld SD OCT (Bioptigen Inc [Research Triangle Park, NC], 2.6 μm resolution) devices were used to acquire horizontal scans through the center of the optic disc and macula. Main Outcome Measures Horizontal optic disc/cup and rim diameters, cup depth, peripapillary retinal nerve fiber layer (RNFL), and thickness of individual retinal layers in participants with ONH and in controls. Results Patients with ONH had significantly smaller discs (P < 0.03 and P < 0.001 compared with unaffected eye and healthy controls, respectively), horizontal cup diameter (P < 0.02 for both), and cup depth (P < 0.02 and P < 0.01, respectively). In the macula, significantly thinner RNFL (nasally), ganglion cell layer (GCL) (nasally and temporally), inner plexiform layer (IPL) (nasally), outer nuclear layer (ONL) (nasally), and inner segment (centrally and temporally) were found in patients with ONH compared with the control group (P < 0.05 for all comparisons). Continuation of significantly thicker GCL, IPL, and outer plexiform layer in the central retinal area (i.e., foveal hypoplasia) was found in more than 80% of patients with ONH. Clinically unaffected fellow eyes of patients with ONH showed mild features of underdevelopment. Visual acuity and presence of septo-optic dysplasia were associated with changes in GCL and IPL. Sensitivity and specificity for the detection of ONH based on disc and retinal optical coherence tomography (OCT) parameters were >80%. Conclusions Our study provides evidence of retinal changes in ONH. In addition to thinning of retina layers mainly involving the RNFL and GCL, signs reminiscent of foveal hypoplasia were observed in patients with ONH. Optic nerve and foveal parameters measured using OCT showed high sensitivity and specificity for detecting ONH, demonstrating their useful for clinical diagnosis. PMID:25939636

Stress fracture of the proximal humeral epiphysis in an elite junior badminton player.

PubMed Central

Boyd, K T; Batt, M E

1997-01-01

An elite junior badminton player presented with a chronic painful dominant shoulder after an intense training course. An acute stress fracture to the proximal humeral epiphysis was found. Two-plane radiography will identify abnormalities of the growth plate but comparative films of the unaffected side may also be required to differentiate subtle changes. Rest with subsequent rehabilitation is the appropriate management of these injuries although ideally they should be subjected to primary prevention. Images Figure 1 Figure 2 PMID:9298564

Melanin-based color of plumage: role of condition and of feathers' microstructure

USGS Publications Warehouse

D'Alba, Liliana; Van Hemert, Caroline R.; Spencer, Karen A.; Heidinger, Britt J.; Gill, Lisa; Evans, Neil P.; Monaghan, Pat; Handel, Colleen M.; Shawkey, Matthew D.

2014-01-01

Whether melanin-based colors honestly signal a bird's condition during the growth of feathers is controversial, and it is unclear if or how the physiological processes underlying melanogenesis or color-imparting structural feather microstructure may be adversely affected by condition. Here we report results from two experiments designed to measure the effect of condition on expression of eumelanic and pheomelanic coloration in black-capped chickadees (Poecile atricapillus) and zebra finches (Taeniopygia guttata), respectively. In chickadees, we compared feathers of birds affected and unaffected by avian keratin disorder, while in zebra finches we compared feathers of controls with feathers of those subjected to an unpredictable food supply during development. In both cases we found that control birds had brighter feathers (higher total reflectance) and more barbules, but similar densities of melanosomes. In addition, the microstructure of the feathers explained variation in color more strongly than did melanosome density. Together, these results suggest that melanin-based coloration may in part be condition-dependent, but that this may be driven by changes in keratin and feather development, rather than melanogenesis itself. Researchers should be cautious when assigning variation in melanin-based color to melanin alone and microstructure of the feather should be taken into account.

Reduced absorption and enhanced synthesis of cholesterol in patients with cystic fibrosis: a preliminary study of plasma sterols.

PubMed

Gelzo, Monica; Sica, Concetta; Elce, Ausilia; Dello Russo, Antonio; Iacotucci, Paola; Carnovale, Vincenzo; Raia, Valeria; Salvatore, Donatello; Corso, Gaetano; Castaldo, Giuseppe

2016-09-01

Low cholesterol is typically observed in the plasma of patients with cystic fibrosis (CF) contrasting with the subcellular accumulation of cholesterol demonstrated in CF cells and in mice models. However, the homeostasis of cholesterol has not been well investigated in patients with CF. We studied the plasma of 26 patients with CF and 33 unaffected controls campesterol and β-sitosterol as markers of intestinal absorption and lathosterol as a marker of de novo cholesterol biosynthesis by gas chromatography (GC-FID and GC-MS). Plasma campesterol and β-sitosterol results were significantly (p=0.01) lower while plasma lathosterol was significantly higher (p=0.001) in patients with CF as compared to control subjects. Plasma cholesterol results were significantly lower (p=0.01) in CF patients. Our data suggest that the impaired intestinal absorption of exogenous sterols in patients with CF stimulates the endogenous synthesis of cholesterol, but the levels of total cholesterol in plasma remain lower. This may be due to the CFTR dysfunction that reduces cholesterol blood excretion causing the accumulation of cholesterol in liver cells and in other tissues contributing to trigger CF chronic inflammation.

Automatic processing influences free recall: converging evidence from the process dissociation procedure and remember-know judgments.

PubMed

McCabe, David P; Roediger, Henry L; Karpicke, Jeffrey D

2011-04-01

Dual-process theories of retrieval suggest that controlled and automatic processing contribute to memory performance. Free recall tests are often considered pure measures of recollection, assessing only the controlled process. We report two experiments demonstrating that automatic processes also influence free recall. Experiment 1 used inclusion and exclusion tasks to estimate recollection and automaticity in free recall, adopting a new variant of the process dissociation procedure. Dividing attention during study selectively reduced the recollection estimate but did not affect the automatic component. In Experiment 2, we replicated the results of Experiment 1, and subjects additionally reported remember-know-guess judgments during recall in the inclusion condition. In the latter task, dividing attention during study reduced remember judgments for studied items, but know responses were unaffected. Results from both methods indicated that free recall is partly driven by automatic processes. Thus, we conclude that retrieval in free recall tests is not driven solely by conscious recollection (or remembering) but also by automatic influences of the same sort believed to drive priming on implicit memory tests. Sometimes items come to mind without volition in free recall.

Pharmacologic Atrial Natriuretic Peptide Reduces Human Leg Capillary Filtration

NASA Technical Reports Server (NTRS)

Watenpaugh, Donald E.; Vissing, Susanne F.; Lane, Lynda D.; Buckey, Jay C.; Firth, Brian G.; Erdman, William; Hargens, Alan R.; Blomqvist, C. Gunnar

1995-01-01

Atrial natriuretic peptide (ANP) is produced and secreted by atrial cells. We measured calf capillary filtration rate with prolonged venous-occlusion plethysmography of supine healthy male subjects during pharmacologic infusion of ANP (48 pmol/kg/min for 15 min; n = 6) and during placebo infusion (n = 7). Results during infusions were compared to prior control measurements. ANP infusion increased plasma (ANP) from 30 +/- 4 to 2,568 +/- 595 pmol/L. Systemic hemoconcentration occurred during ANP infusion: mean hematocrit and plasma colloid osmotic pressure increased 4.6 and 11.3%, respectively, relative to preinfusion baseline values (p less than 0.05). Mean calf filtration, however, was significantly reduced from 0.15 to 0.08 ml/100 ml/min with ANP. Heart rate increased 20% with ANP infusion, whereas blood pressure was unchanged. Calf conductance (blood flow/ arterial pressure) and venous compliance were unaffected by ANP infusion. Placebo infusion had no effect relative to prior baseline control measurements. Although ANP induced systemic capillary filtration, in the calf, filtration was reduced with ANP. Therefore, pharmacologic ANP infusion enhances capillary filtration from the systemic circulation, perhaps at upper body or splanchnic sites or both, while having the opposite effect in the leg.

Mechanism of pancreatic polypeptide release in man.

PubMed

Adrian, T E; Besterman, H S; Cooke, T J; Bloom, S R; Barnes, A J; Russell, R C

1977-01-22

Pancreatic polypeptide (P.P.) is a potent hormonal peptide which has been isolated from the pancreas. Its role in human physiology and pathology is not yet established. After a standard hospital lunch the plasma concentration of P.P. showed a rapid and identical rise in 10 healthy controls, 11 duodenal-ulcer patients, and 6 post-vagotomy patients but remained undetectable in 4 totally pancreatectomised subjects. In contrast plasma-P.P. was unaffected by intravenous administration of glucose, aminoacids, or fat. However, during intravenous infusion of caerulein, a cholecystokinin analogue, P.P. rose by nearly five-fold, and an even greater rise was seen after intravenous injection of Boots secretin. In 19 duodenal-ulcer patients insulin hypoglycaemia produced a rapid rise in plasma-P.P. but this did not occur in any of the 17 patients studied after a truncal vagotomy. Thus P.P. is released by oral but not intravenous nutriments and the existence of an entero-P.P. axis is postulated. One component of this axis may be the vagal innervation but the normal postprandial rise seen after vagotomy suggests that other control mechanisms, such as the intestinal hormones, are more important.

Abnormalities in the fatty acid composition of the postmortem entorhinal cortex of patients with schizophrenia, bipolar disorder, and major depressive disorder.

PubMed

Hamazaki, Kei; Hamazaki, Tomohito; Inadera, Hidekuni

2013-11-30

Previous studies of postmortem orbitofrontal cortex have shown abnormalities in levels of n-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA), in individuals with schizophrenia, bipolar disorder, and major depressive disorder (MDD). We have previously measured PUFA levels in the postmortem hippocampus from patients with schizophrenia or bipolar disorder and control subjects; however, we found no significant differences between the groups except for small changes in n-6 PUFAs. Furthermore, our study of the postmortem amygdala showed no significant differences in major PUFAs in individuals with schizophrenia, bipolar disorder, or MDD in comparison with controls. In the present study, we investigated whether there were any changes in PUFAs in the entorhinal cortexes of patients with schizophrenia (n=15), bipolar disorder (n=15), or MDD (n=15) compared with unaffected controls (n=15) matched for characteristics including age and sex. In contrast to previous studies of the orbitofrontal cortex and hippocampus, we found no significant differences in major PUFAs. However, we found a 34.3% decrease in docosapentaenoic acid (DPA) (22:5n-3) in patients with MDD and an 8.7% decrease in docosatetraenoic acid (22:4n-6) in those with schizophrenia, compared with controls. Changes in PUFAs in patients with these psychiatric disorders may be specific to certain brain regions. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Caffeine Consuming Children and Adolescents Show Altered Sleep Behavior and Deep Sleep

PubMed Central

Aepli, Andrina; Kurth, Salome; Tesler, Noemi; Jenni, Oskar G.; Huber, Reto

2015-01-01

Caffeine is the most commonly ingested psychoactive drug worldwide with increasing consumption rates among young individuals. While caffeine leads to decreased sleep quality in adults, studies investigating how caffeine consumption affects children’s and adolescents’ sleep remain scarce. We explored the effects of regular caffeine consumption on sleep behavior and the sleep electroencephalogram (EEG) in children and adolescents (10–16 years). While later habitual bedtimes (Caffeine 23:14 ± 11.4, Controls 22:17 ± 15.4) and less time in bed were found in caffeine consumers compared to the control group (Caffeine 08:10 ± 13.3, Controls 09:03 ± 16.1), morning tiredness was unaffected. Furthermore, caffeine consumers exhibited reduced sleep EEG slow-wave activity (SWA, 1–4.5 Hz) at the beginning of the night compared to controls (20% ± 9% average reduction across all electrodes and subjects). Comparable reductions were found for alpha activity (8.25–9.75 Hz). These effects, however, disappeared in the morning hours. Our findings suggest that caffeine consumption in adolescents may lead to later bedtimes and reduced SWA, a well-established marker of sleep depth. Because deep sleep is involved in recovery processes during sleep, further research is needed to understand whether a caffeine-induced loss of sleep depth interacts with neuronal network refinement processes that occur during the sensitive period of adolescent development. PMID:26501326

Modulatory effects of psychopathy on Wisconsin Card Sorting Test performance in male offenders with Antisocial Personality Disorder.

PubMed

Pera-Guardiola, Vanessa; Batalla, Iolanda; Bosque, Javier; Kosson, David; Pifarré, Josep; Hernández-Ribas, Rosa; Goldberg, Ximena; Contreras-Rodríguez, Oren; Menchón, José M; Soriano-Mas, Carles; Cardoner, Narcís

2016-01-30

Neuropsychological deficits in executive functions (EF) have been linked to antisocial behavior and considered to be cardinal to the onset and persistence of severe antisocial and aggressive behavior. However, when psychopathy is present, prior evidence suggests that the dorsolateral prefrontal cortex is unaffected leading to intact EF. Ninety-one male offenders with Antisocial Personality Disorder (ASPD) and 24 controls completed the Wisconsin Card Sorting Test (WCST). ASPD individuals were grouped in three categories according to Psychopathy Checklist-Revised (PCL-R) scores (low, medium and high). We hypothesized that ASPD offenders with high PCL-R scores will not differ from healthy controls in EF and will show better EF performance in comparison with subjects with low PCL-R scores. Results showed that ASPD offenders with low PCL-R scores committed more perseverative errors and responses than controls and offenders with high PCL-R scores, which did not differ from healthy controls. Moreover, scores on Factor 1 and the interpersonal facet of the PCL-R were predictors of better WCST performance. Our results suggest a modulatory role of psychopathy in the cognitive performance of ASPD offenders, and provide further evidence supporting that offenders with ASPD and psychopathy are characterized by a cognitive profile different from those with ASPD without psychopathy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Effect of hypnotic suggestion on the delayed-type hypersensitivity response.

PubMed

Locke, S E; Ransil, B J; Zachariae, R; Molay, F; Tollins, K; Covino, N A; Danforth, D

1994-07-06

To determine whether individuals selected for good general health, high hypnotizability, and the ability to alter skin temperature under hypnotic suggestion can influence the delayed-type hypersensitivity (DTH) response to varicella-zoster (VZ) antigen under hypnotic suggestion. A blinded clinical trial using a repeated measures design with subjects serving as their own controls. Subjects were randomly assigned to undergo a predetermined sequence of four different experimental conditions, occurring at weekly intervals, with each condition including VZ skin testing: (1) hypnosis with suggestions to enhance the DTH response to VZ antigen; (2) hypnosis with suggestions to suppress the DTH response; (3) hypnosis with suggestions for relaxation only; and (4) skin testing without hypnosis. A National Institutes of Health-supported clinical research center in a teaching hospital. A stratified sample of 24 ambulatory, healthy, highly hypnotizable, volunteer college students selected for their above-average ability to alter skin temperature after hypnotic suggestions and their positive baseline responses to VZ antigen. There were 11 males and 13 females with a mean +/- SD age of 22 +/- 6 years. The mean +/- SD hypnotizability score (Harvard Group Scale of Hypnotic Susceptibility) was 11 +/- 1. Intradermal skin testing with VZ antigen (Mantoux method) and hypnotic suggestion. Areas of induration of the DTH response measured at 24 and 48 hours after injection of antigen. The area of the DTH response was not affected by the experimental interventions. The area of erythema was likewise unaffected. Our subjects were unable to alter their DTH responses using hypnotic suggestion.

Effects of ventilation rate per person and per floor area on perceived air quality, sick building syndrome symptoms, and decision-making.

PubMed

Maddalena, R; Mendell, M J; Eliseeva, K; Chan, W R; Sullivan, D P; Russell, M; Satish, U; Fisk, W J

2015-08-01

Ventilation rates (VRs) in buildings must adequately control indoor levels of pollutants; however, VRs are constrained by the energy costs. Experiments in a simulated office assessed the effects of VR per occupant on perceived air quality (PAQ), Sick Building Syndrome (SBS) symptoms, and decision-making performance. A parallel set of experiments assessed the effects of VR per unit floor area on the same outcomes. Sixteen blinded healthy young adult subjects participated in each study. Each exposure lasted four hours and each subject experienced two conditions in a within-subject study design. The order of presentation of test conditions, day of testing, and gender were balanced. Temperature, relative humidity, VRs, and concentrations of pollutants were monitored. Online surveys assessed PAQ and SBS symptoms and a validated computer-based tool measured decision-making performance. Neither changing the VR per person nor changing the VR per floor area, had consistent statistically significant effects on PAQ or SBS symptoms. However, reductions in either occupant-based VR or floor-area-based VR had a significant and independent negative impact on most decision-making measures. These results indicate that the changes in VR employed in the study influence performance of healthy young adults even when PAQ and SBS symptoms are unaffected. The study results indicate the importance of avoiding low VRs per person and low VRs per floor area to minimize decrements in cognitive performance. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Differentiating occupational asthmatics from non-occupational asthmatics and irritant-exposed workers.

PubMed

Anees, W; Blainey, D; Moore, V C; Robertson, K; Burge, P S

2011-05-01

Serial peak expiratory flow (PEF) records have been recommended as a first-line investigation in workers suspected as having occupational asthma (OA). To determine which PEF variability index best differentiates workers with OA from non-occupational asthmatics and unaffected irritant-exposed workers. PEF was measured at least four times daily for at least 3 weeks in three groups of subjects: (i) forty healthy grain-exposed farmers and dockers, (ii) forty-two consecutive workers with independently confirmed OA and (iii) forty-eight non-occupational asthmatics. Indices of PEF variability were compared between groups. The difference in mean PEF between rest and work periods best separated the occupational asthmatic workers from the others. The upper 95% confidence limit of this index for grain-exposed workers was 2.8% of predicted PEF (16 l/min) and 3.3% (15 l/min) for non-occupational asthmatics. Sensitivity for diagnosing OA using this index was 70%. An increase in diurnal variation on workdays of >7% had a sensitivity of only 27% for the diagnosis of OA. The difference between maximum PEF on workdays and minimum PEF on rest days had a sensitivity of <10% against non-occupational asthmatic controls. Difference in mean PEF between workdays and rest days is the best simple index for differentiating subjects with OA from those with non-OA or irritant-exposed healthy subjects. Differences >16 l/min are unlikely to be due to significant irritant exposure in healthy workers.

Growth and Psychological Development in Postoperative Patients With Anterior Encephaloceles.

PubMed

Dutta, Hemonta Kumar; Khangkeo, Chow Wachana; Baruah, Kaberi; Borbora, Debasish

2017-06-01

Anterior encephaloceles are rare malformations that are frequently associated with other brain anomalies. This study evaluates the growth and psychological development of children following encephalocele repair. Growth and psychological assessment was done in 24 children with only encephalocele (group I); nine children with encephalocele and hydrocephalus (group II); seven children with encephalocele, hydrocephalus, and secondary malformations (group III); and 40 apparently healthy control subjects. Psychological assessment was done by evaluating intelligence and temperament. Single-stage repair was performed in 38 children, and two underwent multistage repair. Major postoperative complications were noted in three individuals. The follow-up period ranged from 12 to 168 months, and during this time the growth velocity declined significantly among group II and group III patients when compared with control subjects. After adjusting the body mass index for age, our data revealed that group III participants had a significantly (P = 0.02) lower body mass index than the control group. Group III also had poor indices for intelligence quotient (P ≤ 0.01) and temperament (P ≤ 0.01). Female patients had lower temperament indices when compared with unaffected females with regard to approach withdrawal (P ≤ 0.01), mood (P = 0.026), and intensity (P = 0.03). Overall, increased disease severity adversely affected the psychological indices. Individuals with anterior encephalocele without associated intracranial defects had excellent postoperative outcomes in terms of growth and psychological developments. Hydrocephalus and agenesis of corpus callosum had the least impact on psychological development. However, the presence of secondary brain defects led to developmental delays. Gender differences in temperament may suggest a need for distinct treatment regimens to assess psychosocial well-being for males and females. Copyright © 2017 Elsevier Inc. All rights reserved.

Sensorimotor adaptation of point-to-point arm movements after spaceflight: the role of internal representation of gravity force in trajectory planning.

PubMed

Gaveau, Jérémie; Paizis, Christos; Berret, Bastien; Pozzo, Thierry; Papaxanthis, Charalambos

2011-08-01

After an exposure to weightlessness, the central nervous system operates under new dynamic and sensory contexts. To find optimal solutions for rapid adaptation, cosmonauts have to decide whether parameters from the world or their body have changed and to estimate their properties. Here, we investigated sensorimotor adaptation after a spaceflight of 10 days. Five cosmonauts performed forward point-to-point arm movements in the sagittal plane 40 days before and 24 and 72 h after the spaceflight. We found that, whereas the shape of hand velocity profiles remained unaffected after the spaceflight, hand path curvature significantly increased 1 day after landing and returned to the preflight level on the third day. Control experiments, carried out by 10 subjects under normal gravity conditions, showed that loading the arm with varying loads (from 0.3 to 1.350 kg) did not affect path curvature. Therefore, changes in path curvature after spaceflight cannot be the outcome of a control process based on the subjective feeling that arm inertia was increased. By performing optimal control simulations, we found that arm kinematics after exposure to microgravity corresponded to a planning process that overestimated the gravity level and optimized movements in a hypergravity environment (∼1.4 g). With time and practice, the sensorimotor system was recalibrated to Earth's gravity conditions, and cosmonauts progressively generated accurate estimations of the body state, gravity level, and sensory consequences of the motor commands (72 h). These observations provide novel insights into how the central nervous system evaluates body (inertia) and environmental (gravity) states during sensorimotor adaptation of point-to-point arm movements after an exposure to weightlessness.

ω-3 Long-Chain Polyunsaturated Fatty Acids and Fatty Acid Desaturase Activity Ratios as Eventual Endophenotypes for ADHD.

PubMed

Henríquez-Henríquez, Marcela; Solari, Sandra; Várgas, Gisela; Vásquez, Luis; Allende, Fidel; Castañón S, Carla; Tenorio, Marcela; Quiroga Gutiérrez, Teresa

2015-11-01

Epidemiological studies suggest that long-chain polyunsaturated fatty acids (LC-PUFAs) may be suitable as endophenotypes for ADHD. To be appropriated vulnerability traits, endophenotypes should be altered in unaffected relatives of index cases. Serum profiles of LC-PUFAs in unaffected relatives of ADHD patients remain understudied. The main objective of this study was to compare serum LC-PUFAs in ADHD patients, unaffected relatives of index cases, and general-population unaffected participants. LC-PUFA profiles of 72 participants (27 ADHD patients, 27 unaffected relatives, and 18 general-population participants) were obtained by gas chromatography-mass spectrometry (GC-MS). Groups were compared by parametrical statistics. Unaffected females from the general population presented lower Docosapentaenoic acid (DPA; p = .0012) and a-linolenic acid (ALA; p = .0091) levels compared with ADHD females and unaffected relatives. In addition, docosahexaenoic acid (DHA)/ALA and DHA/DPA ratios, addressing desaturase activity, were significantly lower in ADHD patients and unaffected relatives of ADHD patients in the female-subgroup (p = .022 and .04, respectively). DHA/ALA, DHA/DPA, serum DPA, and serum ALA may be suitable as endophenotypes for ADHD women. © The Author(s) 2012.

Attention skills and executive functioning in children with Noonan syndrome and their unaffected siblings.

PubMed

Pierpont, Elizabeth I; Tworog-Dube, Erica; Roberts, Amy E

2015-04-01

Emerging research indicates that gene mutations within the RAS-MAPK signaling cascade, which cause Noonan syndrome and related disorders, affect neurophysiologic activity in brain regions underlying attention and executive functions. The present study examined whether children with Noonan syndrome are at heightened risk for symptoms of attention-deficit-hyperactivity disorder (ADHD) and executive dysfunction relative to an unaffected sibling comparison group, and investigated three key aspects of behavioral attention: auditory attention, sustained attention, and response inhibition. Children and adolescents with Noonan syndrome (n=32, 17 males, 15 females, mean age 11y 3mo, SD 3y) and their unaffected siblings (n=16, eight males, eight females, mean age 11y, SD 3y 6mo) were administered standardized tests of intellectual functioning and clinic-based measures of behavioral attention. Parent ratings of ADHD symptoms, executive functioning, and behavior were also obtained. Children with Noonan syndrome demonstrated higher rates of past ADHD diagnosis, as well as reduced performance compared with unaffected siblings on behavioral attention measures. Parent-rated functional impairments in attention, social skills, working memory, and self-monitoring were more prevalent in the Noonan syndrome group. The relationship between attention regulation skills (sustained attention and inhibitory control) and intellectual test performance was significantly stronger in the Noonan syndrome group than the comparison group. Clinical screening/evaluation for ADHD and executive dysfunction in Noonan syndrome is recommended to facilitate appropriate intervention and to address functional impact on daily life activities. © 2014 Mac Keith Press.

Cryptogenic Stroke and Nonstenosing Intracranial Calcified Atherosclerosis.

PubMed

Kamel, Hooman; Gialdini, Gino; Baradaran, Hediyeh; Giambrone, Ashley E; Navi, Babak B; Lerario, Michael P; Min, James K; Iadecola, Costantino; Gupta, Ajay

2017-04-01

Because some cryptogenic strokes may result from large-artery atherosclerosis that goes unrecognized as it causes <50% luminal stenosis, we compared the prevalence of nonstenosing intracranial atherosclerotic plaques ipsilateral to cryptogenic cerebral infarcts versus the unaffected side using imaging biomarkers of calcium burden. In a prospective stroke registry, we identified patients with cerebral infarction limited to the territory of one internal carotid artery (ICA). We included patients with stroke of undetermined etiology and, as controls, patients with cardioembolic stroke. We used noncontrast computed tomography to measure calcification in both intracranial ICAs, including qualitative calcium scoring and quantitative scoring utilizing the Agatston-Janowitz (AJ) calcium scoring. Within subjects, the Wilcoxon signed-rank sum test for nonparametric paired data was used to compare the calcium burden in the ICA upstream of the infarction versus the ICA on the unaffected side. We obtained 440 calcium measures from 110 ICAs in 55 patients. Among 34 patients with stroke of undetermined etiology, we found greater calcium in the ICA ipsilateral to the infarction (mean Modified Woodcock Visual Scale score, 6.7 ± 4.6) compared with the contralateral side (5.4 ± 4.1) (P = .005). Among 21 patients with cardioembolic stroke, we found no difference in calcium burden ipsilateral to the infarction (6.7 ± 5.9) versus the contralateral side (7.3 ± 6.3) (P = .13). The results were similar using quantitative calcium measurements, including the AJ calcium scores. In patients with strokes of undetermined etiology, the burden of calcified intracranial large-artery plaque was associated with downstream cerebral infarction. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Association between UTI and urinary tract abnormalities: a case-control study in Erbil City/Iraq.

PubMed

AlKhateeb, N E; Al Azzawi, S; Al Tawil, N G

2014-12-01

To determine the proportion of ultrasound abnormalities of the urinary system between two groups of children: affected with urinary tract infection (UTI) and unaffected (control). Further, to determine the most common microorganisms causing UTI in those children with urinary tract abnormalities. A case-control study was carried out in Erbil, Iraq between September and December 2012. Ultrasound examinations were carried out on 64 children affected with UTI and on 64 unaffected with UTI (control) in order to detect differences, in the presence of abnormalities, in the urinary tract between the two groups. A majority (59.4%) of children affected with UTI had ultrasound abnormalities, compared with 26.6% of the control group (P<0.001). Escherichia coli was the most common microorganism in both groups, although the difference was not statistically significant. More than one half (75%) of patients with UTI were female, compared with 25% who were male (P<0.001). More than one half of the children in the present study who presented with UTI were found to have ultrasound abnormalities. E. coli was the most common causative pathogen for children with or without ultrasound abnormalities. Copyright © 2014 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Association of an MHC Class II Haplotype with Increased Risk of Polymyositis in Hungarian Vizsla Dogs

PubMed Central

Massey, Jonathan; Rothwell, Simon; Rusbridge, Clare; Tauro, Anna; Addicott, Diane; Chinoy, Hector; Cooper, Robert G.; Ollier, William E. R.; Kennedy, Lorna J.

2013-01-01

A breed-specific polymyositis is frequently observed in the Hungarian Vizsla. Beneficial clinical response to immunosuppressive therapies has been demonstrated which points to an immune-mediated aetiology. Canine inflammatory myopathies share clinical and histological similarities with the human immune-mediated myopathies. As MHC class II associations have been reported in the human conditions we investigated whether an MHC class II association was present in the canine myopathy seen in this breed. 212 Hungarian Vizsla pedigree dogs were stratified both on disease status and degree of relatedness to an affected dog. This generated a group of 29 cases and 183 “graded” controls: 93 unaffected dogs with a first degree affected relative, 44 unaffected dogs with a second degree affected relative, and 46 unaffected dogs with no known affected relatives. Eleven DLA class II haplotypes were identified, of which, DLA-DRB1*02001/DQA1*00401/DQB1*01303, was at significantly raised frequency in cases compared to controls (OR = 1.92, p = 0.032). When only control dogs with no family history of the disease were compared to cases, the association was further strengthened (OR = 4.08, p = 0.00011). Additionally, a single copy of the risk haplotype was sufficient to increase disease risk, with the risk substantially increasing for homozygotes. There was a trend of increasing frequency of this haplotype with degree of relatedness, indicating low disease penetrance. These findings support the hypothesis of an immune-mediated aetiology for this canine myopathy and give credibility to potentially using the Hungarian Vizsla as a genetic model for comparative studies with human myositis. PMID:23457575

Single and Combined Effects of Air, Road, and Rail Traffic Noise on Sleep and Recuperation

PubMed Central

Basner, Mathias; Müller, Uwe; Elmenhorst, Eva-Maria

2011-01-01

Study Objective: Traffic noise disturbs sleep and may impair recuperation. There is limited information on single and combined effects of air, road, and rail traffic noise on sleep and recuperation. Design: Repeated measures. Setting: Polysomnographic laboratory study. Participants: 72 healthy subjects, mean ± standard deviation 40 ± 13 years, range 18-71 years, 32 male. Interventions: Exposure to 40, 80, or 120 rail, road, and/or air traffic noise events. Measurement and Results: Subjects were investigated for 11 consecutive nights, which included 8 noise exposure nights and one noise-free control night. Noise effects on sleep structure and continuity were subtle, even in nights with combined exposure, most likely because of habituation and an increase in arousal thresholds both within and across nights. However, cardiac arousals did not habituate across nights. Noise exposure significantly affected subjective assessments of sleep quality and recuperation, whereas objective performance was unaffected, except for a small increase in mean PVT reaction time (+4 ms, adjusted P < 0.05). Road traffic noise led to the strongest changes in sleep structure and continuity, whereas subjective assessments of sleep were worse after nights with air and rail traffic noise exposure. In contrast to daytime annoyance, cortical arousal probabilities and cardiac responses were significantly lower for air than for road and rail traffic noise (all P < 0.0001). These differences were explained by sound pressure level rise time and high frequency (> 3 kHz) noise event components. Conclusions: Road, rail, and air traffic noise differentially affect objective and subjective assessments of sleep. Differences in the degree of noise-induced sleep fragmentation between traffic modes were explained by the specific spectral and temporal composition of noise events, indicating potential targets for active and passive noise control. Field studies are needed to validate our findings in a setting with higher ecologic validity. Citation: Basner M; Müller U; Elmenhorst EM. Single and combined effects of air, road, and rail traffic noise on sleep and recuperation. SLEEP 2011;34(1):11-23. PMID:21203365

The effects of citalopram and fluoxetine on sexual behavior in healthy men: evidence of delayed ejaculation and unaffected sexual desire. A randomized, placebo-controlled, double-blind, double-dummy, parallel group study.

PubMed

Madeo, Bruno; Bettica, Paolo; Milleri, Stefano; Balestrieri, Antonio; Granata, Antonio R M; Carani, Cesare; Rochira, Vincenzo

2008-10-01

Selective serotonin reuptake inhibitors (SSRIs) are known to induce delayed orgasm and delayed ejaculation, while their effect on other aspects of sexual function, such as sexual motivation, arousal, and erectile function are unclear. In order to evaluate the effect of chronic administration of two SSRIs, citalopram and fluoxetine, on normal sexual function, we studied the parameters of male sexual behavior, erectile function, and ejaculation on 48 healthy male volunteers, aged 29.5 +/- 4.9, in a randomized, placebo-controlled, double-blind, double-dummy study. Methods. The subjects were randomized to receive placebo (16 subjects), or fluoxetine (20 mg/day) (16 subjects) or citalopram (20 mg/day) for the first week, and 40 mg/day in the following 3 weeks (16 subjects). Sexual function was investigated at the screening and at the end of the study by means of test of penile erection (TPE) and masturbation ejaculation latency time (MELT) performed during visual erotic stimulation, and at each visit by self-filled questionnaires (International Index Erectile Function [IIEF-15] and Golombock Rust Inventory of Sexual Satisfaction [GRISS]). All the erectile parameters, evaluated by means of RigiScan Plus during TPE, were not significantly different when both fluoxetine and citalopram were compared with placebo. A delay in the ejaculation time was observed both during citalopram and during fluoxetine treatment when compared with placebo, reaching a statistical significance only with citalopram. During the treatment with citalopram and fluoxetine, the IIEF-15 score of all items decreased except for those items related to sexual desire; however, the scores were significantly lower only for the citalopram treatment. The treatment with citalopram or with fluoxetine was confirmed to delay ejaculation, but was significant only for citalopram. Citalopram and fluoxetine did not affect sexual desire. Citalopram and fluoxetine did not directly affect penile erection as objectively assessed by RigiScan, although an impairment in the subjective assessment of erectile function was observed, but was significant only for citalopram, and it was thought to be a possible consequence of the delayed ejaculation perceived as a trouble.

The Video Head Impulse Test (vHIT) of Semicircular Canal Function - Age-Dependent Normative Values of VOR Gain in Healthy Subjects.

PubMed

McGarvie, Leigh A; MacDougall, Hamish G; Halmagyi, G Michael; Burgess, Ann M; Weber, Konrad P; Curthoys, Ian S

2015-01-01

The video Head Impulse Test (vHIT) is now widely used to test the function of each of the six semicircular canals individually by measuring the eye rotation response to an abrupt head rotation in the plane of the canal. The main measure of canal adequacy is the ratio of the eye movement response to the head movement stimulus, i.e., the gain of the vestibulo-ocular reflex (VOR). However, there is a need for normative data about how VOR gain is affected by age and also by head velocity, to allow the response of any particular patient to be compared to the responses of healthy subjects in their age range. In this study, we determined for all six semicircular canals, normative values of VOR gain, for each canal across a range of head velocities, for healthy subjects in each decade of life. The VOR gain was measured for all canals across a range of head velocities for at least 10 healthy subjects in decade age bands: 10-19, 20-29, 30-39, 40-49, 50-59, 60-69, 70-79, 80-89. The compensatory eye movement response to a small, unpredictable, abrupt head rotation (head impulse) was measured by the ICS impulse prototype system. The same operator delivered every impulse to every subject. Vestibulo-ocular reflex gain decreased at high head velocities, but was largely unaffected by age into the 80- to 89-year age group. There were some small but systematic differences between the two directions of head rotation, which appear to be largely due to the fact that in this study only the right eye was measured. The results are considered in relation to recent evidence about the effect of age on VOR performance. These normative values allow the results of any particular patient to be compared to the values of healthy people in their age range and so allow, for example, detection of whether a patient has a bilateral vestibular loss. VOR gain, as measured directly by the eye movement response to head rotation, seems largely unaffected by aging.

Recognition of facial emotion and affective prosody in children with ASD (+ADHD) and their unaffected siblings.

PubMed

Oerlemans, Anoek M; van der Meer, Jolanda M J; van Steijn, Daphne J; de Ruiter, Saskia W; de Bruijn, Yvette G E; de Sonneville, Leo M J; Buitelaar, Jan K; Rommelse, Nanda N J

2014-05-01

Autism is a highly heritable and clinically heterogeneous neuropsychiatric disorder that frequently co-occurs with other psychopathologies, such as attention-deficit/hyperactivity disorder (ADHD). An approach to parse heterogeneity is by forming more homogeneous subgroups of autism spectrum disorder (ASD) patients based on their underlying, heritable cognitive vulnerabilities (endophenotypes). Emotion recognition is a likely endophenotypic candidate for ASD and possibly for ADHD. Therefore, this study aimed to examine whether emotion recognition is a viable endophenotypic candidate for ASD and to assess the impact of comorbid ADHD in this context. A total of 90 children with ASD (43 with and 47 without ADHD), 79 ASD unaffected siblings, and 139 controls aged 6-13 years, were included to test recognition of facial emotion and affective prosody. Our results revealed that the recognition of both facial emotion and affective prosody was impaired in children with ASD and aggravated by the presence of ADHD. The latter could only be partly explained by typical ADHD cognitive deficits, such as inhibitory and attentional problems. The performance of unaffected siblings could overall be considered at an intermediate level, performing somewhat worse than the controls and better than the ASD probands. Our findings suggest that emotion recognition might be a viable endophenotype in ASD and a fruitful target in future family studies of the genetic contribution to ASD and comorbid ADHD. Furthermore, our results suggest that children with comorbid ASD and ADHD are at highest risk for emotion recognition problems.

Three dysconnectivity patterns in treatment-resistant schizophrenia patients and their unaffected siblings.

PubMed

Wang, Jicai; Cao, Hongbao; Liao, Yanhui; Liu, Weiqing; Tan, Liwen; Tang, Yanqing; Chen, Jindong; Xu, Xiufeng; Li, Haijun; Luo, Chunrong; Liu, Chunyu; Ries Merikangas, Kathleen; Calhoun, Vince; Tang, Jinsong; Shugart, Yin Yao; Chen, Xiaogang

2015-01-01

Among individuals diagnosed with schizophrenia, approximately 20%-33% are recognized as treatment-resistant schizophrenia (TRS) patients. These TRS patients suffer more severely from the disease but struggle to benefit from existing antipsychotic treatments. A few recent studies suggested that schizophrenia may be caused by impaired synaptic plasticity that manifests as functional dysconnectivity in the brain, however, few of those studies focused on the functional connectivity changes in the brains of TRS groups. In this study, we compared the whole brain connectivity variations in TRS patients, their unaffected siblings, and healthy controls. Connectivity network features between and within the 116 automated anatomical labeling (AAL) brain regions were calculated and compared using maps created with three contrasts: patient vs. control, patient vs. sibling, and sibling vs. To evaluate the predictive power of the selected features, we performed a multivariate classification approach. We also evaluated the influence of six important clinical measures (e.g. age, education level) on the connectivity features. This study identified abnormal significant connectivity changes of three patterns in TRS patients and their unaffected siblings: 1) 69 patient-specific connectivity (PCN); 2) 102 shared connectivity (SCN); and 3) 457 unshared connectivity (UCN). While the first two patterns were widely reported by previous non-TRS specific studies, we were among the first to report widespread significant connectivity differences between TRS patient groups and their healthy sibling groups. Observations of this study may provide new insights for the understanding of the neurophysiological mechanisms of TRS.

Executive Function and Adaptive Behavior in Muenke Syndrome.

PubMed

Yarnell, Colin M P; Addissie, Yonit A; Hadley, Donald W; Guillen Sacoto, Maria J; Agochukwu, Nneamaka B; Hart, Rachel A; Wiggs, Edythe A; Platte, Petra; Paelecke, Yvonne; Collmann, Hartmut; Schweitzer, Tilmann; Kruszka, Paul; Muenke, Maximilian

2015-08-01

To investigate executive function and adaptive behavior in individuals with Muenke syndrome using validated instruments with a normative population and unaffected siblings as controls. Participants in this cross-sectional study included individuals with Muenke syndrome (P250R mutation in FGFR3) and their mutation-negative siblings. Participants completed validated assessments of executive functioning (Behavior Rating Inventory of Executive Function [BRIEF]) and adaptive behavior skills (Adaptive Behavior Assessment System, Second Edition [ABAS-II]). Forty-four with a positive FGFR3 mutation, median age 9 years, range 7 months to 52 years were enrolled. In addition, 10 unaffected siblings served as controls (5 males, 5 females; median age, 13 years; range, 3-18 years). For the General Executive Composite scale of the BRIEF, 32.1% of the cohort had scores greater than +1.5 SD, signifying potential clinical significance. For the General Adaptive Composite of the ABAS-II, 28.2% of affected individuals scored in the 3rd-8th percentile of the normative population, and 56.4% were below the average category (<25th percentile). Multiple regression analysis did not identify craniosynostosis as a predictor of BRIEF (P = .70) or ABAS-II scores (P = .70). In the sibling pair analysis, affected siblings performed significantly poorer on the BRIEF General Executive Composite and the ABAS-II General Adaptive Composite. Individuals with Muenke syndrome are at an increased risk for developing adaptive and executive function behavioral changes compared with a normative population and unaffected siblings. Published by Elsevier Inc.

Neonatal stress affects the aging trajectory of female rats on the endocrine, temperature, and ventilatory responses to hypoxia.

PubMed

Fournier, Sébastien; Gulemetova, Roumiana; Baldy, Cécile; Joseph, Vincent; Kinkead, Richard

2015-04-01

Human and animal studies on sleep-disordered breathing and respiratory regulation show that the effects of sex hormones are heterogeneous. Because neonatal stress results in sex-specific disruption of the respiratory control in adult rats, we postulate that it might affect respiratory control modulation induced by ovarian steroids in female rats. The hypoxic ventilatory response (HVR) of adult female rats exposed to neonatal maternal separation (NMS) is ∼30% smaller than controls (24), but consequences of NMS on respiratory control in aging female rats are unknown. To address this issue, whole body plethysmography was used to evaluate the impact of NMS on the HVR (12% O2, 20 min) of middle-aged (MA; ∼57 wk old) female rats. Pups subjected to NMS were placed in an incubator 3 h/day for 10 consecutive days (P3 to P12). Controls were undisturbed. To determine whether the effects were related to sexual hormone decline or aging per se, experiments were repeated on bilaterally ovariectomized (OVX) young (∼12 wk old) adult female rats. OVX and MA both reduced the HVR significantly in control rats but had little effect on the HVR of NMS females. OVX (but not aging) reduced the anapyrexic response in both control and NMS animals. These results show that hormonal decline decreases the HVR of control animals, while leaving that of NMS female animals unaffected. This suggests that neonatal stress alters the interaction between sex hormone regulation and the development of body temperature, hormonal, and ventilatory responses to hypoxia. Copyright © 2015 the American Physiological Society.

Method to fabricate functionalized conical nanopores

DOEpatents

Small, Leo J.; Spoerke, Erik David; Wheeler, David R.

2016-07-12

A pressure-based chemical etch method is used to shape polymer nanopores into cones. By varying the pressure, the pore tip diameter can be controlled, while the pore base diameter is largely unaffected. The method provides an easy, low-cost approach for conically etching high density nanopores.

A histopathological study of bulbar conjunctival flaps occurring in 2 contact lens wearers.

PubMed

Markoulli, Maria; Francis, Ian C; Yong, Jim; Jalbert, Isabelle; Carnt, Nicole; Cole, Nerida; Papas, Eric

2011-09-01

To study the histopathology of paralimbal bulbar conjunctival flaps occurring secondary to soft contact lens wear. Slit-lamp biomicroscopy using sodium fluorescein, cobalt blue light, and a Wratten filter was used to observe the presence, location, and dimensions of bulbar conjunctival flaps presenting in a cohort of contact lens wearers. Two subjects who exhibited such flaps agreed to undergo conjunctival biopsy. Tissue samples, obtained from the region of the flap, and an adjacent unaffected area were processed by standard histopathological methods. In the first subject, analysis of the flap tissue showed even collagen distribution and overall normal histology. The flap of the second subject displayed a mild focal increase in collagen and mild degeneration of collagen, but no increase in elastic tissue. Conjunctival epithelium was normal in both cases. In these 2 subjects, conjunctival flap tissue either was normal or showed only minimal abnormality. There is insufficient evidence for significant pathological change on the time scale of this study.

Gravity and perceptual stability during translational head movement on earth and in microgravity.

PubMed

Jaekl, P; Zikovitz, D C; Jenkin, M R; Jenkin, H L; Zacher, J E; Harris, L R

2005-01-01

We measured the amount of visual movement judged consistent with translational head movement under normal and microgravity conditions. Subjects wore a virtual reality helmet in which the ratio of the movement of the world to the movement of the head (visual gain) was variable. Using the method of adjustment under normal gravity 10 subjects adjusted the visual gain until the visual world appeared stable during head movements that were either parallel or orthogonal to gravity. Using the method of constant stimuli under normal gravity, seven subjects moved their heads and judged whether the virtual world appeared to move "with" or "against" their movement for several visual gains. One subject repeated the constant stimuli judgements in microgravity during parabolic flight. The accuracy of judgements appeared unaffected by the direction or absence of gravity. Only the variability appeared affected by the absence of gravity. These results are discussed in relation to discomfort during head movements in microgravity. c2005 Elsevier Ltd. All rights reserved.

A randomized, controlled trial of interactive, multimedia software for patient colonoscopy education.

PubMed

Shaw, M J; Beebe, T J; Tomshine, P A; Adlis, S A; Cass, O W

2001-02-01

The purpose of our study was to assess the effectiveness of computer-assisted instruction (CAI) in patients having colonoscopies. We conducted a randomized, controlled trial in large, multispecialty clinic. Eighty-six patients were referred for colonoscopies. The interventions were standard education versus standard education plus CAI, and the outcome measures were anxiety, comprehension, and satisfaction. Computer-assisted instruction had no effect on patients' anxiety. The group receiving CAI demonstrated better overall comprehension (p < 0.001). However, Comprehension of certain aspects of serious complications and appropriate postsedation behavior were unaffected by educational method. Patients in the CAI group were more likely to indicate satisfaction with the amount of information provided when compared with the standard education counterparts (p = 0.001). Overall satisfaction was unaffected by educational method. Computer-assisted instruction for colonoscopy provided better comprehension and greater satisfaction with the adequacy of education than standard education. Computer-assisted instruction helps physicians meet their educational responsibilities with no decrement to the interpersonal aspects of the patient-physician relationship.

Mental Health of Children Living in Foster Families in Rural Rwanda: The Role of HIV and the Family Environment.

PubMed

Nduwimana, Estella; Mukunzi, Sylvere; Ng, Lauren C; Kirk, Catherine M; Bizimana, Justin I; Betancourt, Theresa S

2017-06-01

Fostering children is common in sub-Saharan Africa, but few studies examine these children's mental health needs. This study investigated the impact of living in a foster family on the mental health of HIV-positive, HIV-affected and HIV-unaffected children (n = 681 aged 10-17) in rural Rwanda. Regression analyses assessed the impact of living in a foster family on mental health, parenting, and daily hardships; multiple mediation analyses assessed whether family factors mediated the association between foster status and mental health. HIV-positive children were eight times more likely to live in foster families than HIV-unaffected children. Being HIV-affected was predictive of depression and irritability symptoms after controlling for family factors. Controlling for HIV-status, foster children had more symptoms of depression, anxiety, and irritability than non-fostered children. Positive parenting fully mediated the association between foster status and mental health. Mental health and parenting interventions for foster children and HIV-affected children may improve child outcomes.

Hypertrophy of proximal tubular epithelial cells induced by low pH in vitro is independent of ammoniagenesis.

PubMed

Bevington, A; Millwater, C J; Walls, J

1994-01-01

Metabolic acidosis can lead to tubular hypertrophy in vivo. This is thought to arise from stimulation of renal production of ammonia, a known hypertrophic agent. To examine this effect in vitro, confluent opossum (OK) proximal tubular epithelial cells were cultured at acidic pH (7.21 +/- 0.02) or at control pH (7.37 +/- 0.01) for 4 days. Protein content was 9% higher at acidic pH whereas DNA content was unaffected. The resulting increase in mean cell size (protein/DNA ratio) was 10% but correlated inversely with the mass of cells in control wells, varying from +48% at low cell mass to -14% at high cell mass. In contrast, low pH decreased 3H-thymidine incorporation by 9%. However, ammonia production was unaffected. These changes in protein/DNA ratio and 3H-thymidine incorporation cannot therefore be attributed to acid-induced ammoniagenesis and imply that low pH exerts a more direct effect on tubular cell growth than previously envisaged.

Pulmonary arterial hypertension reduces energy efficiency of right, but not left, rat ventricular trabeculae.

PubMed

Pham, Toan; Nisbet, Linley; Taberner, Andrew; Loiselle, Denis; Han, June-Chiew

2018-04-01

Pulmonary arterial hypertension (PAH) triggers right ventricle (RV) hypertrophy and left ventricle (LV) atrophy, which progressively leads to heart failure. We designed experiments under conditions mimicking those encountered by the heart in vivo that allowed us to investigate whether consequent structural and functional remodelling of the ventricles affects their respective energy efficiencies. We found that peak work output was lower in RV trabeculae from PAH rats due to reduced extent and velocity of shortening. However, their suprabasal enthalpy was unaffected due to increased activation heat, resulting in reduced suprabasal efficiency. There was no effect of PAH on LV suprabasal efficiency. We conclude that the mechanism underlying the reduced energy efficiency of hypertrophied RV tissues is attributable to the increased energy cost of Ca 2+ cycling, whereas atrophied LV tissues still maintain normal mechano-energetic performance. Pulmonary arterial hypertension (PAH) greatly increases the afterload on the right ventricle (RV), triggering RV hypertrophy, which progressively leads to RV failure. In contrast, the disease reduces the passive filling pressure of the left ventricle (LV), resulting in LV atrophy. We investigated whether these distinct structural and functional consequences to the ventricles affect their respective energy efficiencies. We studied trabeculae isolated from both ventricles of Wistar rats with monocrotaline-induced PAH and their respective Control groups. Trabeculae were mounted in a calorimeter at 37°C. While contracting at 5 Hz, they were subjected to stress-length work-loops over a wide range of afterloads. They were subsequently required to undergo a series of isometric contractions at various muscle lengths. In both protocols, stress production, length change and suprabasal heat output were simultaneously measured. We found that RV trabeculae from PAH rats generated higher activation heat, but developed normal active stress. Their peak external work output was lower due to reduced extent and velocity of shortening. Despite lower peak work output, suprabasal enthalpy was unaffected, thereby rendering suprabasal efficiency lower. Crossbridge efficiency, however, was unaffected. In contrast, LV trabeculae from PAH rats maintained normal mechano-energetic performance. Pulmonary arterial hypertension reduces the suprabasal energy efficiency of hypertrophied right ventricular tissues as a consequence of the increased energy cost of Ca 2+ cycling. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Effect of light-emitting diode colour temperature on magnifier reading performance of the visually impaired.

PubMed

Wolffsohn, James S; Palmer, Eshmael; Rubinstein, Martin; Eperjesi, Frank

2012-09-01

As light-emitting diodes become more common as the light source for low vision aids, the effect of illumination colour temperature on magnifier reading performance was investigated. Reading ability (maximum reading speed, critical print size, threshold near visual acuity) using Radner charts and subjective preference was assessed for 107 participants with visual impairment using three stand magnifiers with light emitting diode illumination colour temperatures of 2,700 K, 4,500 K and 6,000 K. The results were compared with distance visual acuity, prescribed magnification, age and the primary cause of visual impairment. Reading speed, critical print size and near visual acuity were unaffected by illumination colour temperature (p > 0.05). Reading metrics decreased with worsening acuity and higher levels of prescribed magnification but acuity was unaffected by age. Each colour temperature was preferred and disliked by a similar number of patients and was unrelated to distance visual acuity, prescribed magnification and age (p > 0.05). Patients had better near acuity (p = 0.002), critical print size (p = 0.034) and maximum reading speed (p < 0.001), and the improvement in near from distance acuity was greater (p = 0.004) with their preferred rather than least-liked colour temperature illumination. A range of colour temperature illuminations should be offered to all visually impaired individuals prescribed with an optical magnifier for near tasks to optimise subjective and objective benefits. © 2012 The Authors. Clinical and Experimental Optometry © 2012 Optometrists Association Australia.

Reduction of novel circulating long-chain fatty acids in colorectal cancer patients is independent of tumor burden and correlates with age

PubMed Central

2010-01-01

Background Serum levels of novel hydroxy polyunsaturated ultra long-chain fatty acids (hPULCFAs) have been previously shown to be reduced in pre-treatment CRC patients compared to disease-free subjects, independent of disease stage. However, whether reduced levels of hPULCFAs result from the presence of cancer is currently unknown, as is the distribution of hPULCFAs in the general population. The following studies were carried out to assess whether conventional therapy would result in restoration of systemic hPULCFAs in CRC patients, and to investigate the relationship between hPULCFA levels and age. Methods Tandem mass spectrometry was used to determine serum levels of the 28 carbon-containing hPULCFA C28H46O4 (CRC-446) in the following cohorts: two independent Japanese CRC populations following surgical tumor removal (n = 86), a North American Caucasian CRC cohort (n = 150) following post-surgery combination chemo/radiation therapy, 990 randomly selected anonymized serum samples from subjects ranging between 11 and 99 years of age, as well as longitudinally collected serum samples from healthy normals (n = 8, up to 90 weeks) and stage IV CRC subjects on combination therapy (n = 12, up to 63 weeks). Results Serum CRC-446 levels in CRC subjects were significantly lower than controls (mean of 0.297 ± 0.07 ug/ml in controls versus 0.092 ± 0.03 in CRCs, p < 0.001), and were unaffected by surgical tumor removal or by chemo/radiation treatment (p > 0.05 between pre vs post surgery). CRC-446 levels showed a strong inverse association with age (p < E-11) across the randomly-selected cohort of 990 subjects, with no correlation observed in the CRC-positive subjects. Longitudinal intra-subject results, however, showed relatively stable CRC-446 levels over the short term of up to 90 weeks in both disease-free subjects and late-stage CRC patients. Conclusions Our findings show that CRC-446 levels are not affected by conventional CRC treatment and inversely correlate with age, which suggest that reduced serum CRC-446 levels likely exist prior to the development of CRC. Extrapolation of the results to a simple screening scenario showed that, compared to fecal blood testing, pre-colonoscopy screening using serum CRC-446 levels would require 80% fewer colonoscopies, would identify risk in subjects under the age of 50, and would result in increased numbers of early cases detected. The precise role these serum metabolites play in the aetiology of cancer development remains to be determined. PMID:21114854

Inter-rater reliability of kinesthetic measurements with the KINARM robotic exoskeleton.

PubMed

Semrau, Jennifer A; Herter, Troy M; Scott, Stephen H; Dukelow, Sean P

2017-05-22

Kinesthesia (sense of limb movement) has been extremely difficult to measure objectively, especially in individuals who have survived a stroke. The development of valid and reliable measurements for proprioception is important to developing a better understanding of proprioceptive impairments after stroke and their impact on the ability to perform daily activities. We recently developed a robotic task to evaluate kinesthetic deficits after stroke and found that the majority (~60%) of stroke survivors exhibit significant deficits in kinesthesia within the first 10 days post-stroke. Here we aim to determine the inter-rater reliability of this robotic kinesthetic matching task. Twenty-five neurologically intact control subjects and 15 individuals with first-time stroke were evaluated on a robotic kinesthetic matching task (KIN). Subjects sat in a robotic exoskeleton with their arms supported against gravity. In the KIN task, the robot moved the subjects' stroke-affected arm at a preset speed, direction and distance. As soon as subjects felt the robot begin to move their affected arm, they matched the robot movement with the unaffected arm. Subjects were tested in two sessions on the KIN task: initial session and then a second session (within an average of 18.2 ± 13.8 h of the initial session for stroke subjects), which were supervised by different technicians. The task was performed both with and without the use of vision in both sessions. We evaluated intra-class correlations of spatial and temporal parameters derived from the KIN task to determine the reliability of the robotic task. We evaluated 8 spatial and temporal parameters that quantify kinesthetic behavior. We found that the parameters exhibited moderate to high intra-class correlations between the initial and retest conditions (Range, r-value = [0.53-0.97]). The robotic KIN task exhibited good inter-rater reliability. This validates the KIN task as a reliable, objective method for quantifying kinesthesia after stroke.

Dynamic Stability and Gravitational Balancing of Multiple Extended Bodies

NASA Technical Reports Server (NTRS)

Quadrelli, Marco

2008-01-01

Feasibility of a non-invasive compensation scheme was analyzed for precise positioning of a massive extended body in free fall using gravitational forces influenced by surrounding source masses in close proximity. The N-body problem of classical mechanics is a paradigm used to gain insight into the physics of the equivalent N-body problem subject to control forces. The analysis addressed how a number of control masses move around the proof mass so that the proof mass position can be accurately and remotely compensated when exogenous disturbances are acting on it, while its sensitivity to gravitational waves remains unaffected. Past methods to correct the dynamics of the proof mass have considered active electrostatic or capacitive methods, but the possibility of stray capacitances on the surfaces of the proof mass have prompted the investigation of other alternatives, such as the method presented in this paper. While more rigorous analyses of the problem should be carried out, the data show that, by means of a combined feedback and feed-forward control approach, the control masses succeeded in driving the proof mass along the specified trajectory, which implies that the proof mass can, in principle, be balanced via gravitational forces only while external perturbations are acting on it. This concept involves the dynamic stability of a group of massive objects interacting gravitationally under active control, and can apply to drag-free control of spacecraft during missions, to successor gravitational wave space borne sensors, or to any application requiring flying objects to be precisely controlled in position and attitude relative to another body via gravitational interactions only.

Exon expression in lymphoblastoid cell lines from subjects with schizophrenia before and after glucose deprivation

PubMed Central

Martin, Maureen V; Rollins, Brandi; Sequeira, P Adolfo; Mesén, Andrea; Byerley, William; Stein, Richard; Moon, Emily A; Akil, Huda; Jones, Edward G; Watson, Stanley J; Barchas, Jack; DeLisi, Lynn E; Myers, Richard M; Schatzberg, Alan; Bunney, William E; Vawter, Marquis P

2009-01-01

Background The purpose of this study was to examine the effects of glucose reduction stress on lymphoblastic cell line (LCL) gene expression in subjects with schizophrenia compared to non-psychotic relatives. Methods LCLs were grown under two glucose conditions to measure the effects of glucose reduction stress on exon expression in subjects with schizophrenia compared to unaffected family member controls. A second aim of this project was to identify cis-regulated transcripts associated with diagnosis. Results There were a total of 122 transcripts with significant diagnosis by probeset interaction effects and 328 transcripts with glucose deprivation by probeset interaction probeset effects after corrections for multiple comparisons. There were 8 transcripts with expression significantly affected by the interaction between diagnosis and glucose deprivation and probeset after correction for multiple comparisons. The overall validation rate by qPCR of 13 diagnosis effect genes identified through microarray was 62%, and all genes tested by qPCR showed concordant up- or down-regulation by qPCR and microarray. We assessed brain gene expression of five genes found to be altered by diagnosis and glucose deprivation in LCLs and found a significant decrease in expression of one gene, glutaminase, in the dorsolateral prefrontal cortex (DLPFC). One SNP with previously identified regulation by a 3' UTR SNP was found to influence IRF5 expression in both brain and lymphocytes. The relationship between the 3' UTR rs10954213 genotype and IRF5 expression was significant in LCLs (p = 0.0001), DLPFC (p = 0.007), and anterior cingulate cortex (p = 0.002). Conclusion Experimental manipulation of cells lines from subjects with schizophrenia may be a useful approach to explore stress related gene expression alterations in schizophrenia and to identify SNP variants associated with gene expression. PMID:19772658

Mutations in the satellite cell gene MEGF10 cause a recessive congenital myopathy with minicores.

PubMed

Boyden, Steven E; Mahoney, Lane J; Kawahara, Genri; Myers, Jennifer A; Mitsuhashi, Satomi; Estrella, Elicia A; Duncan, Anna R; Dey, Friederike; DeChene, Elizabeth T; Blasko-Goehringer, Jessica M; Bönnemann, Carsten G; Darras, Basil T; Mendell, Jerry R; Lidov, Hart G W; Nishino, Ichizo; Beggs, Alan H; Kunkel, Louis M; Kang, Peter B

2012-05-01

We ascertained a nuclear family in which three of four siblings were affected with an unclassified autosomal recessive myopathy characterized by severe weakness, respiratory impairment, scoliosis, joint contractures, and an unusual combination of dystrophic and myopathic features on muscle biopsy. Whole genome sequence from one affected subject was filtered using linkage data and variant databases. A single gene, MEGF10, contained nonsynonymous mutations that co-segregated with the phenotype. Affected subjects were compound heterozygous for missense mutations c.976T > C (p.C326R) and c.2320T > C (p.C774R). Screening the MEGF10 open reading frame in 190 patients with genetically unexplained myopathies revealed a heterozygous mutation, c.211C > T (p.R71W), in one additional subject with a similar clinical and histological presentation as the discovery family. All three mutations were absent from at least 645 genotyped unaffected control subjects. MEGF10 contains 17 atypical epidermal growth factor-like domains, each of which contains eight cysteine residues that likely form disulfide bonds. Both the p.C326R and p.C774R mutations alter one of these residues, which are completely conserved in vertebrates. Previous work showed that murine Megf10 is required for preserving the undifferentiated, proliferative potential of satellite cells, myogenic precursors that regenerate skeletal muscle in response to injury or disease. Here, knockdown of megf10 in zebrafish by four different morpholinos resulted in abnormal phenotypes including unhatched eggs, curved tails, impaired motility, and disorganized muscle tissue, corroborating the pathogenicity of the human mutations. Our data establish the importance of MEGF10 in human skeletal muscle and suggest satellite cell dysfunction as a novel myopathic mechanism.

Structural changes of macula and optic disk of the fellow eye in patients with nonarteritic anterior ischemic optic neuropathy.

PubMed

Duman, R; Yavas, G F; Veliyev, I; Dogan, M; Duman, R

2018-05-10

The aim was to assess the ganglion cell complex (GCC) thickness, retinal nerve fiber layer (RNFL) thickness and optic disk features in the affected eyes (AE) and unaffected fellow eyes (FE) of subjects with unilateral nonarteritic anterior ischemic optic neuropathy (NAION) and to compare with healthy control eyes (CE) using spectral domain-optical coherence tomography (SD-OCT). This study included 28 patients and age, sex and refraction-matched 28 control subjects. Mean GCC thickness and peripapillary RNFL thickness in four quadrants measured by cirrus SD-OCT were evaluated in both AE and FE of patients and CE. In addition, optic disk measurements obtained with OCT were evaluated. Mean GCC thickness was significantly lower in AE compared with both FE and CE (P < 0.001), and mean GCC thickness in FE was significantly lower than CE (P = 0.022). In addition, mean RNFL thickness in superior and nasal quadrants significantly decreased in FE compared with CE (P = 0.020 and 0.010, respectively). Furthermore, AE had significantly greater optic disk cupping compared with both FE and CE (P < 0.001). GCC and RNFL thickness decreased significantly at late stages of NAION, in both AE and FE compared with CE, suggesting that some subclinical structural changes may occur in FE despite lack of obvious visual symptoms. In addition, there was no significant difference in optic disk features between the CE and FE. And significantly greater optic disk cupping in the AE compared with both FE and CE supports the acquired enlargement of cupping after the onset of NAION.

The Role of Left Hemispheric Structures for Emotional Processing as a Monitor of Bodily Reaction and Felt Chill - a Case-Control Functional Imaging Study.

PubMed

Grunkina, Viktoria; Holtz, Katharina; Klepzig, Kai; Neubert, Jörg; Horn, Ulrike; Domin, Martin; Hamm, Alfons O; Lotze, Martin

2016-01-01

Background: The particular function of the left anterior human insula on emotional arousal has been illustrated with several case studies. Only after left hemispheric insula lesions, patients lose their pleasure in habits such as listening to joyful music. In functional magnetic resonance imaging studies (fMRI) activation in the left anterior insula has been associated with both processing of emotional valence and arousal. Tight interactions with different areas of the prefrontal cortex are involved in bodily response monitoring and cognitive appraisal of a given stimulus. Therefore, a large left hemispheric lesion including the left insula should impair the bodily response of chill experience (objective chill response) but leave the cognitive aspects of chill processing (subjective chill response) unaffected. Methods: We investigated a patient (MC) with a complete left hemispheric media cerebral artery stroke, testing fMRI representation of pleasant (music) and unpleasant (harsh sounds) chill response. Results: Although chill response to both pleasant and unpleasant rated sounds was confirmed verbally at passages also rated as chilling by healthy participants, skin conductance response was almost absent in MC. For a healthy control (HC) objective and subjective chill response was positively associated. Bilateral prefrontal fMRI-response to chill stimuli was sustained in MC whereas insula activation restricted to the right hemisphere. Diffusion imaging together with lesion maps revealed that left lateral tracts were completely damaged but medial prefrontal structures were intact. Conclusion: With this case study we demonstrate how bodily response and cognitive appraisal are differentially participating in the internal monitor of chill response.

APC+/− alters colonic fibroblast proteome in FAP

PubMed Central

Dixon, Maketa P.; Blagoi, Elena L.; Nicolas, Emmanuelle; Seeholzer, Steven H.; Cheng, David; He, Yin A.; Coudry, Renata A.; Howard, Sharon D.; Riddle, Dawn M.; Cooper, Harry S.; Boman, Bruce M.; Conrad, Peggy; Crowell, James A.; Bellacosa, Alfonso; Knudson, Alfred; Yeung, Anthony T.; Kopelovich, Levy

2011-01-01

Here we compared the proteomes of primary fibroblast cultures derived from morphologically normal colonic mucosa of familial adenomatous polyposis (FAP) patients with those obtained from unaffected controls. The expression signature of about 19% of total fibroblast proteins separates FAP mutation carriers from unaffected controls (P < 0.01). More than 4,000 protein spots were quantified by 2D PAGE analysis, identifying 368 non-redundant proteins and 400 of their isoforms. Specifically, all three classes of cytoskeletal filaments and their regulatory proteins were altered as were oxidative stress response proteins. Given that FAP fibroblasts showed heightened sensitivity to transformation by KiMSV and SV40 including elevated levels of the p53 protein, events controlled in large measure by the Ras suppressor protein-1 (RSU-1) and oncogenic DJ-1, here we show decreased RSU1 and augmented DJ-1 expression in both fibroblasts and crypt-derived epithelial cells from morphologically normal colonic mucosa of FAP gene-carriers. The results indicate that heterozygosity for a mutant APC tumor suppressor gene alters the proteomes of both colon-derived normal fibroblasts in a gene-specific manner, consistent with a “one-hit” effect. PMID:21411865

The association between social anhedonia, withdrawal and psychotic experiences in general and high-risk populations.

PubMed

Velthorst, Eva; Meijer, Carin

2012-07-01

Social anhedonia (SA) and withdrawal are clinically relevant phenomena in schizophrenia. To examine the nature of the overlap between SA, withdrawal and positive symptoms, we investigated whether the co-occurrence of these phenotypes is more prominent in siblings of patients with a psychotic disorder compared to healthy controls, and if this association is independent of the amount of distress caused by psychotic experiences (PEs). Data were derived from 646 unaffected siblings and 326 healthy controls who were included in the Dutch Genetic Risk and Outcome in Psychosis (GROUP) study. PEs were assessed with the Community Assessment of Psychic Experiences and the Structured Interview for Schizotypy-Revised was used to examine social anhedonia and withdrawal. Our results show relatively small but significant cross-sectional associations between SA, withdrawal and PEs in unaffected siblings and none in the control group, irrespective of the level of distress caused by PEs. The findings of the present study suggest that the overlap between SA, withdrawal and psychotic symptoms often reported in schizophrenia patients, may at least partly reflect a shared genetic vulnerability, instead of merely being either a state marker of - or reaction to - acute psychotic symptoms. Copyright © 2012. Published by Elsevier B.V.

Nummular eczema: An addition of senile xerosis and unique cutaneous reactivities to environmental aeroallergens.

PubMed

Aoyama, H; Tanaka, M; Hara, M; Tabata, N; Tagami, H

1999-01-01

The pathogenesis of nummular eczema (NE) is still unknown. It often develops on the lower legs of elderly individuals with xerotic changes during the winter months. Such winter exacerbation is also observed in atopic dermatitis, in which there is a high incidence of cutaneous immune reactivities against environmental aeroallergens. Because of the total lack of information about skin reactivities in NE patients, we performed immunological as well as functional studies in their uninvolved skin. Prick tests and chamber scarification patch tests for representative aeroallergens were conducted on the flexor surface of the forearm in 26 NE patients, in 21 age-matched elderly persons without NE and in 43 healthy young controls. We found that the elderly subjects, regardless of their background, showed a significantly higher immediate skin reactivity to Candida albicans than the young controls. In contrast, patch testing revealed that, unlike the age-matched elderly subjects who showed a decrease in incidence of positive patch test reactions, the NE patients retained delayed contact sensitivity at a level comparable to that of the young healthy controls. They showed a significantly higher percentage of positive patch test reactions to Dermatophagoides farinae allergen (46%) and house dust allergen (35%) than the age-matched controls. Moreover, they also showed a significantly higher percentage of delayed hypersensitive reactions to C. albicans allergen (85%) than the age-matched controls (48%). Noninvasive functional assessment of the stratum corneum (SC) in unaffected skin areas of the lower legs in 8 NE patients demonstrated that, though the water barrier function of the SC was comparable to that of the age-matched controls, they showed a significantly lower hydration state of the SC than the age-matched controls. The xerotic skin of elderly individuals facilitates the development of cracking and fissuring of the skin surface in dry and cold winter. Such damage in the SC is sometimes aggravated by inadvertent scratching due to pruritus, allowing skin permeation of various environmental allergens. They may induce eczematous changes in those with preserved adequate delayed hypersensitivity despite their advanced age.

Dominance of the Unaffected Hemisphere Motor Network and Its Role in the Behavior of Chronic Stroke Survivors

PubMed Central

Bajaj, Sahil; Housley, Stephen N.; Wu, David; Dhamala, Mukesh; James, G. A.; Butler, Andrew J.

2016-01-01

Balance of motor network activity between the two brain hemispheres after stroke is crucial for functional recovery. Several studies have extensively studied the role of the affected brain hemisphere to better understand changes in motor network activity following stroke. Very few studies have examined the role of the unaffected brain hemisphere and confirmed the test–retest reliability of connectivity measures on unaffected hemisphere. We recorded blood oxygenation level dependent functional magnetic resonance imaging (fMRI) signals from nine stroke survivors with hemiparesis of the left or right hand. Participants performed a motor execution task with affected hand, unaffected hand, and both hands simultaneously. Participants returned for a repeat fMRI scan 1 week later. Using dynamic causal modeling (DCM), we evaluated effective connectivity among three motor areas: the primary motor area (M1), the premotor cortex (PMC) and the supplementary motor area for the affected and unaffected hemispheres separately. Five participants’ manual motor ability was assessed by Fugl-Meyer Motor Assessment scores and root-mean square error of participants’ tracking ability during a robot-assisted game. We found (i) that the task performance with the affected hand resulted in strengthening of the connectivity pattern for unaffected hemisphere, (ii) an identical network of the unaffected hemisphere when participants performed the task with their unaffected hand, and (iii) the pattern of directional connectivity observed in the affected hemisphere was identical for tasks using the affected hand only or both hands. Furthermore, paired t-test comparison found no significant differences in connectivity strength for any path when compared with one-week follow-up. Brain-behavior linear correlation analysis showed that the connectivity patterns in the unaffected hemisphere more accurately reflected the behavioral conditions than the connectivity patterns in the affected hemisphere. Above findings enrich our knowledge of unaffected brain hemisphere following stroke, which further strengthens our neurobiological understanding of stroke-affected brain and can help to effectively identify and apply stroke-treatments. PMID:28082882

Cortical GABA markers identify a molecular subtype of psychotic and bipolar disorders.

PubMed

Volk, D W; Sampson, A R; Zhang, Y; Edelson, J R; Lewis, D A

2016-09-01

Deficits in gamma aminobutyric acid (GABA) neuron-related markers, including the GABA-synthesizing enzyme GAD67, the calcium-binding protein parvalbumin, the neuropeptide somatostatin, and the transcription factor Lhx6, are most pronounced in a subset of schizophrenia subjects identified as having a 'low GABA marker' (LGM) molecular phenotype. Furthermore, schizophrenia shares degrees of genetic liability, clinical features and cortical circuitry abnormalities with schizoaffective disorder and bipolar disorder. Therefore, we determined the extent to which a similar LGM molecular phenotype may also exist in subjects with these disorders. Transcript levels for GAD67, parvalbumin, somatostatin, and Lhx6 were quantified using quantitative PCR in prefrontal cortex area 9 of 184 subjects with a diagnosis of schizophrenia (n = 39), schizoaffective disorder (n = 23) or bipolar disorder (n = 35), or with a confirmed absence of any psychiatric diagnoses (n = 87). A blinded clustering approach was employed to determine the presence of a LGM molecular phenotype across all subjects. Approximately 49% of the subjects with schizophrenia, 48% of the subjects with schizoaffective disorder, and 29% of the subjects with bipolar disorder, but only 5% of unaffected subjects, clustered in the cortical LGM molecular phenotype. These findings support the characterization of psychotic and bipolar disorders by cortical molecular phenotype which may help elucidate more pathophysiologically informed and personalized medications.

Efficacy and Safety of Cannabidiol and Tetrahydrocannabivarin on Glycemic and Lipid Parameters in Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Pilot Study.

PubMed

Jadoon, Khalid A; Ratcliffe, Stuart H; Barrett, David A; Thomas, E Louise; Stott, Colin; Bell, Jimmy D; O'Sullivan, Saoirse E; Tan, Garry D

2016-10-01

Cannabidiol (CBD) and Δ(9)-tetrahydrocannabivarin (THCV) are nonpsychoactive phytocannabinoids affecting lipid and glucose metabolism in animal models. This study set out to examine the effects of these compounds in patients with type 2 diabetes. In this randomized, double-blind, placebo-controlled study, 62 subjects with noninsulin-treated type 2 diabetes were randomized to five treatment arms: CBD (100 mg twice daily), THCV (5 mg twice daily), 1:1 ratio of CBD and THCV (5 mg/5 mg, twice daily), 20:1 ratio of CBD and THCV (100 mg/5 mg, twice daily), or matched placebo for 13 weeks. The primary end point was a change in HDL-cholesterol concentrations from baseline. Secondary/tertiary end points included changes in glycemic control, lipid profile, insulin sensitivity, body weight, liver triglyceride content, adipose tissue distribution, appetite, markers of inflammation, markers of vascular function, gut hormones, circulating endocannabinoids, and adipokine concentrations. Safety and tolerability end points were also evaluated. Compared with placebo, THCV significantly decreased fasting plasma glucose (estimated treatment difference [ETD] = -1.2 mmol/L; P < 0.05) and improved pancreatic β-cell function (HOMA2 β-cell function [ETD = -44.51 points; P < 0.01]), adiponectin (ETD = -5.9 × 10(6) pg/mL; P < 0.01), and apolipoprotein A (ETD = -6.02 μmol/L; P < 0.05), although plasma HDL was unaffected. Compared with baseline (but not placebo), CBD decreased resistin (-898 pg/ml; P < 0.05) and increased glucose-dependent insulinotropic peptide (21.9 pg/ml; P < 0.05). None of the combination treatments had a significant impact on end points. CBD and THCV were well tolerated. THCV could represent a new therapeutic agent in glycemic control in subjects with type 2 diabetes. © 2016 by the American Diabetes Association.

Effect of food on early drug exposure from extended-release stimulants: results from the Concerta, Adderall XR Food Evaluation (CAFE) Study.

PubMed

Auiler, J F; Liu, K; Lynch, J M; Gelotte, C K

2002-01-01

Stimulant therapy is the mainstay of treatment for children, adolescents and adults with attention-deficit/hyperactivity disorder (ADHD). Once-daily, extended-release oral formulations offer long acting control of symptoms by modifying drug delivery and absorption. In particular, consistency in early drug exposure is important for symptom control during school or work hours. Because these once-daily formulations are usually taken in the morning, the timing of the doses with breakfast is important. This study compared the effect of a high-fat breakfast on early drug exposure from a morning dose of two extended-release stimulant formulations: the osmotic-controlled OROS tablet of methylphenidate HCI (CONCERTA) and the capsule containing extended-release beads of mixed amphetamine salts (ADDERALL XR). The study had a single-dose, open-label, randomised, four-treatment, crossover design in which healthy subjects received either 36 mg CONCERTA or 20 mg ADDERALL XR in the morning after an overnight fast or a high-fat breakfast. Serial blood samples were collected over 28h to determine plasma concentrations of methylphenidate and amphetamine. The food effect on early drug exposure and the pharmacokinetic profiles up to 8 h after dosing of the two extended-release stimulants were directly compared using partial area (AUC(p4h), AUC(p6h) and AUC(p8h)) fed/fasted ratios. Amphetamine concentrations were markedly lower when the subjects had eaten breakfast, resulting in lower early drug exposures (p < 0.0001). By contrast, methylphenidate concentrations over the same 8 h were unaffected by breakfast, providing consistent levels of early drug exposure. Therefore, as a child's or adult's eating pattern varies, methylphenidate exposure over the first 8 h would be expected to have less day-to-day variation compared with amphetamine exposure. The osmotic-controlled OROS tablet provides a reliable and consistent delivery of methylphenidate HCI, independent of food, for patients with ADHD.

Assessment of Type I Interferon Signaling in Pediatric Inflammatory Disease.

PubMed

Rice, Gillian I; Melki, Isabelle; Frémond, Marie-Louise; Briggs, Tracy A; Rodero, Mathieu P; Kitabayashi, Naoki; Oojageer, Anthony; Bader-Meunier, Brigitte; Belot, Alexandre; Bodemer, Christine; Quartier, Pierre; Crow, Yanick J

2017-02-01

Increased type I interferon is considered relevant to the pathology of a number of monogenic and complex disorders spanning pediatric rheumatology, neurology, and dermatology. However, no test exists in routine clinical practice to identify enhanced interferon signaling, thus limiting the ability to diagnose and monitor treatment of these diseases. Here, we set out to investigate the use of an assay measuring the expression of a panel of interferon-stimulated genes (ISGs) in children affected by a range of inflammatory diseases. A cohort study was conducted between 2011 and 2016 at the University of Manchester, UK, and the Institut Imagine, Paris, France. RNA PAXgene blood samples and clinical data were collected from controls and symptomatic patients with a genetically confirmed or clinically well-defined inflammatory phenotype. The expression of six ISGs was measured by quantitative polymerase chain reaction, and the median fold change was used to calculate an interferon score (IS) for each subject compared to a previously derived panel of 29 controls (where +2 SD of the control data, an IS of >2.466, is considered as abnormal). Results were correlated with genetic and clinical data. Nine hundred ninety-two samples were analyzed from 630 individuals comprising symptomatic patients across 24 inflammatory genotypes/phenotypes, unaffected heterozygous carriers, and controls. A consistent upregulation of ISG expression was seen in 13 monogenic conditions (455 samples, 265 patients; median IS 10.73, interquartile range (IQR) 5.90-18.41), juvenile systemic lupus erythematosus (78 samples, 55 patients; median IS 10.60, IQR 3.99-17.27), and juvenile dermatomyositis (101 samples, 59 patients; median IS 9.02, IQR 2.51-21.73) compared to controls (78 samples, 65 subjects; median IS 0.688, IQR 0.427-1.196), heterozygous mutation carriers (89 samples, 76 subjects; median IS 0.862, IQR 0.493-1.942), and individuals with non-molecularly defined autoinflammation (89 samples, 69 patients; median IS 1.07, IQR 0.491-3.74). An assessment of six ISGs can be used to define a spectrum of inflammatory diseases related to enhanced type I interferon signaling. If future studies demonstrate that the IS is a reactive biomarker, this measure may prove useful both in the diagnosis and the assessment of treatment efficacy.

[Postural control in idiopathic scoliosis: comparison between healthy and scoliotic subjects].

PubMed

Silferi, V; Rougier, P; Labelle, H; Allard, P

2004-05-01

To assess the effects of idiopathic scoliosis on undisturbed postural control in young female teenagers. The centre of pressure (CP) displacements, measured through a force platform, were decomposed into two elementary components in order to differentiate the net postural performance, as revealed by the horizontal motions of the centre of gravity (CGh) and the level of muscular activity expressed by the vertical difference CP-CGv. The CG horizontal displacements were estimated from those of the CP with a low pass filter taking into account the subjects' anthropometry. Fifteen healthy teenagers and fifteen teenagers with idiopathic scoliosis were asked to stand still upright for three successive trials of 64s, rest periods of similar duration being allowed between each trial. The results indicate differences in the postural control between the two populations: scoliotic CG motions are more important than those of healthy subjects. In the medio-lateral direction, the CGh motions can be primarily explained by the concomitant increase observed at the CP-CGv level. To be more precise, one should have in mind that the CP-CGv amplitudes determine the horizontal acceleration communicated to CGh. On the other hand, despite significative increases of the CP-CGv in the antero-posterior direction, the CGh motions appear to be unaffected by these initial conditions. This feature suggests that appropriate control mechanisms can intervene in this antero-posterior direction for the scoliotic group whereas a similar organization cannot be observed in the medio-lateral direction. The differences observed in the postural performance for the healthy and scoliotic groups can be explained in various ways. The capacity of the scoliotic group to counteract huge CP-CGv motions may be linked to the location of the postural muscles involved in this control: the triceps surae for the antero-posterior direction, and the abductor-adductor hip muscles for the medio-lateral one. Only the action of the latter group can be indeed perturbed by the specific constraints occurring at the hip level and resulting from the scoliosis. On the other hand, the general increase of the CP-CGv motions, by expressing an overwhelming muscular activity in the whole set of postural muscles, does suggest that the drive of the descending motor commands is largely modulated and is likely the consequence of a central disfunctionning.

Machine learning derived risk prediction of anorexia nervosa.

PubMed

Guo, Yiran; Wei, Zhi; Keating, Brendan J; Hakonarson, Hakon

2016-01-20

Anorexia nervosa (AN) is a complex psychiatric disease with a moderate to strong genetic contribution. In addition to conventional genome wide association (GWA) studies, researchers have been using machine learning methods in conjunction with genomic data to predict risk of diseases in which genetics play an important role. In this study, we collected whole genome genotyping data on 3940 AN cases and 9266 controls from the Genetic Consortium for Anorexia Nervosa (GCAN), the Wellcome Trust Case Control Consortium 3 (WTCCC3), Price Foundation Collaborative Group and the Children's Hospital of Philadelphia (CHOP), and applied machine learning methods for predicting AN disease risk. The prediction performance is measured by area under the receiver operating characteristic curve (AUC), indicating how well the model distinguishes cases from unaffected control subjects. Logistic regression model with the lasso penalty technique generated an AUC of 0.693, while Support Vector Machines and Gradient Boosted Trees reached AUC's of 0.691 and 0.623, respectively. Using different sample sizes, our results suggest that larger datasets are required to optimize the machine learning models and achieve higher AUC values. To our knowledge, this is the first attempt to assess AN risk based on genome wide genotype level data. Future integration of genomic, environmental and family-based information is likely to improve the AN risk evaluation process, eventually benefitting AN patients and families in the clinical setting.

Unique cortical physiology associated with ipsilateral hand movements and neuroprosthetic implications.

PubMed

Wisneski, Kimberly J; Anderson, Nicholas; Schalk, Gerwin; Smyth, Matt; Moran, Daniel; Leuthardt, Eric C

2008-12-01

Brain computer interfaces (BCIs) offer little direct benefit to patients with hemispheric stroke because current platforms rely on signals derived from the contralateral motor cortex (the same region injured by the stroke). For BCIs to assist hemiparetic patients, the implant must use unaffected cortex ipsilateral to the affected limb. This requires the identification of distinct electrophysiological features from the motor cortex associated with ipsilateral hand movements. In this study we studied 6 patients undergoing temporary placement of intracranial electrode arrays. Electrocorticographic (ECoG) signals were recorded while the subjects engaged in specific ipsilateral or contralateral hand motor tasks. Spectral changes were identified with regards to frequency, location, and timing. Ipsilateral hand movements were associated with electrophysiological changes that occur in lower frequency spectra, at distinct anatomic locations, and earlier than changes associated with contralateral hand movements. In a subset of 3 patients, features specific to ipsilateral and contralateral hand movements were used to control a cursor on a screen in real time. In ipsilateral derived control this was optimal with lower frequency spectra. There are distinctive cortical electrophysiological features associated with ipsilateral movements which can be used for device control. These findings have implications for patients with hemispheric stroke because they offer a potential methodology for which a single hemisphere can be used to enhance the function of a stroke induced hemiparesis.

Effect of a cane on sit-to-stand transfer in subjects with hemiparesis.

PubMed

Hu, Po-Ting; Lin, Kwan-Hwa; Lu, Tung-Wu; Tang, Pei-Fang; Hu, Ming-Hsia; Lai, Jin-Shin

2013-03-01

The aim of this study was to determine the effect of using a cane on movement time, joint moment, weight symmetry, and muscle activation patterns during sit-to-stand (STS) transfer in healthy subjects and subjects who have had a stroke. Nine subjects with hemiparesis (mean [SD] age, 61.11 [12.83] yrs) and nine healthy adults (mean [SD] age, 63.11 [10.54] yrs) were included. The subjects with hemiparesis performed STS transfer in two randomly assigned conditions: (1) without a cane and (2) with a cane. The healthy subjects performed only STS transfer without a cane. A three-dimensional motion system, force plates, and eletromyography were used to examine STS transfer. The symmetry index between the two limbs was calculated. The movement time of the subjects with hemiparesis in both conditions without a cane and with a cane was longer than that of the healthy subjects without a cane (P < 0.025). However, STS transfer with a cane in the subjects with hemiparesis resulted in shorter movement time, greater knee extensor moment of the paretic limb, and more symmetry of weight bearing than in those without a cane (P < 0.05). The sequence of muscle onset tended to improve with a cane in the subjects with hemiparesis. Cane use may promote more symmetrical STS transfers rather than compensation by the unaffected limb.

Xenomelia: a new right parietal lobe syndrome.

PubMed

McGeoch, Paul D; Brang, David; Song, Tao; Lee, Roland R; Huang, Mingxiong; Ramachandran, V S

2011-12-01

Damage to the right parietal lobe has long been associated with various disorders of body image. The authors have recently suggested that an unusual behavioural condition in which otherwise rational individuals desire the amputation of a healthy limb might also arise from right parietal dysfunction. Four subjects who desired the amputation of healthy legs (two right, one left and one, at first, bilateral and then left only) were recruited and underwent magnetoencephalography (MEG) scans during tactile stimulation of sites above and below the desired amputation line. Regions of interest (ROIs) in each hemisphere (superior parietal lobule (SPL), inferior parietal lobule, S1, M1, insula, premotor cortex and precuneus) were defined using FreeSurfer software. Analysis of average MEG activity across the 40-140 ms post-stimulation timeframe was carried out using an unpaired t test. This revealed significantly reduced activation only in the right SPL ROI for the subjects' affected legs when compared with both subjects' unaffected legs and that of controls. The right SPL is a cortical area that appears ideally placed to unify disparate sensory inputs to create a coherent sense of having a body. The authors propose that inadequate activation of the right SPL leads to the unnatural situation in which the sufferers can feel the limb in question being touched without it actually incorporating into their body image, with a resulting desire for amputation. The authors introduce the term 'xenomelia' as a more appropriate name than apotemnophilia or body integrity identity disorder, for what appears to be an unrecognised right parietal lobe syndrome.

Inheritance of proportionate dwarfism in Angus cattle.

PubMed

Latter, M R; Latter, B D H; Wilkins, J F; Windsor, P A

2006-04-01

To determine the mode of inheritance of congenital proportionate dwarfism in Angus and Angus crossbred cattle, initially detected in two commercial beef herds in northern New South Wales. Matings of normal carrier sires to unrelated cows of diverse breeds, and of one carrier sire to his unaffected daughters. An unrelated Piedmontese bull was also mated to unaffected daughters of the carrier sires. Two carrier Angus bulls and nine unaffected daughters, all of whom were completely indistinguishable from normal animals, were purchased for controlled breeding studies under known nutritional and disease conditions. Affected and carrier individuals were examined for the presence of obvious chromosomal abnormalities. Angus dwarfism has been successfully reproduced under controlled experimental conditions over successive years using unrelated dams and is undoubtedly heritable. The high frequency of occurrence of affected individuals (23/61 = 0.38 +/- .06) among the progeny of matings of the Angus sires to unrelated females of diverse breeding is not compatible with recessive inheritance, because of the negligible frequency of proportionate dwarfism in the breeds of the dams. Both paternal and maternal transmission of the defect was demonstrated, so that imprinting in the strict sense of a gene that is only expressed when received from the male parent appears not to be involved. Tested individuals showed no evidence of gross chromosomal abnormality. Dominant autosomal inheritance with incomplete penetrance was indicated by the lack of expression of the defective gene in the two Angus sires and in three unaffected daughters who produced dwarf calves from matings to the Piedmontese bull. The mode of inheritance is that of a single autosomal dominant gene with a penetrance coefficient of 0.75 +/- 0.12, estimated from the observed incidence of 23/61 affected offspring of the two carrier Angus bulls mated to unrelated dams. Simple genetic models involving either (i) an unstable mutant which changes at high frequency to the expressed dominant dwarfing allele during gametogenesis, or (ii) a dominant allele with penetrance determined by an unlinked modifying locus, are shown to be compatible with the experimental data. Both models indicate that penetrance of the dwarfing gene may possibly be higher in matings involving carrier daughters of the two Angus bulls.

Chemical shift-based MRI to measure fat fractions in dystrophic skeletal muscle

PubMed Central

Triplett, William T.; Baligand, Celine; Forbes, Sean C.; Willcocks, Rebecca J.; Lott, Donovan J.; DeVos, Soren; Pollaro, Jim; Rooney, William D.; Sweeney, H. Lee; Bönnemann, Carsten; Wang, Dah-Jyuu; Vandenborne, Krista; Walter, Glenn A.

2014-01-01

Purpose The relationship between FF determined based on multiple TE, unipolar GE images and 1H-MRS was evaluated using different models for fat-water decomposition, signal-to-noise ratios (SNR), and excitation flip angles. Methods A combination of single voxel proton spectroscopy (1H-MRS) and gradient echo (GE) imaging was used to determine muscle fat fractions (FF) in both normal and dystrophic muscles. In order to cover a large range of FF, the soleus and vastus lateralis muscles of 22 unaffected control (CON), 16 subjects with Collagen VI (COL6), and 71 subjects with Duchenne muscular dystrophy (DMD) were studied. 1H-MRS based FF were corrected for the increased muscle 1H2O T1 and T2 values observed in dystrophic muscles. Results Excellent agreement was found between co-registered FF derived from GE images fit to a multipeak model with noise bias correction and the relaxation corrected 1H-MRS FF (y= 0.93×+0.003; R2=0.96) across the full range of FF. Relaxation corrected 1H-MRS FF and imaging based FF were significantly elevated (p<0.01) in both COL6 and DMD muscles. Conclusion FF, T2, and T1 were all sensitive to muscle involvement in dystrophic muscle. MRI offered an additional advantage over single voxel spectroscopy in that the tissue heterogeneity in FF could be readily determined. PMID:24006208

Genotype Phenotype Relationships in Neurofibromatosis 2

DTIC Science & Technology

2001-10-01

stop (t2187c). 200 unrelated individuals (90 with NF2, 24 controls with schwannomatosis , and 86 unaffected controls) were screened for this change and...Allelic expression of the NF2 gene in neurofibromatosis 2 and schwannomatosis . Neurogenetics 2:101-108 (1999) Andrade A under the mentorship of Mia...LB, MacCollin M, Parry D, Kluwe L, Lynch J, Jones D, Gusella J. Allelic expression of the NF2 gene in neurofibromatosis 2 and schwannomatosis

Genotype Phenotype Relationships in Neurofibromatosis 2

DTIC Science & Technology

2000-10-01

schwannomatosis , and 86 unaffected controls) were screened for this change and 69 were heterozygous (34.5%). 21 heterozygous specimens from control individuals...Jacoby LB, MacCollin M, Parry D, Kluwe L, Lynch J, Jones D, Gusella J. Allelic expression of the NF2 gene in neurofibromatosis 2 and schwannomatosis ...Jones D, Gusella J. Allelic expression of the NF2 gene in neurofibromatosis 2 and schwannomatosis . Neurogenetics 2:101-108 (1999) Kluwe L, Mautner V

Sleep restriction alters the hypothalamic-pituitary-adrenal response to stress

NASA Technical Reports Server (NTRS)

Meerlo, P.; Koehl, M.; van der Borght, K.; Turek, F. W.

2002-01-01

Chronic sleep restriction is an increasing problem in many countries and may have many, as yet unknown, consequences for health and well being. Studies in both humans and rats suggest that sleep deprivation may activate the hypothalamic-pituitary-adrenal (HPA) axis, one of the main neuroendocrine stress systems. However, few attempts have been made to examine how sleep loss affects the HPA axis response to subsequent stressors. Furthermore, most studies applied short-lasting total sleep deprivation and not restriction of sleep over a longer period of time, as often occurs in human society. Using the rat as our model species, we investigated: (i) the HPA axis activity during and after sleep deprivation and (ii) the effect of sleep loss on the subsequent HPA response to a novel stressor. In one experiment, rats were subjected to 48 h of sleep deprivation by placing them in slowly rotating wheels. Control rats were placed in nonrotating wheels. In a second experiment, rats were subjected to an 8-day sleep restriction protocol allowing 4 h of sleep each day. To test the effects of sleep loss on subsequent stress reactivity, rats were subjected to a 30-min restraint stress. Blood samples were taken at several time points and analysed for adrenocorticotropic hormone (ACTH) and corticosterone. The results show that ACTH and corticosterone concentrations were elevated during sleep deprivation but returned to baseline within 4 h of recovery. After 1 day of sleep restriction, the ACTH and corticosterone response to restraint stress did not differ between control and sleep deprived rats. However, after 48 h of total sleep deprivation and after 8 days of restricted sleep, the ACTH response to restraint was significantly reduced whereas the corticosterone response was unaffected. These results show that sleep loss not only is a mild activator of the HPA axis itself, but also affects the subsequent response to stress. Alterations in HPA axis regulation may gradually appear under conditions of long total sleep deprivation but also after repeated sleep curtailment.

Knee joint changes in patients with neglected developmental hip dysplasia: a prospective case-control study.

PubMed

Li, Qiwei; Kadhim, Muayad; Zhang, Lijun; Cheng, Xiangjun; Zhao, Qun; Li, Lianyong

2014-12-01

Few reports are available describing knee changes in neglected developmental dysplasia of the hip (DDH). The purpose of this study was to assess the radiographic morphology of knee joints in adults with neglected DDH. Thirty-seven patients (35 females and two males) with neglected DDH were prospectively recruited with an average age of 32.6 years. Twenty-three patients had unilateral and 14 patients had bilateral neglected DDH. Thirty-seven healthy individuals were recruited to form a matched control group. Three groups of knee joints were examined: affected knees (on the same side of the neglected DDH), unaffected knees (contralateral to the neglected DDH in patients with unilateral involvement), and control knees. A series of radiographic parameters of the knee joint were measured in the coronal and sagittal plane, and they were compared between patients and normal controls. In the coronal plane, the affected knees had increased valgus angulation related to increased height of the medial femoral condyle, decreased height of the lateral femoral condyle and decreased lateral distal femoral angle compared to control knees. In the sagittal plane, both distal femoral and proximal tibial joints of the affected knees developed a decrease in posterior angles. Additionally, the unaffected knees also developed radiographic changes compared to control knees. Patients with neglected DDH may develop changes in both knee joints. These changes should be considered during surgery to the hip, femur and knee to prevent potential complications. Level 2. Copyright © 2014 Elsevier B.V. All rights reserved.

A Closer Look at Siblings of Patients with Schizophrenia: The Association of Depression History and Sex with Cognitive Phenotypes

PubMed Central

Wisner, Krista M.; Elvevåg, Brita; Gold, James M.; Weinberger, Daniel R.; Dickinson, Dwight

2010-01-01

Background Siblings of patients with schizophrenia show impaired cognition and an increased prevalence of depression history. Although sex has been shown to moderate cognition in patients, this effect has not been examined in siblings. Here we elucidate how a history of depression and sex influences cognition in siblings unaffected by schizophrenia. Methods Unaffected siblings of patients with schizophrenia and unrelated healthy controls were evaluated neuropsychologically and completed structured clinical interviews. Participants with a depression history or no psychiatric history were selected for the sample. Cognitive performance of siblings (n = 366) and controls (n = 680) was first examined. Second, cognition of participants with a depression history and those without a psychiatric history was compared while additionally investigating the role of schizophrenia risk and sex. Results Relative to controls, siblings, with and without a psychiatric history, demonstrated significant (p < .05) cognitive deficits. Depression history impaired cognition in siblings, but not in controls; whereas sex affected cognition in both siblings and controls. In siblings alone, sex significantly interacted with depression history to influence cognition. This interaction revealed that in male - but not female - siblings a history of depression was associated with greater cognitive impairments. Conclusion A history of depression impairs cognition in siblings, but not in controls. Moreover, depression history interacts with sex and demonstrates that only cognition in male siblings is significantly and additionally compromised by a history of depression. This interaction may be an important consideration for future phenotype and genetic association studies. PMID:21030214

Simultaneous Force Regression and Movement Classification of Fingers via Surface EMG within a Unified Bayesian Framework.

PubMed

Baldacchino, Tara; Jacobs, William R; Anderson, Sean R; Worden, Keith; Rowson, Jennifer

2018-01-01

This contribution presents a novel methodology for myolectric-based control using surface electromyographic (sEMG) signals recorded during finger movements. A multivariate Bayesian mixture of experts (MoE) model is introduced which provides a powerful method for modeling force regression at the fingertips, while also performing finger movement classification as a by-product of the modeling algorithm. Bayesian inference of the model allows uncertainties to be naturally incorporated into the model structure. This method is tested using data from the publicly released NinaPro database which consists of sEMG recordings for 6 degree-of-freedom force activations for 40 intact subjects. The results demonstrate that the MoE model achieves similar performance compared to the benchmark set by the authors of NinaPro for finger force regression. Additionally, inherent to the Bayesian framework is the inclusion of uncertainty in the model parameters, naturally providing confidence bounds on the force regression predictions. Furthermore, the integrated clustering step allows a detailed investigation into classification of the finger movements, without incurring any extra computational effort. Subsequently, a systematic approach to assessing the importance of the number of electrodes needed for accurate control is performed via sensitivity analysis techniques. A slight degradation in regression performance is observed for a reduced number of electrodes, while classification performance is unaffected.

Familial covariation of facial emotion recognition and IQ in schizophrenia.

PubMed

Andric, Sanja; Maric, Nadja P; Mihaljevic, Marina; Mirjanic, Tijana; van Os, Jim

2016-12-30

Alterations in general intellectual ability and social cognition in schizophrenia are core features of the disorder, evident at the illness' onset and persistent throughout its course. However, previous studies examining cognitive alterations in siblings discordant for schizophrenia yielded inconsistent results. Present study aimed to investigate the nature of the association between facial emotion recognition and general IQ by applying genetically sensitive cross-trait cross-sibling design. Participants (total n=158; patients, unaffected siblings, controls) were assessed using the Benton Facial Recognition Test, the Degraded Facial Affect Recognition Task (DFAR) and the Wechsler Adult Intelligence Scale-III. Patients had lower IQ and altered facial emotion recognition in comparison to other groups. Healthy siblings and controls did not significantly differ in IQ and DFAR performance, but siblings exhibited intermediate angry facial expression recognition. Cross-trait within-subject analyses showed significant associations between overall DFAR performance and IQ in all participants. Within-trait cross-sibling analyses found significant associations between patients' and siblings' IQ and overall DFAR performance, suggesting their familial clustering. Finally, cross-trait cross-sibling analyses revealed familial covariation of facial emotion recognition and IQ in siblings discordant for schizophrenia, further indicating their familial etiology. Both traits are important phenotypes for genetic studies and potential early clinical markers of schizophrenia-spectrum disorders. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Neuro-Mechanics of Recumbent Leg Cycling in Post-Acute Stroke Patients.

PubMed

Ambrosini, Emilia; De Marchis, Cristiano; Pedrocchi, Alessandra; Ferrigno, Giancarlo; Monticone, Marco; Schmid, Maurizio; D'Alessio, Tommaso; Conforto, Silvia; Ferrante, Simona

2016-11-01

Cycling training is strongly applied in post-stroke rehabilitation, but how its modular control is altered soon after stroke has been not analyzed yet. EMG signals from 9 leg muscles and pedal forces were measured bilaterally during recumbent pedaling in 16 post-acute stroke patients and 12 age-matched healthy controls. Patients were asked to walk over a GaitRite mat and standard gait parameters were computed. Four muscle synergies were extracted through nonnegative matrix factorization in healthy subjects and patients unaffected legs. Two to four synergies were identified in the affected sides and the number of synergies significantly correlated with the Motricity Index (Spearman's coefficient = 0.521). The reduced coordination complexity resulted in a reduced biomechanical performance, with the two-module sub-group showing the lowest work production and mechanical effectiveness in the affected side. These patients also exhibited locomotor impairments (reduced gait speed, asymmetrical stance time, prolonged double support time). Significant correlations were found between cycling-based metrics and gait parameters, suggesting that neuro-mechanical quantities of pedaling can inform on walking dysfunctions. Our findings support the use of pedaling as a rehabilitation method and an assessment tool after stroke, mainly in the early phase, when patients can be unable to perform a safe and active gait training.

FGFR2 molecular analysis and related clinical findings in one Chinese family with Crouzon Syndrome

PubMed Central

Lin, Ying; Liang, Xuanwei; Ai, Siming; Chen, Chuan; Liu, Xialin; Luo, Lixia; Ye, Shaobi; Li, Baoxin; Yang, Huasheng

2012-01-01

Purpose The purposed of this study was to investigate the fibroblast growth factor receptor 2 (FGFR2) gene in one Chinese family with Crouzon syndrome and to characterize the related clinical features. Methods One family underwent complete ophthalmic examinations, and two patients were diagnosed with Crouzon syndrome. Genomic DNA was extracted from leukocytes of peripheral blood collected from the family and 100 unrelated control subjects from the same population. Exons 8 and 10 of FGFR2 were amplified by polymerase chain reaction (PCR) and directly sequenced. We performed ophthalmic examinations, including best-corrected visual acuity, slit-lamp examination, fundus examination, Pentacam, Goldmann perimetry, and computed tomography (CT) of the skull. Results The two patients were affected with shallow orbits and ocular proptosis, accompanied by midface hypoplasia, craniosynostosis, and clinically normal hands and feet. A heterozygous FGFR2 missense mutation c.866A>C (Gln289Pro) in exon 8 was identified in the affected individuals, but not in any of the unaffected family members and the normal controls. Conclusions Although FGFR2 mutations and polymorphisms have been reported in various ethnic groups, especially in the area of osteology, we report, for the first time, the identification of one new FGFR2 mutation in Chinese patients with Crouzon syndrome. PMID:22355256

Higher-order language dysfunctions as a possible neurolinguistic endophenotype for schizophrenia: Evidence from patients and their unaffected first degree relatives.

PubMed

Pawełczyk, Agnieszka; Łojek, Emila; Żurner, Natalia; Gawłowska-Sawosz, Marta; Pawełczyk, Tomasz

2018-05-31

The purpose of the study was to examine the presence of pragmatic dysfunctions in first episode (FE) subjects and their healthy first degree relatives as a potential endophenotype for schizophrenia. Thirty-four FE patients, 34 parents of the patients (REL) and 32 healthy controls (HC) took part in the study. Pragmatic language functions were evaluated with the Right Hemisphere Language Battery, attention and executive functions were controlled, as well as age and education level. The parents differed from HC but not from their FE offspring with regard to overall level of language and communication and the general knowledge component of language processing. The FE participants differed from HC in comprehension of inferred meaning, emotional prosody, discourse dimensions, overall level of language and communication, language processing with regard to general knowledge and communication competences. The FE participants differed from REL regarding discourse dimensions. Our findings suggest that pragmatic dysfunctions may act as vulnerability markers of schizophrenia; their assessment may help in the diagnosis of early stages of the illness and in understanding its pathophysiology. In future research the adoptive and biological parents of schizophrenia patients should be compared to elucidate which language failures reflect genetic vulnerability and which ones environmental factors. Copyright © 2018. Published by Elsevier B.V.

Pharmacologic Atrial Natriuretic Peptide Reduces Human Leg Capillary Filtration

NASA Technical Reports Server (NTRS)

Watenpaugh, Donald E.; Vissing, Susanne F.; Lane, Lynda D.; Buckey, Jay C.; Firth, Brian G.; Erdman, William; Hargens, Alan R.; Blomqvist, C. Gunnar

1995-01-01

Atrial natriuretic peptide (ANP) is produced and secreted by atrial cells. We measured calf capillary filtration rate with prolonged venous-occlusion plethys-mography of supine health male subjects during pharmacologic infusion of ANP (48 pmol/kg/min for 15 min; n equals 6) and during placebo infusion (n equals 7). Results during infusions were compared to prior control measurements. ANP infusion increased plasma (ANP) from 30 plus or minus 4 to 2,568 plus or minus 595 pmol/L. Systemic hemoconcentration occurred during ANP infusion; mean hematocrit and plasma colloid osmotic pressure increased 4.6 and 11.3 percent respectively, relative to pre-infusion baseline values (p is less than 0.05). Mean calf filtration, however was significantly reduced from 0.15 to 0.08 ml/100 ml/min with ANP. Heart rate increased 20 percent with ANP infusion, wheras blood pressure was unchanged. Calf conductance (blood flow/arterial pressure) and venous compliance were unaffected by ANP infusion. Placebo infusion had no effect relative to prior baseline control measurements. Although ANP induced systemic capillary filtration, in the calf, filtration was reduced with ANP. Therefore, phamacologic ANP infusion enhances capillary filtration from the systemic circulation, perhaps at upper body or splanchic sites or both, while having the opposite effect in the leg.

Third season weed control in blackberries using synthetic ground covers

USDA-ARS?s Scientific Manuscript database

Synthetic weed barriers, which have shown promise in a first fruiting season ‘Kiowa’ blackberry (Rubus spp) planting (near Monte Alto, TX; Lat. 26º 26’N), were evaluated for a second fruiting season in 2008. Weed removal times were significantly shorter and material integrity unaffected by time (Ma...

Metabolic Imbalance Associated with Methylation Dysregulation and Oxidative Damage in Children with Autism

ERIC Educational Resources Information Center

Melnyk, Stepan; Fuchs, George J.; Schulz, Eldon; Lopez, Maya; Kahler, Stephen G.; Fussell, Jill J.; Bellando, Jayne; Pavliv, Oleksandra; Rose, Shannon; Seidel, Lisa; Gaylor, David W.; James, S. Jill

2012-01-01

Oxidative stress and abnormal DNA methylation have been implicated in the pathophysiology of autism. We investigated the dynamics of an integrated metabolic pathway essential for cellular antioxidant and methylation capacity in 68 children with autism, 54 age-matched control children and 40 unaffected siblings. The metabolic profile of unaffected…

Sleep Problems among Taiwanese Children with Autism, Their Siblings and Typically Developing Children

ERIC Educational Resources Information Center

Chou, Miao-Chun; Chou, Wen-Jiun; Chiang, Huey-Ling; Wu, Yu-Yu; Lee, Ju-Chin; Wong, Ching-Ching; Gau, Susan Shur-Fen

2012-01-01

The current study compared the sleep schedules, sleep problems among children with autism, their siblings and typically developing children, and to explore other associated factors with sleep problems. We conducted a case-control study consisting 110 children with autistic disorder, 125 unaffected siblings, and 110 age-, sex-, and parental…

Does the Cognitive Architecture of Simplex and Multiplex ASD Families Differ?

ERIC Educational Resources Information Center

Oerlemans, Anoek M.; Hartman, Catharina A.; Franke, Barbara; Buitelaar, Jan K.; Rommelse, Nanda N. J.

2016-01-01

Children with an autism spectrum disorder (ASD) and their unaffected siblings from 54 simplex (SPX, one individual in the family affected) and 59 multiplex (MPX, two or more individuals affected) families, and 124 controls were assessed on intelligence, social cognition and executive functions. SPX and MPX ASD probands displayed similar cognitive…

PPM1D Mosaic Truncating Variants in Ovarian Cancer Cases May Be Treatment-Related Somatic Mutations

PubMed Central

Pharoah, Paul D. P.; Song, Honglin; Dicks, Ed; Intermaggio, Maria P.; Harrington, Patricia; Baynes, Caroline; Alsop, Kathryn; Bogdanova, Natalia; Cicek, Mine S.; Cunningham, Julie M.; Fridley, Brooke L.; Gentry-Maharaj, Aleksandra; Hillemanns, Peter; Lele, Shashi; Lester, Jenny; McGuire, Valerie; Moysich, Kirsten B.; Poblete, Samantha; Sieh, Weiva; Sucheston-Campbell, Lara; Widschwendter, Martin; Whittemore, Alice S.; Dörk, Thilo; Menon, Usha; Odunsi, Kunle; Goode, Ellen L.; Karlan, Beth Y.; Bowtell, David D.; Gayther, Simon A.; Ramus, Susan J.

2016-01-01

Mosaic truncating mutations in the protein phosphatase, Mg2+/Mn2+-dependent, 1D (PPM1D) gene have recently been reported with a statistically significantly greater frequency in lymphocyte DNA from ovarian cancer case patients compared with unaffected control patients. Using massively parallel sequencing (MPS) we identified truncating PPM1D mutations in 12 of 3236 epithelial ovarian cancer (EOC) case patients (0.37%) but in only one of 3431 unaffected control patients (0.03%) (P = .001). All statistical tests were two-sided. A combination of Sanger sequencing, pyrosequencing, and MPS data suggested that 12 of the 13 mutations were mosaic. All mutations were identified in post-chemotherapy treatment blood samples from case patients (n = 1827) (average 1234 days post-treatment in carriers) rather than from cases collected pretreatment (less than 14 days after diagnosis, n = 1384) (P = .002). These data suggest that PPM1D variants in EOC cases are primarily somatic mosaic mutations caused by treatment and are not associated with germline predisposition to EOC. PMID:26823519

Mental Health of Children Living in Foster Families in Rural Rwanda: The Role of HIV and the Family Environment

PubMed Central

Nduwimana, Estella; Mukunzi, Sylvere; Ng, Lauren C.; Kirk, Catherine M.; Bizimana, Justin I.; Betancourt, Theresa S.

2016-01-01

Fostering children is common in sub-Saharan Africa, but few studies examine these children’s mental health needs. This study investigated the impact of living in a foster family on the mental health of HIV-positive, HIV-affected and HIV-unaffected children (n = 681 aged 10–17) in rural Rwanda. Regression analyses assessed the impact of living in a foster family on mental health, parenting, and daily hardships; multiple mediation analyses assessed whether family factors mediated the association between foster status and mental health. HIV-positive children were eight times more likely to live in foster families than HIV-unaffected children. Being HIV-affected was predictive of depression and irritability symptoms after controlling for family factors. Controlling for HIV-status, foster children had more symptoms of depression, anxiety, and irritability than non-fostered children. Positive parenting fully mediated the association between foster status and mental health. Mental health and parenting interventions for foster children and HIV-affected children may improve child outcomes. PMID:27578000

Identification of missense mutations in the Norrie disease gene associated with advanced retinopathy of prematurity.

PubMed

Shastry, B S; Pendergast, S D; Hartzer, M K; Liu, X; Trese, M T

1997-05-01

Retinopathy of prematurity (ROP) is a retinal vascular disease occurring in infants with short gestational age and low birth weight and can lead to retinal detachment (ROP stages 4 and 5). X-linked familial exudative vitreoretinopathy is phenotypically similar to ROP and has been associated with mutations in the Norrie disease (ND) gene in some cases. To determine if similar mutations in the ND gene may play a role in the development of advanced ROP. Clinical examination and molecular genetic analysis were performed on 16 children, including 2 dizygotic and 1 monozygotic twin pairs, and their parents from 13 families. Sequencing of the amplified products revealed missense mutations (R121W and L108P) in the third exon of the ND gene in 4 patients. These mutations were not present in an unaffected premature twin, 2 children with regressed stage 3 ROP, the parents, or in 50 unrelated healthy control subjects. These findings suggest that mutations in the ND gene may play a role in the development of severe ROP in premature infants.

Polycyclic aromatic hydrocarbon levels and measures of oxidative stress in the Mediterranean endemic bivalve Pinna nobilis exposed to the Don Pedro oil spill.

PubMed

Sureda, Antoni; Tejada, Silvia; Box, Antonio; Deudero, Salud

2013-06-15

The fan mussel (Pinna nobilis Linné, 1758) is the largest endemic Mediterranean bivalve subject to strict protection as an endangered species. Antioxidant biomarkers in P. nobilis gills for biomonitoring marine pollution were researched after the Don Pedro oil spill. Two sampling locations on the east and southeast of the island of Ibiza (Western Mediterranean, Spain) were selected, one extensively affected by the oil spill and the other unaffected (control area). Mussels were sampled 1 month, 6 months and 1 year after the accident. Polycyclic aromatic hydrocarbon levels and antioxidant enzymes significantly increased as result of the oil spill in all sampling periods (p<0.05). Oxidative damage in lipids significantly increased in the mussels collected in the affected area (p<0.05), though such damage was back to normal after 1 year. In conclusion, the Don Pedro oil spill induced a situation of oxidative stress on P. nobilis that continued a year later. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mitigating Motion Base Safety Issues: The NASA LaRC CMF Implementation

NASA Technical Reports Server (NTRS)

Bryant, Richard B., Jr.; Grupton, Lawrence E.; Martinez, Debbie; Carrelli, David J.

2005-01-01

The NASA Langley Research Center (LaRC), Cockpit Motion Facility (CMF) motion base design has taken advantage of inherent hydraulic characteristics to implement safety features using hardware solutions only. Motion system safety has always been a concern and its implementation is addressed differently by each organization. Some approaches rely heavily on software safety features. Software which performs safety functions is subject to more scrutiny making its approval, modification, and development time consuming and expensive. The NASA LaRC's CMF motion system is used for research and, as such, requires that the software be updated or modified frequently. The CMF's customers need the ability to update the simulation software frequently without the associated cost incurred with safety critical software. This paper describes the CMF engineering team's approach to achieving motion base safety by designing and implementing all safety features in hardware, resulting in applications software (including motion cueing and actuator dynamic control) being completely independent of the safety devices. This allows the CMF safety systems to remain intact and unaffected by frequent research system modifications.

Can Video Self-Modeling Improve Affected Limb Reach and Grasp Ability in Stroke Patients?

PubMed

Steel, Kylie Ann; Mudie, Kurt; Sandoval, Remi; Anderson, David; Dogramaci, Sera; Rehmanjan, Mohammad; Birznieks, Ingvars

2018-01-01

The authors examined whether feedforward video self-modeling (FF VSM) would improve control over the affected limb, movement self-confidence, movement self-consciousness, and well-being in 18 stroke survivors. Participants completed a cup transport task and 2 questionnaires related to psychological processes pre- and postintervention. Pretest video footage of the unaffected limb performing the task was edited to create a best-of or mirror-reversed training DVD, creating the illusion that patients were performing proficiently with the affected limb. The training yielded significant improvements for the forward movement of the affected limb compared to the unaffected limb. Significant improvements were also seen in movement self-confidence, movement self-consciousness, and well-being. FF VSM appears to be a viable way to improve motor ability in populations with movement disorders.

Increased susceptibility of skin from HERDA (Hereditary Equine Regional Dermal Asthenia)-affected horses to bacterial collagenase degradation: a potential contributing factor to the clinical signs of HERDA.

PubMed

Rashmir-Raven, Ann; Lavagnino, Michael; Sedlak, Aleksa; Gardner, Keri; Arnoczky, Steven

2015-12-01

Hereditary equine regional dermal asthenia (HERDA) is a genetic disorder of collagen resulting in fragile, hyper-extensible skin and ulcerative lesions. The predominance of skin lesions have been shown to occur on the dorsum of HERDA-affected horses. While this has been postulated to be due to increased exposure to sunlight of these areas, the precise pathological mechanism which causes this to occur is unclear. We hypothesized that an increase in collagenase activity, that has been associated with the exposure of dermal fibroblasts to sunlight, will significantly degrade the material properties of skin from HERDA-affected horses when compared to unaffected controls. Six unaffected and seven HERDA-affected horses, all euthanized for other reasons. Full-thickness skin samples from similar locations on each horse were collected and cut into uniform strips and their material properties (tensile modulus) determined by mechanical testing before (n = 12 samples/horse) or after (n = 12 samples/horse) incubation in bacterial collagenase at 37°C for 6 h. The change in modulus following treatment was then compared between HERDA-affected and unaffected horses using a Student's t-test. The modulus of skin from HERDA-affected horses decreased significantly more than that from unaffected horses following collagenase treatment (54 ± 7% versus 30 ± 16%, P = 0.004). The significant decrease in the modulus of skin from HERDA-affected horses following collagenase exposure suggests that their altered collagen microarchitecture is more susceptible to enzymatic degradation and may explain the localization of skin lesions in HERDA-affected horses to those areas of the body most exposed to sunlight. These findings appear to support the previously reported benefits of sunlight restriction in HERDA-affected horses. © 2015 ESVD and ACVD.

Separate Influences of Birth Order and Gravidity/Parity on the Development of Systemic Sclerosis

PubMed Central

COCKRILL, TONYA; del JUNCO, DEBORAH J.; ARNETT, FRANK C.; ASSASSI, SHERVIN; TAN, FILEMON K.; McNEARNEY, TERRY; FISCHBACH, MICHAEL; PERRY, MARILYN; MAYES, MAUREEN D.

2010-01-01

Objective Birth order has been valuable in revealing the role of environmental influences on the risk of developing certain diseases such as allergy and atopy. In addition, pregnancy has profound effects on the immune system such as short-term effects that permit fetal survival as well as longer-term effects that could influence late-onset diseases. In order to better evaluate these influences, we studied the association of birth order and gravidity/parity as risk factors for systemic sclerosis (SSc; scleroderma). Methods Data regarding SSc cases and their unaffected sibling controls were obtained from the Scleroderma Family Registry and DNA Repository. The case-sibling design was used to minimize confounding due to differences in age, race, ethnicity, or calendar time. The gravidity/parity analysis was based on sibships with at least one SSc-affected and one unaffected sister. Results Birth order was examined in 974 sibships, comparing SSc cases (n = 987) with their unaffected siblings (n = 3,088). The risk of scleroderma increased with increasing birth order (odds ratio [OR] 1.25, 95% confidence interval [95% CI] 1.06–1.50 for birth order 2–5; OR 2.22, 95% CI 1.57–3.15 for birth order 6–9; and OR 3.53, 95% CI 1.68–7.45 for birth order 10–15). Gravidity/parity was analyzed in 168 sibships (256 unaffected sisters, 172 SSc cases). We found an association between a history of one or more pregnancies and SSc (OR 2.8). Conclusion Birth order and pregnancy were independently associated with a higher risk of developing SSc. These findings suggest that immune development in early childhood and/or pregnancy-associated events, including but not limited to microchimerism, plays a role in SSc susceptibility. PMID:20391489

Separate influences of birth order and gravidity/parity on the development of systemic sclerosis.

PubMed

Cockrill, Tonya; del Junco, Deborah J; Arnett, Frank C; Assassi, Shervin; Tan, Filemon K; McNearney, Terry; Fischbach, Michael; Perry, Marilyn; Mayes, Maureen D

2010-03-01

Birth order has been valuable in revealing the role of environmental influences on the risk of developing certain diseases such as allergy and atopy. In addition, pregnancy has profound effects on the immune system such as short-term effects that permit fetal survival as well as longer-term effects that could influence late-onset diseases. In order to better evaluate these influences, we studied the association of birth order and gravidity/parity as risk factors for systemic sclerosis (SSc; scleroderma). Data regarding SSc cases and their unaffected sibling controls were obtained from the Scleroderma Family Registry and DNA Repository. The case-sibling design was used to minimize confounding due to differences in age, race, ethnicity, or calendar time. The gravidity/parity analysis was based on sibships with at least one SSc-affected and one unaffected sister. Birth order was examined in 974 sibships, comparing SSc cases (n = 987) with their unaffected siblings (n = 3,088). The risk of scleroderma increased with increasing birth order (odds ratio [OR] 1.25, 95% confidence interval [95% CI] 1.06-1.50 for birth order 2-5; OR 2.22, 95% CI 1.57-3.15 for birth order 6-9; and OR 3.53, 95% CI 1.68-7.45 for birth order 10-15). Gravidity/parity was analyzed in 168 sibships (256 unaffected sisters, 172 SSc cases). We found an association between a history of one or more pregnancies and SSc (OR 2.8). Birth order and pregnancy were independently associated with a higher risk of developing SSc. These findings suggest that immune development in early childhood and/or pregnancy-associated events, including but not limited to microchimerism, plays a role in SSc susceptibility.

Ebola and Marburg virus diseases in Africa: increased risk of outbreaks in previously unaffected areas?

PubMed

Changula, Katendi; Kajihara, Masahiro; Mweene, Aaron S; Takada, Ayato

2014-09-01

Filoviral hemorrhagic fever (FHF) is caused by ebolaviruses and marburgviruses, which both belong to the family Filoviridae. Egyptian fruit bats (Rousettus aegyptiacus) are the most likely natural reservoir for marburgviruses and entry into caves and mines that they stay in has often been associated with outbreaks of MVD. On the other hand, the natural reservoir for ebola viruses remains elusive; however, handling of wild animal carcasses has been associated with some outbreaks of EVD. In the last two decades, there has been an increase in the incidence of FHF outbreaks in Africa, some being caused by a newly found virus and some occurring in previously unaffected areas such as Guinea, Liberia and Sierra Leone, in which the most recent EVD outbreak occurred in 2014. Indeed, the predicted geographic distribution of filoviruses and their potential reservoirs in Africa includes many countries in which FHF has not been reported. To minimize the risk of virus dissemination in previously unaffected areas, there is a need for increased investment in health infrastructure in African countries, policies to facilitate collaboration between health authorities from different countries, implementation of outbreak control measures by relevant multi-disciplinary teams and education of the populations at risk. © 2014 The Societies and Wiley Publishing Asia Pty Ltd.

Paternal age of schizophrenia probands and endophenotypic differences from unaffected siblings.

PubMed

Schmeidler, James; Lazzeroni, Laura C; Swerdlow, Neal R; Ferreira, Rui P; Braff, David L; Calkins, Monica E; Cadenhead, Kristin S; Freedman, Robert; Green, Michael F; Greenwood, Tiffany A; Gur, Raquel E; Gur, Ruben C; Light, Gregory A; Olincy, Ann; Nuechterlein, Keith H; Radant, Allen D; Seidman, Larry J; Siever, Larry J; Stone, William S; Sprock, Joyce; Sugar, Catherine A; Tsuang, Debby W; Tsuang, Ming T; Turetsky, Bruce I; Silverman, Jeremy M

2014-09-30

We evaluated the discrepancy of endophenotypic performance between probands with schizophrenia and unaffected siblings by paternal age at proband birth, a possible marker for de novo mutations. Pairs of schizophrenia probands and unaffected siblings (N=220 pairs) were evaluated on 11 neuropsychological or neurophysiological endophenotypes previously identified as heritable. For each endophenotype, the sibling-minus-proband differences were transformed to standardized scores. Then for each pair, the average discrepancy was calculated from its standardized scores. We tested the hypothesis that the discrepancy is associated with paternal age, controlling for the number of endophenotypes shared between proband and his or her sibling, and proband age, which were both associated with paternal age. The non-significant association between the discrepancy and paternal age was in the opposite direction from the hypothesis. Of the 11 endophenotypes only sensori-motor dexterity was significant, but in the opposite direction. Eight other endophenotypes were also in the opposite direction, but not significant. The results did not support the hypothesized association of increased differences between sibling/proband pairs with greater paternal age. A possible explanation is that the identification of heritable endophenotypes was based on samples for which schizophrenia was attributable to inherited rather than de novo/non-inherited causes. Published by Elsevier Ireland Ltd.

Neurocognitive functioning in parents of schizophrenia patients: Attentional and executive performance vary with genetic loading.

PubMed

Schulze-Rauschenbach, Svenja; Lennertz, Leonhard; Ruhrmann, Stephan; Petrovsky, Nadine; Ettinger, Ulrich; Pukrop, Ralf; Dreher, Jan; Klosterkötter, Joachim; Maier, Wolfgang; Wagner, Michael

2015-12-30

Neuropsychological deficits are candidate endophenotypes of schizophrenia which can assist to explain the neurocognitive impact of genetic risk variants. The identification of endophenotypes is often based on the familiality of these phenotypes. Several studies demonstrate neuropsychological deficits in unaffected biological relatives of schizophrenia patients without differentiating between genetic and non-genetic factors underlying these deficits. We assessed N=129 unaffected biological parents of schizophrenia patients, N=28 schizophrenia patients (paranoid subtype), and N=143 controls without a family history of schizophrenia with an extensive neuropsychological test battery. Direct comparison of N=22 parents with an ancestral history of schizophrenia (more likely carriers, MLC) and N=17 of their spouses without such a history (less likely carriers, LLC) allowed the separation of genetic and non-genetic aspects in cognition. Overall, parents showed significant deficits in neuropsychological tasks from all cognitive domains with medium effect sizes. Direct comparisons of MLC- and LLC-parents showed that attentional and executive tasks were most strongly affected by genetic loading. To conclude, unaffected parents of schizophrenia patients showed modest yet significant impairments in attention, memory, and executive functioning. In particular, attentional and executive impairments varied most strongly with genetic loading for schizophrenia, prioritising these dysfunctions for genotype-endophenotype analyses. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Is attention to detail a similarly strong candidate endophenotype for anorexia nervosa and bulimia nervosa?

PubMed

Roberts, Marion E; Tchanturia, Kate; Treasure, Janet L

2013-08-01

To investigate whether attention to detail is a similarly strong candidate endophenotype of anorexia (AN) and bulimia nervosa (BN), and to explore the incidence and clinical correlates of attention to detail. A total of 266 women (including AN, BN, recovered AN, unaffected sisters of AN/BN & control women) undertook a thorough clinical assessment and were administered two neuropsychological measures of attention to detail (Group Embedded Figure Test; Rey-Osterrieth Complex Figure). Superior attention to detail was found across all AN groups including recovered AN and unaffected AN sisters. Those with BN and their unaffected sisters showed a profile more consistent with poor global integration. The combined effect of superior attention to detail and poor global integration ("weak coherence") was present in 42.3% of active cases and corresponded with a more severe illness, elevated obsessive-compulsive symptoms, and a higher likelihood of comorbid clinical anxiety and self-harm. Attention to detail is a stronger candidate endophenotype of AN compared to BN, where poor global integration may be more relevant. The unique contribution of both aspects of weak coherence (superior attention to detail/poor global integration) requires further exploration and understanding in both eating disorders. Integrating cognitive remediation of these traits into treatment for the subset of patients it is relevant for may improve outcome.

Analysis of retinal capillaries in patients with type 1 diabetes and nonproliferative diabetic retinopathy using adaptive optics imaging.

PubMed

Lombardo, Marco; Parravano, Mariacristina; Serrao, Sebastiano; Ducoli, Pietro; Stirpe, Mario; Lombardo, Giuseppe

2013-09-01

To illustrate a noninvasive method to analyze the retinal capillary lumen caliber in patients with Type 1 diabetes. Adaptive optics imaging of the retinal capillaries were acquired in two parafoveal regions of interest in eyes with nonproliferative diabetic retinopathy and unaffected controls. Measures of the retinal capillary lumen caliber were quantified using an algorithm written in Matlab by an independent observer in a masked manner. Comparison of the adaptive optics images with red-free and color wide fundus retinography images was also assessed. Eight eyes with nonproliferative diabetic retinopathy (eight patients, study group), no macular edema, and preserved visual acuity and eight control eyes (eight healthy volunteers; control group) were analyzed. The repeatability of capillary lumen caliber measurements was 0.22 μm (3.5%) with the 95% confidence interval between 0.12 and 0.31 μm in the study group. It was 0.30 μm (4.1%) with the 95% confidence interval between 0.16 and 0.43 μm in the control group. The average capillary lumen caliber was significantly narrower in eyes with nonproliferative diabetic retinopathy (6.27 ± 1.63 μm) than in the control eyes (7.31 ± 1.59 μm, P = 0.002). The authors demonstrated a noninvasive method to analyze, with micrometric scale of resolution, the lumen of retinal capillaries. The parafoveal capillaries were narrower in patients with Type 1 diabetes and nonproliferative diabetic retinopathy than in healthy subjects, showing the potential capability of adaptive optics imaging to detect pathologic variations of the retinal microvascular structures in vaso-occlusive diseases.

Prefrontal involvement related to cognitive impairment in progressive muscular atrophy.

PubMed

Raaphorst, Joost; van Tol, Marie-José; Groot, Paul F C; Altena, Ellemarije; van der Werf, Ysbrand D; Majoie, Charles B; van der Kooi, Anneke J; van den Berg, Leonard H; Schmand, Ben; de Visser, Marianne; Veltman, Dick J

2014-08-26

To examine brain activation patterns during verbal fluency performance in patients with progressive muscular atrophy (PMA) and amyotrophic lateral sclerosis (ALS). fMRI was used to examine the blood oxygen level-dependent response during letter and category fluency performance in 18 patients with PMA, 21 patients with ALS, and 17 healthy control subjects, matched for age and education. fMRI results are reported at p<0.05, family-wise error (FWE)-corrected for multiple comparisons. We analyzed effects of performance, age-related white matter changes (ARWMC), and regional brain volumes; all participants underwent neuropsychological investigation. Disease duration of patients with PMA (mean 26.0 months, SD 13.6) and ALS (22.2 months, SD 11.4) was comparable. Patients with PMA and ALS had mild to moderate disease severity and showed impaired letter fluency compared with controls. Between-group analysis showed a main effect of group in the left inferior frontal gyrus (IFG, Brodmann area 45) during letter fluency, which was unaffected by performance, ARWMC, and IFG volume: patients with PMA showed lower activation than controls but higher than that of patients with ALS (ALS

Effect of Posterior Horn Medial Meniscus Root Tear on In Vivo Knee Kinematics.

PubMed

Marsh, Chelsea A; Martin, Daniel E; Harner, Christopher D; Tashman, Scott

2014-07-01

Medial meniscus root tear (MMRT) is a recently recognized yet frequently missed meniscal tear pattern that biomechanically creates an environment approaching meniscal deficiency. The purpose of this study was to assess the effect of MMRT on tibiofemoral kinematics and arthrokinematics during daily activities by comparing the injured knees of subjects with isolated MMRT to their uninjured contralateral knees. The hypothesis was that the injured knee will demonstrate significantly more lateral tibial translation and adduction than the uninjured knee, and that the medial compartment will exhibit significantly different arthrokinematics than the lateral compartment in the affected limb. Cross-sectional study; Level of evidence, 3. Seven subjects with isolated MMRT were recruited and volumetric, density-based 3-dimensional models of their distal femurs and proximal tibia were created from computed tomography scans. High-speed, biplane radiographs were obtained of both their affected and unaffected knees. Moving 3-dimensional models of tibiofemoral kinematics were calculated using model-based tracking to assess overall kinematic variables and specific measures of tibiofemoral joint contact. The affected knees of the subjects were then compared to their unaffected contralateral knees. Affected knees demonstrated significantly more lateral tibial translation than the uninjured contralateral limb in all dynamic activities. Additionally, the medial compartment displayed greater amounts of mobility than the lateral compartment in the injured limbs. This study suggests that MMRT causes significant changes in in vivo knee kinematics and arthrokinematics and that the magnitude of these changes is influenced by dynamic task difficulty. Medial meniscus root tears lead to significant changes in joint arthrokinematics, with increased lateral tibial translation and greater medial compartment excursion. With complete root tears, essentially 100% of circumferential fibers are lost. This study will further our knowledge of meniscal deficiency and osteoarthritis and provide a baseline for more common forms of medial meniscal injuries (vertical, horizontal, radial), with various degrees of circumferential fiber function remaining.

Ipsilesional motor deficits following stroke reflect hemispheric specializations for movement control.

PubMed

Schaefer, Sydney Y; Haaland, Kathleen Y; Sainburg, Robert L

2007-08-01

Recent reports of functional impairment in the 'unaffected' limb of stroke patients have suggested that these deficits vary with the side of lesion. This not only supports the idea that the ipsilateral hemisphere contributes to arm movements, but also implies that such contributions are lateralized. We have previously suggested that the left and right hemispheres are specialized for controlling different features of movement. In reaching movements, the non-dominant arm appears better adapted for achieving accurate final positions and the dominant arm for specifying initial trajectory features, such as movement direction and peak acceleration. The purpose of this study was to determine whether different features of control could characterize ipsilesional motor deficits following stroke. Healthy control subjects and patients with either left- or right-hemisphere damage performed targeted single-joint elbow movements of different amplitudes in their ipsilateral hemispace. We predicted that left-hemisphere damage would produce deficits in specification of initial trajectory features, while right-hemisphere damage would produce deficits in final position accuracy. Consistent with our predictions, patients with left, but not right, hemisphere damage showed reduced modulation of acceleration amplitude. However, patients with right, but not left, hemisphere damage showed significantly larger errors in final position, which corresponded to reduced modulation of acceleration duration. Neither patient group differed from controls in terms of movement speed. Instead, the mechanisms by which speed was specified, through modulation of acceleration amplitude and modulation of acceleration duration, appeared to be differentially affected by left- and right-hemisphere damage. These findings support the idea that each hemisphere contributes differentially to the control of initial trajectory and final position, and that ipsilesional deficits following stroke reflect this lateralization in control.

Cognitive demand and predictive adaptational responses in dynamic stability control.

PubMed

Bohm, Sebastian; Mersmann, Falk; Bierbaum, Stefanie; Dietrich, Ralf; Arampatzis, Adamantios

2012-09-21

We studied the effects of a concurrent cognitive task on predictive motor control, a feedforward mechanism of dynamic stability control, during disturbed gait in young and old adults. Thirty-two young and 27 elderly male healthy subjects participated and were randomly assigned to either control or dual task groups. By means of a covered exchangeable element the surface condition on a gangway could be altered to induce gait perturbations. The experimental protocol included a baseline on hard surface and an adaptation phase with twelve trials on soft surface. After the first, sixth and last soft surface trial, the surface condition was changed to hard (H1-3), to examine after-effects and, thus, to quantify predictive motor control. Dynamic stability was assessed using the 'margin of stability (MoS)' as a criterion for the stability state of the human body (extrapolated center of mass concept). In H1-3 the young participants significantly increased the MoS at touchdown of the disturbed leg compared to baseline. The magnitude and the rate of these after-effects were unaffected by the dual task condition. The old participants presented a trend to after-effects (i.e., increase of MoS) in H3 but only under the dual task condition.In conclusion, the additional cognitive demand did not compromise predictive motor control during disturbed walking in the young and old participants. In contrast to the control group, the old dual task group featured a trend to predictive motor adjustments, which may be a result of a higher state of attention or arousal due to the dual task paradigm. Copyright © 2012 Elsevier Ltd. All rights reserved.

SOX2, OTX2 and PAX6 analysis in subjects with anophthalmia and microphthalmia.

PubMed

Mauri, Lucia; Franzoni, Alessandra; Scarcello, Manuela; Sala, Stefano; Garavelli, Livia; Modugno, Alessandra; Grammatico, Paola; Patrosso, Maria Cristina; Piozzi, Elena; Del Longo, Alessandra; Gesu, Giovanni P; Manfredini, Emanuela; Primignani, Paola; Damante, Giuseppe; Penco, Silvana

2015-02-01

Anophthalmia (A) and microphthalmia (M) are rare developmental anomalies that have significant effects on visual activity. In fraction of A/M subjects, single genetic defects have been identified as causative. In this study we analysed 65 Italian A/M patients, 21 of whom are syndromic, for mutations in SOX2, OTX2 and PAX6 genes. In syndromic patients the presence of genome imbalances through array CGH was also investigated. No mutations were found for OTX2 and PAX6 genes. Three causative SOX2 mutations were found in subjects with syndromic A. In a subject with syndromic signs and monolateral M, two de novo 6.26 Mb and 1.37 Mb deletions in 4q13.2q13.3 have been identified. A SOX2 missense (p.Ala161Ser) mutation was found in 1 out of 39 a subject with non-syndromic monolateral M. Alanine at position 161 is conserved along phylogeny and the p.Ala161Ser mutation is estimated pathogenic by in silico analysis. However, this mutation was also present in the unaffected patient's daughter. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Parametric modulation of neural activity during face emotion processing in unaffected youth at familial risk for bipolar disorder.

PubMed

Brotman, Melissa A; Deveney, Christen M; Thomas, Laura A; Hinton, Kendra E; Yi, Jennifer Y; Pine, Daniel S; Leibenluft, Ellen

2014-11-01

Both patients with pediatric bipolar disorder (BD) and unaffected youth at familial risk (AR) for the illness show impairments in face emotion labeling. Few studies, however, have examined brain regions engaged in AR youth when processing emotional faces. Moreover, studies have yet to explore neural responsiveness to subtle changes in face emotion in AR youth. Sixty-four unrelated youth, including 20 patients with BD, 15 unaffected AR youth, and 29 healthy comparisons (HC), completed functional magnetic resonance imaging. Neutral faces were morphed with angry or happy faces in 25% intervals. In specific phases of the task, youth alternatively made explicit (hostility) or implicit (nose width) ratings of the faces. The slope of blood oxygenated level-dependent activity was calculated across neutral to angry and neutral to happy face stimuli. Behaviorally, both subjects with BD (p ≤ 0.001) and AR youth (p ≤ 0.05) rated faces as less hostile relative to HC. Consistent with this, in response to increasing anger on the face, patients with BD and AR youth showed decreased modulation in the amygdala and inferior frontal gyrus (IFG; BA 46) compared to HC (all p ≤ 0.05). Amygdala dysfunction was present across both implicit and explicit rating conditions, but IFG modulation deficits were specific to the explicit condition. With increasing happiness, AR youth showed aberrant modulation in the IFG, which was also sensitive to task demands (all p ≤ 0.05). Decreased amygdala and IFG modulation in patients with BD and AR youth may be pathophysiological risk markers for BD, and may underlie the social cognition and face emotion labeling deficits observed in BD and AR youth. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Secretory leukocyte protease inhibitor protein regulates the penetrance of frontotemporal lobar degeneration in progranulin mutation carriers.

PubMed

Ghidoni, Roberta; Flocco, Rosa; Paterlini, Anna; Glionna, Michela; Caruana, Loredana; Tonoli, Elisa; Binetti, Giuliano; Benussi, Luisa

2014-01-01

The discovery that mutations in the gene encoding for progranulin (GRN) cause frontotemporal lobar degeneration (FTLD) and other neurodegenerative diseases leading to dementia has brought renewed interest in progranulin and its functions in the central nervous system. Full length progranulin is preserved from cleavage by secretory leukocyte protease inhibitor (SLPI), one of the smallest serine protease inhibitor circulating in plasma. Herein, we investigated the relationship between circulating SLPI and progranulin in affected and unaffected subjects belonging to 26 Italian pedigrees carrying GRN null mutations. In GRN null mutation carriers, we demonstrated: i) an increase of circulating SLPI levels in affected subjects; ii) an age-related upregulation of the serine-protease inhibitor in response to lifetime progranulin shortage; and iii) a delay in the age of onset in subjects with the highest SLPI protein levels. The study of SLPI and its relation to progranulin suggests the existence of unexpected molecular players in progranulin-associated neurodegeneration.

Dysfunctional family environment in affected versus unaffected offspring of parents with bipolar disorder.

PubMed

Ferreira, Guilherme S; Moreira, Carolina R L; Kleinman, Ana; Nader, Edmir C G P; Gomes, Bernardo Carramão; Teixeira, Ana Maria A; Rocca, Cristiana C Almeida; Nicoletti, Mark; Soares, Jair C; Busatto, Geraldo F; Lafer, Beny; Caetano, Sheila C

2013-11-01

Children of parents with bipolar disorder (BD) are at heightened risk for developing mood and other psychiatric disorders. We proposed to evaluate the environment of families with at least one parent with BD type I (BDF) with affected offspring (aBDF) and unaffected offspring (uBDF) compared with control families without a history of DSM-IV Axis I disorder (CF). We used the Family Environment Scale (FES) to evaluate 47 BDF (aBDF + uBDF) and 30 CF. Parents were assessed through the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). Diagnosis of the offspring was determined through the Schedule for Affective Disorders and Schizophrenia for School-Age Children/Present and Lifetime Version (K-SADS-PL) interview. There were statistically significant differences between aBDF, uBDF and CF in cohesion (p = 0.003), intellectual-cultural orientation (p = 0.01), active-recreational orientation (p = 0.007), conflict (p = 0.001), control (p = 0.01), moral-religious emphasis (p = 0.01) and organization (p = 0.001). The aBDF showed higher levels of control (p = 0.02) when compared to the uBDF. Families with a BD parent presented more dysfunctional interactions among members. Moreover, the presence of BD or other psychiatric disorders in the offspring of parents with BD is associated with higher levels of control. These results highlight the relevance of psychosocial interventions to improve resilience and family interactions.

Evaluation of mirrored muscle activity in patients with Complex Regional Pain Syndrome.

PubMed

Bank, Paulina J M; Peper, C Lieke E; Marinus, Johan; Beek, Peter J; van Hilten, Jacobus J

2014-10-01

Motor dysfunction in Complex Regional Pain Syndrome (CRPS) has been associated with bilateral changes in central motor processing, suggesting abnormal coupling between the affected and unaffected limb. We evaluated the occurrence of involuntary muscle activity in a limb during voluntary movements of the contralateral limb (i.e., mirror activity) in unilaterally affected patients to examine disinhibition of contralateral motor activity in CRPS. Mirror activity was examined during unimanual rhythmic flexion-extension movements of the wrist through in-depth analysis of electromyography recordings from the passive arm in 20 CRPS patients and 40 controls. The number of mirror-epochs was comparable for both arms in both CRPS patients and controls. Mirror-epochs in the affected arm of patients were comparable to those in controls. Mirror-epochs in the unaffected arm were shorter and showed less resemblance (in terms of rhythm and timing) to activity of the homologous muscle in the moving arm compared to mirror-epochs in controls. No evidence for disinhibition of contralateral motor activity was found during unimanual movement. Although motor dysfunction in CRPS has been associated with bilateral changes in cortical motor processing, the present findings argue against disinhibition of interhemispheric projections to homologous muscles in the contralateral limb during unimanual movement. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Gait Balance Disorder by Thalamic Infarction with the Disorder of Interstitial Nucleus of Cajal

PubMed Central

Kurosu, A.; Hayashi, Y.; Wada, K.; Nagaoka, M.

2011-01-01

The interstitial nucleus of Cajal (INC) is thought to play an important role in torsional/vertical eye position and head posture, and disorders of the INC induce abnormal ocular movements and head tilt. Our patients with ocular tilt reactions simultaneously also had disturbances in ambulatory balance, yet no reports address the loss of balance control induced by disorders of the INC. We examined the ambulatory disturbances induced by INC lesion. We experienced three patients with ocular movement disorders and abnormal head tilt due to thalamic infarction. We performed ophthalmic examinations on and checked the balance of them. With funduscopy, abnormal cycloduction was seen in the unaffected side and normal cycloduction was observed in the affected side. Nevertheless, Hess charts showed distortions in the visual image of both eyes. They all had disorders of balance control. We tried to treat them using the Bobath approach for improving their ambulatory balance. With subsequent improvements in balance control it was possible for them to take short walks, but it was difficult to make any improvements in their ocular movement. The INC is related to balance control of ambulation and disorders of the INC induce ambulatory disturbances. Cycloduction was only observed in the unaffected side, but Hess charts showed distortions of the visual image in both eyes. Ambulation was briefly improved, but diplopia persisted in these patients. PMID:21769260

California Verbal Learning Test-II performance in schizophrenia as a function of ascertainment strategy: comparing the first and second phases of the Consortium on the Genetics of Schizophrenia (COGS).

PubMed

Stone, William S; Mesholam-Gately, Raquelle I; Braff, David L; Calkins, Monica E; Freedman, Robert; Green, Michael F; Greenwood, Tiffany A; Gur, Raquel E; Gur, Ruben C; Lazzeroni, Laura C; Light, Gregory A; Nuechterlein, Keith H; Olincy, Ann; Radant, Allen D; Siever, Larry J; Silverman, Jeremy M; Sprock, Joyce; Sugar, Catherine A; Swerdlow, Neal R; Tsuang, Debby W; Tsuang, Ming T; Turetsky, Bruce I; Seidman, Larry J

2015-04-01

The first phase of the Consortium on the Genetics of Schizophrenia (COGS-1) showed performance deficits in learning and memory on the California Verbal Learning Test, Second Edition (CVLT-II) in individuals with schizophrenia (SZ), compared to healthy comparison subjects (HCS). A question is whether the COGS-1 study, which used a family study design (i.e. studying relatively intact families), yielded "milder" SZ phenotypes than those acquired subsequently in the COGS-2 case-control design that did not recruit unaffected family members. CVLT-II performance was compared for the COGS-1 and COGS-2 samples. Analyses focused on learning, recall and recognition variables, with age, gender and education as covariates. Analyses of COGS-2 data explored effects of additional covariates and moderating factors in CVLT-II performance. 324 SZ subjects and 510 HCS had complete CVLT-II and covariate data in COGS-1, while 1356 SZ and 1036 HCS had complete data in COGS-2. Except for recognition memory, analysis of covariance showed significantly worse performance in COGS-2 on all CVLT-II variables for SZ and HCS, and remained significant in the presence of the covariates. Performance in each of the 5 learning trials differed significantly. However, effect sizes comparing cases and controls were comparable across the two studies. COGS-2 analyses confirmed SZ performance deficits despite effects of multiple significant covariates and moderating factors. CVLT-II performance was worse in COGS-2 than in COGS-1 for both the SZ and the HCS in this large cohort, likely due to cohort effects. Demographically corrected data yield a consistent pattern of performance across the two studies in SZ. Copyright © 2014. Published by Elsevier B.V.

California Verbal Learning Test-II performance in schizophrenia as a function of ascertainment strategy: Comparing the first and second phases of the Consortium on the Genetics of Schizophrenia (COGS)

PubMed Central

Stone, William S.; Mesholam-Gately, Raquelle I.; Braff, David L.; Calkins, Monica E.; Freedman, Robert; Green, Michael F.; Greenwood, Tiffany A.; Gur, Raquel E.; Gur, Ruben C.; Lazzeroni, Laura C.; Light, Gregory A.; Nuechterlein, Keith H.; Olincy, Ann; Radant, Allen D.; Siever, Larry J.; Silverman, Jeremy M.; Sprock, Joyce; Sugar, Catherine A.; Swerdlow, Neal R.; Tsuang, Debby W.; Tsuang, Ming T.; Turetsky, Bruce I.; Seidman, Larry J.

2018-01-01

The first phase of the Consortium on the Genetics of Schizophrenia (COGS-1) showed performance deficits in learning and memory on the California Verbal Learning Test, Second Edition (CVLT-II) in individuals with schizophrenia (SZ), compared to healthy comparison subjects (HCS). A question is whether the COGS-1 study, which used a family study design (i.e. studying relatively intact families), yielded “milder” SZ phenotypes than those acquired subsequently in the COGS-2 case–control design that did not recruit unaffected family members. CVLT-II performance was compared for the COGS-1 and COGS-2 samples. Analyses focused on learning, recall and recognition variables, with age, gender and education as covariates. Analyses of COGS-2 data explored effects of additional covariates and moderating factors in CVLT-II performance. 324 SZ subjects and 510 HCS had complete CVLT-II and covariate data in COGS-1, while 1356 SZ and 1036 HCS had complete data in COGS-2. Except for recognition memory, analysis of covariance showed significantly worse performance in COGS-2 on all CVLT-II variables for SZ and HCS, and remained significant in the presence of the covariates. Performance in each of the 5 learning trials differed significantly. However, effect sizes comparing cases and controls were comparable across the two studies. COGS-2 analyses confirmed SZ performance deficits despite effects of multiple significant covariates and moderating factors. CVLT-II performance was worse in COGS-2 than in COGS-1 for both the SZ and the HCS in this large cohort, likely due to cohort effects. Demographically corrected data yield a consistent pattern of performance across the two studies in SZ. PMID:25497440

Paternal age effect: Replication in schizophrenia with intriguing dissociation between bipolar with and without psychosis.

PubMed

Lehrer, Douglas S; Pato, Michele T; Nahhas, Ramzi W; Miller, Brian R; Malaspina, Dolores; Buckley, Peter F; Sobell, Janet L; Walsh-Messinger, Julie; Genomic Psychiatry Cohort Consortium; Pato, Carlos N

2016-06-01

Advanced paternal age (APA) is a risk factor for schizophrenia (Sz) and bipolar disorder (BP). Putative mechanisms include heritable genetic factors, de novo mutations, and epigenetic mechanisms. Few studies have explored phenotypic features associated with APA. The Genomic Psychiatry Cohort established a clinically characterized repository of genomic samples from subjects with a Sz-BP diagnosis or unaffected controls, 12,975 with parental age information. We estimated relative risk ratios for Sz, schizoaffective depressed and bipolar types (SA-D, SA-B), and BP with and without history of psychotic features (PF) relative to the control group, comparing each paternal age group to the reference group 20-24 years. All tests were two-sided with adjustment for multiple comparisons. Subjects with fathers age 45+ had significantly higher risk for all diagnoses except for BP w/o PF. APA also bore no significant relation to family psychiatric history. In conclusion, we replicated APA as a risk factor for Sz. To our knowledge, this is the first published report of APA in a BP sample stratified by psychosis history, extending this association only in BP w/PF. This suggests that phenotypic expression of the APA effect in Sz-BP spectrum is psychosis, per se, rather than other aspects of these complex disorders. The lack of a significant relationship between paternal age and familial disease patterns suggests that underlying mechanisms of the paternal age effect may involve a complex interaction of heritable and non-heritable factors. The authors discuss implications and testable hypotheses, starting with a focus on genetic mechanisms and endophenotypic expressions of dopaminergic function. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Increased blood flow in the anterior humeral circumflex artery correlates with night pain in patients with rotator cuff tear.

PubMed

Terabayashi, Nobuo; Watanabe, Tsuneo; Matsumoto, Kazu; Takigami, Iori; Ito, Yoshiki; Fukuta, Masashi; Akiyama, Haruhiko; Shimizu, Katsuji

2014-09-01

Night pain is a particularly vexing symptom in patients with rotator cuff tear. It disturbs sleep and decreases quality of life, and there is no consensus regarding its etiology. Based on arthroscopic surgical observations of synovitis around the rotator interval or capsule surface in rotator cuff tear, we hypothesized that blood flow from the artery feeding the capsule increases blood supply to the synovium. This study aimed to investigate the relationship between blood flow and night pain using pulse Doppler ultrasonography. A series of 47 consecutive patients with rotator cuff tear was evaluated. The peak systolic velocity and resistance index of blood flow in the ascending branch of the anterior humeral circumflex artery were evaluated using pulse Doppler ultrasonography. We also investigated 20 normal shoulders in healthy volunteers. The peak systolic velocity and resistance index were compared between affected and unaffected sides in patients and between dominant and nondominant sides in controls. Anterior humeral circumflex artery peak systolic velocity and resistance index did not differ between sides in control subjects or in patients with rotator cuff tear without night pain. However, anterior humeral circumflex artery peak systolic velocity and resistance index did differ significantly between sides in patients with rotator cuff tear with night pain. This study revealed anterior humeral circumflex artery hemodynamics in patients with rotator cuff tear and normal subjects using Doppler ultrasonography. Night pain, particularly involving aching, appears to be related to the hemodynamics. These findings suggest that investigating the hemodynamics of patients with rotator cuff tear with night pain may lead to greater understanding of the etiology of this symptom.

Exploring the impact of visual and movement based priming on a motor intervention in the acute phase post-stroke in persons with severe hemiparesis of the upper extremity

PubMed Central

Patel, Jigna; Qiu, Qinyin; Yarossi, Mathew; Merians, Alma; Massood, Supriya; Tunik, Eugene; Adamovich, Sergei; Fluet, Gerard

2016-01-01

Purpose Explore the potential benefits of using priming methods prior to an active hand task in the acute phase post-stroke in persons with severe upper extremity hemiparesis. Methods Five individuals were trained using priming techniques including virtual reality (VR) based visual mirror feedback and contralaterally controlled passive movement strategies prior to training with an active pinch force modulation task. Clinical, kinetic, and neurophysiological measurements were taken pre and post the training period. Clinical measures were taken at six months post training. Results The two priming simulations and active training were well tolerated early after stroke. Priming effects were suggested by increased maximal pinch force immediately after visual and movement based priming. Despite having no clinically observable movement distally, the subjects were able to volitionally coordinate isometric force and muscle activity (EMG) in a pinch tracing task. The Root Mean Square Error (RMSE) of force during the pinch trace task gradually decreased over the training period suggesting learning may have occurred. Changes in motor cortical neurophysiology were seen in the unaffected hemisphere using Transcranial Magnetic Stimulation (TMS) mapping. Significant improvements in motor recovery as measured by the Action Research Arm Test (ARAT) and the Upper Extremity Fugl Meyer Assessment (UEFMA) were demonstrated at six months post training by three of the five subjects. Conclusion This study suggests that an early hand-based intervention using visual and movement based priming activities and a scaled motor task allows participation by persons without the motor control required for traditionally presented rehabilitation and testing. PMID:27636200

Large motor units are selectively affected following a stroke.

PubMed

Lukács, M; Vécsei, L; Beniczky, S

2008-11-01

Previous studies have revealed a loss of functioning motor units in stroke patients. However, it remained unclear whether the motor units are affected randomly or in some specific pattern. We assessed whether there is a selective loss of the large (high recruitment threshold) or the small (low recruitment threshold) motor units following a stroke. Forty-five stroke patients and 40 healthy controls participated in the study. Macro-EMG was recorded from the abductor digiti minimi muscle at two levels of force output (low and high). The median macro motor unit potential (macro-MUP) amplitude on the paretic side was compared with those on the unaffected side and in the controls. In the control group and on the unaffected side, the macro-MUPs were significantly larger at the high force output than at the low one. However, on the paretic side the macro-MUPs at the high force output had the same amplitude as those recorded at the low force output. These changes correlated with the severity of the paresis. Following a stroke, there is a selective functional loss of the large, high-threshold motor units. These changes are related to the severity of the symptoms. Our findings furnish further insight into the pathophysiology of the motor deficit following a stroke.

A Novel SLC27A4 Splice Acceptor Site Mutation in Great Danes with Ichthyosis.

PubMed

Metzger, Julia; Wöhlke, Anne; Mischke, Reinhard; Hoffmann, Annalena; Hewicker-Trautwein, Marion; Küch, Eva-Maria; Naim, Hassan Y; Distl, Ottmar

2015-01-01

Ichthyoses are a group of various different types of hereditary disorders affecting skin cornification. They are characterized by hyperkeratoses of different severity levels and are associated with a dry and scaling skin. Genome-wide association analysis of nine affected and 13 unaffected Great Danes revealed a genome-wide significant peak on chromosome 9 at 57-58 Mb in the region of SLC27A4. Sequence analysis of genomic DNA of SLC27A4 revealed the non-synonymous SNV SLC27A4:g.8684G>A in perfect association with ichthyosis-affection in Great Danes. The mutant transcript of SLC27A4 showed an in-frame loss of 54 base pairs in exon 8 probably induced by a new splice acceptor site motif created by the mutated A- allele of the SNV. Genotyping 413 controls from 35 different breeds of dogs and seven wolves revealed that this mutation could not be found in other populations except in Great Danes. Affected dogs revealed high amounts of mutant transcript but only low levels of the wild type transcript. Targeted analyses of SLC27A4 protein from skin tissues of three affected and two unaffected Great Danes indicated a markedly reduced or not detectable wild type and truncated protein levels in affected dogs but a high expression of wild type SLC27A4 protein in unaffected controls. Our data provide evidence of a new splice acceptor site creating SNV that results in a reduction or loss of intact SLC27A4 protein and probably explains the severe skin phenotype in Great Danes. Genetic testing will allow selective breeding to prevent ichthyosis-affected puppies in the future.