Displaying chest X-ray by beamer or monitor: comparison of diagnostic accuracy for subtle abnormalities.

PubMed

Kuiper, L M; Thijs, A; Smulders, Y M

2012-01-01

The advent of beamer projection of radiological images raises the issue of whether such projection compromises diagnostic accuracy. The purpose of this study was to evaluate whether beamer projection of chest X-rays is inferior to monitor display. We selected 53 chest X-rays with subtle abnormalities and 15 normal X-rays. The images were independently judged by a senior radiologist and a senior pulmonologist with a state-of-art computer monitor. We used their unanimous or consensus judgment as the reference test. Subsequently, four observers (one senior pulmonologist, one senior radiologist and one resident from each speciality) judged these X-rays on a standard clinical computer monitor and with beamer projection. We compared the number of correct results for each method. Overall, the sensitivity and specificity did not differ between monitor and beamer projection. Separate analyses in senior and junior examiners suggested that senior examiners had a moderate loss of diagnostic accuracy (8% lower sensitivity, pp<0.05, and 6% lower specificity, p=ns) associated with the use of beamer projection, whereas juniors showed similar performance on both imaging modalities. These initial data suggest that beamer projection may be associated with a small loss of diagnostic accuracy in specific subgroups of physicians. This finding illustrates the need for more extensive studies.

Gait Profile Score in multiple sclerosis patients with low disability.

PubMed

Morel, Eric; Allali, Gilles; Laidet, Magali; Assal, Frédéric; Lalive, Patrice H; Armand, Stéphane

2017-01-01

Gait abnormalities are subtle in multiple sclerosis (MS) patients with low disability and need to be better determined. As a biomechanical approach, the Gait Profile Score (GPS) is used to assess gait quality by combining nine gait kinematic variables in one single value. This study aims i) to establish if the GPS can detect gait impairments and ii) to compare GPS with discrete spatiotemporal and kinematic parameters in low-disabled MS patients. Thirty-four relapsing-remitting MS patients with an Expanded Disability Status Scale (EDSS) score ≤2 (mean age 36.32±8.72 years; 12 men, 22 women; mean EDSS 1.19±0.8) and twenty-two healthy controls (mean age 36.85±7.87 years; 6 men, 16 women) matched for age, weight, height, body mass index and gender underwent an instrumented gait analysis. No significant difference in GPS values and in spatiotemporal parameters was found between patients and controls. However patients showed a significant alteration at the ankle and pelvis level. GPS fails to identify gait abnormalities in low-disabled MS patients, although kinematic analysis revealed subtle gait alterations. Future studies should investigate other methods to assess gait impairments with a gait score in low-disabled MS patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Fluorescent nanodiamond tracking reveals intraneuronal transport abnormalities induced by brain-disease-related genetic risk factors

NASA Astrophysics Data System (ADS)

Haziza, Simon; Mohan, Nitin; Loe-Mie, Yann; Lepagnol-Bestel, Aude-Marie; Massou, Sophie; Adam, Marie-Pierre; Le, Xuan Loc; Viard, Julia; Plancon, Christine; Daudin, Rachel; Koebel, Pascale; Dorard, Emilie; Rose, Christiane; Hsieh, Feng-Jen; Wu, Chih-Che; Potier, Brigitte; Herault, Yann; Sala, Carlo; Corvin, Aiden; Allinquant, Bernadette; Chang, Huan-Cheng; Treussart, François; Simonneau, Michel

2017-05-01

Brain diseases such as autism and Alzheimer's disease (each inflicting >1% of the world population) involve a large network of genes displaying subtle changes in their expression. Abnormalities in intraneuronal transport have been linked to genetic risk factors found in patients, suggesting the relevance of measuring this key biological process. However, current techniques are not sensitive enough to detect minor abnormalities. Here we report a sensitive method to measure the changes in intraneuronal transport induced by brain-disease-related genetic risk factors using fluorescent nanodiamonds (FNDs). We show that the high brightness, photostability and absence of cytotoxicity allow FNDs to be tracked inside the branches of dissociated neurons with a spatial resolution of 12 nm and a temporal resolution of 50 ms. As proof of principle, we applied the FND tracking assay on two transgenic mouse lines that mimic the slight changes in protein concentration (∼30%) found in the brains of patients. In both cases, we show that the FND assay is sufficiently sensitive to detect these changes.

Abnormal Neural Activation to Faces in the Parents of Children with Autism

PubMed Central

Yucel, G. H.; Belger, A.; Bizzell, J.; Parlier, M.; Adolphs, R.; Piven, J.

2015-01-01

Parents of children with an autism spectrum disorder (ASD) show subtle deficits in aspects of social behavior and face processing, which resemble those seen in ASD, referred to as the “Broad Autism Phenotype ” (BAP). While abnormal activation in ASD has been reported in several brain structures linked to social cognition, little is known regarding patterns in the BAP. We compared autism parents with control parents with no family history of ASD using 2 well-validated face-processing tasks. Results indicated increased activation in the autism parents to faces in the amygdala (AMY) and the fusiform gyrus (FG), 2 core face-processing regions. Exploratory analyses revealed hyper-activation of lateral occipital cortex (LOC) bilaterally in autism parents with aloof personality (“BAP+”). Findings suggest that abnormalities of the AMY and FG are related to underlying genetic liability for ASD, whereas abnormalities in the LOC and right FG are more specific to behavioral features of the BAP. Results extend our knowledge of neural circuitry underlying abnormal face processing beyond those previously reported in ASD to individuals with shared genetic liability for autism and a subset of genetically related individuals with the BAP. PMID:25056573

Subclinical Cushing's syndrome: current concepts and trends.

PubMed

Zografos, George N; Perysinakis, Iraklis; Vassilatou, Evangeline

2014-01-01

Clinically inapparent adrenal masses which are incidentally detected have become a common problem in everyday practice. Approximately 5-20% of adrenal incidentalomas present subclinical cortisol hypersecretion which is characterized by subtle alterations of the hypothalamic-pituitary-adrenal axis due to adrenal autonomy. This disorder has been described as subclinical Cushing's syndrome, since there is no typical clinical phenotype. The diagnosis of subclinical Cushing's syndrome is based on biochemical evaluation; however, there is still no consensus for the biochemical diagnostic criteria. An abnormal 1mg dexamethasone suppression test (DST) as initial screening test in combination with at least one other abnormal test of the hypothalamic-pituitary-adrenal axis has been advocated by most experts for the diagnosis of subclinical Cushing's syndrome. DST is the main method of establishing the diagnosis, while there is inhomogeneity of the information that other tests provide. Arterial hypertension, diabetes mellitus type 2 or impaired glucose tolerance, central obesity, osteoporosis/vertebral fractures and dyslipidemia are considered as detrimental effects of chronic subtle cortisol excess, although there is no proven causal relationship between subclinical cortisol hypersecretion and these morbidities. Therapeutic strategies include careful observation along with medical treatment of morbidities potentially related to subtle cortisol hypersecretion versus laparoscopic adrenalectomy. The optimal management of patients with subclinical Cushing's syndrome is not yet defined. The conservative approach is appropriate for the majority of these patients; however, the duration of follow-up and the frequency of periodical evaluation still remain open issues. Surgical resection may be beneficial for patients with hypertension, diabetes mellitus type 2 or abnormal glucose tolerance and obesity.

Abnormal Neural Activation to Faces in the Parents of Children with Autism.

PubMed

Yucel, G H; Belger, A; Bizzell, J; Parlier, M; Adolphs, R; Piven, J

2015-12-01

Parents of children with an autism spectrum disorder (ASD) show subtle deficits in aspects of social behavior and face processing, which resemble those seen in ASD, referred to as the "Broad Autism Phenotype " (BAP). While abnormal activation in ASD has been reported in several brain structures linked to social cognition, little is known regarding patterns in the BAP. We compared autism parents with control parents with no family history of ASD using 2 well-validated face-processing tasks. Results indicated increased activation in the autism parents to faces in the amygdala (AMY) and the fusiform gyrus (FG), 2 core face-processing regions. Exploratory analyses revealed hyper-activation of lateral occipital cortex (LOC) bilaterally in autism parents with aloof personality ("BAP+"). Findings suggest that abnormalities of the AMY and FG are related to underlying genetic liability for ASD, whereas abnormalities in the LOC and right FG are more specific to behavioral features of the BAP. Results extend our knowledge of neural circuitry underlying abnormal face processing beyond those previously reported in ASD to individuals with shared genetic liability for autism and a subset of genetically related individuals with the BAP. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The impact of radiology expertise upon the localization of subtle pulmonary lesions

NASA Astrophysics Data System (ADS)

Robinson, John W.; Brennan, Patrick C.; Mello-Thoms, Claudia; Lewis, Sarah J.

2016-03-01

Rationale and objectives: This study investigates the influence of radiology expertise in the correct localization of lesions when radiologists are requested to complete an observer task. Specifically, the ability to detect pulmonary lesions of different subtleties is explored in relation to radiologists' reported specialty. Materials and Methods: Institutional ethics was granted. Ten radiologists (5 thoracic, 5 non-thoracic) interpreted 40 posterior-anterior (PA) chest x-rays (CXRs) consisting of 21 normal and 19 abnormal cases (solitary pulmonary nodule). The abnormal cases contained a solitary nodule with an established subtlety (subtlety 5 = obvious to subtlety 1 = extremely subtle). Radiologists read the test set and identified any pulmonary nodule using a 1-5 confidence scale (1=no pulmonary nodule to 5=highest confidence case contains a pulmonary lesion). The radiologists interpreted the image bank twice and the cases were randomized for each reader between reads. Results: The Kruskal-Wallis test identified that subtlety of nodules significantly influenced the sensitivity of nonthoracic radiologists (P=<0.0001) and thoracic radiologists (P=<0.0001). A Wilcoxon rank test demonstrated a significant difference in sensitivity for radiologist specialisation (P=0.013), with thoracic radiologists better compared to non-thoracic radiologists (mean sensitivity 0.479 and 0.389 respectively). The sensitivity of nodule detection decreased when comparing subtlety 4 to 3, 3 to 2 and 2 to 1 for non-thoracic and thoracic radiologists'with the subtlety 3 to subtlety 2 being significant (P=0.014) for non thoracic radiologists while thoracic radiologists' demonstrated a decrease but no transitions between subtlety were significant. The most noticeable, and interesting, effect was with the thoracic radiologists' with the average means of subtlety 2 and 1 being almost the same and closely comparable to level 3. Conclusion: Results from this study indicate that expertise in chest radiology does significantly impact upon the sensitivity of radiologists in detecting pulmonary lesions of varying subtlety. Thoracic radiologists had a consistently higher sensitivity with subtle, very subtle and extremely subtle nodules.

Diagnosing subtle palatal anomalies: Validation of video-analysis and assessment protocol for diagnosing occult submucous cleft palate.

PubMed

Rourke, Ryan; Weinberg, Seth M; Marazita, Mary L; Jabbour, Noel

2017-09-01

Submucous cleft palate (SMCP) classically involves bifid uvula, zona pellucida, and notched hard palate. However, patients may present with more subtle anatomic abnormalities. The ability to detect these abnormalities is important for surgeons managing velopharyngeal dysfunction (VPD) or considering adenoidectomy. Validate an assessment protocol for diagnosis of occult submucous cleft palate (OSMCP) and identify physical examination features present in patients with OSMCP in the relaxed and activated palate positions. Study participants included patients referred to a pediatric VPD clinic with concern for hypernasality or SMCP. Using an appropriately encrypted iPod touch, transoral video was obtained for each patient with the palate in the relaxed and activated positions. The videos were reviewed by two otolaryngologists in normal speed and slow-motion, as needed, and a questionnaire was completed by each reviewer pertaining to the anatomy and function of the palate. 47 patients, with an average age of 4.6 years, were included in the study over a one-year period. Four videos were unusable due to incomplete view of the palate. The most common palatal abnormality noted was OSMCP, diagnosed by each reviewer in 26/43 and 30/43 patients respectively. Using the assessment protocol, agreement on palatal diagnosis was 83.7% (kappa = 0.68), indicating substantial agreement, with the most prevalent anatomic features being vaulted palate elevation (96%) and visible notching of hard palate (75%). The diagnosis of subtle palatal anomalies is difficult and can be subjective. Using the proposed video-analysis method and assessment protocol may improve reliability of diagnosis of OSMCP. Copyright © 2017 Elsevier B.V. All rights reserved.

The Application of MRI for Depiction of Subtle Blood Brain Barrier Disruption in Stroke

PubMed Central

Israeli, David; Tanne, David; Daniels, Dianne; Last, David; Shneor, Ran; Guez, David; Landau, Efrat; Roth, Yiftach; Ocherashvilli, Aharon; Bakon, Mati; Hoffman, Chen; Weinberg, Amit; Volk, Talila; Mardor, Yael

2011-01-01

The development of imaging methodologies for detecting blood-brain-barrier (BBB) disruption may help predict stroke patient's propensity to develop hemorrhagic complications following reperfusion. We have developed a delayed contrast extravasation MRI-based methodology enabling real-time depiction of subtle BBB abnormalities in humans with high sensitivity to BBB disruption and high spatial resolution. The increased sensitivity to subtle BBB disruption is obtained by acquiring T1-weighted MRI at relatively long delays (~15 minutes) after contrast injection and subtracting from them images acquired immediately after contrast administration. In addition, the relatively long delays allow for acquisition of high resolution images resulting in high resolution BBB disruption maps. The sensitivity is further increased by image preprocessing with corrections for intensity variations and with whole body (rigid+elastic) registration. Since only two separate time points are required, the time between the two acquisitions can be used for acquiring routine clinical data, keeping the total imaging time to a minimum. A proof of concept study was performed in 34 patients with ischemic stroke and 2 patients with brain metastases undergoing high resolution T1-weighted MRI acquired at 3 time points after contrast injection. The MR images were pre-processed and subtracted to produce BBB disruption maps. BBB maps of patients with brain metastases and ischemic stroke presented different patterns of BBB opening. The significant advantage of the long extravasation time was demonstrated by a dynamic-contrast-enhancement study performed continuously for 18 min. The high sensitivity of our methodology enabled depiction of clear BBB disruption in 27% of the stroke patients who did not have abnormalities on conventional contrast-enhanced MRI. In 36% of the patients, who had abnormalities detectable by conventional MRI, the BBB disruption volumes were significantly larger in the maps than in conventional MRI. These results demonstrate the advantages of delayed contrast extravasation in increasing the sensitivity to subtle BBB disruption in ischemic stroke patients. The calculated disruption maps provide clear depiction of significant volumes of BBB disruption unattainable by conventional contrast-enhanced MRI. PMID:21209786

The application of MRI for depiction of subtle blood brain barrier disruption in stroke.

PubMed

Israeli, David; Tanne, David; Daniels, Dianne; Last, David; Shneor, Ran; Guez, David; Landau, Efrat; Roth, Yiftach; Ocherashvilli, Aharon; Bakon, Mati; Hoffman, Chen; Weinberg, Amit; Volk, Talila; Mardor, Yael

2010-12-26

The development of imaging methodologies for detecting blood-brain-barrier (BBB) disruption may help predict stroke patient's propensity to develop hemorrhagic complications following reperfusion. We have developed a delayed contrast extravasation MRI-based methodology enabling real-time depiction of subtle BBB abnormalities in humans with high sensitivity to BBB disruption and high spatial resolution. The increased sensitivity to subtle BBB disruption is obtained by acquiring T1-weighted MRI at relatively long delays (~15 minutes) after contrast injection and subtracting from them images acquired immediately after contrast administration. In addition, the relatively long delays allow for acquisition of high resolution images resulting in high resolution BBB disruption maps. The sensitivity is further increased by image preprocessing with corrections for intensity variations and with whole body (rigid+elastic) registration. Since only two separate time points are required, the time between the two acquisitions can be used for acquiring routine clinical data, keeping the total imaging time to a minimum. A proof of concept study was performed in 34 patients with ischemic stroke and 2 patients with brain metastases undergoing high resolution T1-weighted MRI acquired at 3 time points after contrast injection. The MR images were pre-processed and subtracted to produce BBB disruption maps. BBB maps of patients with brain metastases and ischemic stroke presented different patterns of BBB opening. The significant advantage of the long extravasation time was demonstrated by a dynamic-contrast-enhancement study performed continuously for 18 min. The high sensitivity of our methodology enabled depiction of clear BBB disruption in 27% of the stroke patients who did not have abnormalities on conventional contrast-enhanced MRI. In 36% of the patients, who had abnormalities detectable by conventional MRI, the BBB disruption volumes were significantly larger in the maps than in conventional MRI. These results demonstrate the advantages of delayed contrast extravasation in increasing the sensitivity to subtle BBB disruption in ischemic stroke patients. The calculated disruption maps provide clear depiction of significant volumes of BBB disruption unattainable by conventional contrast-enhanced MRI.

MR imaging findings in the reticular formation in siblings with MPV17-related mitochondrial depletion syndrome.

PubMed

Merkle, A N; Nascene, D R; McKinney, A M

2012-03-01

Hepatocerebral MPV17-MDS is quite rare (<30 confirmed cases), with limited findings described on MR imaging. We report 2 siblings having abnormalities within the reticular formation of the lower brain stem and within the reticulospinal tracts at the cervicocranial junction on T2WI. The presence of these MR imaging findings (relative to previous reports) raises the possibility that they represent subtle but characteristic findings corresponding to clinically observed abnormalities of tone encountered with this recently described disorder.

Further expansion of the mutational spectrum of spondylo-meta-epiphyseal dysplasia with abnormal calcification.

PubMed

Ürel-Demir, Gizem; Simsek-Kiper, Pelin Ozlem; Akgün-Doğan, Özlem; Göçmen, Rahşan; Wang, Zheng; Matsumoto, Naomichi; Miyake, Noriko; Utine, Gülen Eda; Nishimura, Gen; Ikegawa, Shiro; Boduroglu, Koray

2018-06-08

Spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type, is a rare autosomal recessive disorder of the skeleton characterized by disproportionate short stature with narrow chest and dysmorphic facial features. The skeletal manifestations include platyspondyly, short flared ribs, short tubular bones with abnormal metaphyses and epiphyses, severe brachydactyly, and premature stippled calcifications in the cartilage. The abnormal calcifications are so distinctive as to point to the definitive diagnosis. However, they may be too subtle to attract diagnostic attention in infancy. Homozygous variants in DDR2 cause this disorder. We report on a 5-year-old girl with the classic phenotype of SMED, SL-AC in whom a novel homozygous nonsense mutation in DDR2 was detected using exome sequencing.

Mild Cognitive Impairment as a single sign of brain hemiatrophy in patient with Localized Scleroderma and Parry-Romberg Syndrome.

PubMed

Klimiec, Elzbieta; Klimkowicz-Mrowiec, Aleksandra

2016-01-01

Neurologic involvement is well recognized in Systemic Scleroderma and increasingly reported in Localized Scleroderma. MRI brain abnormalities are often associated with symptoms such as seizures or headaches. In some cases they may be clinically silent. We describe a 23 years old female with head, trunk and limbs scleroderma who developed Parry-Romberg Syndrome. Brain MRI showed ipsilateral temporal lobe atrophy without any prominent neurologic symptoms. Neuropsychological examination revealed Mild Cognitive Impairment. During the 7 years of follow up we have noticed progression of face atrophy but no progression of brain atrophy. Cognitive functions have been stable. This case highlight that major MRI brain abnormalities in LS may occur with only subtle clinical manifestation such as Mild Cognitive Impairment. Copyright © 2016 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Multivariate pattern analysis reveals subtle brain anomalies relevant to the cognitive phenotype in neurofibromatosis type 1.

PubMed

Duarte, João V; Ribeiro, Maria J; Violante, Inês R; Cunha, Gil; Silva, Eduardo; Castelo-Branco, Miguel

2014-01-01

Neurofibromatosis Type 1 (NF1) is a common genetic condition associated with cognitive dysfunction. However, the pathophysiology of the NF1 cognitive deficits is not well understood. Abnormal brain structure, including increased total brain volume, white matter (WM) and grey matter (GM) abnormalities have been reported in the NF1 brain. These previous studies employed univariate model-driven methods preventing detection of subtle and spatially distributed differences in brain anatomy. Multivariate pattern analysis allows the combination of information from multiple spatial locations yielding a discriminative power beyond that of single voxels. Here we investigated for the first time subtle anomalies in the NF1 brain, using a multivariate data-driven classification approach. We used support vector machines (SVM) to classify whole-brain GM and WM segments of structural T1 -weighted MRI scans from 39 participants with NF1 and 60 non-affected individuals, divided in children/adolescents and adults groups. We also employed voxel-based morphometry (VBM) as a univariate gold standard to study brain structural differences. SVM classifiers correctly classified 94% of cases (sensitivity 92%; specificity 96%) revealing the existence of brain structural anomalies that discriminate NF1 individuals from controls. Accordingly, VBM analysis revealed structural differences in agreement with the SVM weight maps representing the most relevant brain regions for group discrimination. These included the hippocampus, basal ganglia, thalamus, and visual cortex. This multivariate data-driven analysis thus identified subtle anomalies in brain structure in the absence of visible pathology. Our results provide further insight into the neuroanatomical correlates of known features of the cognitive phenotype of NF1. Copyright © 2012 Wiley Periodicals, Inc.

Cognition and brain development in children with benign epilepsy with centrotemporal spikes.

PubMed

Garcia-Ramos, Camille; Jackson, Daren C; Lin, Jack J; Dabbs, Kevin; Jones, Jana E; Hsu, David A; Stafstrom, Carl E; Zawadzki, Lucy; Seidenberg, Michael; Prabhakaran, Vivek; Hermann, Bruce P

2015-10-01

Benign epilepsy with centrotemporal spikes (BECTS), the most common focal childhood epilepsy, is associated with subtle abnormalities in cognition and possible developmental alterations in brain structure when compared to healthy participants, as indicated by previous cross-sectional studies. To examine the natural history of BECTS, we investigated cognition, cortical thickness, and subcortical volumes in children with new/recent onset BECTS and healthy controls (HC). Participants were 8-15 years of age, including 24 children with new-onset BECTS and 41 age- and gender-matched HC. At baseline and 2 years later, all participants completed a cognitive assessment, and a subset (13 BECTS, 24 HC) underwent T1 volumetric magnetic resonance imaging (MRI) scans focusing on cortical thickness and subcortical volumes. Baseline cognitive abnormalities associated with BECTS (object naming, verbal learning, arithmetic computation, and psychomotor speed/dexterity) persisted over 2 years, with the rate of cognitive development paralleling that of HC. Baseline neuroimaging revealed thinner cortex in BECTS compared to controls in frontal, temporal, and occipital regions. Longitudinally, HC showed widespread cortical thinning in both hemispheres, whereas BECTS participants showed sparse regions of both cortical thinning and thickening. Analyses of subcortical volumes showed larger left and right putamens persisting over 2 years in BECTS compared to HC. Cognitive and structural brain abnormalities associated with BECTS are present at onset and persist (cognition) and/or evolve (brain structure) over time. Atypical maturation of cortical thickness antecedent to BECTS onset results in early identified abnormalities that continue to develop abnormally over time. However, compared to anatomic development, cognition appears more resistant to further change over time. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Potential pitfalls and methods of improving in utero diagnosis of transposition of the great arteries, including the baby bird's beak image.

PubMed

McGahan, John P; Moon-Grady, Anita J; Pahwa, Anokh; Towner, Dena; Rhee-Morris, Laila; Gerscovich, Eugenio O; Fogata, Maria

2007-11-01

The goal of this study was to analyze our recent experience with fetuses with transposition of the great arteries (TGA) to identify potential pitfalls and possible methods to better detect conotruncal anomalies such as TGA. We analyzed all nonreferral obstetric ultrasound examinations in which we performed basic, targeted, or formal fetal echocardiography with a newborn diagnosis of TGA. Nine neonates had TGA. Five of these cases were diagnosed prenatally, and 4 of these had complex congenital heart abnormalities. In these 4 cases, there were abnormalities in the cardiac axis (n = 3), abnormal valves or ventricular size (n = 2), and ventricular septal defects (n = 3) that were detected on the 4-chamber view of the heart. In all cases that were not detected prenatally, both prospective and retrospective reviews of the 4-chamber heart appeared normal. The prospective analyses of the outflow tracts were all interpreted as normal, whereas the retrospective review showed subtle abnormalities such as the "baby bird's beak" image. In review of these cases, there was failure to show the "crisscross" relationship of the outflow tracts. In 1 case, 5 short axis views of the heart, retrospectively showed the artery originating from the left ventricle and bifurcated, representing the pulmonary artery. Transposition of the great arteries may be associated with complex cardiac disease that could be detected on the 4-chamber view of the heart. When the 4-chamber view is normal, it is important to identify the crisscross relationship of the outflow tracts. If this is not done, it is important to document that the pulmonary artery bifurcates and originates from the right ventricle. Five short axis views of the heart may be helpful to detect conotruncal abnormalities.

Two patients with spinocerebellar ataxia type 7 presenting with profound binocular visual loss yet minimal ophthalmoscopic findings

PubMed Central

Thurtell, Matthew J.; Fraser, J. Alexander; Bala, Elisa; Tomsak, Robert L.; Biousse, Valérie; Leigh, R. John; Newman, Nancy J.

2010-01-01

We report two patients with genetically-confirmed spinocerebellar ataxia type 7 (SCA-7), who presented with progressive central visual loss and dyschromatopsia. Ocular funduscopic changes were subtle, with only mild retinal artery attenuation and subtle macular changes. Despite this, the electroretinogram (ERG) was abnormal in both patients. Both patients also had slowing of saccades and partially limited ductions, although neither reported diplopia. Although the older patient had cerebellar ataxia, the younger only had an unsteady tandem gait. This constellation of signs should indicate SCA-7 as a diagnostic possibility, and prompt further investigation with ERG and genetic studies. PMID:19726939

CpG Oligonucleotide and Interleukin 2 stimulation enables higher cytogenetic abnormality detection rates than 12-o-tetradecanolyphorbol-13-acetate in Asian patients with B-cell chronic lymphocytic leukemia (B-CLL).

PubMed

Liaw, Fiona Pui San; Lau, Lai Ching; Lim, Alvin Soon Tiong; Lim, Tse Hui; Lee, Geok Yee; Tien, Sim Leng

2014-12-01

The present study was designed to compare abnormality detection rates using DSP30 + IL2 and 12-O-Tetradecanoylphorbol-13-acetate (TPA) in Asian patients with B-CLL. Hematological specimens from 47 patients (29 newly diagnosed, 18 relapsed) were established as 72 h-DSP30 + IL2 and TPA cultures. Standard methods were employed to identify clonal aberrations by conventional cytogenetics (CC). The B-CLL fluorescence in situ hybridization (FISH) panel comprised ATM, CEP12, D13S25, and TP53 probes. DSP30 + IL2 cultures had a higher chromosomal abnormality detection rate (67 %) compared to TPA (44 %, p < 0.001). The mean number of analyzable metaphases and abnormal metaphases per slide was also higher (p < 0.005, p < 0.001, respectively). Culture success rate, percentage of complex karyotype, and percentage of non-clonal abnormal cell were not significantly different (p > 0.05). Thirteen cases with abnormalities were found exclusively in DSP30 + IL2 cultures compared to one found solely in TPA cultures. DSP30 + IL2 cultures were comparable to the FISH panel in detecting 11q-, +12 and 17p- but not 13q-. It also has a predilection for 11q- bearing leukemic cells compared to TPA. FISH had a higher abnormality detection rate (84.1 %) compared to CC (66.0 %) with borderline significance (p = 0.051), albeit limited by its coverage. In conclusion, DSP30 + IL2 showed a higher abnormality detection rate. However, FISH is indispensable to circumvent low mitotic indices and detect subtle abnormalities.

The association of antipsychotic medication and lithium with brain measures in patients with bipolar disorder.

PubMed

Abramovic, Lucija; Boks, Marco P M; Vreeker, Annabel; Bouter, Diandra C; Kruiper, Caitlyn; Verkooijen, Sanne; van Bergen, Annet H; Ophoff, Roel A; Kahn, René S; van Haren, Neeltje E M

2016-11-01

There is evidence that brain structure is abnormal in patients with bipolar disorder. Lithium intake appears to ׳normalise׳ global and local brain volumes, but effects of antipsychotic medication on brain volume or cortical thickness are less clear. Here, we aim to disentangle disease-specific brain deviations from those induced by antipsychotic medication and lithium intake using a large homogeneous sample of patients with bipolar disorder type I. Magnetic resonance imaging brain scans were obtained from 266 patients and 171 control subjects. Subcortical volumes and global and focal cortical measures (volume, thickness, and surface area) were compared between patients and controls. In patients, the association between lithium and antipsychotic medication intake and global, subcortical and cortical measures was investigated. Patients showed significantly larger lateral and third ventricles, smaller total brain, caudate nucleus, and pallidum volumes and thinner cortex in some small clusters in frontal, parietal and cingulate regions as compared with controls. Lithium-free patients had significantly smaller total brain, thalamus, putamen, pallidum, hippocampus and accumbens volumes compared to patients on lithium. In patients, use of antipsychotic medication was related to larger third ventricle and smaller hippocampus and supramarginal cortex volume. Patients with bipolar disorder show abnormalities in total brain, subcortical, and ventricle volume, particularly in the nucleus caudate and pallidum. Abnormalities in cortical thickness were scattered and clusters were relatively small. Lithium-free patients showed more pronounced abnormalities as compared with those on lithium. The associations between antipsychotic medication and brain volume are subtle and less pronounced than those of lithium. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Exercise-induced menstrual dysfunction.

PubMed

Henley, K; Vaitukaitis, J L

1988-01-01

Menstrual cycle changes associated with vigorous exercise can range widely. They may be only subtle abnormalities, ranging from delayed onset of spontaneous menses or anovulatory cycles to loss of spontaneous menses. They may be more serious, however. Significant adverse bone mineral changes, resulting in clinically significant osteoporosis and fractures, may occur concomitantly with exercise-induced menstrual dysfunction.

Characterization of subtle brain abnormalities in a mouse model of Hedgehog pathway antagonist-induced cleft lip and palate.

PubMed

Lipinski, Robert J; Holloway, Hunter T; O'Leary-Moore, Shonagh K; Ament, Jacob J; Pecevich, Stephen J; Cofer, Gary P; Budin, Francois; Everson, Joshua L; Johnson, G Allan; Sulik, Kathleen K

2014-01-01

Subtle behavioral and cognitive deficits have been documented in patient cohorts with orofacial clefts (OFCs). Recent neuroimaging studies argue that these traits are associated with structural brain abnormalities but have been limited to adolescent and adult populations where brain plasticity during infancy and childhood may be a confounding factor. Here, we employed high resolution magnetic resonance microscopy to examine primary brain morphology in a mouse model of OFCs. Transient in utero exposure to the Hedgehog (Hh) signaling pathway antagonist cyclopamine resulted in a spectrum of facial dysmorphology, including unilateral and bilateral cleft lip and palate, cleft of the secondary palate only, and a non-cleft phenotype marked by midfacial hypoplasia. Relative to controls, cyclopamine-exposed fetuses exhibited volumetric differences in several brain regions, including hypoplasia of the pituitary gland and olfactory bulbs, hyperplasia of the forebrain septal region, and expansion of the third ventricle. However, in affected fetuses the corpus callosum was intact and normal division of the forebrain was observed. This argues that temporally-specific Hh signaling perturbation can result in typical appearing OFCs in the absence of holoprosencephaly--a condition classically associated with Hh pathway inhibition and frequently co-occurring with OFCs. Supporting the premise that some forms of OFCs co-occur with subtle brain malformations, these results provide a possible ontological basis for traits identified in clinical populations. They also argue in favor of future investigations into genetic and/or environmental modulation of the Hh pathway in the etiopathogenesis of orofacial clefting.

Altered Cerebellar Organization and Function in Monoamine Oxidase A Hypomorphic Mice

PubMed Central

Alzghoul, Loai; Bortolato, Marco; Delis, Foteini; Thanos, Panayotis K.; Darling, Ryan D.; Godar, Sean C; Zhang, Junlin; Grant, Samuel; Wang, Gene-Jack; Simpson, Kimberly L.; Chen, Kevin; Volkow, Nora D.; Lin, Rick C.S.; Shih, Jean C.

2012-01-01

Monoamine oxidase A (MAO-A) is the key enzyme for the degradation of brain serotonin (5-hydroxytryptamine, 5-HT), norepinephrine (NE) and dopamine (DA). We recently generated and characterized a novel line of MAO-A hypormorphic mice (MAO-ANeo), featuring elevated monoamine levels, social deficits and perseverative behaviors as well as morphological changes in the basolateral amygdala and orbitofrontal cortex. Here we showed that MAO-ANeo mice displayed deficits in motor control, manifested as subtle disturbances in gait, motor coordination, and balance. Furthermore, magnetic resonance imaging of the cerebellum revealed morphological changes and a moderate reduction in the cerebellar size of MAO- ANeo mice compared to wild type (WT) mice. Histological and immunohistochemical analyses using calbindin-D-28k (CB) expression of Purkinje cells revealed abnormal cerebellar foliation with vermal hypoplasia and decreased in Purkinje cell count and their dendritic density in MAO- ANeo mice compared to WT. Our current findings suggest that congenitally low MAO-A activity leads to abnormal development of the cerebellum. PMID:22971542

Office blood pressure, ambulatory blood pressure monitoring, and echocardiographic abnormalities in women with polycystic ovary syndrome: role of obesity and androgen excess.

PubMed

Luque-Ramírez, Manuel; Martí, David; Fernández-Durán, Elena; Alpañés, Macarena; Álvarez-Blasco, Francisco; Escobar-Morreale, Héctor F

2014-03-01

Whether or not blood pressure (BP) and heart function of women with polycystic ovary syndrome (PCOS) are altered remains unclear, albeit subtle abnormalities in the regulation of BP observed in these women might suggest a mild masculinization of their cardiovascular system. To study the influence of obesity and androgen excess on BP and echocardiographic profiles of women with the syndrome, we conducted a cross-sectional case-control study comparing office and ambulatory BP monitoring, as well as echocardiographic assessments, in 63 premenopausal women with the classic phenotype, 33 nonhyperandrogenic women with regular menses, and 25 young men. Forty-nine subjects were lean and 72 had weight excess (body mass index ≥25 kg/m(2)). Participants had no previous history of hypertension and were nonsmokers. Men showed the highest BP readings, and the lowest readings were observed in control women, whereas women with PCOS had intermediate values. Undiagnosed hypertension was more common in subjects with weight excess irrespective of sex and hyperandrogenism. Women with PCOS and weight excess showed frequencies of previously undiagnosed hypertension that were similar to those of men with weight excess and higher than those observed in nonhyperandrogenic women. Lastly, male sex, weight excess and hypertension, the latter in men as well as in women with PCOS, increased left ventricular wall thickness. In summary, our results show that patients with classic PCOS and weight excess frequently have undiagnosed BP abnormalities, leading to target organ damage.

The prevalence of abnormal preoperative neurological examination in Scheuermann kyphosis: correlation with X-ray, magnetic resonance imaging, and surgical outcome.

PubMed

Cho, Woojin; Lenke, Lawrence G; Bridwell, Keith H; Hu, Guangxun; Buchowski, Jacob M; Dorward, Ian G; Pahys, Joshua M; Cho, Samuel K; Kang, Matthew M; Zebala, Lukas P; Koester, Linda A

2014-10-01

Retrospective. The purpose of this study was to report the prevalence of abnormal neurological findings detected by physical examination in Scheuermann kyphosis and to correlate it to radiographs, magnetic resonance imaging (MRI) findings, and results of operative treatment. There have been sporadic reports about abnormal neurological findings in patients with Scheuermann kyphosis. Among 82 patients with Scheuermann kyphosis who underwent corrective surgery, 69 primary cases were selected. Patients' charts were reviewed retrospectively in terms of pre and postoperative neurological examinations. Sensory or motor change was defined as an abnormal neurological examination. Their duration, associated problems, and various parameters on preoperative radiographs and MRI examinations were also measured to search for any atypical findings associated with an abnormal neurological examination. There were 6 cases (9%) (group AbN), with an abnormal neurological examination ranging from severe myelopathy to a subtle change (e.g., sensory paresthesias on trunk). Five patients recovered to a normal neurological examination after corrective surgery. The remaining 1 patient with severe myelopathy also showed marked improvement and was ambulatory unassisted by 2-year follow-up. In patients with a normal neurological examination (group N, n = 63), only 1 patient had neurological sequelae because of anterior spinal artery syndrome after combined anterior-posterior correction. No preoperative radiographical parameters were significantly different between groups. Average age was 21.3 (AbN) and 18.6 (N) years (P = 0.55). Average preoperative T5-12 kyphosis was 69.0° (AbN) and 72.5° (N) (P = 0.61). Forty-two magnetic resonance images were obtained and all showed typical findings of Scheuermann kyphosis. Five patients in the AbN group (1 patient underwent computed tomography/myelography) and 37 patients in the N group underwent an MRI. The prevalence of abnormal neurological findings in Scheuermann kyphosis was 9%, emphasizing the importance of performing a detailed preoperative neurological examination. If congenital stenosis or a herniated thoracic disc is present, myelopathy can occur. No radiographical findings correlated with the abnormal preoperative neurological examinations. A normal MRI can exist in the face of an abnormal neurological examination, and conversely, a normal neurological examination can be seen with an abnormal MRI. Surgery was successful in alleviating abnormal neurological issues. 4.

Linking Essential Tremor to the Cerebellum: Clinical Evidence.

PubMed

Benito-León, Julián; Labiano-Fontcuberta, Andrés

2016-06-01

Essential tremor (ET) might be a family of diseases unified by the presence of kinetic tremor, but also showing etiological, pathological, and clinical heterogeneity. In this review, we will describe the most significant clinical evidence, which suggests that ET is linked to the cerebellum. Data for this review were identified by searching PUBMED (January 1966 to May 2015) crossing the terms "essential tremor" (ET) and "cerebellum," which yielded 201 entries, 11 of which included the term "cerebellum" in the article title. This was supplemented by articles in the author's files that pertained to this topic. The wide spectrum of clinical features of ET that suggest that it originates as a cerebellar or cerebellar outflow problem include the presence of intentional tremor, gait and balance abnormalities, subtle features of dysarthria, and oculomotor abnormalities, as well as deficits in eye-hand coordination, motor learning deficits, incoordination during spiral drawing task, abnormalities in motor timing and visual reaction time, impairment of social abilities, improvement in tremor after cerebellar stroke, efficacy of deep brain stimulation (which blocks cerebellar outflow), and cognitive dysfunction. It is unlikely, however, that cerebellar dysfunction, per se, fully explains ET-associated dementia, because the cognitive deficits that have been described in patients with cerebellar lesions are generally mild. Overall, a variety of clinical findings suggest that in at least a sizable proportion of patients with ET, there is an underlying abnormality of the cerebellum and/or its pathways.

Gastrointestinal obstruction caused by a radiolucent foreign body in a green iguana (Iguana Iguana)

PubMed Central

Büker, Markus; Foldenauer, Ulrike; Simova-Curd, Stefka; Martig, Sandra; Hatt, Jean-Michel

2010-01-01

This report describes an intestinal obstruction in a green iguana (Iguana iguana). The patient was presented with vomiting and subtle signs of abdominal pain. Radiographs and ultrasound imaging did not reveal any abnormalities. A coeliotomy was performed and a 30-cm piece of absorbent cotton was removed surgically from the large intestine. PMID:20676294

A myelin gene causative of a catatonia-depression syndrome upon aging

PubMed Central

Hagemeyer, Nora; Goebbels, Sandra; Papiol, Sergi; Kästner, Anne; Hofer, Sabine; Begemann, Martin; Gerwig, Ulrike C; Boretius, Susann; Wieser, Georg L; Ronnenberg, Anja; Gurvich, Artem; Heckers, Stephan H; Frahm, Jens; Nave, Klaus-Armin; Ehrenreich, Hannelore

2012-01-01

Severe mental illnesses have been linked to white matter abnormalities, documented by postmortem studies. However, cause and effect have remained difficult to distinguish. CNP (2′,3′-cyclic nucleotide 3′-phosphodiesterase) is among the oligodendrocyte/myelin-associated genes most robustly reduced on mRNA and protein level in brains of schizophrenic, bipolar or major depressive patients. This suggests that CNP reduction might be critical for a more general disease process and not restricted to a single diagnostic category. We show here that reduced expression of CNP is the primary cause of a distinct behavioural phenotype, seen only upon aging as an additional ‘pro-inflammatory hit’. This phenotype is strikingly similar in Cnp heterozygous mice and patients with mental disease carrying the AA genotype at CNP SNP rs2070106. The characteristic features in both species with their partial CNP ‘loss-of-function’ genotype are best described as ‘catatonia-depression’ syndrome. As a consequence of perturbed CNP expression, mice show secondary low-grade inflammation/neurodegeneration. Analogously, in man, diffusion tensor imaging points to axonal loss in the frontal corpus callosum. To conclude, subtle white matter abnormalities inducing neurodegenerative changes can cause/amplify psychiatric diseases. PMID:22473874

The Association of PTSD Symptom Severity with Localized Hippocampus and Amygdala Abnormalities

PubMed Central

Akiki, Teddy J.; Averill, Christopher L.; Wrocklage, Kristen M.; Schweinsburg, Brian; Scott, J. Cobb; Martini, Brenda; Averill, Lynnette A.; Southwick, Steven M.; Krystal, John H.; Abdallah, Chadi G.

2017-01-01

Background The hippocampus and amygdala have been repeatedly implicated in the psychopathology of posttraumatic stress disorder (PTSD). While numerous structural neuroimaging studies examined these two structures in PTSD, these analyses have largely been limited to volumetric measures. Recent advances in vertex-based neuroimaging methods have made it possible to identify specific locations of subtle morphometric changes within a structure of interest. Methods In this cross-sectional study, we used high-resolution magnetic resonance imaging to examine the relationship between PTSD symptomatology, as measured using the Clinician Administered PTSD Scale for the DSM-IV (CAPS), and structural shape of the hippocampus and amygdala using vertex-wise shape analyses in a group of combat-exposed US Veterans (N = 69). Results Following correction for multiple comparisons and controlling for age and cranial volume, we found that participants with more severe PTSD symptoms showed an indentation in the anterior half of the right hippocampus and an indentation in the dorsal region of the right amygdala (corresponding to the centromedial amygdala). Post hoc analysis using stepwise regression suggest that among PTSD symptom clusters, arousal symptoms explain most of the variance in the hippocampal abnormality, whereas re-experiencing symptoms explain most of the variance in the amygdala abnormality. Conclusion The results provide evidence of localized abnormalities in the anterior hippocampus and centromedial amygdala in combat-exposed US Veterans suffering from PTSD symptoms. This novel finding provides a more fine-grained analysis of structural abnormalities in PTSD and may be informative for understanding the neurobiology of the disorder. PMID:28825050

Detection of Cardiac Abnormalities from Multilead ECG using Multiscale Phase Alternation Features.

PubMed

Tripathy, R K; Dandapat, S

2016-06-01

The cardiac activities such as the depolarization and the relaxation of atria and ventricles are observed in electrocardiogram (ECG). The changes in the morphological features of ECG are the symptoms of particular heart pathology. It is a cumbersome task for medical experts to visually identify any subtle changes in the morphological features during 24 hours of ECG recording. Therefore, the automated analysis of ECG signal is a need for accurate detection of cardiac abnormalities. In this paper, a novel method for automated detection of cardiac abnormalities from multilead ECG is proposed. The method uses multiscale phase alternation (PA) features of multilead ECG and two classifiers, k-nearest neighbor (KNN) and fuzzy KNN for classification of bundle branch block (BBB), myocardial infarction (MI), heart muscle defect (HMD) and healthy control (HC). The dual tree complex wavelet transform (DTCWT) is used to decompose the ECG signal of each lead into complex wavelet coefficients at different scales. The phase of the complex wavelet coefficients is computed and the PA values at each wavelet scale are used as features for detection and classification of cardiac abnormalities. A publicly available multilead ECG database (PTB database) is used for testing of the proposed method. The experimental results show that, the proposed multiscale PA features and the fuzzy KNN classifier have better performance for detection of cardiac abnormalities with sensitivity values of 78.12 %, 80.90 % and 94.31 % for BBB, HMD and MI classes. The sensitivity value of proposed method for MI class is compared with the state-of-art techniques from multilead ECG.

High prevalence of subtle and severe menstrual disturbances in exercising women: confirmation using daily hormone measures.

PubMed

De Souza, M J; Toombs, R J; Scheid, J L; O'Donnell, E; West, S L; Williams, N I

2010-02-01

The identification of subtle menstrual cycle disturbances requires daily hormone assessments. In contrast, the identification of severe menstrual disturbances, such as amenorrhea and oligomenorrhea, can be established by clinical observation. The primary purpose of this study was to determine the frequency of subtle menstrual disturbances, defined as luteal phase defects (LPD) or anovulation, in exercising women, with menstrual cycles of 26-35 days, who engage in a variety of sports, both recreational and competitive. Secondly, the prevalence of oligomenorrhea and amenorrhea was also determined via measurement of daily urinary ovarian steroids rather than self report alone. Menstrual status was documented by daily measurements of estrone and pregnanediol glucuronide and luteinizing hormone across two to three consecutive cycles and subsequently categorized as ovulatory (Ovul), LPD, anovulatory (Anov), oligomenorrheic (Oligo) and amenorrheic (Amen) in sedentary (Sed) and exercising (Ex) women. Sed (n = 20) and Ex women (n = 67) were of similar (P > 0.05) age (26.3 +/- 0.8 years), weight (59.3 +/- 1.8 kg), body mass index (22.0 +/- 0.6 kg/m2), age of menarche (12.8 +/- 0.3 years) and gynecological maturity (13.4 +/- 0.9 years). The Sed group exercised less (P < 0.001) (96.7 +/- 39.1 versus 457.1 +/- 30.5 min/week) and had a lower peak oxygen uptake (34.4 +/- 1.4 versus 44.3 +/- 0.6 ml/kg/min) than the Ex group. Among the menstrual cycles studied in the Sed group, the prevalence of subtle menstrual disturbances was only 4.2% (2/48); 95.8% (46/48) of the observed menstrual cycles were ovulatory. This finding stands in stark contrast to that observed in the Ex group where only 50% (60/120) of the observed menstrual cycles were ovulatory and as many as 50% (60/120) were abnormal. Of the abnormal cycles in the Ex group, 29.2% (35/120) were classified as LPD (short, inadequate or both) and 20.8% (25/120) were classified as Anov. Among the cycles of Ex women with severe menstrual disturbances, 3.5% (3/86) of the cycles were Oligo and 33.7% (29/86) were Amen. No cycles of Sed women (0/20) displayed either Oligo or Amen. This study suggests that approximately half of exercising women experience subtle menstrual disturbances, i.e. LPD and anovulation, and that one third of exercising women may be amenorrheic. Estimates of the prevalence of subtle menstrual disturbances in exercising women determined by the presence or absence of short or long cycles does not identify these disturbances. In light of known clinical consequences of menstrual disturbances, these findings underscore the lack of reliability of normal menstrual intervals and self report to infer menstrual status.

Five-year follow-up two-dimensional speckle tracking echocardiography in a juvenile with a double-chambered left ventricle.

PubMed

Harada, Kenji; Mori, Kazuhiro; Ichimiya, Chiyo; Terada, Naho; Iima, Tsutomu; Harada, Takafumi; Fujisawa, Kazutoshi; Kawata, Atsushi; Okada, Ayumi; Yamamoto, Hirofumi; Fujinaga, Hiroyuki

2017-05-01

Double-chambered left ventricle (DCLV) is a particularly rare congenital entity characterized by the presence of two ventricular cavities separated by an abnormal muscle band. An asymptomatic 15-year-old boy was referred to our hospital because of electrocardiographic (ECG) abnormalities. His initial transthoracic echocardiography (TTE) demonstrated a DCLV with mild left ventricular systolic dysfunction. During a 5-year follow-up period, he remained symptom free with no changes in ECG and conventional TTE findings. However, two-dimensional speckle tracking echocardiography revealed a subtle progressive deterioration of left ventricular systolic function during the 5-year follow-up. © 2017, Wiley Periodicals, Inc.

Brain Dysplasia Associated with Ciliary Dysfunction In Infants with Congenital Heart Disease

PubMed Central

Panigrahy, Ashok; Lee, Vincent; Ceschin, Rafael; Zuccoli, Giulio; Beluk, Nancy; Khalifa, Omar; Votava-Smith, Jodie K; DeBrunner, Mark; Munoz, Ricardo; Domnina, Yuliya; Morell, Victor; Wearden, Peter; De Toledo, Joan Sanchez; Devine, William; Zahid, Maliha; Lo, Cecilia W.

2016-01-01

Objective To test for associations between abnormal respiratory ciliary motion (CM) and brain abnormalities in infants with congenital heart disease (CHD) Study design We recruited 35 infants with CHD preoperatively and performed nasal tissue biopsy to assess respiratory CM by videomicroscopy. Cranial ultrasound and brain magnetic resonance imaging were obtained pre- and/or post-operatively and systematically reviewed for brain abnormalities. Segmentation was used to quantitate cerebrospinal fluid and regional brain volumes. Perinatal and perioperative clinical variables were collected. Results A total of 10 (28.5%) patients with CHD had abnormal CM. Abnormal CM was not associated with brain injury, but was correlated with increased extra-axial CSF volume (p<0.001), delayed brain maturation (p<0.05), and a spectrum of subtle dysplasia including the hippocampus (p<0.0078) and olfactory bulb (p<0.034). Abnormal CM was associated with higher composite dysplasia score (p<0.001) and both were correlated with elevated pre-operative serum lactate (p <0.001). Conclusion Abnormal respiratory CM in infants with CHD is associated with a spectrum of brain dysplasia. These findings suggest that ciliary defects may play a role in brain dysplasia in patients with CHD and have the potential to prognosticate neurodevelopmental risks. PMID:27574995

Preliminary evidence of cognitive and brain abnormalities in uncomplicated adolescent obesity.

PubMed

Yau, Po Lai; Kang, Esther H; Javier, David C; Convit, Antonio

2014-08-01

To ascertain whether pediatric obesity without clinically significant insulin resistance (IR) impacts brain structure and function. Thirty obese and 30 matched lean adolescents, all without clinically significant IR or a diagnosis of metabolic syndrome (MetS), received comprehensive endocrine, neuropsychological, and MRI evaluations. Relative to lean adolescents, obese non-IR adolescents had significantly lower academic achievement (i.e., arithmetic and spelling) and tended to score lower on working memory, attention, psychomotor efficiency, and mental flexibility. In line with our prior work on adolescent MetS, memory was unaffected in uncomplicated obesity. Reductions in the thickness of the orbitofrontal and anterior cingulate cortices as well as reductions of microstructural integrity in major white matter tracts without gross volume changes were also uncovered. It was documented, for the first time, that adolescents with uncomplicated obesity already have subtle brain alterations and lower performance in selective cognitive domains. When interpreting these preliminary data in the context of our prior reports of similar, but more extensive brain findings in obese adolescents with MetS and T2DM, it was concluded that "uncomplicated" obesity may also result in subtle brain alterations, suggesting a possible dose effect with more severe metabolic dysregulation giving rise to greater abnormalities. Copyright © 2014 The Obesity Society.

Evaluation of hematological and biochemical parameters of pesticide retailers following occupational exposure to a mixture of pesticides.

PubMed

Neghab, Masoud; Jalilian, Hamed; Taheri, Shekoufeh; Tatar, Mohsen; Haji Zadeh, Zeynab

2018-06-01

This study was undertaken to ascertain whether light occupational exposure to pesticides by retailers might be associated with any liver, kidney, nervous system dysfunction or hematological abnormalities. In this cross-sectional study, 70 male pesticide retailers (cases) and 64 male subjects, randomly selected from the constructions workers of city council contractors, as the referent group, were investigated. Urine and blood samples were taken from all subjects for urine analysis, hematological and biochemical parameters. Data analysis was conducted through SPSS v.19 using t-test and chi-square test. The results of urine analysis showed that the frequency of abnormal urine tests was significantly higher in cases than in referent individuals. Similarly, the results of CBC showed that the mean values of monocyte, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin and platelet distribution width were significantly lower, and mean corpuscular hemoglobin concentration and red blood cell distribution width were significantly higher in retailers. No significant differences were found for other parameters. These findings indicate that an association exists between exposure to pesticides by retailers and early subtle and sub-clinical changes in the urine tests and hematological parameters. Engineering measures are recommended to eliminate exposure to pesticides and to prevent its associated outcomes. Copyright © 2018 Elsevier Inc. All rights reserved.

Abnormalities in metabolite concentrations in tourette's disorder and obsessive-compulsive disorder-A proton magnetic resonance spectroscopy study.

PubMed

Fan, Siyan; Cath, Danielle C; van den Heuvel, Odile A; van der Werf, Ysbrand D; Schöls, Caroline; Veltman, Dick J; Pouwels, Petra J W

2017-03-01

Abnormal glutamatergic transmission in cortico-striato-thalamo-cortical (CSTC) circuits is thought to be involved in the pathophysiology of Tourette's disorder (TD) and obsessive-compulsive disorder (OCD). Using proton magnetic resonance spectroscopy, the current study aimed to investigate regional concentrations of glutamatergic compounds in TD and OCD patients in comparison to healthy control subjects (HC). Twenty-three TD patients, 20 OCD patients and 22 HC were included. Short echo-time single-voxel 3T MRS was obtained from dorsal anterior cingulate cortex (dACC) and midline bilateral thalamus. The 3-group comparison showed a significant difference in choline concentration in the thalamus. Thalamic choline was highest in OCD patients, showing a significant difference with TD, and a trend compared to HC (post-hoc analyses). Glutamine in dACC correlated negatively with tic severity scores in TD patients, while glutamate in thalamus correlated positively with anxiety severity scores in OCD patients. These findings suggest subtle differences in metabolites in CSTC areas between TD and OCD. Alterations of choline concentrations seem to be both regional (only in thalamus, not in dACC) and disease specific in OCD pathology. The findings need replication in larger groups, but encourage further research into glutamatergic metabolites in TD and OCD. Copyright © 2017 Elsevier Ltd. All rights reserved.

The posterolateral corner of the knee.

PubMed

Vinson, Emily N; Major, Nancy M; Helms, Clyde A

2008-02-01

The purpose of this article is to review the clinical importance and MRI appearances of injuries to the posterolateral corner of the knee. Injuries to the posterolateral corner structures of the knee can cause significant disability due to instability, cartilage degeneration, and cruciate graft failure. Becoming familiar with the anatomy of this region can improve one's ability to detect subtle abnormalities and can perhaps lead to improvements in diagnosing and understanding injuries to this area.

Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3.

PubMed

Wang, Xiaoming; McCoy, Portia A; Rodriguiz, Ramona M; Pan, Yanzhen; Je, H Shawn; Roberts, Adam C; Kim, Caroline J; Berrios, Janet; Colvin, Jennifer S; Bousquet-Moore, Danielle; Lorenzo, Isabel; Wu, Gangyi; Weinberg, Richard J; Ehlers, Michael D; Philpot, Benjamin D; Beaudet, Arthur L; Wetsel, William C; Jiang, Yong-Hui

2011-08-01

SHANK3 is a synaptic scaffolding protein enriched in the postsynaptic density (PSD) of excitatory synapses. Small microdeletions and point mutations in SHANK3 have been identified in a small subgroup of individuals with autism spectrum disorder (ASD) and intellectual disability. SHANK3 also plays a key role in the chromosome 22q13.3 microdeletion syndrome (Phelan-McDermid syndrome), which includes ASD and cognitive dysfunction as major clinical features. To evaluate the role of Shank3 in vivo, we disrupted major isoforms of the gene in mice by deleting exons 4-9. Isoform-specific Shank3(e4-9) homozygous mutant mice display abnormal social behaviors, communication patterns, repetitive behaviors and learning and memory. Shank3(e4-9) male mice display more severe impairments than females in motor coordination. Shank3(e4-9) mice have reduced levels of Homer1b/c, GKAP and GluA1 at the PSD, and show attenuated activity-dependent redistribution of GluA1-containing AMPA receptors. Subtle morphological alterations in dendritic spines are also observed. Although synaptic transmission is normal in CA1 hippocampus, long-term potentiation is deficient in Shank3(e4-9) mice. We conclude that loss of major Shank3 species produces biochemical, cellular and morphological changes, leading to behavioral abnormalities in mice that bear similarities to human ASD patients with SHANK3 mutations.

Increased intrapulmonary retention of radiolabeled neutrophils in early oxygen toxicity

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

Rinaldo, J.E.; English, D.; Levine, J.

1988-02-01

Sequential lung injuries, such as oxygen toxicity followed by septicemia, are common during the adult respiratory distress syndrome (ARDS). As these forms of vascular injury may be mediated in part by polymorphonuclear leukocytes (PMN), aberrant interactions between PMN and previously injured pulmonary endothelium are of both theoretical interest and clinical importance. The present study was undertaken to test the hypothesis that early oxygen toxicity at a dose that injuries pulmonary endothelium relatively selectively alters intrapulmonary neutrophil kinetics. Unanesthetized rats breathing 1.0 atmospheres oxygen for 36 h showed ultrastructural endothelial damage but no edema, injury, or neutrophilic inflammation by histologic criteria.more » However, in these oxygen-toxic animals, whereas initial accumulation of radiolabeled PMN in lungs was normal, washout of PMN was abnormal at 120 min after infusion, at which point the pulmonary retention of radiolabeled PMN in the lungs of oxygen-treated animals was significantly higher than in control animals (139% of control, p less than 0.0096). Features of our methodology, including avoidance of osmotic stress and use of paired control animals, appear to have greatly enhanced the sensitivity of radiolabeled neutrophils for detecting a subtle abnormality of neutrophil-endothelial interactions. Our studies in the oxygen toxicity model provide the first demonstration in vivo of abnormal intrapulmonary neutrophil kinetics in early oxygen toxicity prior to the onset of histologic evidence of lung injury or inflammation.« less

Evaluation of coronal shift as an indicator of neuroaxial abnormalities in adolescent idiopathic scoliosis: a prospective study

PubMed Central

2014-01-01

Background In previous studies, many indicator factors have been proposed to select patients who need an MRI screening of the spinal canal. In current study, the clinical and radiologic factors including coronal parameters of the curve were evaluated to find out which indicator is more important. Methods A prospective study included 143 consecutive patients with the diagnosis of adolescent idiopathic scoliosis who were treated between 2010 and 2013 at our spinal clinics. Only patients with normal or subtle neurologic findings were included. All patients were evaluated by a total spine MRI protocol for examination of neuroaxial abnormalities. Known indicators and also coronal shift were analysed in all patients with or without abnormal MRI. Results The incidence of neuroaxial abnormalities was 11.9% (17 of 143); only 5 patients (3.5%) were operated to treat their neuroaxial problem. The significant indicators of the abnormalities in our patients were: younger age at onset, asymmetric superficial abdominal reflex and, coronal shift more than 15 mm (P = 0.03). Some previously known indicators like atypical curves, male gender, double curves and absence of thoracic lordosis were not different between two groups of the patients. Conclusions A total spine MRI is recommended at presentation in patients with younger age, abnormal neurologic findings and severe coronal shift. PMID:25071863

[A case of mosaic ring chromosome 4 with subtelomeric 4p deletion].

PubMed

Kim, Jeong Hyun; Oh, Phil Soo; Na, Hye Yeon; Kim, Sun-Hee; Cho, Hyoun Chan

2009-02-01

Ring chromosome is a structural abnormality that is thought to be the result of fusion and breakage in the short and long arms of chromosome. Wolf-Hirschhorn syndrome (WHS) is a well-known congenital anomaly in the ring chromosome 4 with a partial deletion of the distal short arm. Here we report a 10-month-old male of mosaic ring chromosome 4 with the chief complaint of severe short stature. He showed the height of -4 standard deviation, subtle hypothyroidism and mild atrial septal defect/ventricular septal defect, and also a mild language developmental delay was suspected. Brain magnetic resonance imaging showed multifocal leukomalacia. Chromosomal analysis of the peripheral blood showed the mosaic karyotype with [46,XY,r(4)(p16q35)[84]/45,XY,-4[9]/91,XXYY, dic r(4;4)(p16q35;p16q35)[5]/46,XY,dic r(4;4)(p16q35;p16q35)[2

Early abnormalities of cardiovascular structure and function in middle-aged Korean adults with prehypertension: The Korean Genome Epidemiology study.

PubMed

Kim, Seong Hwan; Cho, Goo-Yeong; Baik, Inkyung; Lim, Sang Yup; Choi, Cheol Ung; Lim, Hong Euy; Kim, Eung Ju; Park, Chang Gyu; Park, Juri; Kim, Jinyoung; Shin, Chol

2011-02-01

Prehypertension is associated with increased cardiovascular morbidity and mortality. However, there are few population-based studies on the changes of cardiovascular structure and function that characterize prehypertension. The aim of this study was to assess whether prehypertension is associated with abnormalities of cardiovascular structure and function in the general Korean population. We analyzed the cross-sectional relationships between prehypertension and cardiovascular structure and function in a sample from the Korean Genome Epidemiology Study. A total of 1,671 individuals (54.5% women; mean age: 53 ± 6 years) without hypertension and diabetes mellitus were enrolled. Cardiovascular structure and function were assessed by conventional echocardiography, tissue Doppler imaging (TDI), carotid ultrasonography, and pulse wave velocity (PWV). The left ventricular (LV) mass index was significantly higher in subjects with prehypertension than in those with normotension (41 ± 8 g/m²·⁷ vs. 38 ± 7 g/m²·⁷, P < 0.001). LV diastolic parameters, such as the E/A ratio, TDI E(a) velocity, and E/E(a) ratio, were also impaired in subjects with prehypertension (all P < 0.001). Compared with normotension, prehypertension was characterized by a significantly higher common carotid artery intima-media thickness and a higher brachial-ankle PWV (all P < 0.001). These abnormalities of cardiovascular structure and function remained significant after adjustment for covariates. In this population-based cohort, we found that subtle alterations in cardiovascular structure and function were already present at the prehypertensive stage. Whether such subtle alterations convey an increased risk of cardiovascular events and whether the changes are reversible with treatment warrant further study.

De novo status epilepticus with isolated aphasia.

PubMed

Flügel, Dominique; Kim, Olaf Chan-Hi; Felbecker, Ansgar; Tettenborn, Barbara

2015-08-01

Sudden onset of aphasia is usually due to stroke. Rapid diagnostic workup is necessary if reperfusion therapy is considered. Ictal aphasia is a rare condition but has to be excluded. Perfusion imaging may differentiate acute ischemia from other causes. In dubious cases, EEG is required but is time-consuming and laborious. We report a case where we considered de novo status epilepticus as a cause of aphasia without any lesion even at follow-up. A 62-year-old right-handed woman presented to the emergency department after nurses found her aphasic. She had undergone operative treatment of varicosis 3 days earlier. Apart from hypertension and obesity, no cardiovascular risk factors and no intake of medication other than paracetamol were reported. Neurological examination revealed global aphasia and right pronation in the upper extremity position test. Computed tomography with angiography and perfusion showed no abnormalities. Electroencephalogram performed after the CT scan showed left-sided slowing with high-voltage rhythmic 2/s delta waves but no clear ictal pattern. Intravenous lorazepam did improve EEG slightly, while aphasia did not change. Lumbar puncture was performed which likely excluded encephalitis. Magnetic resonance imaging showed cortical pathological diffusion imaging (restriction) and cortical hyperperfusion in the left parietal region. Intravenous anticonvulsant therapy under continuous EEG resolved neurological symptoms. The patient was kept on anticonvulsant therapy. Magnetic resonance imaging after 6 months showed no abnormalities along with no clinical abnormalities. Magnetic resonance imaging findings were only subtle, and EEG was without clear ictal pattern, so the diagnosis of aphasic status remains with some uncertainty. However, status epilepticus can mimic stroke symptoms and has to be considered in patients with aphasia even when no previous stroke or structural lesions are detectable and EEG shows no epileptic discharges. Epileptic origin is favored when CT or MR imaging reveal no hypoperfusion. In this case, MRI was superior to CT in detecting hyperperfusion. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.

Profound microcephaly, primordial dwarfism with developmental brain malformations: a new syndrome.

PubMed

Abdel-Salam, Ghada M H; Abdel-Hamid, Mohamed S; Saleem, Sahar N; Ahmed, Mahmoud K H; Issa, Mahmoud; Effat, Laila K; Kayed, Hisham F; Zaki, Maha S; Gaber, Khaled R

2012-08-01

We describe two sibs with a lethal form of profound congenital microcephaly, intrauterine and postnatal growth retardation, subtle skeletal changes, and poorly developed brain. The sibs had striking absent cranial vault with sloping of the forehead, large beaked nose, relatively large ears, and mandibular micro-retrognathia. Brain magnetic resonance imaging (MRI) revealed extremely simplified gyral pattern, large interhemispheric cyst and agenesis of corpus callosum, abnormally shaped hippocampus, and proportionately affected cerebellum and brainstem. In addition, fundus examination showed foveal hypoplasia with optic nerve atrophy. No abnormalities of the internal organs were found. This profound form of microcephaly was identified at 17 weeks gestation by ultrasound and fetal brain MRI helped in characterizing the developmental brain malformations in the second sib. Molecular analysis excluded mutations in potentially related genes such as RNU4ATAC, SLC25A19, and ASPM. These clinical and imaging findings are unlike that of any recognized severe forms of microcephaly which is believed to be a new microcephalic primordial dwarfism (MPD) with developmental brain malformations with most probably autosomal recessive inheritance based on consanguinity and similarly affected male and female sibs. Copyright © 2012 Wiley Periodicals, Inc.

Saccade and cognitive impairment associated with kava intoxication.

PubMed

Cairney, Sheree; Maruff, Paul; Clough, Alan R; Collie, Alex; Currie, Jon; Currie, Bart J

2003-10-01

Kava is an extract from the Piper methysticum Forst. f. plant that has social and spiritual importance in Pacific islands societies. Herbal remedies that contain kava are used for the psychiatric treatment of anxiety and insomnia. Laboratory studies have found only subtle, if any, changes on cognitive or motor functions from the acute effects of consuming small clinical doses of kava products. Intoxication from recreational doses of kava has not been studied. The performance of individuals intoxicated from drinking kava (n=11) was compared with a control group (n=17) using saccade and cognitive tests. On average, intoxicated individuals had consumed 205 g of kava powder each (approximately 150 times clinical doses) in a group session that went for 14.4 h and ended 8 h prior to testing. Intoxicated kava drinkers showed ataxia, tremors, sedation, blepharospasm and elevated liver enzymes (GGT and ALP), together with saccadic dysmetria, saccadic slowing and reduced accuracy performing a visual search task that only became evident as the task complexity increased. Kava intoxication is characterized by specific abnormalities of movement coordination and visual attention but normal performance of complex cognitive functions. Saccade abnormalities suggest disruption of cerebellar and GABAergic functions. Copyright 2003 John Wiley & Sons, Ltd.

Prenatal diagnosis of brain abnormalities in Wolf-Hirschhorn (4p-) syndrome.

PubMed

De Keersmaecker, B; Albert, M; Hillion, Y; Ville, Y

2002-05-01

Although there have been occasional reports of prenatal diagnosis of this syndrome, most cases are diagnosed postnatally. The objective was to evaluate the presence of brain abnormalities in the prenatal diagnosis of Wolf-Hirschhorn syndrome. Prenatal ultrasound and MRI examination of the fetal brain were performed in a case of Wolf-Hirschhorn syndrome. A comprehensive review of Wolf-Hirschhorn syndrome reported between 1960 and 2000 in the literature was carried out. The late diagnosis of a growth-retarded fetus with normal amniotic fluid volume, normal Doppler and negative infection screen calls for a detailed examination of the fetal brain and heart. Multifocal white matter lesions and periventricular cystic changes, which are often attributed to perinatal distress, are possible prenatal features causing suspicion of 4p- syndrome in an IUGR fetus. Subtle abnormalities on ultrasound may suggest a chromosomal problem. Standard cytogenetics cannot always demonstrate a microdeletion. High-resolution banding and molecular analysis can help to confirm the diagnosis. Copyright 2002 John Wiley & Sons, Ltd.

Interstitial 1q21.1 Microdeletion Is Associated with Severe Skeletal Anomalies, Dysmorphic Face and Moderate Intellectual Disability.

PubMed

Gamba, Bruno F; Zechi-Ceide, Roseli M; Kokitsu-Nakata, Nancy M; Vendramini-Pittoli, Siulan; Rosenberg, Carla; Krepischi Santos, Ana C V; Ribeiro-Bicudo, Lucilene; Richieri-Costa, Antonio

2016-11-01

We report on a Brazilian patient with a 1.7-Mb interstitial microdeletion in chromosome 1q21.1. The phenotypic characteristics include microcephaly, a peculiar facial gestalt, cleft lip/palate, and multiple skeletal anomalies represented by malformed phalanges, scoliosis, abnormal modeling of vertebral bodies, hip dislocation, abnormal acetabula, feet anomalies, and delayed neuropsychological development. Deletions reported in this region are clinically heterogeneous, ranging from subtle phenotypic manifestations to severe congenital heart defects and/or neurodevelopmental findings. A few genes within the deleted region are associated with congenital anomalies, mainly the RBM8A , DUF1220 , and HYDIN2 paralogs. Our patient presents with a spectrum of unusual malformations of 1q21.1 deletion syndrome not reported up to date.

Interstitial 1q21.1 Microdeletion Is Associated with Severe Skeletal Anomalies, Dysmorphic Face and Moderate Intellectual Disability

PubMed Central

Gamba, Bruno F.; Zechi-Ceide, Roseli M.; Kokitsu-Nakata, Nancy M.; Vendramini-Pittoli, Siulan; Rosenberg, Carla; Krepischi Santos, Ana C.V.; Ribeiro-Bicudo, Lucilene; Richieri-Costa, Antonio

2016-01-01

We report on a Brazilian patient with a 1.7-Mb interstitial microdeletion in chromosome 1q21.1. The phenotypic characteristics include microcephaly, a peculiar facial gestalt, cleft lip/palate, and multiple skeletal anomalies represented by malformed phalanges, scoliosis, abnormal modeling of vertebral bodies, hip dislocation, abnormal acetabula, feet anomalies, and delayed neuropsychological development. Deletions reported in this region are clinically heterogeneous, ranging from subtle phenotypic manifestations to severe congenital heart defects and/or neurodevelopmental findings. A few genes within the deleted region are associated with congenital anomalies, mainly the RBM8A, DUF1220, and HYDIN2 paralogs. Our patient presents with a spectrum of unusual malformations of 1q21.1 deletion syndrome not reported up to date. PMID:27920638

Neonatal brain resting-state functional connectivity imaging modalities.

PubMed

Mohammadi-Nejad, Ali-Reza; Mahmoudzadeh, Mahdi; Hassanpour, Mahlegha S; Wallois, Fabrice; Muzik, Otto; Papadelis, Christos; Hansen, Anne; Soltanian-Zadeh, Hamid; Gelovani, Juri; Nasiriavanaki, Mohammadreza

2018-06-01

Infancy is the most critical period in human brain development. Studies demonstrate that subtle brain abnormalities during this state of life may greatly affect the developmental processes of the newborn infants. One of the rapidly developing methods for early characterization of abnormal brain development is functional connectivity of the brain at rest. While the majority of resting-state studies have been conducted using magnetic resonance imaging (MRI), there is clear evidence that resting-state functional connectivity (rs-FC) can also be evaluated using other imaging modalities. The aim of this review is to compare the advantages and limitations of different modalities used for the mapping of infants' brain functional connectivity at rest. In addition, we introduce photoacoustic tomography, a novel functional neuroimaging modality, as a complementary modality for functional mapping of infants' brain.

DNA methylation patterns in tissues from mid-gestation bovine foetuses produced by somatic cell nuclear transfer show subtle abnormalities in nuclear reprogramming.

PubMed

Couldrey, Christine; Lee, Rita Sf

2010-03-07

Cloning of cattle by somatic cell nuclear transfer (SCNT) is associated with a high incidence of pregnancy failure characterized by abnormal placental and foetal development. These abnormalities are thought to be due, in part, to incomplete re-setting of the epigenetic state of DNA in the donor somatic cell nucleus to a state that is capable of driving embryonic and foetal development to completion. Here, we tested the hypothesis that DNA methylation patterns were not appropriately established during nuclear reprogramming following SCNT. A panel of imprinted, non-imprinted genes and satellite repeat sequences was examined in tissues collected from viable and failing mid-gestation SCNT foetuses and compared with similar tissues from gestation-matched normal foetuses generated by artificial insemination (AI). Most of the genomic regions examined in tissues from viable and failing SCNT foetuses had DNA methylation patterns similar to those in comparable tissues from AI controls. However, statistically significant differences were found between SCNT and AI at specific CpG sites in some regions of the genome, particularly those associated with SNRPN and KCNQ1OT1, which tended to be hypomethylated in SCNT tissues. There was a high degree of variation between individuals in methylation levels at almost every CpG site in these two regions, even in AI controls. In other genomic regions, methylation levels at specific CpG sites were tightly controlled with little variation between individuals. Only one site (HAND1) showed a tissue-specific pattern of DNA methylation. Overall, DNA methylation patterns in tissues of failing foetuses were similar to apparently viable SCNT foetuses, although there were individuals showing extreme deviant patterns. These results show that SCNT foetuses that had developed to mid-gestation had largely undergone nuclear reprogramming and that the epigenetic signature at this stage was not a good predictor of whether the foetus would develop to term or not.

DNA methylation patterns in tissues from mid-gestation bovine foetuses produced by somatic cell nuclear transfer show subtle abnormalities in nuclear reprogramming

PubMed Central

2010-01-01

Background Cloning of cattle by somatic cell nuclear transfer (SCNT) is associated with a high incidence of pregnancy failure characterized by abnormal placental and foetal development. These abnormalities are thought to be due, in part, to incomplete re-setting of the epigenetic state of DNA in the donor somatic cell nucleus to a state that is capable of driving embryonic and foetal development to completion. Here, we tested the hypothesis that DNA methylation patterns were not appropriately established during nuclear reprogramming following SCNT. A panel of imprinted, non-imprinted genes and satellite repeat sequences was examined in tissues collected from viable and failing mid-gestation SCNT foetuses and compared with similar tissues from gestation-matched normal foetuses generated by artificial insemination (AI). Results Most of the genomic regions examined in tissues from viable and failing SCNT foetuses had DNA methylation patterns similar to those in comparable tissues from AI controls. However, statistically significant differences were found between SCNT and AI at specific CpG sites in some regions of the genome, particularly those associated with SNRPN and KCNQ1OT1, which tended to be hypomethylated in SCNT tissues. There was a high degree of variation between individuals in methylation levels at almost every CpG site in these two regions, even in AI controls. In other genomic regions, methylation levels at specific CpG sites were tightly controlled with little variation between individuals. Only one site (HAND1) showed a tissue-specific pattern of DNA methylation. Overall, DNA methylation patterns in tissues of failing foetuses were similar to apparently viable SCNT foetuses, although there were individuals showing extreme deviant patterns. Conclusion These results show that SCNT foetuses that had developed to mid-gestation had largely undergone nuclear reprogramming and that the epigenetic signature at this stage was not a good predictor of whether the foetus would develop to term or not. PMID:20205951

Status and future concerns of clinical and environmental aluminum toxicology.

PubMed

Flaten, T P; Alfrey, A C; Birchall, J D; Savory, J; Yokel, R A

1996-08-30

A wide range of toxic effects of aluminum (Al) have been demonstrated in plants and aquatic animals in nature, in experimental animals by several routes of exposure, and under different clinical conditions in humans. Aluminum toxicity is a major problem in agriculture, affecting perhaps as much as 40% of arable soils in the world. In fresh waters acidified by acid rain, Al toxicity has led to fish extinction. Aluminum is a very potent neurotoxicant. In humans with chronic renal failure on dialysis, Al causes encephalopathy, osteomalacia, and anemia. There are also reports of such effects in certain patient groups without renal failure. Subtle neurocognitive and psychomotor effects and electroencephalograph (EEG) abnormalities have been reported at plasma Al levels as low as 50 micrograms/L. Infants could be particularly susceptible to Al accumulation and toxicity, reduced renal function being one contributory cause. Recent reports clearly show that Al accumulation occurs in the tissues of workers with long-term occupational exposure to Al dusts or fumes, and also indicate that such exposure may cause subtle neurological effects. Increased efforts should be directed toward defining the full range of potentially harmful effects in humans. To this end, multidisciplinary collaborative research efforts are encouraged, involving scientists from many different specialties. Emphasis should be placed on increasing our understanding of the chemistry of Al in biological systems, and on determining the cellular and molecular mechanisms of Al toxicity.

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

Neurodevelopmental outcome in isolated mild fetal ventriculomegaly: systematic review and meta-analysis.

PubMed

Pagani, G; Thilaganathan, B; Prefumo, F

2014-09-01

The finding of fetal ventriculomegaly is variably associated with other fetal abnormalities and, even when isolated, is thought to be linked to abnormal neurodevelopmental outcome. The aim of this study was to undertake a systematic review and meta-analysis of the current literature to assess the prevalence of neurodevelopmental delay in cases of isolated mild fetal ventriculomegaly, as well as the false-negative rate of prenatal imaging for the diagnosis of associated abnormalities in patients referred for isolated mild ventriculomegaly. Studies that assessed neurodevelopmental outcome in isolated ventriculomegaly were identified from a search of scientific databases. Studies that did not check for karyotype or that excluded cases of bilateral ventriculomegaly were not included in the analysis. Ventriculomegaly was defined as mild when the width of the ventricular atrium was between 10 and 15 mm. Cases in which an associated abnormality (abnormal karyotype, structural abnormality or fetal infection) was observed either before or after birth were not considered as part of the isolated group. Neurodevelopmental delay was defined as an abnormal quotient score, according to the test used. The search yielded 961 possible citations; of these, 904 were excluded by review of the title or abstract as they did not meet the selection criteria. Full manuscripts were retrieved for 57 studies, and 20 were included in the review with a total of 699 cases of isolated mild ventriculomegaly. The overall prevalence of neurodevelopmental delay was 7.9% (95% CI, 4.7-11.1%). Of the 20 studies included in the systematic review, nine reported data on postnatal imaging, showing a prevalence of previously undiagnosed findings of 7.4% (95% CI, 3.1-11.8%). The false-negative rate of prenatal imaging is 7.4% in apparently isolated fetal ventriculomegaly of ≤ 15 mm. The incidence of neurodevelopmental delay in truly isolated ventriculomegaly of ≤ 15 mm is 7.9%. As the latter rate is similar to that noted in the general population, large prospective cohort studies assessing the prevalence of childhood disability, rather than subtle neurodevelopmental delay, are required. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Encoding-related brain activity and accelerated forgetting in transient epileptic amnesia.

PubMed

Atherton, Kathryn E; Filippini, Nicola; Zeman, Adam Z J; Nobre, Anna C; Butler, Christopher R

2018-05-17

The accelerated forgetting of newly learned information is common amongst patients with epilepsy and, in particular, in the syndrome of transient epileptic amnesia (TEA). However, the neural mechanisms underlying accelerated forgetting are poorly understood. It has been hypothesised that interictal epileptiform activity during longer retention intervals disrupts normally established memory traces. Here, we tested a distinct hypothesis-that accelerated forgetting relates to the abnormal encoding of memories. We studied a group of 15 patients with TEA together with matched, healthy control subjects. Despite normal performance on standard anterograde memory tasks, patients showed accelerated forgetting of a word list over one week. We used a subsequent memory paradigm to compare encoding-related brain activity in patients and controls. Participants studied a series of visually presented scenes whilst undergoing functional MRI scanning. Recognition memory for these scenes was then probed outside the scanner after delays of 45 min and of 4 days. Patients showed poorer memory for the scenes compared with controls. In the patients but not the controls, subsequently forgotten stimuli were associated with reduced hippocampal activation at encoding. Furthermore, patients demonstrated reduced deactivation of posteromedial cortex regions upon viewing subsequently remembered stimuli as compared to subsequently forgotten ones. These data suggest that abnormal encoding-related activity in key memory areas of the brain contributes to accelerated forgetting in TEA. We propose that abnormally encoded memory traces may be particularly vulnerable to interference from subsequently encountered material and hence be forgotten more rapidly. Our results shed light on the mechanisms underlying memory impairment in epilepsy, and offer support to the proposal that accelerated forgetting may be a useful marker of subtle dysfunction in memory-related brain systems. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Atypical face shape and genomic structural variants in epilepsy

PubMed Central

Chinthapalli, Krishna; Bartolini, Emanuele; Novy, Jan; Suttie, Michael; Marini, Carla; Falchi, Melania; Fox, Zoe; Clayton, Lisa M. S.; Sander, Josemir W.; Guerrini, Renzo; Depondt, Chantal; Hennekam, Raoul; Hammond, Peter

2012-01-01

Many pathogenic structural variants of the human genome are known to cause facial dysmorphism. During the past decade, pathogenic structural variants have also been found to be an important class of genetic risk factor for epilepsy. In other fields, face shape has been assessed objectively using 3D stereophotogrammetry and dense surface models. We hypothesized that computer-based analysis of 3D face images would detect subtle facial abnormality in people with epilepsy who carry pathogenic structural variants as determined by chromosome microarray. In 118 children and adults attending three European epilepsy clinics, we used an objective measure called Face Shape Difference to show that those with pathogenic structural variants have a significantly more atypical face shape than those without such variants. This is true when analysing the whole face, or the periorbital region or the perinasal region alone. We then tested the predictive accuracy of our measure in a second group of 63 patients. Using a minimum threshold to detect face shape abnormalities with pathogenic structural variants, we found high sensitivity (4/5, 80% for whole face; 3/5, 60% for periorbital and perinasal regions) and specificity (45/58, 78% for whole face and perinasal regions; 40/58, 69% for periorbital region). We show that the results do not seem to be affected by facial injury, facial expression, intellectual disability, drug history or demographic differences. Finally, we use bioinformatics tools to explore relationships between facial shape and gene expression within the developing forebrain. Stereophotogrammetry and dense surface models are powerful, objective, non-contact methods of detecting relevant face shape abnormalities. We demonstrate that they are useful in identifying atypical face shape in adults or children with structural variants, and they may give insights into the molecular genetics of facial development. PMID:22975390

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

Merwe, Celia van der, E-mail: celiavdm@sun.ac.za; Loos, Ben; Swart, Chrisna

Highlights: • Mitochondrial dysfunction observed in patients with parkin-null mutations. • Mitochondrial ATP levels were decreased. • Electron-dense vacuoles were observed in the patients. • Mitochondria from muscle biopsies appeared within normal limits. • One patient did not show these defects possibly due to compensatory mechanisms. - Abstract: Parkinson’s disease (PD), defined as a neurodegenerative disorder, is characterized by the loss of dopaminergic neurons in the substantia nigra in the midbrain. Loss-of-function mutations in the parkin gene are a major cause of autosomal recessive, early-onset PD. Parkin has been implicated in the maintenance of healthy mitochondria, although previous studies showmore » conflicting findings regarding mitochondrial abnormalities in fibroblasts from patients harboring parkin-null mutations. The aim of the present study was to determine whether South African PD patients with parkin mutations exhibit evidence for mitochondrial dysfunction. Fibroblasts were cultured from skin biopsies obtained from three patients with homozygous parkin-null mutations, two heterozygous mutation carriers and two wild-type controls. Muscle biopsies were obtained from two of the patients. The muscle fibers showed subtle abnormalities such as slightly swollen mitochondria in focal areas of the fibers and some folding of the sarcolemma. Although no differences in the degree of mitochondrial network branching were found in the fibroblasts, ultrastructural abnormalities were observed including the presence of electron-dense vacuoles. Moreover, decreased ATP levels which are consistent with mitochondrial dysfunction were observed in the patients’ fibroblasts compared to controls. Remarkably, these defects did not manifest in one patient, which may be due to possible compensatory mechanisms. These results suggest that parkin-null patients exhibit features of mitochondrial dysfunction. Involvement of mitochondria as a key role player in PD pathogenesis will have important implications for the design of new and more effective therapies.« less

Memory, executive, and multidomain subtle cognitive impairment: clinical and biomarker findings.

PubMed

Toledo, Jon B; Bjerke, Maria; Chen, Kewei; Rozycki, Martin; Jack, Clifford R; Weiner, Michael W; Arnold, Steven E; Reiman, Eric M; Davatzikos, Christos; Shaw, Leslie M; Trojanowski, John Q

2015-07-14

We studied the biomarker signatures and prognoses of 3 different subtle cognitive impairment (SCI) groups (executive, memory, and multidomain) as well as the subjective memory complaints (SMC) group. We studied 522 healthy controls in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Cutoffs for executive, memory, and multidomain SCI were defined using participants who remained cognitively normal (CN) for 7 years. CSF Alzheimer disease (AD) biomarkers, composite and region-of-interest (ROI) MRI, and fluorodeoxyglucose-PET measures were compared in these participants. Using a stringent cutoff (fifth percentile), 27.6% of the ADNI participants were classified as SCI. Most single ROI or global-based measures were not sensitive to detect differences between groups. Only MRI-SPARE-AD (Spatial Pattern of Abnormalities for Recognition of Early AD), a quantitative MRI pattern-based global index, showed differences between all groups, excluding the executive SCI group. Atrophy patterns differed in memory SCI and SMC. The CN and the SMC groups presented a similar distribution of preclinical dementia stages. Fifty percent of the participants with executive, memory, and multidomain SCI progressed to mild cognitive impairment or dementia at 7, 5, and 2 years, respectively. Our results indicate that (1) the different SCI categories have different clinical prognoses and biomarker signatures, (2) longitudinally followed CN subjects are needed to establish clinical cutoffs, (3) subjects with SMC show a frontal pattern of brain atrophy, and (4) pattern-based analyses outperform commonly used single ROI-based neuroimaging biomarkers and are needed to detect initial stages of cognitive impairment. © 2015 American Academy of Neurology.

Mirroring the self: testing neurophysiological correlates of disturbed self-experience in schizophrenia spectrum.

PubMed

Sestito, Mariateresa; Raballo, Andrea; Umiltà, Maria Alessandra; Leuci, Emanuela; Tonna, Matteo; Fortunati, Renata; De Paola, Giancarlo; Amore, Mario; Maggini, Carlo; Gallese, Vittorio

2015-01-01

Self-disorders (SDs) have been described as a core schizophrenia spectrum vulnerability phenotype, both in classic and contemporary psychopathological literature. However, such a core phenotype has not yet been investigated adopting a trans-domain approach that combines the phenomenological and the neurophysiological levels of analysis. The aim of this study is to investigate the relation between SDs and subtle, schizophrenia-specific impairments of emotional resonance that are supposed to reflect abnormalities in the mirror neurons mechanism. Specifically, we tested whether electromyographic response to emotional stimuli (i.e. a proxy for subtle changes in facial mimicry and related motor resonance mechanisms) would predict the occurrence of anomalous subjective experiences (i.e. SDs). Eighteen schizophrenia spectrum (SzSp) patients underwent a comprehensive psychopathological examination and were contextually tested with a multimodal paradigm, recording facial electromyographic activity of muscles in response to positive and negative emotional stimuli. Experiential anomalies were explored with the Bonn Scale for the Assessment of Basic Symptoms (BSABS) and then condensed into rational subscales mapping SzSp anomalous self-experiences. SzSp patients showed an imbalance in emotional motor resonance with a selective bias toward negative stimuli, as well as a multisensory integration impairment. Multiple regression analysis showed that electromyographic facial reactions in response to negative stimuli presented in auditory modality specifically and strongly correlated with SD subscore. The study confirms the potential of SDs as target phenotype for neurobiological research and encourages research into disturbed motor/emotional resonance as possible body-level correlate of disturbed subjective experiences in SzSp.

Holt-Oram syndrome and diaphragmatic hernia associate with paracentric inversion of chromosome 8

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

Eswara, M.S.; Batanian, J.R.

1994-09-01

Holt-Oram syndrome (HOS) consists of congenital heart disease, usually atrial septal defect, along with thumb anomalies and occasionally more extensive limb defects. Inheritance is autosomal dominant. Previous reports have associated HOS with cytogenetic abnormalities on chromosomes 4, 14 and 20. Recently a linkage study has suggested a HOS locus on chromosome 12. We describe another case of HOS with a de novo cytogenetic abnormality. On prenatal ultrasound, IUGR, oligohydramnios and left diaphragmatic hernia were noted. Following delivery, patient was placed on extra-corporeal membrane oxygenation because of severe lung hypoplasia; diaphragmatic hernia was repaired with mesh graft. He expired on daymore » 17 of life. On exam, he had subtle dysmorphic features with hypotelorism and abnormal folding of the ear lobes. He had bilateral radial aplasia, aplasia of thumbs, index and middle fingers, along with the metacarpals. On autopsy he was found to have atrial septal defect of the ostium secundum type, right side aortic arch with vascular ring formation, bicuspid pulmonic valve and severe lung hypoplasia worse on the left. Cytogenetic analysis on blood and skin showed 48,XX,inv(8)(q24.2q13). Chromosome fragility study was negative. Parental chromosomes were normal. Our observation of inv(8)q with HOS and diaphragmatic hernia may indicate genetic heterogeneity with this condition. Regulation of morphogenesis is likely under the control of a hierarchy of genes; multiple loci for conditions such as HOS would not be surprising.« less

Eye movement abnormalities in hermansky-pudlak syndrome.

PubMed

Gradstein, Libe; FitzGibbon, Edmond J; Tsilou, Ekaterini T; Rubin, Benjamin I; Huizing, Marjan; Gahl, William A

2005-08-01

Hermansky-Pudlak Syndrome (HPS) is a type of oculocutaneous albinism associated with a bleeding diathesis and pulmonary fibrosis. Although it is known that patients with HPS exhibit nystagmus, the nature of these abnormal eye movements has not been studied. Twenty-seven patients with HPS, diagnosed by platelet morphology and genetic analysis, underwent a systemic evaluation and complete eye examination. Twenty-five had eye movement recordings using magnetic search coil, infrared, or video oculography. All patients had iris transillumination, foveal hypoplasia, and variable hypopigmentation in skin and eyes. All had bleeding tendencies, and 2 reported excessive bleeding during strabismus surgery. Nine patients had pulmonary fibrosis. Visual acuities ranged from 20/20- to 20/320. Twenty patients had strabismus despite 6 having strabismus surgery previously. Ocular oscillations consistent with congenital nystagmus (CN) were clinically evident in 24 of 27 patients, and half showed periodic alternating nystagmus. In 3 patients without CN, eye movement recordings revealed minimal end-gaze nystagmus, square-wave jerks, drift during fixation and saccades, and low-gain pursuit. These patients had melanin in the posterior pole and better visual acuities than the others (P = 0.002). Most patients with HPS have CN, and many have periodic alternating nystagmus. Some have subtle eye movement abnormalities without clinically evident nystagmus, which can obscure the diagnosis, especially if hypopigmentation is mild. Absence of clinical nystagmus in a child with HPS suggests good vision. Patients with albinism, especially before surgery, should be evaluated for HPS to prevent life-threatening complications.

alpha-Dystroglycan does not play a major pathogenic role in autosomal recessive hereditary inclusion-body myopathy.

PubMed

Broccolini, Aldobrando; Gliubizzi, Carla; Pavoni, Ernesto; Gidaro, Teresa; Morosetti, Roberta; Sciandra, Francesca; Giardina, Bruno; Tonali, Pietro; Ricci, Enzo; Brancaccio, Andrea; Mirabella, Massimiliano

2005-02-01

Mutations of the GNE gene are responsible for autosomal recessive hereditary inclusion-body myopathy (HIBM). In this study we searched for the presence of any significant abnormality of alpha-dystroglycan (alpha-DG), a highly glycosylated component of the dystrophin-glycoprotein complex, in 5 HIBM patients which were previously clinically and genetically characterized. Immunocytochemical and immunoblot analysis showed that alpha-DG extracted from muscle biopsies was normally expressed and displayed its typical molecular mass. Immunoblot analysis on the wheat germ lectin-enriched glycoprotein fraction of muscles and primary myotubes showed a reduced amount of alpha-DG in 4 out of 5 HIBM patients, compared to normal and other diseased muscles. However, such altered lectin-binding behaviour, possibly reflecting a partial hyposialylation of alpha-DG, did not affect the laminin binding properties of alpha-DG. Therefore, the subtle changes within the alpha-DG glycosylation pattern, detected in HIBM muscles, likely do not play a key pathogenic role in this disorder.

The Objective Identification and Quantification of Interstitial Lung Abnormalities in Smokers.

PubMed

Ash, Samuel Y; Harmouche, Rola; Ross, James C; Diaz, Alejandro A; Hunninghake, Gary M; Putman, Rachel K; Onieva, Jorge; Martinez, Fernando J; Choi, Augustine M; Lynch, David A; Hatabu, Hiroto; Rosas, Ivan O; Estepar, Raul San Jose; Washko, George R

2017-08-01

Previous investigation suggests that visually detected interstitial changes in the lung parenchyma of smokers are highly clinically relevant and predict outcomes, including death. Visual subjective analysis to detect these changes is time-consuming, insensitive to subtle changes, and requires training to enhance reproducibility. Objective detection of such changes could provide a method of disease identification without these limitations. The goal of this study was to develop and test a fully automated image processing tool to objectively identify radiographic features associated with interstitial abnormalities in the computed tomography scans of a large cohort of smokers. An automated tool that uses local histogram analysis combined with distance from the pleural surface was used to detect radiographic features consistent with interstitial lung abnormalities in computed tomography scans from 2257 individuals from the Genetic Epidemiology of COPD study, a longitudinal observational study of smokers. The sensitivity and specificity of this tool was determined based on its ability to detect the visually identified presence of these abnormalities. The tool had a sensitivity of 87.8% and a specificity of 57.5% for the detection of interstitial lung abnormalities, with a c-statistic of 0.82, and was 100% sensitive and 56.7% specific for the detection of the visual subtype of interstitial abnormalities called fibrotic parenchymal abnormalities, with a c-statistic of 0.89. In smokers, a fully automated image processing tool is able to identify those individuals who have interstitial lung abnormalities with moderate sensitivity and specificity. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

[3D FSPGR (fast spoiled gradient echo) magnetic resonance imaging in the diagnosis of focal cortical dysplasia in children].

PubMed

Alikhanov, A A; Sinitsyn, V E; Perepelova, E M; Mukhin, K Iu; Demushkina, A A; Omarova, M O; Piliia, S V

2001-01-01

Small dysplastic lesions of the cerebral cortex are often missed by conventional MRI methods. The identification of subtle structural abnormalities by traditional multiplanar rectilinear slices is often limited by the complex convolutional pattern of the brain. We used a method of FSPGR (fast spoiled gradient-echo) of three-dimensional MRI data that improves the anatomical display of the sulcal structure of the hemispheric convexities. It also reduces the asymmetric sampling of gray-white matter that may lead to false-positive results. We present 5 from 12 patients with dysplastic cortical lesions in whom conventional two-dimensional and three-dimensional MRI with multiplanar reformatting was initially considered normal. Subsequent studies using 3D FSPGR identified various types of focal cortical dysplasia in all. These results indicate that an increase in the detection of subtle focal dysplastic lesions may be accomplished when one improves the anatomical display of the brain sulcal structure by performing 3D FSPGR.

The Human Pelvis: Variation in structure and function during gait

PubMed Central

Lewis, Cara L.; Laudicina, Natalie M.; Khuu, Anne; Loverro, Kari L.

2017-01-01

The shift to habitual bipedalism 4–6 million years ago in the hominin lineage created a morphologically and functionally different human pelvis compared to our closest living relatives, the chimpanzees. Evolutionary changes to the shape of the pelvis were necessary for the transition to habitual bipedalism in humans. These changes in the bony anatomy resulted in an altered role of muscle function, influencing bipedal gait. Additionally, there are normal sex-specific variations in the pelvis as well as abnormal variations in the acetabulum. During gait, the pelvis moves in the three planes to produce smooth and efficient motion. Subtle sex-specific differences in these motions may facilitate economical gait despite differences in pelvic structure. The motions of the pelvis and hip may also be altered in the presence of abnormal acetabular structure, especially with acetabular dysplasia. PMID:28297184

Further evidences for sleep instability and impaired spindle-delta dynamics in schizophrenia: a whole-night polysomnography study with neuroloop-gain and sleep-cycle analysis.

PubMed

Sasidharan, Arun; Kumar, Sunil; Nair, Ajay Kumar; Lukose, Ammu; Marigowda, Vrinda; John, John P; Kutty, Bindu M

2017-10-01

Sleep offers a unique window into the brain dysfunctions in schizophrenia. Many past sleep studies have reported abnormalities in both macro-sleep architecture (like increased awakenings) as well as micro-sleep-architecture (like spindle deficits) in patients with schizophrenia (PSZ). The present study attempts to replicate previous reports of macro- and micro-sleep-architectural abnormalities in schizophrenia. In addition, the study also examined sleep-stage changes and spindle-delta dynamics across sleep-cycles to provide further evidence in support of the dysfunctional thalamocortical mechanisms causing sleep instability and poor sleep maintenance associated with schizophrenia pathophysiology. Whole-night polysomnography was carried out among 45 PSZ and 39 age- and gender-matched healthy control subjects. Sleep-stage dynamics were assessed across sleep-cycles using a customized software algorithm. Spindle-delta dynamics across sleep-cycles were determined using neuroloop-gain analysis. PSZ showed macro-sleep architecture abnormalities such as prolonged sleeplessness, increased intermittent-awakenings, long sleep-onset latency, reduced non-rapid eye movement (NREM) stage 2 sleep, increased stage transitions, and poor sleep efficiency. They also showed reduced spindle density (sigma neuroloop-gain) but comparable slow wave density (delta neuroloop-gain) throughout the sleep. Sleep-cycle-wise analysis revealed transient features of sleep instability due to significantly increased intermittent awakenings especially in the first and third sleep-cycles, and unstable and recurrent stage transitions in both NREM (first sleep-cycle) and rapid eye movement (REM) sleep-periods (second sleep-cycle). Spindle deficits were persistent across the first three cycles and were positively correlated with sleep disruption during the subsequent REM sleep. In addition to replicating previously reported sleep deficits in PSZ, the current study showed subtle deficits in NREM-REM alterations across whole-night polysomnography. These results point towards a possible maladaptive interplay between unstable thalamocortical networks, resulting in sleep-cycle-specific instability patterns associated with schizophrenia pathophysiology. Copyright © 2017 Elsevier B.V. All rights reserved.

The instrumented Timed Up and Go test: Potential outcome measure for disease modifying therapies in Parkinson's disease

PubMed Central

Zampieri, Cris; Salarian, Arash; Carlson-Kuhta, Patricia; Aminian, Kamiar; Nutt, John G.; Horak, Fay B.

2011-01-01

The Timed Up and Go (TUG) test has been used to assess balance and mobility in Parkinson’s Disease (PD). However, it is not known if this test is sensitive to subtle abnormalities present in early stages of the disease, when balance and gait problems are not clinically evident but may be detected with instrumented analysis of movement. We hypothesize that postural transitions and arm swing during gait will be the most sensitive characteristics of the TUG for early PD. In the present study, we instrumented the TUG test (iTUG) using portable inertial sensors, and extended the walking distance from 3 meters (traditional TUG) to 7 meters. Twelve subjects with early-to-moderate, untreated PD and 12 healthy individuals participated. Our findings show that although the stopwatch measure of TUG duration did not detect abnormalities in early-to-mid stage PD, the peak arm swing velocity on the more affected side, average turning velocity, cadence and peak trunk rotation velocity were significantly slower. These iTUG parameters were also correlated with the UPDRS Motor Scale. Thus, the iTUG test is sensitive to untreated PD and could potentially detect progression of PD and response to symptomatic and disease-modifying treatments. PMID:19726406

‘I wouldn’t say it’s sexism, except that … It’s all these little subtle things’: Healthcare scientists’ accounts of gender in healthcare science laboratories

PubMed Central

Learmonth, Mark

2013-01-01

We explore healthcare scientists’ accounts of men in healthcare science laboratories. By focussing on subtle masculinist actions that women find disadvantageous to them, we seek to extend knowledge about women’s under-representation in senior positions in healthcare science – despite women being in the majority at junior levels. We maintain that healthcare science continues to be dominated by taken-for-granted masculinities that marginalize women, keeping them in their ‘place’. Our aim is to make visible the subtle practices that are normally invisible by showing masculinities in action. Principally using feminist analyses, our findings show that both women and men are often unaware of taken-for-granted masculinist actions, and even when women do notice, they rarely challenge the subtle sexist behaviour.

Comparison of flat-panel digital to conventional film-screen radiography in detection of experimentally created lesions of the equine third metacarpal bone.

PubMed

Moorman, Valerie J; Marshall, John F; Devine, Dustin V; Payton, Mark; Jann, Henry W; Bahr, Robert

2009-01-01

Radiographic diagnosis of equine bone disease using digital radiography is prevalent in veterinary practice. However, the diagnostic quality of digital vs. conventional radiography has not been compared systematically. We hypothesized that digital radiography would be superior to film-screen radiography for detection of subtle lesions of the equine third metacarpal bone. Twenty-four third metacarpal bones were collected from horses euthanized for reasons other than orthopedic disease. Bones were dissected free of soft tissue and computed tomography was performed to ensure that no osseous abnormalities were present. Subtle osseous lesions were produced in the dorsal cortex of the third metacarpal bones, and the bones were radiographed in a soft tissue phantom using indirect digital and conventional radiography at standard exposures. Digital radiographs were printed onto film. Three Diplomates of the American College of Veterinary Radiology evaluated the radiographs for the presence or absence of a lesion. Receiver operator characteristic curves were constructed, and the area under these curves were compared to assess the ability of the digital and film-screen radiographic systems to detect lesions. The area under the ROC curves for film-screen and digital radiography were 0.87 and 0.90, respectively (P = 0.59). We concluded that the digital radiographic system was comparable to the film-screen system for detection of subtle lesions of the equine third metacarpal bone.

Brain imaging in normal kids: a community-based MRI study in Malawian children.

PubMed

Potchen, M J; Kampondeni, S D; Mallewa, M; Taylor, T E; Birbeck, G L

2013-04-01

To collect normative MRI data for effective clinical and research applications. Such data may also offer insights into common neurological insults. We identified a representative, community-based sample of children aged 9-14 years. Children were screened for neurodevelopmental problems. Demographic data, medical history and environmental exposures were ascertained. Eligible children underwent the Neurologic Examination for Subtle Signs (NESS) and a brain MRI. Descriptive findings and analyses to identify risk factors for MRI abnormalities are detailed. One hundred and two of 170 households screened had age-appropriate children. Two of 102 children had neurological problems - one each with cerebral palsy and epilepsy. Ninety-six of 100 eligible children were enrolled. Mean age was 11.9 years (SD 1.5), and 43 (45%) were boys. No acute MRI abnormalities were seen. NESS abnormalities were identified in 6 of 96 children (6%). Radiographic evidence of sinusitis in 29 children (30%) was the most common MRI finding. Brain abnormalities were found in 16 (23%): mild diffuse atrophy in 4 (4%), periventricular white matter changes/gliosis in 6 (6%), multifocal punctuate subcortical white matter changes in 2 (2%), vermian atrophy in 1 (1%), empty sella in 3 (3%) and multifocal granulomas with surrounding gliosis in 1 (1%). Having an abnormal MRI was not associated with age, sex, antenatal problems, early malnutrition, febrile seizures, an abnormal neurological examination or housing quality (all P values >0.05). No predictors of radiographic sinusitis were identified. Incidental brain MRI abnormalities are common in normal Malawian children. The incidental atrophy and white matter abnormalities seen in this African population have not been reported among incidental findings from US populations, suggesting Malawi-specific exposures may be the cause. © 2013 Blackwell Publishing Ltd.

The evaluation of eye pain with a normal ocular exam.

PubMed

Lee, Andrew G; Brazis, Paul W

2003-12-01

Eye pain with or without associated head or face pain is a common complaint to the ophthalmologist. The ocular exam may reveal the etiology (e.g., corneal disease, angle closure glaucoma) but typically the exam is normal. This paper reviews the evaluation and management of eye pain with a "normal" ocular exam, including: 1) subtle findings on ocular exam; 2) transient findings on exam, and 3) no abnormal ocular findings. Ophthalmologists should be aware of the various etiologies for eye pain and the specific and distinctive features that make the diagnosis.

Correlations between time required for radiological diagnoses, readers' performance, display environments, and difficulty of cases

NASA Astrophysics Data System (ADS)

Gur, David; Rockette, Howard E.; Sumkin, Jules H.; Hoy, Ronald J.; Feist, John H.; Thaete, F. Leland; King, Jill L.; Slasky, B. S.; Miketic, Linda M.; Straub, William H.

1991-07-01

In a series of large ROC studies, the authors analyzed the time radiologists took to diagnose PA chest images as a function of observer performance indices (Az), display environments, and difficulty of cases. Board-certified radiologists interpreted at least 600 images each for the presence or absence of one or more of the following abnormalities: interstitial disease, nodule, and pneumothorax. Results indicated that there exists a large inter- reader variability in the time required to diagnose PA chest images. There is no correlation between a reader's specific median reading time and his/her performance. Time generally increases as the number of abnormalities on a single image increases and for cases with subtle abnormalities. Results also indicated that, in general, the longer the time for interpretation of a specific case (within reader), the further the observer's confidence ratings were from the truth. These findings were found to hold true regardless of the display mode. These results may have implications with regards to the appropriate methodology that should be used for imaging systems evaluations and for measurements of productivity for radiologists.

Identification of a duplication of Xq28 associated with bilateral periventricular nodular heterotopia.

PubMed Central

Fink, J M; Dobyns, W B; Guerrini, R; Hirsch, B A

1997-01-01

Bilateral periventricular nodular heterotopia (BPNH) is a malformation of neuronal migration and is characterized by nodules of heterotopic gray matter lining the lateral ventricles of the brain. The majority of BPNH patients are female and have epilepsy as a sole clinical manifestation of their disease. Familial BPNH has been mapped to Xq28 by linkage analysis. A multiple congenital anomaly-mental retardation syndrome (BPNH/MR) was recently delineated in three unrelated boys with BPNH, cerebellar hypoplasia, severe mental retardation, epilepsy, and syndactyly. High-resolution chromosome analysis revealed a subtle abnormality of Xq28 in one of the boys with BPNH/MR syndrome. FISH with cosmids and YACs from Xq28 further characterized this abnormality as a 2.25-3.25-Mb inverted duplication. No abnormality of Xq28 was detected by G-banding or FISH in the other two boys. These data support the linkage assignment of BPNH to band Xq28 and narrow the critical region to the distal 2.25-3.25 Mb of Xq28. Images Figure 1 Figure 3 Figure 4 Figure 5 PMID:9311743

Motor system hyperconnectivity in juvenile myoclonic epilepsy: a cognitive functional magnetic resonance imaging study.

PubMed

Vollmar, Christian; O'Muircheartaigh, Jonathan; Barker, Gareth J; Symms, Mark R; Thompson, Pamela; Kumari, Veena; Duncan, John S; Janz, Dieter; Richardson, Mark P; Koepp, Matthias J

2011-06-01

Juvenile myoclonic epilepsy is the most frequent idiopathic generalized epilepsy syndrome. It is characterized by predominant myoclonic jerks of upper limbs, often provoked by cognitive activities, and typically responsive to treatment with sodium valproate. Neurophysiological, neuropsychological and imaging studies in juvenile myoclonic epilepsy have consistently pointed towards subtle abnormalities in the medial frontal lobes. Using functional magnetic resonance imaging with an executive frontal lobe paradigm, we investigated cortical activation patterns and interaction between cortical regions in 30 patients with juvenile myoclonic epilepsy and 26 healthy controls. With increasing cognitive demand, patients showed increasing coactivation of the primary motor cortex and supplementary motor area. This effect was stronger in patients still suffering from seizures, and was not seen in healthy controls. Patients with juvenile myoclonic epilepsy showed increased functional connectivity between the motor system and frontoparietal cognitive networks. Furthermore, we found impaired deactivation of the default mode network during cognitive tasks with persistent activation in medial frontal and central regions in patients. Coactivation in the motor cortex and supplementary motor area with increasing cognitive load and increased functional coupling between the motor system and cognitive networks provide an explanation how cognitive effort can cause myoclonic jerks in juvenile myoclonic epilepsy. The supplementary motor area represents the anatomical link between these two functional systems, and our findings may be the functional correlate of previously described structural abnormalities in the medial frontal lobe in juvenile myoclonic epilepsy.

Functional MRI evidence for fine motor praxis dysfunction in children with persistent speech disorders

PubMed Central

Redle, Erin; Vannest, Jennifer; Maloney, Thomas; Tsevat, Rebecca K.; Eikenberry, Sarah; Lewis, Barbara; Shriberg, Lawrence D.; Tkach, Jean; Holland, Scott K.

2014-01-01

Children with persistent speech disorders (PSD) often present with overt or subtle motor deficits; the possibility that speech disorders and motor deficits could arise from a shared neurological base is currently unknown. Functional MRI (fMRI) was used to examine the brain networks supporting fine motor praxis in children with PSD and without clinically identified fine motor deficits. Methods This case-control study included 12 children with PSD (mean age 7.42 years, 4 female) and 12 controls (mean age 7.44 years, 4 female). Children completed behavioral evaluations using standardized motor assessments and parent reported functional measures. During fMRI scanning, participants completed a cued finger tapping task contrasted passive listening. A general linear model approach identified brain regions associated with finger tapping in each group and regions that differed between groups. The relationship between regional fMRI activation and fine motor skill was assessed using a regression analysis. Results Children with PSD had significantly poorer results for rapid speech production and fine motor praxis skills, but did not differ on classroom functional skills. Functional MRI results showed that children with PSD had significantly more activation in the cerebellum during finger tapping. Positive correlations between performance on a fine motor praxis test and activation multiple cortical regions were noted for children with PSD but not for controls. Conclusions Over-activation in the cerebellum during a motor task may reflect a subtle abnormality in the non-speech motor neural circuitry in children with PSD. PMID:25481413

Microsensors and wireless system for monitoring epilepsy

NASA Astrophysics Data System (ADS)

Whitchurch, Ashwin K.; Ashok, B. H.; Kumaar, Raman V.; Sarukesi, K.; Jose, K. A.; Varadan, Vijay K.

2003-07-01

Epilepsy is a form of brain disorder caused by abnormal discharges of neurons. The most common manifestations of epilepsy are seizures which could affect visual, aural and motor abilities of a person. Absence epilepsy is a form of epilepsy common mostly in children. The most common manifestations of absence epilepsy are staring and transient loss of responsiveness. Also, subtle motor activities may occur. Due to the subtle nature of these symptoms, episodes of absence epilepsy may often go unrecognized for long periods of time or be mistakenly attributed to attention deficit disorder or daydreaming. Spells of absence epilepsy may last about 10 seconds and occur hundreds of times each day. Patients have no recollections of the events occurred during those seizures and will resume normal activity without any postictal symptoms. The EEG during such episodes of Absence epilepsy shows intermittent activity of 3 Hz generalized spike and wave complexes. As EEG is the only way of detecting such symptoms, it is required to monitor the EEG of the patient for a long time, usually the whole day. This requires that the patient be connected to the EEG recorder all the time and thus remain only in the bed. So, effectively the EEG is being monitored only when the patient is stationary. The wireless monitoring system described in this paper aims at eliminating this constraint and enables the physician to monitor the EEG when the patient resumes his normal activities. This approach could even help the doctor identify possible triggers of absence epilepsy.

Is 2D speckle tracking echocardiography useful for detecting and monitoring myocardial dysfunction in adult m.3243A>G carriers? - a retrospective pilot study.

PubMed

Koene, S; Timmermans, J; Weijers, G; de Laat, P; de Korte, C L; Smeitink, J A M; Janssen, M C H; Kapusta, L

2017-03-01

Cardiomyopathy is a common complication of mitochondrial disorders, associated with increased mortality. Two dimensional speckle tracking echocardiography (2DSTE) can be used to quantify myocardial deformation. Here, we aimed to determine the usefulness of 2DSTE in detecting and monitoring subtle changes in myocardial dysfunction in carriers of the 3243A>G mutation in mitochondrial DNA. In this retrospective pilot study, 30 symptomatic and asymptomatic carriers of the mitochondrial 3243A>G mutation of whom two subsequent echocardiograms were available were included. We measured longitudinal, circumferential and radial strain using 2DSTE. Results were compared to published reference values. Speckle tracking was feasible in 90 % of the patients for longitudinal strain. Circumferential and radial strain showed low face validity (low number of images with sufficient quality; suboptimal tracking) and were therefore rejected for further analysis. Global longitudinal strain showed good face validity, and was abnormal in 56-70 % (depending on reference values used) of the carriers (n = 27). Reproducibility was good (mean difference of 0.83 for inter- and 0.40 for intra-rater reproducibility; ICC 0.78 and 0.89, respectively). The difference between the first and the second measurement exceeded the measurement variance in 39 % of the cases (n = 23; feasibility of follow-up 77 %). Even in data collected as part of clinical care, two-dimensional strain echocardiography seems a feasible method to detect and monitor subtle changes in longitudinal myocardial deformation in adult carriers of the mitochondrial 3243A>G mutation. Based on our data and the reported accuracy of global longitudinal strain in other studies, we suggest the use of global longitudinal strain in a prospective follow-up or intervention study.

Detailed von Willebrand factor multimer analysis in patients with von Willebrand disease in the European study, molecular and clinical markers for the diagnosis and management of type 1 von Willebrand disease (MCMDM-1VWD).

PubMed

Budde, U; Schneppenheim, R; Eikenboom, J; Goodeve, A; Will, K; Drewke, E; Castaman, G; Rodeghiero, F; Federici, A B; Batlle, J; Pérez, A; Meyer, D; Mazurier, C; Goudemand, J; Ingerslev, J; Habart, D; Vorlova, Z; Holmberg, L; Lethagen, S; Pasi, J; Hill, F; Peake, I

2008-05-01

Type 1 von Willebrand disease (VWD) is a congenital bleeding disorder characterized by a partial quantitative deficiency of plasma von Willebrand factor (VWF) in the absence of structural and/or functional VWF defects. Accurate assessment of the quantity and quality of plasma VWF is difficult but is a prerequisite for correct classification. To evaluate the proportion of misclassification of patients historically diagnosed with type 1 VWD using detailed analysis of the VWF multimer structure. Previously diagnosed type 1 VWD families and healthy controls were recruited by 12 expert centers in nine European countries. Phenotypic characterization comprised plasma VWF parameters and multimer analysis using low- and intermediate-resolution gels combined with an optimized visualization system. VWF genotyping was performed in all index cases (ICs). Abnormal multimers were present in 57 out of 150 ICs; however, only 29 out of these 57 (51%) had VWF ristocetin cofactor to antigen ratio below 0.7. In most cases multimer abnormalities were subtle, and only two cases had a significant loss of the largest multimers. Of the cases previously diagnosed as type 1 VWD, 38% showed abnormal multimers. Depending on the classification criteria used, 22 out of these 57 cases (15% of the total cohort) may be reclassified as type 2, emphasizing the requirement for multimer analysis compared with a mere ratio of VWF functional parameters and VWF:Ag. This is further supported by the finding that even slightly aberrant multimers are highly predictive for the presence of VWF mutations.

Chronic sensory stroke with and without central pain is associated with bilaterally distributed sensory abnormalities as detected by quantitative sensory testing.

PubMed

Krause, Thomas; Asseyer, Susanna; Geisler, Frederik; Fiebach, Jochen B; Oeltjenbruns, Jochen; Kopf, Andreas; Villringer, Kersten; Villringer, Arno; Jungehulsing, Gerhard J

2016-01-01

Approximately 20% of patients suffering from stroke with pure or predominant sensory symptoms (referred to as sensory stroke patients) develop central poststroke pain (CPSP). It is largely unknown what distinguishes these patients from those who remain pain free. Using quantitative sensory testing (QST), we analyzed the somatosensory profiles of 50 patients with chronic sensory stroke, of which 25 suffered from CPSP. As compared with reference data from healthy controls, patients with CPSP showed alterations of thermal and mechanical thresholds on the body area contralateral to their stroke (P < 0.01). Patients with sensory stroke but without CPSP (non-pain sensory stroke [NPSS] patients) exhibited similar albeit less pronounced contralesional changes. Paradoxical heat sensation (PHS) and dynamic mechanical allodynia (DMA) showed higher values in CPSP, and an elevated cold detection threshold (CDT) was seen more often in CPSP than in patients with NPSS (P < 0.05). In patients with CPSP, changes in CDT, PHS, dynamic mechanical allodynia, and temporal pain summation (wind-up ratio) each correlated with the presence of pain (P < 0.05). On the homologous ipsilesional body area, both patient groups showed additional significant abnormalities as compared with the reference data, which strongly resembled the contralesional changes. In summary, our analysis reveals that CPSP is associated with impaired temperature perception and positive sensory signs, but differences between patients with CPSP and NPSS are subtle. Both patients with CPSP and NPSS show considerable QST changes on the ipsilesional body side. These results are in part paralleled by recent findings of bilaterally spread cortical atrophy in CPSP and might reflect chronic maladaptive cortical plasticity, particularly in patients with CPSP.

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

PubMed

Bonavita, Simona; Tedeschi, Gioacchino; Gallo, Antonio

2013-01-01

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

Morphostructural MRI Abnormalities Related to Neuropsychiatric Disorders Associated to Multiple Sclerosis

PubMed Central

Bonavita, Simona; Tedeschi, Gioacchino; Gallo, Antonio

2013-01-01

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

Isolated hypogonadotropic hypogonadism with SOX2 mutation and anophthalmia/microphthalmia in offspring

PubMed Central

Stark, Zornitza; Storen, Rebecca; Bennetts, Bruce; Savarirayan, Ravi; Jamieson, Robyn V

2011-01-01

Isolated hypogonadotropic hypogonadism (IHH) is a genetically heterogeneous condition in which patients frequently require assisted reproduction to achieve fertility. In patients with IHH who are otherwise well, no particular increased risk of congenital anomalies in the resultant offspring has been highlighted. Heterozygous mutations in SOX2 are the commonest single-gene cause of anophthalmia/microphthalmia (A/M) and sometimes result in pituitary abnormalities. We report a family with a novel frameshift mutation in the SOX2 transactivation domain, p.Gly280AlafsX91, resulting in bilateral anophthalmia and subtle endocrinological abnormalities in a male sibling, and unilateral microphthalmia in a female sibling. The mutation is present in their mother who has IHH, but has no eye disorders or other anomalies. She underwent assisted reproduction to achieve fertility. This report has important implications for the evaluation of patients with IHH, particularly in the setting of planned infertility treatment. PMID:21326281

Isolated hypogonadotropic hypogonadism with SOX2 mutation and anophthalmia/microphthalmia in offspring.

PubMed

Stark, Zornitza; Storen, Rebecca; Bennetts, Bruce; Savarirayan, Ravi; Jamieson, Robyn V

2011-07-01

Isolated hypogonadotropic hypogonadism (IHH) is a genetically heterogeneous condition in which patients frequently require assisted reproduction to achieve fertility. In patients with IHH who are otherwise well, no particular increased risk of congenital anomalies in the resultant offspring has been highlighted. Heterozygous mutations in SOX2 are the commonest single-gene cause of anophthalmia/microphthalmia (A/M) and sometimes result in pituitary abnormalities. We report a family with a novel frameshift mutation in the SOX2 transactivation domain, p.Gly280AlafsX91, resulting in bilateral anophthalmia and subtle endocrinological abnormalities in a male sibling, and unilateral microphthalmia in a female sibling. The mutation is present in their mother who has IHH, but has no eye disorders or other anomalies. She underwent assisted reproduction to achieve fertility. This report has important implications for the evaluation of patients with IHH, particularly in the setting of planned infertility treatment.

Multislice CT urography: state of the art.

PubMed

Noroozian, M; Cohan, R H; Caoili, E M; Cowan, N C; Ellis, J H

2004-01-01

Recent improvements in helical CT hardware and software have provided imagers with the tools to obtain an increasingly large number of very thin axial images. As a result, a number of new applications for multislice CT have recently been developed, one of which is CT urography. The motivation for performing CT urography is the desire to create a single imaging test that can completely assess the kidneys and urinary tract for urolithiasis, renal masses and mucosal abnormalities of the renal collecting system, ureters and bladder. Although the preferred technique for performing multislice CT urography has not yet been determined and results are preliminary, early indications suggest that this examination can detect even subtle benign and malignant urothelial abnormalities and that it has the potential to completely replace excretory urography within the next several years. An important limitation of multislice CT urography is increased patient radiation exposure encountered when some of the more thorough recommended techniques are utilized.

The Human Pelvis: Variation in Structure and Function During Gait.

PubMed

Lewis, Cara L; Laudicina, Natalie M; Khuu, Anne; Loverro, Kari L

2017-04-01

The shift to habitual bipedalism 4-6 million years ago in the hominin lineage created a morphologically and functionally different human pelvis compared to our closest living relatives, the chimpanzees. Evolutionary changes to the shape of the pelvis were necessary for the transition to habitual bipedalism in humans. These changes in the bony anatomy resulted in an altered role of muscle function, influencing bipedal gait. Additionally, there are normal sex-specific variations in the pelvis as well as abnormal variations in the acetabulum. During gait, the pelvis moves in the three planes to produce smooth and efficient motion. Subtle sex-specific differences in these motions may facilitate economical gait despite differences in pelvic structure. The motions of the pelvis and hip may also be altered in the presence of abnormal acetabular structure, especially with acetabular dysplasia. Anat Rec, 300:633-642, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Discordant detection of monosomy 7 by GTG-banding and FISH in a patient with Shwachman-Diamond syndrome without evidence of myelodysplastic syndrome or acute myelogenous leukemia.

PubMed

Sokolic, R A; Ferguson, W; Mark, H F

1999-12-01

The myelodysplastic syndromes (MDS) are a group of hematologic disorders commonly affecting elderly persons and often leading to acute myelogenous leukemia (AML). Although rare in children, when MDS does occur, it is frequently part of a congenital disorder such as Shwachman-Diamond syndrome (SDS). Monosomy 7 and/or deletion of part or all of 7q are poor prognostic signs in MDS and AML, although the pathophysiologic relationship between this finding and MDS or AML is unclear. Shwachman-Diamond syndrome is an inherited illness characterized by exocrine pancreatic insufficiency and by congenital neutropenia. Patients with SDS are at increased risk of developing myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). Because monosomy 7 is a poor prognostic sign in MDS and AML, establishing its presence is important. However, different methods of detection of monosomy 7 may lead to different results in some patients. We present the case of a 10-year-old girl known to have SDS, who had a bone marrow aspiration and biopsy done to rule out MDS and AML. By light microscopy, the patient's bone marrow was unremarkable. GTG-banding showed the following karyotype: 45,XX,-C[3]/47,XX,+C[1]/46,XX[45]. Fluorescence in situ hybridization (FISH) was performed with a chromosome 7-specific alpha-satellite probe (D7Z1). Almost all (373 of 376) cells exhibited only one chromosome 7 signal. A second marrow aspiration done 6 months later showed an essentially normal karyotype by GTG-banding. Fluorescence in situ hybridization with the same chromosome 7 probe showed 230 of 250 cells to be monosomic for chromosome 7. A whole chromosome 7 painting probe demonstrated disomy for chromosome 7 in 90 of 90 cells; however, subtle heteromorphism in the centromeric regions of the 2 copies of chromosome 7 was noted in some cells. This case demonstrates that FISH and GTG-banding can give discordant results, that the two should be viewed as complementary technologies, and that both have a place in a full karyotypic analysis. Furthermore, this case demonstrates for the first time that heteromorphism and/or subtle structural abnormalities of chromosome 7, previously associated with MDS and AML, can exist without clinical or morphologic signs of these illnesses. It will be of interest to further study the relationship, if any, between SDS and various structural abnormalities of chromosome 7 in MDS and AML, and to elucidate the molecular mechanisms of pathogenesis, physiology, and treatment of these disorders.

A Significant Proportion of Pediatric Morphea En Coup De Sabre and Parry-Romberg Syndrome Patients Have Neuroimaging Findings

PubMed Central

Chiu, Yvonne E.; Vora, Sheetal; Kwon, Eun-Kyung M.; Maheshwari, Mohit

2012-01-01

Background/Objectives En coup de sabre (ECDS) and Parry-Romberg syndrome (PRS) are variants of linear morphea on the head and neck that can be associated with neurologic manifestations. Intracranial abnormalities on computed tomography (CT) and magnetic resonance imaging (MRI) can be present in a significant proportion of patients. Methods We describe 32 pediatric patients from our institution with ECDS or PRS, in whom neuroimaging was performed in 21 cases. We also review 51 additional patients from the literature. Results Nineteen percent of the children at our institution had intracranial abnormalities on MRI, half of whom were asymptomatic. Hyperintensities on T2-weighted sequences were the most common finding, present in all patients who had intracranial abnormalities on MRI. Seizures and headaches were the most common neurologic symptom, affecting 13% and 9% of our population, respectively. The presence of neurologic symptoms was not correlated with neuroimaging abnormalities as 2 asymptomatic patients had marked MRI findings, while the MRI was abnormal in only 2/9 symptomatic patients. Similarly, the severity of the superficial disease did not predict neurologic involvement; a patient with subtle skin involvement had striking MRI findings and seizures while another patient with a bony defect had no brain parenchymal involvement. Conclusions Neurologic symptoms and neuroimaging abnormalities are found in a surprisingly substantial percentage of children with ECDS and PRS. Early recognition of neurologic involvement is necessary as it affects treatment choices. As clinical predictors of intracranial abnormalities are poor, strong consideration should be given to obtaining an MRI prior to treatment initiation to assist in management decisions and establish a baseline examination. PMID:23106674

Increased placental trophoblast inclusions in placenta accreta.

PubMed

Adler, E; Madankumar, R; Rosner, M; Reznik, S E

2014-12-01

Trophoblast inclusions (TIs) are often found in placentas of genetically abnormal gestations. Although best documented in placentas from molar pregnancies and chromosomal aneuploidy, TIs are also associated with more subtle genetic abnormalities, and possibly autism. Less than 3% of non-aneuploid, non-accreta placentas have TIs. We hypothesize that placental genetics may play a role in the development of placenta accreta and aim to study TIs as a potential surrogate indicator of abnormal placental genetics. Forty cases of placenta accreta in the third trimester were identified in a search of the medical records at one institution. Forty two third trimester control placentas were identified by a review of consecutively received single gestation placentas with no known genetic abnormalities and no diagnosis of placenta accreta. Forty percent of cases with placenta accreta demonstrated TIs compared to 2.4% of controls. More invasive placenta accretas (increta and percreta) were more likely to demonstrate TIs than accreta (47% versus 20%). Prior cesarean delivery was more likely in accreta patients than controls (67% versus 9.5%). Placenta accreta is thought to be the result of damage to the endometrium predisposing to abnormal decidualization and invasive trophoblast growth into the myometrium. However, the etiology of accreta is incompletely understood with accreta frequently occurring in women without predisposing factors and failing to occur in predisposed patients. This study has shown that TIs are present at increased rates in cases of PA. Further studies are needed to discern what underlying pathogenic mechanisms are in common between abnormal placentation and the formation of TIs. Published by Elsevier Ltd.

Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes.

PubMed

Chao, Hsiao-Tuan; Chen, Hongmei; Samaco, Rodney C; Xue, Mingshan; Chahrour, Maria; Yoo, Jong; Neul, Jeffrey L; Gong, Shiaoching; Lu, Hui-Chen; Heintz, Nathaniel; Ekker, Marc; Rubenstein, John L R; Noebels, Jeffrey L; Rosenmund, Christian; Zoghbi, Huda Y

2010-11-11

Mutations in the X-linked MECP2 gene, which encodes the transcriptional regulator methyl-CpG-binding protein 2 (MeCP2), cause Rett syndrome and several neurodevelopmental disorders including cognitive disorders, autism, juvenile-onset schizophrenia and encephalopathy with early lethality. Rett syndrome is characterized by apparently normal early development followed by regression, motor abnormalities, seizures and features of autism, especially stereotyped behaviours. The mechanisms mediating these features are poorly understood. Here we show that mice lacking Mecp2 from GABA (γ-aminobutyric acid)-releasing neurons recapitulate numerous Rett syndrome and autistic features, including repetitive behaviours. Loss of MeCP2 from a subset of forebrain GABAergic neurons also recapitulates many features of Rett syndrome. MeCP2-deficient GABAergic neurons show reduced inhibitory quantal size, consistent with a presynaptic reduction in glutamic acid decarboxylase 1 (Gad1) and glutamic acid decarboxylase 2 (Gad2) levels, and GABA immunoreactivity. These data demonstrate that MeCP2 is critical for normal function of GABA-releasing neurons and that subtle dysfunction of GABAergic neurons contributes to numerous neuropsychiatric phenotypes.

Childhood obstructive sleep-disordered breathing: a clinical update and discussion of technological innovations and challenges.

PubMed

Halbower, Ann C; Ishman, Stacey L; McGinley, Brian M

2007-12-01

Childhood sleep-disordered breathing (SDB) has been known to be associated with health and cognitive impacts for more than a century, and yet our understanding of this disorder is in its infancy. Neuropsychological consequences in children with snoring or subtle breathing disturbances not meeting the traditional definition of sleep apnea suggest that "benign, or primary snoring" may be clinically significant, and that the true prevalence of SDB might be underestimated. There is no standard definition of SDB in children. The polysomnographic technology used in many sleep laboratories may be inadequate to diagnose serious but subtle forms of clinically important airflow limitation. In the last several years, advances in digital technology as well as new observational studies of respiratory and arousal patterns in large populations of healthy children have led to alternative views of what constitutes sleep-related breathing and arousal abnormalities that may refine our diagnostic criteria. This article reviews our knowledge of childhood SDB, highlights recent advances in technology, and discusses diagnostic and treatment strategies that will advance the management of children with pediatric SDB.

Controversies in the definition and treatment of idiopathic short stature (ISS).

PubMed

Pedicelli, Stefania; Peschiaroli, Emanuela; Violi, Enrica; Cianfarani, Stefano

2009-01-01

The term idiopathic short stature (ISS) refers to short children with no identifiable disorder of the growth hormone (GH)/insulin like growth factor (IGF) axis and no other endocrine, genetic or organ system disorder. This heterogeneous group of short children without GH deficiency (GHD) includes children with constitutional delay of growth and puberty, familial short stature, or both, as well as those with subtle cartilage and bone dysplasias. In rare cases, ISS is due to IGF molecular abnormalities. In this review we tackle the major challenges in the definition and treatment of ISS.

Orbital chondroma rodens in a dog.

PubMed

Pletcher, J M; Koch, S A; Stedham, M A

1979-07-15

A chondroma rodens involving the superficial medial aspect of the right orbit was diagnosed in a 9-year-old dog referred because of chronic unilateral epiphora. Examination revealed several ophthalmic abnormalities attributable to a space-occupying mass in the superficial medial aspect of the orbit. The mass was excised; however, regrowths at the primary site necessitated additional surgical interventions. The dog was given radiation therapy, which provided encouraging results. Subtle histologic differences as well as differing epidemiologic features suggest that chondroma rodens is not analogous to the human entity of juvenile aponeurotic fibroma, to which it has been compared in the past.

Material Separation Using Dual-Energy CT: Current and Emerging Applications.

PubMed

Patino, Manuel; Prochowski, Andrea; Agrawal, Mukta D; Simeone, Frank J; Gupta, Rajiv; Hahn, Peter F; Sahani, Dushyant V

2016-01-01

Dual-energy (DE) computed tomography (CT) offers the opportunity to generate material-specific images on the basis of the atomic number Z and the unique mass attenuation coefficient of a particular material at different x-ray energies. Material-specific images provide qualitative and quantitative information about tissue composition and contrast media distribution. The most significant contribution of DE CT-based material characterization comes from the capability to assess iodine distribution through the creation of an image that exclusively shows iodine. These iodine-specific images increase tissue contrast and amplify subtle differences in attenuation between normal and abnormal tissues, improving lesion detection and characterization in the abdomen. In addition, DE CT enables computational removal of iodine influence from a CT image, generating virtual noncontrast images. Several additional materials, including calcium, fat, and uric acid, can be separated, permitting imaging assessment of metabolic imbalances, elemental deficiencies, and abnormal deposition of materials within tissues. The ability to obtain material-specific images from a single, contrast-enhanced CT acquisition can complement the anatomic knowledge with functional information, and may be used to reduce the radiation dose by decreasing the number of phases in a multiphasic CT examination. DE CT also enables generation of energy-specific and virtual monochromatic images. Clinical applications of DE CT leverage both material-specific images and virtual monochromatic images to expand the current role of CT and overcome several limitations of single-energy CT. (©)RSNA, 2016.

Assessment of Motor Function, Sensory Motor Gating and Recognition Memory in a Novel BACHD Transgenic Rat Model for Huntington Disease

PubMed Central

Abada, Yah-se K.; Nguyen, Huu Phuc; Schreiber, Rudy; Ellenbroek, Bart

2013-01-01

Rationale Huntington disease (HD) is frequently first diagnosed by the appearance of motor symptoms; the diagnosis is subsequently confirmed by the presence of expanded CAG repeats (> 35) in the HUNTINGTIN (HTT) gene. A BACHD rat model for HD carrying the human full length mutated HTT with 97 CAG-CAA repeats has been established recently. Behavioral phenotyping of BACHD rats will help to determine the validity of this model and its potential use in preclinical drug discovery studies. Objectives The present study seeks to characterize the progressive emergence of motor, sensorimotor and cognitive deficits in BACHD rats. Materials and Methods Wild type and transgenic rats were tested from 1 till 12 months of age. Motor tests were selected to measure spontaneous locomotor activity (open field) and gait coordination. Sensorimotor gating was assessed in acoustic startle response paradigms and recognition memory was evaluated in an object recognition test. Results Transgenic rats showed hyperactivity at 1 month and hypoactivity starting at 4 months of age. Motor coordination imbalance in a Rotarod test was present at 2 months and gait abnormalities were seen in a Catwalk test at 12 months. Subtle sensorimotor changes were observed, whereas object recognition was unimpaired in BACHD rats up to 12 months of age. Conclusion The current BACHD rat model recapitulates certain symptoms from HD patients, especially the marked motor deficits. A subtle neuropsychological phenotype was found and further studies are needed to fully address the sensorimotor phenotype and the potential use of BACHD rats for drug discovery purposes. PMID:23874679

Functional MRI evidence for fine motor praxis dysfunction in children with persistent speech disorders.

PubMed

Redle, Erin; Vannest, Jennifer; Maloney, Thomas; Tsevat, Rebecca K; Eikenberry, Sarah; Lewis, Barbara; Shriberg, Lawrence D; Tkach, Jean; Holland, Scott K

2015-02-09

Children with persistent speech disorders (PSD) often present with overt or subtle motor deficits; the possibility that speech disorders and motor deficits could arise from a shared neurological base is currently unknown. Functional MRI (fMRI) was used to examine the brain networks supporting fine motor praxis in children with PSD and without clinically identified fine motor deficits. This case-control study included 12 children with PSD (mean age 7.42 years, four female) and 12 controls (mean age 7.44 years, four female). Children completed behavioral evaluations using standardized motor assessments and parent reported functional measures. During fMRI scanning, participants completed a cued finger tapping task contrasted passive listening. A general linear model approach identified brain regions associated with finger tapping in each group and regions that differed between groups. The relationship between regional fMRI activation and fine motor skill was assessed using a regression analysis. Children with PSD had significantly poorer results for rapid speech production and fine motor praxis skills, but did not differ on classroom functional skills. Functional MRI results showed that children with PSD had significantly more activation in the cerebellum during finger tapping. Positive correlations between performance on a fine motor praxis test and activation multiple cortical regions were noted for children with PSD but not for controls. Over-activation in the cerebellum during a motor task may reflect a subtle abnormality in the non-speech motor neural circuitry in children with PSD. Copyright © 2014 Elsevier B.V. All rights reserved.

A new method for precise determination of endograft position and apposition in the aortic neck after endovascular aortic aneurysm repair.

PubMed

VAN Noort, Kim; Schuurmann, Richte C; Slump, Cornelis H; Vos, Jan A; Devries, Jean P

2016-10-01

Follow-up imaging after endovascular aortic aneurysm repair (EVAR) focuses on detection of gross abnormalities: endoleaks and significant (>10 mm) migration. Precise determination of endograft position and wall apposition may predict late complications. We present a new measurement method to determine precise position and apposition of endografts in the aortic neck. Four patients were selected from our EVAR database. These patients had late (>1 year) type IA endoleak or >1 cm endograft migration. Twenty patients with uneventful follow-up were measured as controls. The new software adds six parameters to define endograft position and neck apposition: fabric distance to renal arteries, tilt, endograft expansion (% of the maximum original diameter), neck surface, apposition surface, and shortest apposition length. These parameters were determined on preoperative and all available postoperative CT-scans, to detect subtle changes during follow-up. All patients with endoleak or migration had increases in fabric distance, tilt, or endograft expansion or decrease of apposition surface. Changes occurred at least one CT scan before the endoleak or migration was noted in the CT reports. The patient without complications showed no changes in position or apposition during follow-up. The new measurement method detected subtle changes in endograft position and apposition during CT follow-up, not recognized initially. It can potentially determine endograft movements and decrease of apposition surface before they lead to complications like type IA endoleaks or uncorrectable migration. A larger follow-up study comparing complicated and non-complicated EVAR patients is needed to corroborate these results.

BAEP and E.M.G. changes from whiplash injuries.

PubMed

Serra, L L; Gallicchio, B; Serra, F P; Grillo, G; Ferrari, M

1994-12-01

The frequent negativity of neuroradiological changes after neck injury despite the constant complaints (neck pain and stiffness, limited neck movements, arm pains) experienced after a motor vehicle crash has led us to verify the diagnostic and prognostic validity of different neurophysiological tests in these patients. To this aim 120 young patients (67 females and 53 males) referred for a whiplash syndrome aged 18-31 years without neuroradiological abnormalities have been submitted to EMG and BAEP studies immediately after the traffic accident and after six months. Constant slowing of median MNCV and SNCV and ulnar SNCV without changes in morphology, amplitude and duration of MAP and SAP have been observed in 92 patients, with persistent abnormalities in 64 cases after six months. Increase in I-III or I-V interpeak interval of BAEP have been observed unilaterally in 45 patients and bilaterally in 32 ones without changes in absolute latencies and V/I amplitude ratio, with persistence of such abnormalities in 31 and 16 patients respectively after six months. Simultaneous abnormalities of all neurophysiological tests have been observed in 31 patients, with unmodified recordings after six months in 24 patients. The above findings could be accounted for subtle cerebral lesions and a possible damage to brain stem structures as claimed by Ettlin et al. (1992). The usefulness of the above proposed neurophysiological tests in assessment of asymptomatic dysfunction of central motor and sensory pathways in whiplash injuries is discussed.

Stability of auditory discrimination and novelty processing in physiological aging.

PubMed

Raggi, Alberto; Tasca, Domenica; Rundo, Francesco; Ferri, Raffaele

2013-01-01

Complex higher-order cognitive functions and their possible changes with aging are mandatory objectives of cognitive neuroscience. Event-related potentials (ERPs) allow investigators to probe the earliest stages of information processing. N100, Mismatch negativity (MMN) and P3a are auditory ERP components that reflect automatic sensory discrimination. The aim of the present study was to determine if N100, MMN and P3a parameters are stable in healthy aged subjects, compared to those of normal young adults. Normal young adults and older participants were assessed using standardized cognitive functional instruments and their ERPs were obtained with an auditory stimulation at two different interstimulus intervals, during a passive paradigm. All individuals were within the normal range on cognitive tests. No significant differences were found for any ERP parameters obtained from the two age groups. This study shows that aging is characterized by a stability of the auditory discrimination and novelty processing. This is important for the arrangement of normative for the detection of subtle preclinical changes due to abnormal brain aging.

Lead contamination around secondary smelters: estimation of dispersal and accumulation by humans.

PubMed

Roberts, T M; Hutchinson, T C; Paciga, J; Chattopadhyay, A; Jervis, R E; VanLoon, J; Parkinson, D K

1974-12-20

A high rate of lead fallout around two secondary lead smelters originated mainly from episodal large-particulate emissions from low-level fugitive sources rather than from stack fumes. The lead content of dustfall, and consequently of soil, vegetation, and outdoor dust, decreased exponentially with distance from the two smelters. Between 13 and 30 percent of the children living in the contaminated areas had absorbed excessive amounts of lead (more than 40 micrograms per 100 milliliters of blood and more than 100 micrograms per gram of hair) as compared with less than 1 percent in a control group. A relationship between blood and hair was established which indicated that the absorption was fairly constant for most children examined. It seemned that the ingestion of contaminated dirt and dusts rather than "paint pica" was the major route of lead intake. Metabolic changes were found in most of 21 children selected from those with excessive lead absorption; 10 to 15 percent of this group showed subtle neurological dysfunctions and minor psychomotor abnormalities.

Brain metabolic correlates of decision making in amnestic mild cognitive impairment.

PubMed

Griffith, H Randall; Okonkwo, Ozioma C; den Hollander, Jan A; Belue, Katherine; Copeland, Jacqueline; Harrell, Lindy E; Brockington, John C; Clark, David G; Marson, Daniel C

2010-01-01

Persons with amnestic mild cognitive impairment (MCI) have subtle impairments in medical decision-making capacity (MDC). We examined the relationship between proton magnetic resonance spectroscopy (MRS) and MDC in MCI. Twenty-nine MCI patients and 42 controls underwent MRS to obtain ratios of N-acetylaspartate (NAA)/Creatine (Cr), Choline (Cho)/Cr, and myo-Inositol (mI)/Cr of the posterior cingulate. They also completed the Capacity to Consent to Treatment Instrument (CCTI), a vignette-based instrument measuring decisional standards of expressing choice, appreciating consequences of choice, providing rational reasons for choice, and understanding treatment choices. Patients showed abnormal MRS ratios of mI/Cr and Cho/Cr compared to controls, and impairments on the CCTI understanding and reasoning Standards. Performance on the reasoning standard of the CCTI was correlated with NAA/Cr (r = .46, p < .05). The relationship of NAA/Cr with decision-making suggests a role for posterior cortical neuronal functioning in performance of complex IADLs in MCI.

Drosophila PLP assembles pericentriolar clouds that promote centriole stability, cohesion and MT nucleation.

PubMed

Roque, Helio; Saurya, Saroj; Pratt, Metta B; Johnson, Errin; Raff, Jordan W

2018-02-01

Pericentrin is a conserved centrosomal protein whose dysfunction has been linked to several human diseases. It has been implicated in many aspects of centrosome and cilia function, but its precise role is unclear. Here, we examine Drosophila Pericentrin-like-protein (PLP) function in vivo in tissues that form both centrosomes and cilia. Plp mutant centrioles exhibit four major defects: (1) They are short and have subtle structural abnormalities; (2) They disengage prematurely, and so overduplicate; (3) They organise fewer cytoplasmic MTs during interphase; (4) When forming cilia, they fail to establish and/or maintain a proper connection to the plasma membrane-although, surprisingly, they can still form an axoneme-like structure that can recruit transition zone (TZ) proteins. We show that PLP helps assemble "pericentriolar clouds" of electron-dense material that emanate from the central cartwheel spokes and spread outward to surround the mother centriole. We propose that the partial loss of these structures may largely explain the complex centriole, centrosome and cilium defects we observe in Plp mutant cells.

Real-Time Vision-Based Stiffness Mapping †.

PubMed

Faragasso, Angela; Bimbo, João; Stilli, Agostino; Wurdemann, Helge Arne; Althoefer, Kaspar; Asama, Hajime

2018-04-26

This paper presents new findings concerning a hand-held stiffness probe for the medical diagnosis of abnormalities during palpation of soft-tissue. Palpation is recognized by the medical community as an essential and low-cost method to detect and diagnose disease in soft-tissue. However, differences are often subtle and clinicians need to train for many years before they can conduct a reliable diagnosis. The probe presented here fills this gap providing a means to easily obtain stiffness values of soft tissue during a palpation procedure. Our stiffness sensor is equipped with a multi degree of freedom (DoF) Aurora magnetic tracker, allowing us to track and record the 3D position of the probe whilst examining a tissue area, and generate a 3D stiffness map in real-time. The stiffness probe was integrated in a robotic arm and tested in an artificial environment representing a good model of soft tissue organs; the results show that the sensor can accurately measure and map the stiffness of a silicon phantom embedded with areas of varying stiffness.

Combination of behaviorally sub-effective doses of glutamate NMDA and dopamine D1 receptor antagonists impairs executive function.

PubMed

Desai, Sagar J; Allman, Brian L; Rajakumar, Nagalingam

2017-04-14

Impairment of executive function is a core feature of schizophrenia. Preclinical studies indicate that injections of either N-methyl d-aspartate (NMDA) or dopamine D 1 receptor blockers impair executive function. Despite the prevailing notion based on postmortem findings in schizophrenia that cortical areas have marked suppression of glutamate and dopamine, recent in vivo imaging studies suggest that abnormalities of these neurotransmitters in living patients may be quite subtle. Thus, we hypothesized that modest impairments in both glutamate and dopamine function can act synergistically to cause executive dysfunction. In the present study, we investigated the effect of combined administration of "behaviorally sub-effective" doses of NMDA and dopamine D 1 receptor antagonists on executive function. An operant conditioning-based set-shifting task was used to assess behavioral flexibility in rats that were systemically injected with NMDA and dopamine D 1 receptor antagonists individually or in combination prior to task performance. Separate injections of the NMDA receptor antagonist, MK-801, and the dopamine D 1 receptor antagonist, SCH 23390, at low doses did not impair set-shifting; however, the combined administration of these same behaviorally sub-effective doses of the antagonists significantly impaired the performance during set-shifting without affecting learning, retrieval of the memory of the initial rule, latency of responses or the number of omissions. The combined treatment also produced an increased number of perseverative errors. Our results indicate that NMDA and D 1 receptor blockade act synergistically to cause behavioral inflexibility, and as such, subtle abnormalities in glutamatergic and dopaminergic systems may act cooperatively to cause deficits in executive function. Copyright © 2017 Elsevier B.V. All rights reserved.

Automated airway evaluation system for multi-slice computed tomography using airway lumen diameter, airway wall thickness and broncho-arterial ratio

NASA Astrophysics Data System (ADS)

Odry, Benjamin L.; Kiraly, Atilla P.; Novak, Carol L.; Naidich, David P.; Lerallut, Jean-Francois

2006-03-01

Pulmonary diseases such as bronchiectasis, asthma, and emphysema are characterized by abnormalities in airway dimensions. Multi-slice computed tomography (MSCT) has become one of the primary means to depict these abnormalities, as the availability of high-resolution near-isotropic data makes it possible to evaluate airways at oblique angles to the scanner plane. However, currently, clinical evaluation of airways is typically limited to subjective visual inspection only: systematic evaluation of the airways to take advantage of high-resolution data has not proved practical without automation. We present an automated method to quantitatively evaluate airway lumen diameter, wall thickness and broncho-arterial ratios. In addition, our method provides 3D visualization of these values, graphically illustrating the location and extent of disease. Our algorithm begins by automatic airway segmentation to extract paths to the distal airways, and to create a map of airway diameters. Normally, airway diameters decrease as paths progress distally; failure to taper indicates abnormal dilatation. Our approach monitors airway lumen diameters along each airway path in order to detect abnormal profiles, allowing even subtle degrees of pathologic dilatation to be identified. Our method also systematically computes the broncho-arterial ratio at every terminal branch of the tree model, as a ratio above 1 indicates potentially abnormal bronchial dilatation. Finally, the airway wall thickness is computed at corresponding locations. These measurements are used to highlight abnormal branches for closer inspection, and can be summed to compute a quantitative global score for the entire airway tree, allowing reproducible longitudinal assessment of disease severity. Preliminary tests on patients diagnosed with bronchiectasis demonstrated rapid identification of lack of tapering, which also was confirmed by corresponding demonstration of elevated broncho-arterial ratios.

MRI as a tool to study brain structure from mouse models for mental retardation

NASA Astrophysics Data System (ADS)

Verhoye, Marleen; Sijbers, Jan; Kooy, R. F.; Reyniers, E.; Fransen, E.; Oostra, B. A.; Willems, Peter; Van der Linden, Anne-Marie

1998-07-01

Nowadays, transgenic mice are a common tool to study brain abnormalities in neurological disorders. These studies usually rely on neuropathological examinations, which have a number of drawbacks, including the risk of artefacts introduced by fixation and dehydration procedures. Here we present 3D Fast Spin Echo Magnetic Resonance Imaging (MRI) in combination with 2D and 3D segmentation techniques as a powerful tool to study brain anatomy. We set up MRI of the brain in mouse models for the fragile X syndrome (FMR1 knockout) and Corpus callosum hypoplasia, mental Retardation, Adducted thumbs, Spastic paraplegia and Hydrocephalus (CRASH) syndrome (L1CAM knockout). Our major goal was to determine qualitative and quantitative differences in specific brain structures. MRI of the brain of fragile X and CRASH patients has revealed alterations in the size of specific brain structures, including the cerebellar vermis and the ventricular system. In the present MRI study of the brain from fragile X knockout mice, we have measured the size of the brain, cerebellum and 4th ventricle, which were reported as abnormal in human fragile X patients, but found no evidence for altered brain regions in the mouse model. In CRASH syndrome, the most specific brain abnormalities are vermis hypoplasia and abnormalities of the ventricular system with some degree of hydrocephalus. With the MRI study of L1CAM knockout mice we found vermis hypoplasia, abnormalities of the ventricular system including dilatation of the lateral and the 4th ventricles. These subtle abnormalities were not detected upon standard neuropathological examination. Here we proved that this sensitive MRI technique allows to measure small differences which can not always be detected by means of pathology.

Pain empathy in schizophrenia: an fMRI study

PubMed Central

Jimenez, Amy M.; Lee, Junghee; Wynn, Jonathan K.; Eisenberger, Naomi I.; Green, Michael F.

2016-01-01

Abstract Although it has been proposed that schizophrenia is characterized by impaired empathy, several recent studies found intact neural responses on tasks measuring the affective subdomain of empathy. This study further examined affective empathy in 21 schizophrenia outpatients and 21 healthy controls using a validated pain empathy paradigm with two components: (i) observing videos of people described as medical patients who were receiving a painful sound stimulation treatment; (ii) listening to the painful sounds (to create regions of interest). The observing videos component incorporated experimental manipulations of perspective taking (instructions to imagine ‘Self’ vs ‘Other’ experiencing pain) and cognitive appraisal (information about whether treatment was ‘Effective’ vs ‘Not Effective’). When considering activation across experimental conditions, both groups showed similar dorsal anterior cingulate cortex (dACC) and anterior insula (AI) activation while merely observing others in pain. However, there were group differences associated with perspective taking: controls showed relatively greater dACC and AI activation for the Self vs Other contrast whereas patients showed relatively greater activation in these and additional regions for the Other vs Self contrast. Although patients demonstrated grossly intact neural activity while observing others in pain, they showed more subtle abnormalities when required to toggle between imagining themselves vs others experiencing pain. PMID:26746181

Pain empathy in schizophrenia: an fMRI study.

PubMed

Horan, William P; Jimenez, Amy M; Lee, Junghee; Wynn, Jonathan K; Eisenberger, Naomi I; Green, Michael F

2016-05-01

Although it has been proposed that schizophrenia is characterized by impaired empathy, several recent studies found intact neural responses on tasks measuring the affective subdomain of empathy. This study further examined affective empathy in 21 schizophrenia outpatients and 21 healthy controls using a validated pain empathy paradigm with two components: (i) observing videos of people described as medical patients who were receiving a painful sound stimulation treatment; (ii) listening to the painful sounds (to create regions of interest). The observing videos component incorporated experimental manipulations of perspective taking (instructions to imagine 'Self' vs 'Other' experiencing pain) and cognitive appraisal (information about whether treatment was 'Effective' vs 'Not Effective'). When considering activation across experimental conditions, both groups showed similar dorsal anterior cingulate cortex (dACC) and anterior insula (AI) activation while merely observing others in pain. However, there were group differences associated with perspective taking: controls showed relatively greater dACC and AI activation for the Self vs Other contrast whereas patients showed relatively greater activation in these and additional regions for the Other vs Self contrast. Although patients demonstrated grossly intact neural activity while observing others in pain, they showed more subtle abnormalities when required to toggle between imagining themselves vs others experiencing pain. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Oesophageal dysphagia: manifestations and diagnosis.

PubMed

Zerbib, Frank; Omari, Taher

2015-06-01

Oesophageal dysphagia is a common symptom, which might be related to severe oesophageal diseases such as carcinomas. Therefore, an organic process must be ruled out in the first instance by endoscopy in all patients presenting with dysphagia symptoms. The most prevalent obstructive aetiologies are oesophageal cancer, peptic strictures and eosinophilic oesophagitis. Eosinophilic oesophagitis is one of the most common causes of dysphagia in adults and children, thus justifying the need to obtain oesophageal biopsy samples from all patients presenting with unexplained dysphagia. With the advent of standardized high-resolution manometry and specific metrics to characterize oesophageal motility, the Chicago classification has become a gold-standard algorithm for manometric diagnosis of oesophageal motor disorders. In addition, sophisticated investigations and analysis methods that combine pressure and impedance measurement are currently in development. In the future, these techniques might be able to detect subtle pressure abnormalities during bolus transport, which could further explain pathophysiology and symptoms. The degree to which novel approaches will help distinguish dysphagia caused by motor abnormalities from functional dysphagia still needs to be determined.

Novel bandlike signal abnormality suggestive of heterotopia in patient with a KCNQ1 frameshift mutation.

PubMed

Sabharwal, Priyanka; Devinsky, Orrin; M Shepherd, Timothy

2017-12-01

Malformations of cortical development are associated with epilepsy and cognitive dysfunction, and can occur in patients with SCN1A ion channel mutations. We report a novel and subtle bandlike subcortical heterotopia on integrated positron emission tomography-magnetic resonance imaging ( PET-MRI) in a patient with treatment-resistant epilepsy due to a de novo KCNQ1 frameshift mutation. Our case highlights the potential for other channel mutations to cause both epilepsy and cortical malformations. Further scrutiny of high contrast resolution MRI studies is warranted for patients with KCNQ1 and other epilepsy genes to further define their extended phenotype.

Anesthesia, surgery, illness and Alzheimer's disease.

PubMed

Eckenhoff, Roderic G; Laudansky, Krzysztof F

2013-12-02

Patients and their families have, for many decades, detected subtle changes in cognition subsequent to surgery, and only recently has this been subjected to scientific scrutiny. Through a combination of retrospective human studies, small prospective biomarker studies, and experiments in animals, it is now clear that durable consequences of both anesthesia and surgery occur, and that these intersect with the normal processes of aging, and the abnormal processes of chronic neurodegeneration. It is highly likely that inflammatory cascades are at the heart of this intersection, and if confirmed, this suggests a therapeutic strategy to mitigate enhanced neuropathology in vulnerable surgical patients. Copyright © 2012 Elsevier Inc. All rights reserved.

Diagnosis and classification of pancreatic and duodenal injuries in emergency radiology.

PubMed

Linsenmaier, Ulrich; Wirth, Stefan; Reiser, Maximilian; Körner, Markus

2008-10-01

Pancreatic and duodenal injuries after blunt abdominal trauma are rare; however, delays in diagnosis and treatment can significantly increase morbidity and mortality. Multidetector computed tomography (CT) has a major role in early diagnosis of pancreatic and duodenal injuries. Detecting the often subtle signs of injury with whole-body CT can be difficult because this technique usually does not include a dedicated protocol for scanning the pancreas. Specific injury patterns in the pancreas and duodenum often have variable expression at early posttraumatic multidetector CT: They may be hardly visible, or there may be considerable exudate, hematomas, organ ruptures, or active bleeding. An accurate multidetector CT technique allows optimized detection of subtle abnormalities. In duodenal injuries, differentiation between a contusion of the duodenal wall or mural hematoma and a duodenal perforation is vital. In pancreatic injuries, determination of involvement of the pancreatic duct is essential. The latter conditions require immediate surgical intervention. Use of organ injury scales and a surgical classification adapted for multidetector CT enables classification of organ injuries for trauma scoring, treatment planning, and outcome control. In addition, multidetector CT reliably demonstrates potential complications of duodenal and pancreatic injuries, such as posttraumatic pancreatitis, pseudocysts, fistulas, exudates, and abscesses. (c) RSNA, 2008.

Digital mammography: comparative performance of color LCD and monochrome CRT displays.

PubMed

Samei, Ehsan; Poolla, Ananth; Ulissey, Michael J; Lewin, John M

2007-05-01

To evaluate the comparative performance of high-fidelity liquid crystal display (LCD) and cathode ray tube (CRT) devices for mammography applications, and to assess the impact of LCD viewing angle on detection accuracy. Ninety 1 k x 1 k images were selected from a database of digital mammograms: 30 without any abnormality present, 30 with subtle masses, and 30 with subtle microcalcifications. The images were used with waived informed consent, Health Insurance Portability and Accountability Act compliance, and Institutional Review Board approval. With postprocessing presentation identical to those of the commercial mammography system used, 1 k x 1 k sections of images were viewed on a monochrome CRT and a color LCD in native grayscale, and with a grayscale representative of images viewed from a 30 degrees or 50 degrees off-normal viewing angle. Randomized images were independently scored by four experienced breast radiologists for the presence of lesions using a 0-100 grading scale. To compare diagnostic performance of the display modes, observer scores were analyzed using receiver operating characteristic (ROC) and analysis of variance. For masses and microcalcifications, the detection rate in terms of the area under the ROC curve (A(z)) showed a 2% increase and a 4% decrease from CRT to LCD, respectively. However, differences were not statistically significant (P > .05). The viewing angle data showed better microcalcification detection but lower mass detection at 30 degrees viewing orientation. The overall results varied notably from observer to observer yielding no statistically discernible trends across all observers, suggesting that within the 0-50 degrees viewing angle range and in a controlled observer experiment, the variation in the contrast response of the LCD has little or no impact on the detection of mammographic lesions. Although CRTs and LCDs differ in terms of angular response, resolution, noise, and color, these characteristics seem to have little influence on the detection of mammographic lesions. The results suggest comparable performance in clinical applications of the two devices.

Clinical, biochemical, and neuropsychiatric evaluation of a patient with a contiguous gene syndrome due to a microdeletion Xp11.3 including the Norrie disease locus and monoamine oxidase (MAOA and MAOB) genes.

PubMed

Collins, F A; Murphy, D L; Reiss, A L; Sims, K B; Lewis, J G; Freund, L; Karoum, F; Zhu, D; Maumenee, I H; Antonarakis, S E

1992-01-01

Norrie disease is a rare X-linked recessive disorder characterized by blindness from infancy. The gene for Norrie disease has been localized to Xp11.3. More recently, the genes for monoamine oxidase (MAOA, MAOB) have been mapped to the same region. This study evaluates the clinical, biochemical, and neuropsychiatric data in an affected male and 2 obligate heterozygote females from a single family with a submicroscopic deletion involving Norrie disease and MAO genes. The propositus was a profoundly retarded, blind male; he also had neurologic abnormalities including myoclonus and stereotopy-habit disorder. Both obligate carrier females had a normal IQ. The propositus' mother met diagnostic criteria for "chronic hypomania and schizotypal features." The propositus' MAO activity was undetectable and the female heterozygotes had reduced levels comparable to patients receiving MAO inhibiting antidepressants. MAO substrate and metabolite abnormalities were found in the propositus' plasma and CSF. This study indicates that subtle biochemical and possibly neuropsychiatric abnormalities may be detected in some heterozygotes with the microdeletion in Xp11.3 due to loss of the gene product for the MAO genes; this deletion can also explain some of the complex phenotype of this contiguous gene syndrome in the propositus.

ERP evidence of preserved early memory function in term infants with neonatal encephalopathy following therapeutic hypothermia.

PubMed

Pfister, Katie M; Zhang, Lei; Miller, Neely C; Hultgren, Solveig; Boys, Chris J; Georgieff, Michael K

2016-12-01

Neonatal encephalopathy (NE) carries high risk for neurodevelopmental impairments. Therapeutic hypothermia (TH) reduces this risk, particularly for moderate encephalopathy (ME). Nevertheless, these infants often have subtle functional deficits, including abnormal memory function. Detection of deficits at the earliest possible time-point would allow for intervention during a period of maximal brain plasticity. Recognition memory function in 22 infants with NE treated with TH was compared to 23 healthy controls using event-related potentials (ERPs) at 2 wk of age. ERPs were recorded to mother's voice alternating with a stranger's voice to assess attentional responses (P2), novelty detection (slow wave), and discrimination between familiar and novel (difference wave). Development was tested at 12 mo using the Bayley Scales of Infant Development, Third Edition (BSID-III). The NE group showed similar ERP components and BSID-III scores to controls. However, infants with NE showed discrimination at midline leads (P = 0.01), whereas controls showed discrimination in the left hemisphere (P = 0.05). Normal MRI (P = 0.05) and seizure-free electroencephalogram (EEG) (P = 0.04) correlated positively with outcomes. Infants with NE have preserved recognition memory function after TH. The spatially different recognition memory processing after early brain injury may represent compensatory changes in the brain circuitry and reflect a benefit of TH.

Gut-lung crosstalk in pulmonary involvement with inflammatory bowel diseases.

PubMed

Wang, Hui; Liu, Jing-Shi; Peng, Shao-Hua; Deng, Xi-Yun; Zhu, De-Mao; Javidiparsijani, Sara; Wang, Gui-Rong; Li, Dai-Qiang; Li, Long-Xuan; Wang, Yi-Chun; Luo, Jun-Ming

2013-10-28

Pulmonary abnormalities, dysfunction or hyper-reactivity occurs in association with inflammatory bowel disease (IBD) more frequently than previously recognized. Emerging evidence suggests that subtle inflammation exists in the airways among IBD patients even in the absence of any bronchopulmonary symptoms, and with normal pulmonary functions. The pulmonary impairment is more pronounced in IBD patients with active disease than in those in remission. A growing number of case reports show that the IBD patients develop rapidly progressive respiratory symptoms after colectomy, with failure to isolate bacterial pathogens on repeated sputum culture, and often request oral corticosteroid therapy. All the above evidence indicates that the inflammatory changes in both the intestine and lung during IBD. Clinical or subclinical pulmonary inflammation accompanies the main inflammation of the bowel. Although there are clinical and epidemiological reports of chronic inflammation of the pulmonary and intestinal mucosa in IBD, the detailed mechanisms of pulmonary-intestinal crosstalk remain unknown. The lung has no anatomical connection with the main inflammatory site of the bowel. Why does the inflammatory process shift from the gastrointestinal tract to the airways? The clinical and subclinical pulmonary abnormalities, dysfunction, or hyper-reactivity among IBD patients need further evaluation. Here, we give an overview of the concordance between chronic inflammatory reactions in the airways and the gastrointestinal tract. A better understanding of the possible mechanism of the crosstalk among the distant organs will be beneficial in identifying therapeutic strategies for mucosal inflammatory diseases such as IBD and allergy.

Gut-lung crosstalk in pulmonary involvement with inflammatory bowel diseases

PubMed Central

Wang, Hui; Liu, Jing-Shi; Peng, Shao-Hua; Deng, Xi-Yun; Zhu, De-Mao; Javidiparsijani, Sara; Wang, Gui-Rong; Li, Dai-Qiang; Li, Long-Xuan; Wang, Yi-Chun; Luo, Jun-Ming

2013-01-01

Pulmonary abnormalities, dysfunction or hyper-reactivity occurs in association with inflammatory bowel disease (IBD) more frequently than previously recognized. Emerging evidence suggests that subtle inflammation exists in the airways among IBD patients even in the absence of any bronchopulmonary symptoms, and with normal pulmonary functions. The pulmonary impairment is more pronounced in IBD patients with active disease than in those in remission. A growing number of case reports show that the IBD patients develop rapidly progressive respiratory symptoms after colectomy, with failure to isolate bacterial pathogens on repeated sputum culture, and often request oral corticosteroid therapy. All the above evidence indicates that the inflammatory changes in both the intestine and lung during IBD. Clinical or subclinical pulmonary inflammation accompanies the main inflammation of the bowel. Although there are clinical and epidemiological reports of chronic inflammation of the pulmonary and intestinal mucosa in IBD, the detailed mechanisms of pulmonary-intestinal crosstalk remain unknown. The lung has no anatomical connection with the main inflammatory site of the bowel. Why does the inflammatory process shift from the gastrointestinal tract to the airways? The clinical and subclinical pulmonary abnormalities, dysfunction, or hyper-reactivity among IBD patients need further evaluation. Here, we give an overview of the concordance between chronic inflammatory reactions in the airways and the gastrointestinal tract. A better understanding of the possible mechanism of the crosstalk among the distant organs will be beneficial in identifying therapeutic strategies for mucosal inflammatory diseases such as IBD and allergy. PMID:24187454

Progressive Functional Impairments of Hippocampal Neurons in a Tauopathy Mouse Model

PubMed Central

Ciupek, Sarah M.; Cheng, Jingheng; Ali, Yousuf O.; Lu, Hui-Chen

2015-01-01

The age-dependent progression of tau pathology is a major characteristic of tauopathies, including Alzheimer's disease (AD), and plays an important role in the behavioral phenotypes of AD, including memory deficits. Despite extensive molecular and cellular studies on tau pathology, it remains to be determined how it alters the neural circuit functions underlying learning and memory in vivo. In rTg4510 mice, a Tau-P301L tauopathy model, hippocampal place fields that support spatial memories are abnormal at old age (7–9 months) when tau tangles and neurodegeneration are extensive. However, it is unclear how the abnormality in the hippocampal circuit function arises and progresses with the age-dependent progression of tau pathology. Here we show that in young (2–4 months of age) rTg4510 mice, place fields of hippocampal CA1 cells are largely normal, with only subtle differences from those of age-matched wild-type control mice. Second, high-frequency ripple oscillations of local field potentials in the hippocampal CA1 area are significantly reduced in young rTg4510 mice, and even further deteriorated in old rTg4510 mice. The ripple reduction is associated with less bursty firing and altered synchrony of CA1 cells. Together, the data indicate that deficits in ripples and neuronal synchronization occur before overt deficits in place fields in these mice. The results reveal a tau-pathology-induced progression of hippocampal functional changes in vivo. PMID:26019329

Assessment of cerebral blood flow with magnetic resonance imaging in children with sickle cell disease: A quantitative comparison with transcranial Doppler ultrasonography.

PubMed

Croal, Paula L; Leung, Jackie; Kosinski, Przemyslaw; Shroff, Manohar; Odame, Isaac; Kassner, Andrea

2017-11-01

Transcranial Doppler ultrasonography (TCD) is a clinical tool for stratifying ischemic stroke risk by identifying abnormal elevations in blood flow velocity (BFV) in the middle cerebral artery (MCA). However, TCD is not effective at screening for subtle neurologic injury such as silent cerebral infarcts. To better understand this disparity, we compared TCD measures of BFV with tissue-level cerebral blood flow (CBF) using arterial spin-labeling MRI in children with and without sickle cell disease, and correlated these measurements against clinical hematologic measures of disease severity. TCD and MRI assessment were performed in 13 pediatric sickle cell disease patients and eight age-matched controls. Using MRI measures of MCA diameter and territory weight, TCD measures of BFV in the MCA [cm/s] were converted into units of CBF [ml min -1 100 g -1 ] for comparison. There was no significant association between TCD measures of BFV in the MCA and corresponding MRI measures of CBF in patients ( r  =   .28, p  =   .39) or controls ( r  =   .10, p  =   .81). After conversion from BFV into units of CBF, a strong association was observed between TCD and MRI measures ( r  =   .67, p  =   .017 in patients, r  =   .86, p  =   .006 in controls). While BFV in the MCA showed a lack of correlation with arterial oxygen content, an inverse association was observed for CBF measurements. This study demonstrates that BFV in the MCA cannot be used as a surrogate marker for tissue-level CBF in children with sickle cell disease. Therefore, TCD alone may not be sufficient for understanding and predicting subtle pathophysiology in this population, highlighting the potential clinical value of tissue-level CBF.

Breast screening: What can the interval cancer review teach us? Are we perhaps being a bit too hard on ourselves?

PubMed

Lekanidi, Katerina; Dilks, Phil; Suaris, Tamara; Kennett, Steffan; Purushothaman, Hema

2017-09-01

The aim of this study was to determine the features that make interval cancers apparent on the preceding screening mammogram and determine whether changes in the ways of performing the interval cancer review will affect the true interval cancer rate. This study was approved by the clinical governance committee. Mammograms of women diagnosed with an interval cancer were included in the study if they had been allocated to either the "suspicious signs" group or "subtle signs" group, during the historic interval cancer review. Three radiologists, individually and blinded to the site of interval cancer, reviewed the mammograms and documented the presence, site, characteristics and classification of any abnormality. Findings were compared with the appearances of the abnormality at the site of subsequent cancer development by a different breast radiologist. The chi-squared test was used in the analysis of the results, seeking associations between recall concordance and cancer mammographic or histological characteristics. 111/590 interval cancers fulfilled the study inclusion criteria. In 17% of the cases none of the readers identified the relevant abnormality on the screening mammogram. 1/3 readers identified the relevant lesion in 22% of the cases, 2/3 readers in 28% of cases and all 3 readers in 33% of cases. The commonest unanimously recalled abnormality was microcalcification and the most challenging mammographic abnormality to detect was asymmetric density. We did not find any statistically significant association between recall concordance and time to interval cancer, position of lesion in the breast, breast density or cancer grade. Even the simple step of performing an independent blinded review of interval cancers reduces the rate of interval cancers classified as missed by up to 39%. Copyright © 2017 Elsevier B.V. All rights reserved.

Pigmentary Maculopathy Associated with Chronic Exposure to Pentosan Polysulfate Sodium.

PubMed

Pearce, William A; Chen, Rui; Jain, Nieraj

2018-05-22

To describe the clinical features of a unique pigmentary maculopathy noted in the setting of chronic exposure to pentosan polysulfate sodium (PPS), a therapy for interstitial cystitis (IC). Retrospective case series. Six adult patients evaluated by a single clinician between May 1, 2015, and October 1, 2017. Patients were identified by query of the electronic medical record system. Local records were reviewed, including results of the clinical examination, retinal imaging, and visual function assessment with static perimetry and electroretinography. Molecular testing assessed for known macular dystrophy and mitochondrial cytopathy genotypes. Mean best-corrected visual acuity (BCVA; in logarithm of the minimum angle of resolution units), median cumulative PPS exposure, subjective nature of the associated visual disturbance, qualitative examination and imaging features, and molecular testing results. The median age at presentation was 60 years (range, 37-62 years). All patients received PPS for a diagnosis of IC, with a median cumulative exposure of 2263 g (range, 1314-2774 g), over a median duration of exposure of 186 months (range, 144-240 months). Most patients (4 of 6) reported difficulty reading as the most bothersome symptom. Mean BCVA was 0.1±0.18 logarithm of the minimum angle of resolution. On fundus examination, nearly all eyes showed subtle paracentral hyperpigmentation at the level of the retinal pigment epithelium (RPE) with a surrounding array of vitelliform-like deposits. Four eyes of 2 patients showed paracentral RPE atrophy, and no eyes demonstrated choroidal neovascularization. Multimodal retinal imaging demonstrated abnormality of the RPE generally contained in a well-delineated area in the posterior pole. None of the 4 patients who underwent molecular testing of nuclear DNA returned a pathogenic mutation. Additionally, all 6 patients showed negative results for pathogenic variants in the mitochondrial gene MTTL1. We describe a novel and possibly avoidable maculopathy associated with chronic exposure to PPS. Patients reported symptoms of difficulty reading and prolonged dark adaptation despite generally intact visual acuity and subtle funduscopic findings. Multimodal imaging and functional studies are suggestive of a primary RPE injury. Additional investigation is warranted to explore causality further. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Clinical biochemistry

NASA Technical Reports Server (NTRS)

Alexander, W. C.; Leach, C. S.; Fischer, C. L.

1975-01-01

The objectives of the biochemical studies conducted for the Apollo program were (1) to provide routine laboratory data for assessment of preflight crew physical status and for postflight comparisons; (2) to detect clinical or pathological abnormalities which might have required remedial action preflight; (3) to discover as early as possible any infectious disease process during the postflight quarantine periods following certain missions; and (4) to obtain fundamental medical knowledge relative to man's adjustment to and return from the space flight environment. The accumulated data presented suggest that these requirements were met by the program described. All changes ascribed to the space flight environment were subtle, whereas clinically significant changes were consistent with infrequent illnesses unrelated to the space flight exposure.

The Effect Of Digital Unsharp Masking On The Detectability Of Interstitial Infiltrates And Pneumothoraces

NASA Astrophysics Data System (ADS)

MacMahon, Heber; Vyborny, Carl; Sabeti, Victoria; Metz, Charles; Doi, Kunio

1985-09-01

A potential advantage of digital radiographic systems is their ability to enhance images by various types of processing. Digital unsharp masking is one of the simplest and potentially most useful forms of enhancement. The efficacy of unsharp masking in clinical radiologic diagnosis has not been investigated systematically, however. The effect of digital unsharp masking on the detectability of two types of subtle abnormalities, pneumothorax and interstitial infiltrate, was studied in an observer performance test. An ROC analysis of this preliminary data suggests that unsharp masking may improve diagnostic accuracy for pneumothorax. Radiologists' performance in identifying interstitial infiltrates was degraded by the image processing, however, and false positive diagnoses tended to be more frequent.

Imaging and Screening of Cancer of the Small Bowel.

PubMed

Kim, Jin Sil; Park, Seong Ho; Hansel, Stephanie; Fletcher, Joel G

2017-11-01

Delayed diagnosis of small bowel cancers frequently occurs and may arise because of many factors, including low incidence of disease, difficult endoscopic access, lack of mucosal mass or abnormality, subtle radiologic features, and low index of clinical suspicion. As small bowel cancers are rare and their causes are largely unknown, routine population-based screening of asymptomatic patients to find precursor lesions or early cancers is ineffective. However, targeted screening/surveillance strategies are used in specific at-risk and symptomatic patient populations. This article reviews issues regarding early diagnosis of small bowel cancers, with focus on state-of-the-art cross-sectional imaging techniques. Copyright © 2017 Elsevier Inc. All rights reserved.

Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma: magnifying endoscopy findings.

PubMed

Law, T T; Tong, Daniel; Wong, Sam W H; Chan, S Y; Law, Simon

2015-04-01

Gastric mucosa-associated lymphoid tissue lymphoma is uncommon and most patients have an indolent clinical course. The clinical presentation and endoscopic findings can be subtle and diagnosis can be missed on white light endoscopy. Magnifying endoscopy may help identify the abnormal microstructural and microvascular patterns, and target biopsies can be performed. We describe herein the case of a 64-year-old woman with Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma diagnosed by screening magnification endoscopy. Helicobacter pylori-eradication therapy was given and she received biological therapy. She is in clinical remission after treatment. The use of magnification endoscopy in gastric mucosa-associated lymphoid tissue lymphoma and its management are reviewed.

Accurate registration of temporal CT images for pulmonary nodules detection

NASA Astrophysics Data System (ADS)

Yan, Jichao; Jiang, Luan; Li, Qiang

2017-02-01

Interpretation of temporal CT images could help the radiologists to detect some subtle interval changes in the sequential examinations. The purpose of this study was to develop a fully automated scheme for accurate registration of temporal CT images for pulmonary nodule detection. Our method consisted of three major registration steps. Firstly, affine transformation was applied in the segmented lung region to obtain global coarse registration images. Secondly, B-splines based free-form deformation (FFD) was used to refine the coarse registration images. Thirdly, Demons algorithm was performed to align the feature points extracted from the registered images in the second step and the reference images. Our database consisted of 91 temporal CT cases obtained from Beijing 301 Hospital and Shanghai Changzheng Hospital. The preliminary results showed that approximately 96.7% cases could obtain accurate registration based on subjective observation. The subtraction images of the reference images and the rigid and non-rigid registered images could effectively remove the normal structures (i.e. blood vessels) and retain the abnormalities (i.e. pulmonary nodules). This would be useful for the screening of lung cancer in our future study.

Real-Time Vision-Based Stiffness Mapping †

PubMed Central

Althoefer, Kaspar; Asama, Hajime

2018-01-01

This paper presents new findings concerning a hand-held stiffness probe for the medical diagnosis of abnormalities during palpation of soft-tissue. Palpation is recognized by the medical community as an essential and low-cost method to detect and diagnose disease in soft-tissue. However, differences are often subtle and clinicians need to train for many years before they can conduct a reliable diagnosis. The probe presented here fills this gap providing a means to easily obtain stiffness values of soft tissue during a palpation procedure. Our stiffness sensor is equipped with a multi degree of freedom (DoF) Aurora magnetic tracker, allowing us to track and record the 3D position of the probe whilst examining a tissue area, and generate a 3D stiffness map in real-time. The stiffness probe was integrated in a robotic arm and tested in an artificial environment representing a good model of soft tissue organs; the results show that the sensor can accurately measure and map the stiffness of a silicon phantom embedded with areas of varying stiffness. PMID:29701704

Drosophila PLP assembles pericentriolar clouds that promote centriole stability, cohesion and MT nucleation

PubMed Central

Pratt, Metta B.; Johnson, Errin

2018-01-01

Pericentrin is a conserved centrosomal protein whose dysfunction has been linked to several human diseases. It has been implicated in many aspects of centrosome and cilia function, but its precise role is unclear. Here, we examine Drosophila Pericentrin-like-protein (PLP) function in vivo in tissues that form both centrosomes and cilia. Plp mutant centrioles exhibit four major defects: (1) They are short and have subtle structural abnormalities; (2) They disengage prematurely, and so overduplicate; (3) They organise fewer cytoplasmic MTs during interphase; (4) When forming cilia, they fail to establish and/or maintain a proper connection to the plasma membrane—although, surprisingly, they can still form an axoneme-like structure that can recruit transition zone (TZ) proteins. We show that PLP helps assemble “pericentriolar clouds” of electron-dense material that emanate from the central cartwheel spokes and spread outward to surround the mother centriole. We propose that the partial loss of these structures may largely explain the complex centriole, centrosome and cilium defects we observe in Plp mutant cells. PMID:29425198

Haploinsufficiency of MeCP2-interacting transcriptional co-repressor SIN3A causes mild intellectual disability by affecting the development of cortical integrity.

PubMed

Witteveen, Josefine S; Willemsen, Marjolein H; Dombroski, Thaís C D; van Bakel, Nick H M; Nillesen, Willy M; van Hulten, Josephus A; Jansen, Eric J R; Verkaik, Dave; Veenstra-Knol, Hermine E; van Ravenswaaij-Arts, Conny M A; Wassink-Ruiter, Jolien S Klein; Vincent, Marie; David, Albert; Le Caignec, Cedric; Schieving, Jolanda; Gilissen, Christian; Foulds, Nicola; Rump, Patrick; Strom, Tim; Cremer, Kirsten; Zink, Alexander M; Engels, Hartmut; de Munnik, Sonja A; Visser, Jasper E; Brunner, Han G; Martens, Gerard J M; Pfundt, Rolph; Kleefstra, Tjitske; Kolk, Sharon M

2016-08-01

Numerous genes are associated with neurodevelopmental disorders such as intellectual disability and autism spectrum disorder (ASD), but their dysfunction is often poorly characterized. Here we identified dominant mutations in the gene encoding the transcriptional repressor and MeCP2 interactor switch-insensitive 3 family member A (SIN3A; chromosome 15q24.2) in individuals who, in addition to mild intellectual disability and ASD, share striking features, including facial dysmorphisms, microcephaly and short stature. This phenotype is highly related to that of individuals with atypical 15q24 microdeletions, linking SIN3A to this microdeletion syndrome. Brain magnetic resonance imaging showed subtle abnormalities, including corpus callosum hypoplasia and ventriculomegaly. Intriguingly, in vivo functional knockdown of Sin3a led to reduced cortical neurogenesis, altered neuronal identity and aberrant corticocortical projections in the developing mouse brain. Together, our data establish that haploinsufficiency of SIN3A is associated with mild syndromic intellectual disability and that SIN3A can be considered to be a key transcriptional regulator of cortical brain development.

Hyperspectral Image Enhancement and Mixture Deep-Learning Classification of Corneal Epithelium Injuries.

PubMed

Noor, Siti Salwa Md; Michael, Kaleena; Marshall, Stephen; Ren, Jinchang

2017-11-16

In our preliminary study, the reflectance signatures obtained from hyperspectral imaging (HSI) of normal and abnormal corneal epithelium tissues of porcine show similar morphology with subtle differences. Here we present image enhancement algorithms that can be used to improve the interpretability of data into clinically relevant information to facilitate diagnostics. A total of 25 corneal epithelium images without the application of eye staining were used. Three image feature extraction approaches were applied for image classification: (i) image feature classification from histogram using a support vector machine with a Gaussian radial basis function (SVM-GRBF); (ii) physical image feature classification using deep-learning Convolutional Neural Networks (CNNs) only; and (iii) the combined classification of CNNs and SVM-Linear. The performance results indicate that our chosen image features from the histogram and length-scale parameter were able to classify with up to 100% accuracy; particularly, at CNNs and CNNs-SVM, by employing 80% of the data sample for training and 20% for testing. Thus, in the assessment of corneal epithelium injuries, HSI has high potential as a method that could surpass current technologies regarding speed, objectivity, and reliability.

Selective incivility: immigrant groups experience subtle workplace discrimination at different rates.

PubMed

Krings, Franciska; Johnston, Claire; Binggeli, Steve; Maggiori, Christian

2014-10-01

Immigrants play an increasingly important role in local labor markets. Not only do they grow steadily in number but also in cultural, educational, and skill diversity, underlining the necessity to distinguish between immigrant groups when studying discrimination against immigrants. We examined immigrant employees' subtle discrimination experiences in a representative sample in Switzerland, controlling for dispositional influences. Results showed that mainly members of highly competitive immigrant groups, from immediate neighbor countries, experienced workplace incivility and that these incivility experiences were related to higher likelihoods of perceived discrimination at work. This research confirms recent accounts that successful but disliked groups are particularly likely to experience subtle interpersonal discrimination. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Cervical spine MRI in patients with negative CT: A prospective, multicenter study of the Research Consortium of New England Centers for Trauma (ReCONECT).

PubMed

Maung, Adrian A; Johnson, Dirk C; Barre, Kimberly; Peponis, Thomas; Mesar, Tomaz; Velmahos, George C; McGrail, Daniel; Kasotakis, George; Gross, Ronald I; Rosenblatt, Michael S; Sihler, Kristen C; Winchell, Robert J; Cholewczynski, Walter; Butler, Kathryn L; Odom, Stephen R; Davis, Kimberly A

2017-02-01

Although cervical spine CT (CSCT) accurately detects bony injuries, it may not identify all soft tissue injuries. Although some clinicians rely exclusively on a negative CT to remove spine precautions in unevaluable patients or patients with cervicalgia, others use MRI for that purpose. The objective of this study was to determine the rates of abnormal MRI after a negative CSCT. Blunt trauma patients who either were unevaluable or had persistent midline cervicalgia and underwent an MRI of the C-spine after a negative CSCT were enrolled prospectively in eight Level I and II New England trauma centers. Demographics, injury patterns, CT and MRI results, and any changes in cervical spine management as a result of MRI imaging were recorded. A total of 767 patients had MRI because of cervicalgia (43.0%), inability to evaluate (44.1%), or both (9.4%). MRI was abnormal in 23.6% of all patients, including ligamentous injury (16.6%), soft tissue swelling (4.3%), vertebral disc injury (1.4%), and dural hematomas (1.3%). Rates of abnormal neurological signs or symptoms were not different among patients with normal versus abnormal MRI. (15.2 vs. 18.8%, p = 0.25). The c-collar was removed in 88.1% of patients with normal MRI and 13.3% of patients with an abnormal MRI. No patient required halo placement, but 11 patients underwent cervical spine surgery after the MRI results. Six of the eleven had neurological signs or symptoms. In a select population of patients, MRI identified additional injuries in 23.6% of patients despite a normal CSCT. It is uncertain if this is a true limitation of CT technology or represents subtle injuries missed in the interpretation of the scan. The clinical significance of these abnormal MRI findings cannot be determined from this study group. Therapeutic study, level IV.

The assessment of ovulation by a combination of ultrasound and detailed serial hormone profiles in 35 women with long-standing unexplained infertility.

PubMed

Petsos, P; Chandler, C; Oak, M; Ratcliffe, W A; Wood, R; Anderson, D C

1985-06-01

We have examined for the presence of subtle hormonal abnormalities in women with long-standing unexplained infertility. For a full cycle serum LH, FSH, progesterone and oestradiol levels were measured about three times a week, and serial ultrasound scans of the ovaries made until the time of apparent ovulation. The results on 45 cycles in 35 women with unexplained infertility and in three normal volunteers are presented. Normal ovulatory cycles were defined by a length of 26-32 d, and progressive follicular maturation followed by disappearance or abrupt reduction in size of a follicle within 48 h of the recorded LH peak, followed by progressive and sustained rise in serum progesterone levels to more than 25 nmol/l and a luteal phase length of greater than or equal to 13 d. Thirty spontaneous cycles (28 women) were clearly normal while 15 spontaneous cycles (12 women) were abnormal. Abnormalities included luteinization of an unruptured follicle (eight cycles), absence of follicular development (two cycles), poor follicular development (two cycles), persistence of a large ovarian cyst from the preceeding cycle (two cycles) and one aluteal cycle. Six of the abnormal cycles were characterized hormonally by inappropriate elevation of serum LH levels throughout. If this study had been based only on serial ultrasound scans, all results on abnormal cycles might have been misinterpreted. If it had been conducted only with (multiple) progesterone determinations and the level of greater than 25 nmol/l had been taken as indicative of ovulation nine clearly abnormal cycles would have been considered as normal. We conclude that the combination of the hormonal and ultrasound assessment of ovulation increases our confidence for confirmation of normality and reveals various ovulatory disorders which are possibly due to an endocrinological defect or defects.

Subclinical hypothyroidism in childhood - current knowledge and open issues.

PubMed

Salerno, Mariacarolina; Capalbo, Donatella; Cerbone, Manuela; De Luca, Filippo

2016-12-01

Subclinical hypothyroidism is defined as serum levels of TSH above the upper limit of the reference range, in the presence of normal concentrations of total T 4 or free T 4 . This biochemical profile might be an indication of mild hypothyroidism, with a potential increased risk of metabolic abnormalities and cardiovascular disease recorded among adults. Whether subclinical hypothyroidism results in adverse health outcomes among children is a matter of debate and so management of this condition remains challenging. Mild forms of untreated subclinical hypothyroidism do not seem to be associated with impairments in growth, bone health or neurocognitive outcome. However, ongoing scientific investigations have highlighted the presence of subtle proatherogenic abnormalities among children with modest elevations in their TSH levels. Although current findings are insufficient to recommend levothyroxine treatment for all children with mild asymptomatic forms of subclinical hypothyroidism, they highlight the potential need for assessment of cardiovascular risk among children with this condition. Increased understanding of the early metabolic risk factors associated with subclinical hypothyroidism in childhood will help to improve the management of affected individuals.

Classification of pulmonary airway disease based on mucosal color analysis

NASA Astrophysics Data System (ADS)

Suter, Melissa; Reinhardt, Joseph M.; Riker, David; Ferguson, John Scott; McLennan, Geoffrey

2005-04-01

Airway mucosal color changes occur in response to the development of bronchial diseases including lung cancer, cystic fibrosis, chronic bronchitis, emphysema and asthma. These associated changes are often visualized using standard macro-optical bronchoscopy techniques. A limitation to this form of assessment is that the subtle changes that indicate early stages in disease development may often be missed as a result of this highly subjective assessment, especially in inexperienced bronchoscopists. Tri-chromatic CCD chip bronchoscopes allow for digital color analysis of the pulmonary airway mucosa. This form of analysis may facilitate a greater understanding of airway disease response. A 2-step image classification approach is employed: the first step is to distinguish between healthy and diseased bronchoscope images and the second is to classify the detected abnormal images into 1 of 4 possible disease categories. A database of airway mucosal color constructed from healthy human volunteers is used as a standard against which statistical comparisons are made from mucosa with known apparent airway abnormalities. This approach demonstrates great promise as an effective detection and diagnosis tool to highlight potentially abnormal airway mucosa identifying a region possibly suited to further analysis via airway forceps biopsy, or newly developed micro-optical biopsy strategies. Following the identification of abnormal airway images a neural network is used to distinguish between the different disease classes. We have shown that classification of potentially diseased airway mucosa is possible through comparative color analysis of digital bronchoscope images. The combination of the two strategies appears to increase the classification accuracy in addition to greatly decreasing the computational time.

Models and molecular approaches to assessing the effects of the microgravity environment on vertebrate development

NASA Technical Reports Server (NTRS)

Wolgemuth, D. J.; Murashov, A. K.

1995-01-01

The extent to which gravity, and especially the lack thereof, can affect normal development in higher organisms is poorly understood. Underlying this question is the assumption that normal development depends on the embryo's ability to maintain a programmed temporal and spatial coordination of morphogenetic events. There are several reports documenting the apparently normal development of several vertebrate species, including mammals, under conditions of exposure to space flight during various periods of the development process. Evidence to the contrary also exists and it is therefore likely that some alterations in morphology do occur in a microgravity environment. Although subsequent development may appear overtly normal, more subtle abnormalities result. In all studies, the evaluation is restricted by the few numbers of specimens that can be examined and the relatively insensitive techniques for assessing potentially subtle effects. In the present discussion, we summarize some observations of mammalian development made in microgravity and consider which stages might be expected to be differentially sensitive to altered gravity conditions. While we emphasize mammalian development, we discuss the suitability of another model system for examining such effects in a cross-species context. Furthermore, we consider recent developments in our understanding of the molecular genetic program regulating embryogenesis that could serve as markers for assessing perturbations of development.

Neurologic and developmental features of the Smith-Magenis syndrome (del 17p11.2).

PubMed

Gropman, Andrea L; Duncan, Wallace C; Smith, Ann C M

2006-05-01

The Smith-Magenis syndrome is a rare, complex multisystemic disorder featuring, mental retardation and multiple congenital anomalies caused by a heterozygous interstitial deletion of chromosome 17p11.2. The phenotype of Smith-Magenis syndrome is characterized by a distinct pattern of features including infantile hypotonia, generalized complacency and lethargy in infancy, minor skeletal (brachycephaly, brachydactyly) and craniofacial features, ocular abnormalities, middle ear and laryngeal abnormalities including hoarse voice, as well as marked early expressive speech and language delays, psychomotor and growth retardation, and a 24-hour sleep disturbance. A striking neurobehavioral pattern of stereotypies, hyperactivity, polyembolokoilamania, onychotillomania, maladaptive and self-injurious and aggressive behavior is observed with increasing age. The diagnosis of Smith-Magenis syndrome is based upon the clinical recognition of a constellation of physical, developmental, and behavioral features in combination with a sleep disorder characterized by inverted circadian rhythm of melatonin secretion. Many of the features of Smith-Magenis syndrome are subtle in infancy and early childhood, and become more recognizable with advancing age. Infants are described as looking "cherubic" with a Down syndrome-like appearance, whereas with age the facial appearance is that of relative prognathism. Early diagnosis requires awareness of the often subtle clinical and neurobehavioral phenotype of the infant period. Speech delay with or without hearing loss is common. Most children are diagnosed in mid-childhood when the features of the disorder are most recognizable and striking. While improvements in cytogenetic analysis help to bring cases to clinical recognition at an earlier age, this review seeks to increase clinical awareness about Smith-Magenis syndrome by presenting the salient features observed at different ages including descriptions of the neurologic and behavioral features. Detailed review of the circadian rhythm disturbance unique to Smith-Magenis syndrome is presented. Suggestions for management of the behavioral and sleep difficulties are discussed in the context of the authors' personal experience in the setting of an ongoing Smith-Magenis syndrome natural history study.

Effects of pelvic skeletal asymmetry on trunk movement: three-dimensional analysis in healthy individuals versus patients with mechanical low back pain.

PubMed

Al-Eisa, Einas; Egan, David; Deluzio, Kevin; Wassersug, Richard

2006-02-01

Comparative analysis and correlational research design were used to investigate the association between anthropometry and biomechanical performance among asymptomatic subjects and patients with low back pain (LBP). To examine the association between pelvic asymmetry and patterns of trunk motion in asymptomatic and LBP subjects. Secondary objective was to investigate the association between restricted trunk motion, laterality of referred pain, and pelvic asymmetry. Subtle pelvic asymmetry (exhibited as either lateral pelvic tilt or iliac rotational asymmetry), which is common among normal individuals, has not been convincingly linked to abnormalities in back movements. Given the difficulty in diagnosing most LBP, a classification using pelvic asymmetry and patterns of movement could be helpful in establishing a rational treatment plan. Fifty-nine subjects with no history of LBP and 54 patients with mechanical unilateral LBP were tested. An anthropometric frame was used to measure pelvic asymmetry in standing. Dynamic motion data, comprised of the principal and coupled movements, were collected using the Qualysis Motion Capture System. While the groups did not differ in the total range of lumbar movement, the LBP group exhibited significantly higher asymmetry in the principal motion. The groups differed significantly in the pattern of coupled rotation during lateral flexion. Asymmetry in lumbar lateral flexion was highly related to two types of pelvic asymmetry: lateral pelvic tilt (LPT) and iliac rotation asymmetry (IRA). Asymmetry in lumbar axial rotation was highly related to IRA but weakly related to LPT. This study demonstrates objective differences in patterns of lumbar movement between asymptomatic subjects and patients with LBP. The study also demonstrates that subtle anatomic abnormality in the pelvis is associated with altered mechanics in the lumbar spine. We suggest that asymmetry of lumbar movement may be a better indicator of functional deficit than the absolute range of movement in LBP.

Functional Analysis of Dopaminergic Systems in a DYT1 Knock-in Mouse Model of Dystonia

PubMed Central

Song, Chang-Hyun; Fan, Xueliang; Exeter, Cicely J.; Hess, Ellen J.; Jinnah, H. A.

2012-01-01

The dystonias are a group of disorders characterized by involuntary twisting movements and abnormal posturing. The most common of the inherited dystonias is DYT1 dystonia, which is due to deletion of a single GAG codon (ΔE) in the TOR1A gene that encodes torsinA. Since some forms of dystonia have been linked with dysfunction of brain dopamine pathways, the integrity of these pathways was explored in a knock-in mouse model of DYT1 dystonia. In DYT1(ΔE) knock-in mice, neurochemical measures revealed only small changes in the content of dopamine or its metabolites in tissue homogenates from caudoputamen or midbrain, but microdialysis studies revealed robust decreases in baseline and amphetamine-stimulated extracellular dopamine in the caudoputamen. Quantitative stereological methods revealed no evidence for striatal or midbrain atrophy, but substantia nigra neurons immunopositive for tyrosine hydroxylase were slightly reduced in numbers and enlarged in size. Behavioral studies revealed subtle abnormalities in gross motor activity and motor coordination without overt dystonia. Neuropharmacological challenges of dopamine systems revealed normal behavioral responses to amphetamine and a minor increase in sensitivity to haloperidol. These results demonstrate that this DYT1(ΔE) knock-in mouse model of dystonia harbors neurochemical and structural changes of the dopamine pathways, as well as motor abnormalities. PMID:22659308

The nature and response to therapy of 196 consecutive injuries seen at a runners' clinic.

PubMed

Pinshaw, R; Atlas, V; Noakes, T D

1984-02-25

We studied a series of 196 running injuries to determine the nature of the common injuries, the type of runners with the different injuries, specific factors causing the most common injuries, and the response of these injuries to correction of the biomechanical abnormalities believed to cause them. The four commonest injuries were 'runner's knee' (peripatellar pain syndrome) (22%), 'shin splints' (posterior tibial stress syndrome) (18%), the iliotibial band friction syndrome (12%), and chronic muscle injuries (11%). Within 8 weeks of following the biomechanically based treatment regimen, between 62% and 77% of the runners with the commonest injuries were completely pain-free and running almost the same training distance as before injury. Only 13% of runners were not helped at all, but most of these had not adhered to the prescribed treatment. The response of the iliotibial band syndrome to treatment was less predictable, however, and some runners who followed the advice faithfully were not helped. These data therefore confirm the importance of biomechanical factors in running injuries and indicate that practitioners involved in the care of injured runners need to know not only how to diagnose the conditions accurately but also which running shoes are appropriate for the different running injuries, how to detect subtle lower limb structural abnormalities, in particular foot abnormalities and leg-length inequalities, and when to prescribe in-shoe orthoses.

Small vessel disease, neurovascular regulation and cognitive impairment: post-mortem studies reveal a complex relationship, still poorly understood.

PubMed

Love, Seth; Miners, J Scott

2017-07-15

The contribution of vascular disease to cognitive impairment is under-recognized and the pathogenesis is poorly understood. This information gap has multiple causes, including a lack of post-mortem validation of clinical diagnoses of vascular cognitive impairment (VCI) or vascular dementia (VaD), the exclusion of cases with concomitant neurodegenerative disease when diagnosing VCI/VaD, and a lack of standardization of neuropathological assessment protocols for vascular disease. Other contributors include a focus on end-stage destructive lesions to the exclusion of more subtle types of diffuse brain injury, on structural abnormalities of arteries and arterioles to the exclusion of non-structural abnormalities and capillary damage, and the use of post-mortem sampling strategies that are biased towards the identification of neurodegenerative pathologies. Recent studies have demonstrated the value of detailed neuropathology in characterizing vascular contributions to cognitive impairment (e.g. in diabetes), and highlight the importance of diffuse white matter changes, capillary damage and vasoregulatory abnormalities in VCI/VaD. The use of standardized, evidence-based post-mortem assessment protocols and the inclusion of biochemical as well as morphological methods in neuropathological studies should improve the accuracy of determination of the contribution of vascular disease to cognitive impairment and clarify the relative contribution of different pathogenic processes to the tissue damage. © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Abolition of lemniscal barrellette patterning in Prrxl1 knockout mice: Effects upon ingestive behavior.

PubMed

Bakalar, Dana; Tamaiev, Jonathan; Zeigler, H Philip; Feinstein, Paul

2015-01-01

Ingestive behaviors in mice are dependent on orosensory cues transmitted via the trigeminal nerve, as confirmed by transection studies. However, these studies cannot differentiate between deficits caused by the loss of the lemniscal pathway vs. the parallel paralemniscal pathway. The paired-like homeodomain protein Prrxl1 is expressed widely in the brain and spinal cord, including the trigeminal system. A knockout of Prrxl1 abolishes somatotopic barrellette patterning in the lemniscal brainstem nucleus, but not in the parallel paralemniscal nucleus. Null animals are significantly smaller than littermates by postnatal day 5, but reach developmental landmarks at appropriate times, and survive to adulthood on liquid diet. A careful analysis of infant and adult ingestive behavior reveals subtle impairments in suckling, increases in time spent feeding and the duration of feeding bouts, feeding during inappropriate times of the day, and difficulties in the mechanics of feeding. During liquid diet feeding, null mice display abnormal behaviors including extensive use of the paws to move food into the mouth, submerging the snout in the diet, changes in licking, and also have difficulty consuming solid chow pellets. We suggest that our Prrxl1(-/-) animal is a valuable model system for examining the genetic assembly and functional role of trigeminal lemniscal circuits in the normal control of eating in mammals and for understanding feeding abnormalities in humans resulting from the abnormal development of these circuits.

Expression intensity, gender and facial emotion recognition: Women recognize only subtle facial emotions better than men.

PubMed

Hoffmann, Holger; Kessler, Henrik; Eppel, Tobias; Rukavina, Stefanie; Traue, Harald C

2010-11-01

Two experiments were conducted in order to investigate the effect of expression intensity on gender differences in the recognition of facial emotions. The first experiment compared recognition accuracy between female and male participants when emotional faces were shown with full-blown (100% emotional content) or subtle expressiveness (50%). In a second experiment more finely grained analyses were applied in order to measure recognition accuracy as a function of expression intensity (40%-100%). The results show that although women were more accurate than men in recognizing subtle facial displays of emotion, there was no difference between male and female participants when recognizing highly expressive stimuli. Copyright © 2010 Elsevier B.V. All rights reserved.

Toll-like receptor 9 deficiency impacts sensory and motor behaviors.

PubMed

Khariv, Veronika; Pang, Kevin; Servatius, Richard J; David, Brian T; Goodus, Matthew T; Beck, Kevin D; Heary, Robert F; Elkabes, Stella

2013-08-01

Toll-like receptors (TLRs) mediate the induction of the innate immune system in response to pathogens, injury and disease. However, they also play non-immune roles and are expressed in the central nervous system (CNS) during prenatal and postnatal stages including adulthood. Little is known about their roles in the CNS in the absence of pathology. Several members of the TLR family have been implicated in the development of neural and cognitive function although the contribution of TLR9 to these processes has not been well defined. The current studies were undertaken to determine whether developmental TLR9 deficiency affects motor, sensory or cognitive functions. We report that TLR9 deficient (TLR9(-/-)) mice show a hyper-responsive sensory and motor phenotype compared to wild type (TLR9(+/+)) controls. This is indicated by hypersensitivity to thermal stimuli in the hot plate paw withdrawal test, enhanced motor-responsivity under anxious conditions in the open field test and greater sensorimotor reactivity in the acoustic startle response. Prepulse inhibition (PPI) of the acoustic startle response was also enhanced, which indicates abnormal sensorimotor gating. In addition, subtle, but significant, gait abnormalities were noted in the TLR9(-/-) mice on the horizontal balance beam test with higher foot slip numbers than TLR9(+/+) controls. In contrast, spatial learning and memory, assessed by the Morris water maze, was similar in the TLR9(-/-) and TLR9(+/+) mice. These findings support the notion that TLR9 is important for the appropriate development of sensory and motor behaviors. Copyright © 2013 Elsevier Inc. All rights reserved.

Clinical and pathological characteristics of hepatotoxicity associated with occupational exposure to dimethylformamide

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

Redlich, C.A.; West, A.B.; Fleming, L.

1990-09-01

The clinical characteristics, laboratory results, and liver biopsy findings of seven workers with toxic liver injury associated with exposure to several solvents, including substantial levels of the widely used solvent dimethylformamide, are presented. Three patients had short exposure (less than 3 months), four long exposure (greater than 1 year). Among those with brief exposure, symptoms included anorexia, abdominal pain, and disulfiram-type reaction. Aminotransferases were markedly elevated with the ratio of alanine aminotransferase to aspartate aminotransferase always greater than 1. Liver biopsy showed focal hepatocellular necrosis and microvesicular steatosis with prominence of smooth endoplasmic reticulum, complex lysosomes, and pleomorphic mitochondria withmore » crystalline inclusions. Among workers with long exposure, symptoms were minimal and enzyme elevations modest. Biopsies showed macrovesicular steatosis, pleomorphic mitochondria without crystalloids, and prominent smooth endoplasmic reticulum, but no evidence of persisting acute injury or fibrosis. Abnormal aminotransferases in both groups may persist for months after removal from exposure, but progression to cirrhosis in continually exposed workers was not observed. We conclude that exposure of these workers to solvents, chiefly dimethylformamide, may result in two variants of toxic liver injury with subtle clinical, laboratory, and morphological features. This may be readily overlooked if occupational history and biopsy histology are not carefully evaluated.« less

Congenital Amusia Persists in the Developing Brain after Daily Music Listening

PubMed Central

Mignault Goulet, Geneviève; Moreau, Patricia; Robitaille, Nicolas; Peretz, Isabelle

2012-01-01

Congenital amusia is a neurodevelopmental disorder that affects about 3% of the adult population. Adults experiencing this musical disorder in the absence of macroscopically visible brain injury are described as cases of congenital amusia under the assumption that the musical deficits have been present from birth. Here, we show that this disorder can be expressed in the developing brain. We found that (10–13 year-old) children exhibit a marked deficit in the detection of fine-grained pitch differences in both musical and acoustical context in comparison to their normally developing peers comparable in age and general intelligence. This behavioral deficit could be traced down to their abnormal P300 brain responses to the detection of subtle pitch changes. The altered pattern of electrical activity does not seem to arise from an anomalous functioning of the auditory cortex, because all early components of the brain potentials, the N100, the MMN, and the P200 appear normal. Rather, the brain and behavioral measures point to disrupted information propagation from the auditory cortex to other cortical regions. Furthermore, the behavioral and neural manifestations of the disorder remained unchanged after 4 weeks of daily musical listening. These results show that congenital amusia can be detected in childhood despite regular musical exposure and normal intellectual functioning. PMID:22606299

Genomic regions controlling shape variation in the first upper molar of the house mouse

PubMed Central

Pantalacci, Sophie; Turner, Leslie M; Steingrimsson, Eirikur; Renaud, Sabrina

2017-01-01

Numerous loci of large effect have been shown to underlie phenotypic variation between species. However, loci with subtle effects are presumably more frequently involved in microevolutionary processes but have rarely been discovered. We explore the genetic basis of shape variation in the first upper molar of hybrid mice between Mus musculus musculus and M. m. domesticus. We performed the first genome-wide association study for molar shape and used 3D surface morphometrics to quantify subtle variation between individuals. We show that many loci of small effect underlie phenotypic variation, and identify five genomic regions associated with tooth shape; one region contained the gene microphthalmia-associated transcription factor Mitf that has previously been associated with tooth malformations. Using a panel of five mutant laboratory strains, we show the effect of the Mitf gene on tooth shape. This is the first report of a gene causing subtle but consistent variation in tooth shape resembling variation in nature. PMID:29091026

Hb Adana (HBA2 or HBA1: c.179G > A) and alpha thalassemia: Genotype-phenotype correlation.

PubMed

Singh, Sharon A; Sarangi, Susmita; Appiah-Kubi, Abena; Hsu, Peihong; Smith, W Byron; Gallagher, Patrick G; Glader, Bertil; Chui, David H K

2018-05-11

Alpha thalassemia due to nondeletional mutations usually leads to more severe disease than that caused by deletional mutations. Devastating outcomes such as hydrops fetalis can occur with two nondeletional mutations, therefore warranting DNA-based workup for suspected carriers with subtle hematological abnormalities for family counseling purposes. We describe three cases with hemoglobin (Hb) Adana, a nondeletional alpha chain mutation, compounded with an alpha globin gene deletion resulting in thalassemia intermedia. We review the literature, draw genotype-phenotype correlations from published cases of Hb Adana, and propose that this correlation can be used by clinicians to help direct diagnostic studies and urge hematologists to thoroughly workup high-risk patients. © 2018 Wiley Periodicals, Inc.

Myocardial Mapping With Cardiac Magnetic Resonance: The Diagnostic Value of Novel Sequences.

PubMed

Sanz, Javier; LaRocca, Gina; Mirelis, Jesús G

2016-09-01

Cardiac magnetic resonance has evolved into a crucial modality for the evaluation of cardiomyopathy due to its ability to characterize myocardial structure and function. In the last few years, interest has increased in the potential of "mapping" techniques that provide direct and objective quantification of myocardial properties such as T1, T2, and T2* times. These approaches enable the detection of abnormalities that affect the myocardium in a diffuse fashion and/or may be too subtle for visual recognition. This article reviews the current state of myocardial T1 and T2-mapping in both health and disease. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Transvenous embolization in spontaneous direct carotid-cavernous fistula in childhood

PubMed Central

Mercado, Glenna B.; Irie, Keiko; Negoro, Makoto; Moriya, Shigeta; Tanaka, Teppei; Ohmura, Masahiro; Sadato, Akiyo; Hayakawa, Motuharu; Sano, Hirotoshi

2011-01-01

Carotid cavernous fistula (CCF) is an abnormal arteriovenous communication in the cavernous sinus. Direct CCF results from a tear in the intracavernous carotid artery. Typically, it has a high flow and usually presents with oculo-orbital venous congestive features such as exophthalmos, chemosis, and sometimes oculomotor or abducens cranial nerve palsy. Indirect CCF generally occurs spontaneously with subtle signs. We report a rare case of spontaneous direct CCF in childhood who did not have the usual history of craniofacial trauma or connective tissue disorder but presented with progressive chemosis and exophthalmos of the right eye. This report aims also to describe the safety and success of transvenous embolization with coils of the superior ophthalmic vein and cavernous sinus through the inferior petrosal sinus. PMID:22059104

Neurological soft signs in individuals with pathological gambling.

PubMed

Elman, Igor; Gurvits, Tamara V; Tschibelu, Evelyne; Spring, Justin D; Lasko, Natasha B; Pitman, Roger K

2013-01-01

Increased neurological soft signs (NSSs) have been found in a number of neuropsychiatric syndromes, including chemical addiction. The present study examined NSSs related to perceptual-motor and visuospatial processing in a behavioral addiction viz., pathological gambling (PG). As compared to mentally healthy individuals, pathological gamblers displayed significantly poorer ability to copy two- and three-dimensional figures, to recognize objects against a background noise, and to orient in space on a road-map test. Results indicated that PG is associated with subtle cerebral cortical abnormalities. Further prospective clinical research is needed to address the NSSs' origin and chronology (e.g., predate or follow the development of PG) as well as their response to therapeutic interventions and/or their ability to predict such a response.

PHACES syndrome associated with carcinoid endobronchial tumor.

PubMed

Mama, Nadia; H'mida, Dorra; Lahmar, Imen; Yacoubi, Mohamed Tahar; Tlili-Graiess, Kalthoum

2014-05-01

PHACES syndrome consists of the constellation of manifestations including posterior fossa anomalies of the brain (most commonly Dandy-Walker malformations), hemangiomas of the face and scalp, arterial abnormalities, cardiac defects, eye anomalies and sternal defects. We present a case with a possible PHACES syndrome including sternal cleft and supraumbilical raphé, precordial skin tag, persistent left superior vena cava and subtle narrowing of the aorta with an endobronchial carcinoid tumor. All these anomalies were discovered on chest multi-detector CT. This is a unique case of PHACES syndrome associated with carcinoid tumor. Review of the literature revealed 3 cases of PHACES syndrome with glial tumor. The authors tried to find the relationship between PHACES syndrome and carcinoid tumors or gliomas, which all derive from the neural crest cells.

Improving the signal subtle feature extraction performance based on dual improved fractal box dimension eigenvectors

NASA Astrophysics Data System (ADS)

Chen, Xiang; Li, Jingchao; Han, Hui; Ying, Yulong

2018-05-01

Because of the limitations of the traditional fractal box-counting dimension algorithm in subtle feature extraction of radiation source signals, a dual improved generalized fractal box-counting dimension eigenvector algorithm is proposed. First, the radiation source signal was preprocessed, and a Hilbert transform was performed to obtain the instantaneous amplitude of the signal. Then, the improved fractal box-counting dimension of the signal instantaneous amplitude was extracted as the first eigenvector. At the same time, the improved fractal box-counting dimension of the signal without the Hilbert transform was extracted as the second eigenvector. Finally, the dual improved fractal box-counting dimension eigenvectors formed the multi-dimensional eigenvectors as signal subtle features, which were used for radiation source signal recognition by the grey relation algorithm. The experimental results show that, compared with the traditional fractal box-counting dimension algorithm and the single improved fractal box-counting dimension algorithm, the proposed dual improved fractal box-counting dimension algorithm can better extract the signal subtle distribution characteristics under different reconstruction phase space, and has a better recognition effect with good real-time performance.

Specific loss of CatSper function is sufficient to compromise fertilizing capacity of human spermatozoa.

PubMed

Williams, Hannah L; Mansell, Steven; Alasmari, Wardah; Brown, Sean G; Wilson, Stuart M; Sutton, Keith A; Miller, Melissa R; Lishko, Polina V; Barratt, Christopher L R; Publicover, Steven J; Martins da Silva, Sarah

2015-12-01

Are significant abnormalities of CatSper function present in IVF patients with normal sperm concentration and motility and if so what is their functional significance for fertilization success? Sperm with a near absence of CatSper current failed to respond to activation of CatSper by progesterone and there was fertilization failure at IVF. In human spermatozoa, Ca(2+) influx induced by progesterone is mediated by CatSper, a sperm-specific Ca(2+) channel. A suboptimal Ca(2+) influx is significantly associated with, and more prevalent in, men with abnormal semen parameters, and is associated with reduced fertilizing capacity. However, abnormalities in CatSper current can only be assessed directly using electrophysiology. There is only one report of a CatSper-deficient man who showed no progesterone potentiated CatSper current. A CatSper 2 genetic abnormality was present but there was no information on the [Ca(2+)]i response to CatSper activation by progesterone. Additionally, the semen samples had indicating significant abnormalities (oligoasthenoteratozoospermia) multiple suboptimal functional responses in the spermatozoon. As such it cannot be concluded that impaired CatSper function alone causes infertility or that CatSper blockade is a potential safe target for contraception. Spermatozoa were obtained from donors and subfertile IVF patients attending a hospital assisted reproductive techniques clinic between January 2013 and December 2014. In total 134 IVF patients, 28 normozoospermic donors and 10 patients recalled due to a history of failed/low fertilization at IVF took part in the study. Samples were primarily screened using the Ca(2+) influx induced by progesterone and, if cell number was sufficient, samples were also assessed by hyperactivation and penetration into viscous media. A defective Ca(2+) response to progesterone was defined using the 99% confidence interval from the distribution of response amplitudes in normozoospermic donors. Samples showing a defective Ca(2+) response were further examined in order to characterize the potential CatSper abnormalities. In men where there was a consistent and robust failure of calcium signalling, a direct assessment of CatSper function was performed using electrophysiology (patch clamping), and a blood sample was obtained for genetic analysis. A total of 101/102 (99%) IVF patients and 22/23 (96%) donors exhibited a normal Ca(2+) response. The mean (± SD) normalized peak response did not differ between donors and IVF patients (2.57 ± 0.68 [n = 34 ejaculates from 23 different donors] versus 2.66 ± 0.68 [n = 102 IVF patients], P = 0.63). In recall patients, 9/10 (90%) showed a normal Ca(2+) response. Three men were initially identified with a defective Ca(2+) influx. However, only one (Patient 1) had a defective response in repeat semen samples. Electrophysiology experiments on sperm from Patient 1 showed a near absence of CatSper current and exon screening demonstrated no mutations in the coding regions of the CatSper complex. There was no increase in penetration of viscous media when the spermatozoa were stimulated with progesterone and importantly there was failed fertilization at IVF. A key limitation relates to working with a specific functional parameter (Ca(2+) influx induced by progesterone) in fresh sperm samples from donors and patients that have limited viability. Therefore, for practical, technical and logistical reasons, some men (∼ 22% of IVF patients) could not be screened. As such the incidence of significant Ca(2+) abnormalities induced by progesterone may be higher than the ∼ 1% observed here. Additionally, we used a strict definition of a defective Ca(2+) influx such that only substantial abnormalities were selected for further study. Furthermore, electrophysiology was only performed on one patient with a robust and repeatable defective calcium response. This man had negligible CatSper current but more subtle abnormalities (e.g. currents present but significantly smaller) may have been present in men with either normal or below normal Ca(2+) influx. These data add significantly to the understanding of the role of CatSper in human sperm function and its impact on male fertility. Remarkably, these findings provide the first direct evidence that CatSper is a suitable and specific target for human male contraception. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

Adults with a history of illicit amphetamine use exhibit abnormal substantia nigra morphology and parkinsonism.

PubMed

Todd, Gabrielle; Pearson-Dennett, Verity; Wilcox, Robert A; Chau, Minh T; Thoirs, Kerry; Thewlis, Dominic; Vogel, Adam P; White, Jason M

2016-04-01

The sonographic appearance of the substantia nigra is abnormally bright and enlarged (hyperechogenic) in young adults with a history of illicit stimulant use. The abnormality is a risk factor for Parkinson's disease. The aim of the current study was to identify the type of illicit stimulant drug associated with substantia nigra hyperechogenicity and to determine if individuals with a history of illicit stimulant use exhibit clinical signs of parkinsonism. We hypothesised that use of amphetamines (primarily methamphetamine) is associated with substantia nigra hyperechogenicity and clinical signs of parkinsonism. The area of echogenic signal in the substantia nigra was measured in abstinent human amphetamine users (n = 27; 33 ± 8 years) and in three control groups comprising a) 'ecstasy' users (n = 19; 23 ± 3 years), b) cannabis users (n = 30; 26 ± 8 years), and c) non-drug users (n = 37; 25 ± 7 years). A subset of subjects (n = 55) also underwent a neurological examination comprising the third and fifth part of the Unified Parkinson's Disease Rating Scale. Area of substantia nigra echogenicity was significantly larger in the amphetamine group (0.276 ± 0.080 cm(2)) than in the control groups (0.200 ± 0.075, 0.190 ± 0.049, 0.191 ± 0.055 cm(2), respectively; P < 0.002). The score on the clinical rating scale was also significantly higher in the amphetamine group (8.4 ± 8.1) than in pooled controls (3.3 ± 2.8; P = 0.002). Illicit use of amphetamines is associated with abnormal substantia nigra morphology and subtle clinical signs of parkinsonism. The results support epidemiological findings linking use of amphetamines, particularly methamphetamine, with increased risk of developing Parkinson's disease later in life. Copyright © 2016 Elsevier Ltd. All rights reserved.

No Association between Cortical Gyrification or Intrinsic Curvature and Attention-deficit/Hyperactivity Disorder in Adolescents and Young Adults.

PubMed

Forde, Natalie J; Ronan, Lisa; Zwiers, Marcel P; Alexander-Bloch, Aaron F; Faraone, Stephen V; Oosterlaan, Jaap; Heslenfeld, Dirk J; Hartman, Catharina A; Buitelaar, Jan K; Hoekstra, Pieter J

2017-01-01

Magnetic resonance imaging (MRI) studies have highlighted subcortical, cortical, and structural connectivity abnormalities associated with attention-deficit/hyperactivity disorder (ADHD). Gyrification investigations of the cortex have been inconsistent and largely negative, potentially due to a lack of sensitivity of the previously used morphological parameters. The innovative approach of applying intrinsic curvature analysis, which is predictive of gyrification pattern, to the cortical surface applied herein allowed us greater sensitivity to determine whether the structural connectivity abnormalities thus far identified at a centimeter scale also occur at a millimeter scale within the cortical surface. This could help identify neurodevelopmental processes that contribute to ADHD. Structural MRI datasets from the NeuroIMAGE project were used [ n = 306 ADHD, n = 164 controls, and n = 148 healthy siblings of individuals with ADHD (age in years, mean(sd); 17.2 (3.4), 16.8 (3.2), and 17.7 (3.8), respectively)]. Reconstructions of the cortical surfaces were computed with FreeSurfer. Intrinsic curvature (taken as a marker of millimeter-scale surface connectivity) and local gyrification index were calculated for each point on the surface (vertex) with Caret and FreeSurfer, respectively. Intrinsic curvature skew and mean local gyrification index were extracted per region; frontal, parietal, temporal, occipital, cingulate, and insula. A generalized additive model was used to compare the trajectory of these measures between groups over age, with sex, scanner site, total surface area of hemisphere, and familiality accounted for. After correcting for sex, scanner site, and total surface area no group differences were found in the developmental trajectory of intrinsic curvature or local gyrification index. Despite the increased sensitivity of intrinsic curvature, compared to gyrification measures, to subtle morphological abnormalities of the cortical surface we found no milimeter-scale connectivity abnormalities associated with ADHD.

Intrahospital teleradiology from the emergency room

NASA Astrophysics Data System (ADS)

Fuhrman, Carl R.; Slasky, B. S.; Gur, David; Lattner, Stefanie; Herron, John M.; Plunkett, Michael B.; Towers, Jeffrey D.; Thaete, F. Leland

1993-09-01

Off-hour operations of the modern emergency room presents a challenge to conventional image management systems. To assess the utility of intrahospital teleradiology systems from the emergency room (ER), we installed a high-resolution film digitizer which was interfaced to a central archive and to a workstation at the main reading room. The system was designed to allow for digitization of images as soon as the films were processed. Digitized images were autorouted to both destinations, and digitized images could be laser printed (if desired). Almost real time interpretations of nonselected cases were performed at both locations (conventional film in the ER and a workstation in the main reading room), and an analysis of disagreements was performed. Our results demonstrate that in spite of a `significant' difference in reporting, `clinically significant differences' were found in less than 5% of cases. Folder management issues, preprocessing, image orientation, and setting reasonable lookup tables for display were identified as the main limitations to the systems' routine use in a busy environment. The main limitation of the conventional film was the identification of subtle abnormalities in the bright regions of the film. Once identified on either system (conventional film or soft display), all abnormalities were visible and detectable on both display modalities.

Local-global classifier fusion for screening chest radiographs

NASA Astrophysics Data System (ADS)

Ding, Meng; Antani, Sameer; Jaeger, Stefan; Xue, Zhiyun; Candemir, Sema; Kohli, Marc; Thoma, George

2017-03-01

Tuberculosis (TB) is a severe comorbidity of HIV and chest x-ray (CXR) analysis is a necessary step in screening for the infective disease. Automatic analysis of digital CXR images for detecting pulmonary abnormalities is critical for population screening, especially in medical resource constrained developing regions. In this article, we describe steps that improve previously reported performance of NLM's CXR screening algorithms and help advance the state of the art in the field. We propose a local-global classifier fusion method where two complementary classification systems are combined. The local classifier focuses on subtle and partial presentation of the disease leveraging information in radiology reports that roughly indicates locations of the abnormalities. In addition, the global classifier models the dominant spatial structure in the gestalt image using GIST descriptor for the semantic differentiation. Finally, the two complementary classifiers are combined using linear fusion, where the weight of each decision is calculated by the confidence probabilities from the two classifiers. We evaluated our method on three datasets in terms of the area under the Receiver Operating Characteristic (ROC) curve, sensitivity, specificity and accuracy. The evaluation demonstrates the superiority of our proposed local-global fusion method over any single classifier.

Adolescent gynecomastia is associated with a high incidence of obesity, dysglycemia, and family background of diabetes mellitus

PubMed Central

Kulshreshtha, Bindu; Arpita, Arora; Rajesh, Patnaik T.; Sameek, Bhattacharya; Dutta, Deep; Neera, Sharma; Mohd, Mohsin

2017-01-01

Background: Gynecomastia during adolescence is common though etiology is not clear. We studied the clinical and hormonal profile of adolescent patients with gynecomastia. Methodology: Patients who had onset of breast development between age 10 and 20 years were included in this study. Their clinical profile, biochemical, and hormonal parameters were studied. Results: Of 94 patients with gynecomastia, 4 had hypogonadotropic hypogonadism, 4 had hypergonadotropic hypogonadism, and 1 had fibroadenosis, but in majority (90.4%), no apparent cause for breast enlargement was evident. In the idiopathic group, majority were obese (63%). Fourteen (16%) patients had impaired fasting glucose or impaired glucose tolerance. Another twenty patients had subtle abnormalities (high 1 h glucose or glucose peak at 2 h). Twenty-nine percent of lean and 38% of obese patients had mild abnormalities in glucose profile. Sixty percent of patients had family background of diabetes. Obese patients had lower testosterone as compared to lean patients; however, estradiol, luteinizing hormone, and follicle-stimulating hormone levels were similar in the two groups. Conclusion: Gynecomastia during adolescence is associated with obesity, dysglycemia, and family background of diabetes mellitus. PMID:28217517

A cognitive neuropsychological approach to the study of delusions in late-onset schizophrenia.

PubMed

Phillips, M L; Howard, R; David, A S

1997-09-01

Hypotheses to explain delusion formation include distorted perceptual processing of meaningful stimuli (e.g. faces), abnormal reasoning, or a combination of both. The study investigated these hypotheses using standardized neuropsychological tests. A three-patient case-study, compared with a small group (n = 8) of age-matched normal control subjects. Hospital in- and outpatients. Age-matched normal controls were from local residential homes. Three subjects with late-onset schizophrenia, two currently deluded and one in remission. Both deluded subjects had persecutory beliefs. One had a delusion of misidentification. All subjects were administered standardized neuropsychological tests of facial processing and tests of verbal reasoning. The test scores of the three patients were compared with published normal values and the age-matched control data. The tests demonstrated impaired matching of unfamiliar faces in deluded subjects, particularly in the subject with delusional misidentification. Increasing the emotional content of logical reasoning problems had a significant effect on the deluded subjects' reasoning but not that of the normal controls. The findings suggest impaired visual processing plus abnormal reasoning in deluded subjects. However, these impairments are relatively subtle given the severity of psychiatric disorder in the patients studied.

Recent publications from the Alzheimer's Disease Neuroimaging Initiative: Reviewing progress toward improved AD clinical trials.

PubMed

Weiner, Michael W; Veitch, Dallas P; Aisen, Paul S; Beckett, Laurel A; Cairns, Nigel J; Green, Robert C; Harvey, Danielle; Jack, Clifford R; Jagust, William; Morris, John C; Petersen, Ronald C; Saykin, Andrew J; Shaw, Leslie M; Toga, Arthur W; Trojanowski, John Q

2017-04-01

The Alzheimer's Disease Neuroimaging Initiative (ADNI) has continued development and standardization of methodologies for biomarkers and has provided an increased depth and breadth of data available to qualified researchers. This review summarizes the over 400 publications using ADNI data during 2014 and 2015. We used standard searches to find publications using ADNI data. (1) Structural and functional changes, including subtle changes to hippocampal shape and texture, atrophy in areas outside of hippocampus, and disruption to functional networks, are detectable in presymptomatic subjects before hippocampal atrophy; (2) In subjects with abnormal β-amyloid deposition (Aβ+), biomarkers become abnormal in the order predicted by the amyloid cascade hypothesis; (3) Cognitive decline is more closely linked to tau than Aβ deposition; (4) Cerebrovascular risk factors may interact with Aβ to increase white-matter (WM) abnormalities which may accelerate Alzheimer's disease (AD) progression in conjunction with tau abnormalities; (5) Different patterns of atrophy are associated with impairment of memory and executive function and may underlie psychiatric symptoms; (6) Structural, functional, and metabolic network connectivities are disrupted as AD progresses. Models of prion-like spreading of Aβ pathology along WM tracts predict known patterns of cortical Aβ deposition and declines in glucose metabolism; (7) New AD risk and protective gene loci have been identified using biologically informed approaches; (8) Cognitively normal and mild cognitive impairment (MCI) subjects are heterogeneous and include groups typified not only by "classic" AD pathology but also by normal biomarkers, accelerated decline, and suspected non-Alzheimer's pathology; (9) Selection of subjects at risk of imminent decline on the basis of one or more pathologies improves the power of clinical trials; (10) Sensitivity of cognitive outcome measures to early changes in cognition has been improved and surrogate outcome measures using longitudinal structural magnetic resonance imaging may further reduce clinical trial cost and duration; (11) Advances in machine learning techniques such as neural networks have improved diagnostic and prognostic accuracy especially in challenges involving MCI subjects; and (12) Network connectivity measures and genetic variants show promise in multimodal classification and some classifiers using single modalities are rivaling multimodal classifiers. Taken together, these studies fundamentally deepen our understanding of AD progression and its underlying genetic basis, which in turn informs and improves clinical trial design. Copyright © 2017. Published by Elsevier Inc.

State-of-the-art magnetic resonance imaging of pancreatic cancer.

PubMed

Schima, Wolfgang; Ba-Ssalamah, Ahmed; Goetzinger, Peter; Scharitzer, Martina; Koelblinger, Claus

2007-12-01

Technical advances of magnetic resonance imaging (MRI), including ultrahigh-field magnetic resonance at 3.0 T, parallel imaging techniques, and multichannel receive coils of the abdomen, have promoted MRI of the pancreas. For adenocarcinoma, which is the most common malignant pancreatic tumor, helical CT has been most often used for detection and staging, but it has limitations in the detection of small cancers 2 cm in diameter or less (sensitivity, 63%). Moreover, it is not very accurate in determining nonresectability, because small liver metastases, peritoneal carcinomatosis, and subtle signs of vascular infiltration may be missed. At ultrahigh field at 3.0 T, gadolinium-enhanced MRI using volume-interpolated 3-dimensional gradient-recalled echo pulse sequences with near-isotropic voxels are very useful for detection of subtle abnormalities. Mangafodipir-enhanced MRI reveals a very high tumor-pancreas contrast, which helps to diagnose small cancers. Contrast-enhanced MRI is a problem-solving tool in case of equivocal CT: it helps to differentiate between cancer and focal pancreatitis. Neuroendocrine carcinoma may present with a spectrum of appearances at MRI, but the primary tumor and liver metastases are hypervascular in approximately 70%. In this article, pancreas imaging protocols for 1.5 and 3.0 T are explained. We present the imaging features of pancreatic cancer and the important questions in staging, which should be addressed by the radiologist.

Subtle hemorrhagic brain injury is associated with neurodevelopmental impairment in infants with repaired congenital heart disease.

PubMed

Soul, Janet S; Robertson, Richard L; Wypij, David; Bellinger, David C; Visconti, Karen J; du Plessis, Adré J; Kussman, Barry D; Scoppettuolo, Lisa A; Pigula, Frank; Jonas, Richard A; Newburger, Jane W

2009-08-01

Perioperative stroke and periventricular leukomalacia have been reported to occur commonly in infants with congenital heart disease. We aimed to determine the incidence and type of brain injury in infants undergoing 2-ventricle repair in infancy and to determine risk factors associated with such injury. Forty-eight infants enrolled in a trial comparing 2 different hematocrits during surgical repair of congenital heart disease underwent brain magnetic resonance imaging scans and neurodevelopmental testing at 1 year of age. Eighteen (38%) of our subjects had tiny foci of hemosiderin by susceptibility imaging, without evidence of abnormalities in corresponding regions on conventional magnetic resonance imaging sequences. Subjects with foci of hemosiderin had a significantly lower Psychomotor Developmental Index at 1 year of age (79.6 +/- 16.5, mean +/- standard deviation) compared with subjects without these foci (89.5 +/- 15.3; P = .04). Older age at surgery and diagnostic group were significantly associated with the presence of hemosiderin foci. Only 1 subject had a small stroke (2%), and 2 subjects had periventricular leukomalacia (4%). Foci of hemosiderin without radiologic evidence of ischemic brain injury are an abnormality associated with adverse neurodevelopmental outcome not previously described in magnetic resonance imaging studies of children with surgically repaired congenital heart disease. The association of hemosiderin foci with older age at surgery and cardiac diagnosis, and not with risk factors associated with brain injury, in previous studies suggests that the cause and pathogenesis of this abnormality are different from ischemic brain lesions reported previously.

Familial Isolated Clubfoot Is Associated with Recurrent Chromosome 17q23.1q23.2 Microduplications Containing TBX4

PubMed Central

Alvarado, David M.; Aferol, Hyuliya; McCall, Kevin; Huang, Jason B.; Techy, Matthew; Buchan, Jillian; Cady, Janet; Gonzales, Patrick R.; Dobbs, Matthew B.; Gurnett, Christina A.

2010-01-01

Clubfoot is a common musculoskeletal birth defect for which few causative genes have been identified. To identify the genes responsible for isolated clubfoot, we screened for genomic copy-number variants with the Affymetrix Genome-wide Human SNP Array 6.0. A recurrent chromosome 17q23.1q23.2 microduplication was identified in 3 of 66 probands with familial isolated clubfoot. The chromosome 17q23.1q23.2 microduplication segregated with autosomal-dominant clubfoot in all three families but with reduced penetrance. Mild short stature was common and one female had developmental hip dysplasia. Subtle skeletal abnormalities consisted of broad and shortened metatarsals and calcanei, small distal tibial epiphyses, and thickened ischia. Several skeletal features were opposite to those described in the reciprocal chromosome 17q23.1q23.2 microdeletion syndrome associated with developmental delay and cardiac and limb abnormalities. Of note, during our study, we also identified a microdeletion at the locus in a sibling pair with isolated clubfoot. The chromosome 17q23.1q23.2 region contains the T-box transcription factor TBX4, a likely target of the bicoid-related transcription factor PITX1 previously implicated in clubfoot etiology. Our result suggests that this chromosome 17q23.1q23.2 microduplication is a relatively common cause of familial isolated clubfoot and provides strong evidence linking clubfoot etiology to abnormal early limb development. PMID:20598276

Scattering and absorption measurements of cervical tissues measures using low cost multi-spectral imaging

NASA Astrophysics Data System (ADS)

Bernat, Amir S.; Bar-Am, Kfir; Cataldo, Leigh; Bolton, Frank J.; Kahn, Bruce S.; Levitz, David

2018-02-01

Cervical cancer is a leading cause of death for women in low resource settings. In order to better detect cervical dysplasia, a low cost multi-spectral colposcope was developed utilizing low costs LEDs and an area scan camera. The device is capable of both traditional colposcopic imaging and multi-spectral image capture. Following initial bench testing, the device was deployed to a gynecology clinic where it was used to image patients in a colposcopy setting. Both traditional colposcopic images and spectral data from patients were uploaded to a cloud server for remote analysis. Multi-spectral imaging ( 30 second capture) took place before any clinical procedure; the standard of care was followed thereafter. If acetic acid was used in the standard of care, a post-acetowhitening colposcopic image was also captured. In analyzing the data, normal and abnormal regions were identified in the colposcopic images by an expert clinician. Spectral data were fit to a theoretical model based on diffusion theory, yielding information on scattering and absorption parameters. Data were grouped according to clinician labeling of the tissue, as well as any additional clinical test results available (Pap, HPV, biopsy). Altogether, N=20 patients were imaged in this study, with 9 of them abnormal. In comparing normal and abnormal regions of interest from patients, substantial differences were measured in blood content, while differences in oxygen saturation parameters were more subtle. These results suggest that optical measurements made using low cost spectral imaging systems can distinguish between normal and pathological tissues.

Breast cancer risk assessment and diagnosis model using fuzzy support vector machine based expert system

NASA Astrophysics Data System (ADS)

Dheeba, J.; Jaya, T.; Singh, N. Albert

2017-09-01

Classification of cancerous masses is a challenging task in many computerised detection systems. Cancerous masses are difficult to detect because these masses are obscured and subtle in mammograms. This paper investigates an intelligent classifier - fuzzy support vector machine (FSVM) applied to classify the tissues containing masses on mammograms for breast cancer diagnosis. The algorithm utilises texture features extracted using Laws texture energy measures and a FSVM to classify the suspicious masses. The new FSVM treats every feature as both normal and abnormal samples, but with different membership. By this way, the new FSVM have more generalisation ability to classify the masses in mammograms. The classifier analysed 219 clinical mammograms collected from breast cancer screening laboratory. The tests made on the real clinical mammograms shows that the proposed detection system has better discriminating power than the conventional support vector machine. With the best combination of FSVM and Laws texture features, the area under the Receiver operating characteristic curve reached .95, which corresponds to a sensitivity of 93.27% with a specificity of 87.17%. The results suggest that detecting masses using FSVM contribute to computer-aided detection of breast cancer and as a decision support system for radiologists.

Remote clinical assessment of gastrointestinal endoscopy (tele-endoscopy): an initial experience.

PubMed Central

Kim, C. Y.; Etemad, B.; Glenn, T. F.; Mackey, H. A.; Viator, G. E.; Wallace, M. B.; Mokhashi, M. S.; Cotton, P. B.; Hawes, R. H.

2000-01-01

BACKGROUND: Gastrointestinal (GI) endoscopy is an effective tool to screen for cancers of the digestive tract. However, access to endoscopy is limited in many parts of South Carolina. This trial is a part of a prospective multi-part study for remote cancer screening in coastal South Carolina. This pilot study was to evaluate the quality of tele-endoscopy for cancer screening. METHODS: 10 patients scheduled for endoscopic procedures were observed simultaneously by the endoscopist and a remote observer connected over a 512 kbps ISDN line. Findings by both were compared for concordance on malignant or premalignant lesions. RESULTS: The image quality was adequate to support remote diagnosis of GI cancer and abnormal lesions by an experienced observer. However, assessment of the esophagogastric junction for Barrett's esophagus was equivocal. CONCLUSIONS: Overall, our tele-endoscopy setup shows great promise for remote supervision or observation of endoscopic procedures done by nurse endoscopists. Tele-endoscopy is both adequate and feasible for diagnosis of most gastrointestinal lesions. Subtle lesions still may be missed in our current setup. However, improvements are being made in our setup to address the problem with resolution prior to further evaluation. PMID:11079918

Hyperspectral Image Enhancement and Mixture Deep-Learning Classification of Corneal Epithelium Injuries

PubMed Central

Md Noor, Siti Salwa; Michael, Kaleena; Marshall, Stephen; Ren, Jinchang

2017-01-01

In our preliminary study, the reflectance signatures obtained from hyperspectral imaging (HSI) of normal and abnormal corneal epithelium tissues of porcine show similar morphology with subtle differences. Here we present image enhancement algorithms that can be used to improve the interpretability of data into clinically relevant information to facilitate diagnostics. A total of 25 corneal epithelium images without the application of eye staining were used. Three image feature extraction approaches were applied for image classification: (i) image feature classification from histogram using a support vector machine with a Gaussian radial basis function (SVM-GRBF); (ii) physical image feature classification using deep-learning Convolutional Neural Networks (CNNs) only; and (iii) the combined classification of CNNs and SVM-Linear. The performance results indicate that our chosen image features from the histogram and length-scale parameter were able to classify with up to 100% accuracy; particularly, at CNNs and CNNs-SVM, by employing 80% of the data sample for training and 20% for testing. Thus, in the assessment of corneal epithelium injuries, HSI has high potential as a method that could surpass current technologies regarding speed, objectivity, and reliability. PMID:29144388

Effects of early human handling on the pain sensitivity of young lambs.

PubMed

Guesgen, Mirjam J; Beausoleil, Ngaio J; Stewart, Mairi

2013-01-01

Pain sensitivity of lambs changes over the first weeks of life. However, the effects of early treatments such as human handling on pain sensitivity are unknown for this species. This study investigated the effects of regular early gentle human handling on the pain sensitivity of lambs, indicated by their behavioural responses to tail docking. Prospective part-blinded experimental study. Twenty-nine singleton Coopworth lambs (females n=14, males n=15). Starting at one day of age, lambs were either handled twice daily for 2 weeks (Handled), were kept in the presence of lambs who were being handled but were not handled themselves (Presence), or were exposed to a human only during routine feeding and care (Control). At 3 weeks of age, all lambs were tail docked using rubber rings. Changes in behaviour due to docking were calculated and change data were analyzed using two-way anova with treatment and test pen as main factors. All lambs showed significant increases in the frequency and duration of behaviours indicative of pain, including 'abnormal' behaviours, and decreases in the frequency and duration of 'normal' behaviours after docking. Handled lambs showed a smaller increase in the time spent lying abnormally after docking than did Control lambs (mean transformed change in proportion of 30 minutes spent±SE: Control 0.55±0.04; Handled 0.38±0.03; Presence 0.48±0.03; C versus H t=3.45, p=0.007). These results provide some evidence that handling early in life may reduce subsequent pain sensitivity in lambs. While the behavioural effects of handling on pain behaviour were subtle, the results suggest, at the very least, that early handling does not increase pain sensitivity in lambs and suggests there is still flexibility postnatally in the pain processing system of a precocial species. © 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

Brainstem Involvement as a Cause of Central Sleep Apnea: Pattern of Microstructural Cerebral Damage in Patients with Cerebral Microangiopathy

PubMed Central

Duning, Thomas; Deppe, Michael; Brand, Eva; Stypmann, Jörg; Becht, Charlotte; Heidbreder, Anna; Young, Peter

2013-01-01

Background The exact underlying pathomechanism of central sleep apnea with Cheyne-Stokes respiration (CSA-CSR) is still unclear. Recent studies have demonstrated an association between cerebral white matter changes and CSA. A dysfunction of central respiratory control centers in the brainstem was suggested by some authors. Novel MR-imaging analysis tools now allow far more subtle assessment of microstructural cerebral changes. The aim of this study was to investigate whether and what severity of subtle structural cerebral changes could lead to CSA-CSR, and whether there is a specific pattern of neurodegenerative changes that cause CSR. Therefore, we examined patients with Fabry disease (FD), an inherited, lysosomal storage disease. White matter lesions are early and frequent findings in FD. Thus, FD can serve as a "model disease" of cerebral microangiopathy to study in more detail the impact of cerebral lesions on central sleep apnea. Patients and Methods Genetically proven FD patients (n = 23) and age-matched healthy controls (n = 44) underwent a cardio-respiratory polysomnography and brain MRI at 3.0 Tesla. We applied different MR-imaging techniques, ranging from semiquantitative measurement of white matter lesion (WML) volumes and automated calculation of brain tissue volumes to VBM of gray matter and voxel-based diffusion tensor imaging (DTI) analysis. Results In 5 of 23 Fabry patients (22%) CSA-CSR was detected. Voxel-based DTI analysis revealed widespread structural changes in FD patients when compared to the healthy controls. When calculated as a separate group, DTI changes of CSA-CSR patients were most prominent in the brainstem. Voxel-based regression analysis revealed a significant association between CSR severity and microstructural DTI changes within the brainstem. Conclusion Subtle microstructural changes in the brainstem might be a neuroanatomical correlate of CSA-CSR in patients at risk of WML. DTI is more sensitive and specific than conventional structural MRI and other advanced MR analyses tools in demonstrating these abnormalities. PMID:23637744

Saturnine curse: a history of lead poisoning

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

Green, D.W.

1985-01-01

Over the past ten years there has been increasing recognition of subacute and chronic lead poisoning and a growing awareness of its pathophysiology and clinical effects. Besides the classic manifestations of abdominal colic, seizures, and anemia progressing to gout, renal disease, and neuropathy, more subtle manifestations are now being increasingly recognized, such as the development of hypertension, neurobehavioral changes, reproductive and endocrine abnormalities, a possible role in carcinogenesis, and an overall increase in morbidity and mortality. Lead was one of the seven metals of antiquity, and it has accompanied the Eurasian and American civilizations since their beginnings. Lead is anmore » extremely pernicious metal with a multitude of adverse effects. The recurring nature of lead poisoning throughout the development of civilization can truly be referred to as the saturnine curse. 16 references.« less

The teratogenic risk.

PubMed

Tuchmann-Duplessis, H

1983-01-01

Reproduction can be impaired in animals and man by drugs and various environmental agents. Depending on the time of exposure--from fertilization through the fetal period and eventually during lactation--the consequences can range from embryotoxicity, gross malformations and a large variety of more subtle morphological, biochemical, and functional abnormalities. The high susceptibility of the embryo to exogenous agents is due to cellular multiplication and differentiation and to the lack of development of the enzyme systems necessary for the detoxification of chemicals. At present, developmental impairments represent the main cause of perinatal mortality and postnatal morbidity. After a review of prenatal physiology and teratogenic principles, the action of selected drugs and environmental agents is analyzed. The potential danger of environmental factors during intrauterine development is of particular concern because of its irreversible nature.

Macular telangiectasia type 2 (MacTel) in a 34-year-old patient.

PubMed

Nicolai, Heleen; Wirix, Mieke; Spielberg, Leigh; Leys, Anita

2014-09-23

We report macular telangiectasia type 2 (MacTel) in a 34-year-old man, the youngest patient so far published with MacTel type 2. The patient presented with metamorphopsia and impaired reading ability. Diagnosis was based on bilateral abnormal macular autofluorescence, perifoveal telangiectasia with fluorescein angiographic hyperfluorescence without cystoid oedema, a small foveal avascular zone, asymmetric configuration of the foveal pit, disruptions in the inner segment/outer segment layer and hyper-reflective haze and spots in the outer nuclear layer. Although MacTel usually manifests with a slowly progressive decrease in visual acuity in the fifth to seventh decades of life, younger patients may occasionally be diagnosed with the disease. Awareness of subtle signs of the condition is essential for early diagnosis. 2014 BMJ Publishing Group Ltd.

Macular telangiectasia type 2 (MacTel) in a 34-year-old patient

PubMed Central

Nicolai, Heleen; Wirix, Mieke; Spielberg, Leigh; Leys, Anita

2014-01-01

We report macular telangiectasia type 2 (MacTel) in a 34-year-old man, the youngest patient so far published with MacTel type 2. The patient presented with metamorphopsia and impaired reading ability. Diagnosis was based on bilateral abnormal macular autofluorescence, perifoveal telangiectasia with fluorescein angiographic hyperfluorescence without cystoid oedema, a small foveal avascular zone, asymmetric configuration of the foveal pit, disruptions in the inner segment/outer segment layer and hyper-reflective haze and spots in the outer nuclear layer. Although MacTel usually manifests with a slowly progressive decrease in visual acuity in the fifth to seventh decades of life, younger patients may occasionally be diagnosed with the disease. Awareness of subtle signs of the condition is essential for early diagnosis. PMID:25249218

The Effect Of Pixel Size On The Detection Rate Of Early Pulmonary Sarcoidosis In Digital Chest Radiographic Systems

NASA Astrophysics Data System (ADS)

MacMahon, Heber; Vyborny, Carl; Powell, Gregory; Doi, Kunio; Metz, Charles E.

1984-08-01

In digital radiography the pixel size used determines the potential spatial resolution of the system. The need for spatial resolution varies depending on the subject matter imaged. In many areas, including the chest, the minimum spatial resolution requirements have not been determined. Sarcoidosis is a disease which frequently causes subtle interstitial infiltrates in the lungs. As the initial step in an investigation designed to determine the minimum pixel size required in digital chest radiographic systems, we have studied 1 mm pixel digitized images on patients with early pulmonary sarcoidosis. The results of this preliminary study suggest that neither mild interstitial pulmonary infiltrates nor other abnormalities such as pneumothoraces may be detected reliably with 1 mm pixel digital images.

Differential brain growth in the infant born preterm: current knowledge and future developments from brain imaging.

PubMed

Counsell, Serena J; Boardman, James P

2005-10-01

Preterm birth is associated with a high prevalence of neuropsychiatric impairment in childhood and adolescence, but the neural correlates underlying these disorders are not fully understood. Quantitative magnetic resonance imaging techniques have been used to investigate subtle differences in cerebral growth and development among children and adolescents born preterm or with very low birth weight. Diffusion tensor imaging and computer-assisted morphometric techniques (including voxel-based morphometry and deformation-based morphometry) have identified abnormalities in tissue microstructure and cerebral morphology among survivors of preterm birth at different ages, and some of these alterations have specific functional correlates. This chapter reviews the literature reporting differential brain development following preterm birth, with emphasis on the morphological changes that correlate with neuropsychiatric impairment.

V. Multi-level analysis of cortical neuroanatomy in Williams syndrome.

PubMed

Galaburda, A M; Bellugi, U

2000-01-01

The purpose of a neuroanatomical analysis of Williams Syndrome (WMS) brains is to help bridge the knowledge of the genetics of this disorder with the knowledge on behavior. Here, we outline findings of cortical neuroanatomy at multiple levels. We describe the gross anatomy with respect to brain shape, cortical folding, and asymmetry. This, as with most neuroanatomical information available in the literature on anatomical-functional correlations, links up best to the behavioral profile. Then, we describe the cytoarchitectonic appearance of the cortex. Further, we report on some histometric results. Finally, we present findings of immunocytochemistry that attempt to link up to the genomic deletion. The gross anatomical findings consist mainly of a small brain that shows curtailment in the posterior-parietal and occipital regions. There is also subtle dysmorphism of cortical folding. A consistent finding is a short central sulcus that does not become opercularized in the interhemispheric fissure, bringing attention to a possible developmental anomaly affecting the dorsal half of the hemispheres. There is also lack of asymmetry in the planum temporale. The cortical cytoarchitecture is relatively normal, with all sampled areas showing features typical of the region from which they are taken. Measurements in area 17 show increased cell size and decreased cell-packing density, which address the issue of possible abnormal connectivity. Immunostaining shows absence of elastin but normal staining for Lim-1 kinase, both of which are products of genes that are part of the deletion. Finally, one serially sectioned brain shows a fair amount of acquired pathology of microvascular origin related most likely to underlying hypertension and heart disease.

UFO in the Arabidopsis inflorescence apex is required for floral-meristem identity and bract suppression.

PubMed

Hepworth, Shelley R; Klenz, Jennifer E; Haughn, George W

2006-03-01

The UNUSUAL FLORAL ORGANS (UFO) gene of Arabidopsis encodes an F-box protein required for the determination of floral-organ and floral-meristem identity. Mutation of UFO leads to dramatic changes in floral-organ type which are well-characterized whereas inflorescence defects are more subtle and less understood. These defects include an increase in the number of secondary inflorescences, nodes that alternate between forming flowers and secondary inflorescences, and nodes in which a single flower is subtended by a bract. Here, we show how inflorescence defects correlate with the abnormal development of floral primordia and establish a temporal requirement for UFO in this process. At the inflorescence apex of ufo mutants, newly formed primordia are initially bract-like. Expression of the floral-meristem identity genes LFY and AP1 are confined to a relatively small adaxial region of these primordia with expression of the bract-identity marker FIL observed in cells that comprise the balance of the primordia. Proliferation of cells in the adaxial region of these early primordia is delayed by several nodes such that primordia appear "chimeric" at several nodes, having visible floral and bract components. However, by late stage 2 of floral development, growth of the bract generally ceases and is overtaken by development of the floral primordium. This abnormal pattern of floral meristem development is not rescued by expression of UFO from the AP1 promoter, indicating that UFO is required prior to AP1 activation for normal development of floral primordia. We propose that UFO and LFY are jointly required in the inflorescence meristem to both promote floral meristem development and inhibit, in a non-cell autonomous manner, growth of the bract.

Brain resting-state networks in adolescents with high-functioning autism: Analysis of spatial connectivity and temporal neurodynamics.

PubMed

Bernas, Antoine; Barendse, Evelien M; Aldenkamp, Albert P; Backes, Walter H; Hofman, Paul A M; Hendriks, Marc P H; Kessels, Roy P C; Willems, Frans M J; de With, Peter H N; Zinger, Svitlana; Jansen, Jacobus F A

2018-02-01

Autism spectrum disorder (ASD) is mainly characterized by functional and communication impairments as well as restrictive and repetitive behavior. The leading hypothesis for the neural basis of autism postulates globally abnormal brain connectivity, which can be assessed using functional magnetic resonance imaging (fMRI). Even in the absence of a task, the brain exhibits a high degree of functional connectivity, known as intrinsic, or resting-state, connectivity. Global default connectivity in individuals with autism versus controls is not well characterized, especially for a high-functioning young population. The aim of this study is to test whether high-functioning adolescents with ASD (HFA) have an abnormal resting-state functional connectivity. We performed spatial and temporal analyses on resting-state networks (RSNs) in 13 HFA adolescents and 13 IQ- and age-matched controls. For the spatial analysis, we used probabilistic independent component analysis (ICA) and a permutation statistical method to reveal the RSN differences between the groups. For the temporal analysis, we applied Granger causality to find differences in temporal neurodynamics. Controls and HFA display very similar patterns and strengths of resting-state connectivity. We do not find any significant differences between HFA adolescents and controls in the spatial resting-state connectivity. However, in the temporal dynamics of this connectivity, we did find differences in the causal effect properties of RSNs originating in temporal and prefrontal cortices. The results show a difference between HFA and controls in the temporal neurodynamics from the ventral attention network to the salience-executive network: a pathway involving cognitive, executive, and emotion-related cortices. We hypothesized that this weaker dynamic pathway is due to a subtle trigger challenging the cognitive state prior to the resting state.

Further Insights in Trichothiodistrophy: A Clinical, Microscopic, and Ultrastructural Study of 20 Cases and Literature Review

PubMed Central

Ferrando, Juan; Mir-Bonafé, José M.; Cepeda-Valdés, Rodrigo; Domínguez, Anna; Ocampo-Candiani, Jorge; García-Veigas, Javier; Gómez-Flores, Minerva; Salas-Alanis, Julio C.

2012-01-01

Background: Trichothiodistrophy (TTD) is a rare autosomal recessive condition that is characterized by a specific congenital hair shaft dysplasia caused by deficiency of sulfur associated with a wide spectrum of multisystem abnormalities. In this article, we study clinical, microscopic, and ultrastructural findings of 20 patients with TTD with the aim to add further insights regarding to this rare condition. Additionally, analyses of our results are compared with those extracted from the literature in order to enhance its comprehensibility. Materials and Methods: Twenty cases of TTD were included: 7 from Mexico and 14 from Spain. Clinical, microscopic, scanning electron microscopy (SEM) studies and X-ray microanalysis (XrMa) were carried out in all of them. Genetic studies were performed in all seven Mexican cases. Patients with xeroderma pigmentosum and xeroderma pigmentosum/TTD-complex were excluded. Results: Cuticular changes and longitudinal crests of the hair shaft were demonstrated. These crests were irregular, disorganized, following the hair longest axis. Hair shaft sulfur deficiency was disposed discontinuously and intermittently rather than uniformly. This severe decrease of sulfur contents was located close to the trichoschisis areas. Only five patients did not show related disturbances. Micro-dolichocephaly was observed in five cases and represented the most frequent facial dysmorphism found. It is also remarkable that all patients with urologic malformations also combined diverse neurologic disorders. Moreover, three Mexican sisters demonstrated the coexistence of scarce pubic vellus hair, developmental delay, onychodystrophy, and maxillar/mandibullar hypoplasia. Conclusions: TTD phenotype has greatly varied from very subtle forms to severe alterations such as neurologic abnormalities, blindness, lamellar ichthyosis and gonadal malformations. Herein, a multisystem study should be performed mandatorily in patients diagnosed with TTD. PMID:23180925

Seismological evidence for long-term and rapidly accelerating magma pressurization preceding the 2009 eruption of Redoubt Volcano, Alaska

NASA Astrophysics Data System (ADS)

Roman, Diana C.; Gardine, Matthew D.

2013-06-01

Successful eruption forecasts are heavily dependent on the recognition of well-established patterns in volcano monitoring data. Therefore, it is critical to develop, in retrospect, an understanding of the physical basis for cases of abnormal precursory behavior, as the basis for (a) a complete understanding of the range of precursory signals that may be expected at a particular volcano and (b) development of new monitoring approaches to detect more subtle signals of the underlying processes responsible for common patterns of seismic unrest. Here, using a hybrid analysis of shear-wave splitting (SWS) and double-couple fault-plane solutions (FPS), we document the timing and nature of local stress field changes in the months to days preceding the 2009 eruption of Redoubt Volcano, Alaska, which was characterized by an abnormally long period of precursory low-frequency seismicity reflected in multiple escalations of alert levels prior to the eruption. We find that an approximately ~90° change in the polarization of fast S-wavelets (Φ) accompanied the earliest signs of seismic unrest in 2008 and continued through the eruption before diminishing in 2009. A similar change in the orientation of VT FPS occurred 18-48 h prior to the eruption onset on March 23, 2009, but almost two months after a strong increase in the rate of shallow VT earthquakes. Combined, our SWS and FPS results show the earliest-, and latest-known changes in seismic monitoring data, respectively, and are suggestive of a protracted period of slow magma ascent followed by a short period of rapidly increasing magma pressurization beneath the volcano. These results demonstrate the power of a combined stress-field analysis for clarifying the processes driving ambiguous seismic unrest at active volcanoes.

Nailfold capillaroscopic changes in patients with systemic lupus erythematosus: correlations with disease activity, skin manifestation and nephritis.

PubMed

Shenavandeh, S; Habibi, S

2017-08-01

Introduction The clinical expression of systemic lupus erythematosus (SLE) is the consequence of endothelial cell damage leading to serious multiple organ dysfunction. The aim of this study was to assess the association between nailfold capillaroscopic changes and disease activity, skin and renal involvement in patients with SLE. Methods Demographic variables, clinical manifestations and laboratory data of 108 patients with SLE were investigated. Nailfold capillaroscopy (NFC) was performed in all patients. Result Morphological changes in NFC were observed in 102 out of 108 (94.4%) SLE patients. Minor changes were found in 33 (30.6%) and major changes in 69 (63.9%) cases. The disease activity was significantly higher in the patients with major changes ( p < 0.002). A higher incidence of microhaemorrhages was seen in patients with active SLE disease ( p < 0.04). In SLE patients with active skin involvement, the disturbed distribution ( p < 0.004) was more frequent and subtle changes ( p < 0.009) were less frequently observed as compared with patients without active skin involvement. In the group of SLE patients with renal involvement, no correlation was found between the capillary abnormalities and the presence of renal involvement ( p > 0.05), except for the elongated capillary loops, which were seen more often in patients with renal involvement than in patients without it ( p < 0.03). Conclusion The results of the study showed that capillary changes (abnormal capillaroscopy) were very common in patients with SLE, although there were no specific patterns like the ones in scleroderma patients, and some changes may be associated with disease activity, especially in patients with active skin involvement.

Brainstem encoding of speech and musical stimuli in congenital amusia: evidence from Cantonese speakers

PubMed Central

Liu, Fang; Maggu, Akshay R.; Lau, Joseph C. Y.; Wong, Patrick C. M.

2015-01-01

Congenital amusia is a neurodevelopmental disorder of musical processing that also impacts subtle aspects of speech processing. It remains debated at what stage(s) of auditory processing deficits in amusia arise. In this study, we investigated whether amusia originates from impaired subcortical encoding of speech (in quiet and noise) and musical sounds in the brainstem. Fourteen Cantonese-speaking amusics and 14 matched controls passively listened to six Cantonese lexical tones in quiet, two Cantonese tones in noise (signal-to-noise ratios at 0 and 20 dB), and two cello tones in quiet while their frequency-following responses (FFRs) to these tones were recorded. All participants also completed a behavioral lexical tone identification task. The results indicated normal brainstem encoding of pitch in speech (in quiet and noise) and musical stimuli in amusics relative to controls, as measured by FFR pitch strength, pitch error, and stimulus-to-response correlation. There was also no group difference in neural conduction time or FFR amplitudes. Both groups demonstrated better FFRs to speech (in quiet and noise) than to musical stimuli. However, a significant group difference was observed for tone identification, with amusics showing significantly lower accuracy than controls. Analysis of the tone confusion matrices suggested that amusics were more likely than controls to confuse between tones that shared similar acoustic features. Interestingly, this deficit in lexical tone identification was not coupled with brainstem abnormality for either speech or musical stimuli. Together, our results suggest that the amusic brainstem is not functioning abnormally, although higher-order linguistic pitch processing is impaired in amusia. This finding has significant implications for theories of central auditory processing, requiring further investigations into how different stages of auditory processing interact in the human brain. PMID:25646077

Brainstem encoding of speech and musical stimuli in congenital amusia: evidence from Cantonese speakers.

PubMed

Liu, Fang; Maggu, Akshay R; Lau, Joseph C Y; Wong, Patrick C M

2014-01-01

Congenital amusia is a neurodevelopmental disorder of musical processing that also impacts subtle aspects of speech processing. It remains debated at what stage(s) of auditory processing deficits in amusia arise. In this study, we investigated whether amusia originates from impaired subcortical encoding of speech (in quiet and noise) and musical sounds in the brainstem. Fourteen Cantonese-speaking amusics and 14 matched controls passively listened to six Cantonese lexical tones in quiet, two Cantonese tones in noise (signal-to-noise ratios at 0 and 20 dB), and two cello tones in quiet while their frequency-following responses (FFRs) to these tones were recorded. All participants also completed a behavioral lexical tone identification task. The results indicated normal brainstem encoding of pitch in speech (in quiet and noise) and musical stimuli in amusics relative to controls, as measured by FFR pitch strength, pitch error, and stimulus-to-response correlation. There was also no group difference in neural conduction time or FFR amplitudes. Both groups demonstrated better FFRs to speech (in quiet and noise) than to musical stimuli. However, a significant group difference was observed for tone identification, with amusics showing significantly lower accuracy than controls. Analysis of the tone confusion matrices suggested that amusics were more likely than controls to confuse between tones that shared similar acoustic features. Interestingly, this deficit in lexical tone identification was not coupled with brainstem abnormality for either speech or musical stimuli. Together, our results suggest that the amusic brainstem is not functioning abnormally, although higher-order linguistic pitch processing is impaired in amusia. This finding has significant implications for theories of central auditory processing, requiring further investigations into how different stages of auditory processing interact in the human brain.

Genetic and Early Clinical Manifestations of Females Heterozygous for Duchenne/Becker Muscular Dystrophy.

PubMed

Papa, Riccardo; Madia, Francesca; Bartolomeo, Domenico; Trucco, Federica; Pedemonte, Marina; Traverso, Monica; Broda, Paolo; Bruno, Claudio; Zara, Federico; Minetti, Carlo; Fiorillo, Chiara

2016-02-01

Female carriers of Duchenne muscular dystrophy (DMD), although usually asymptomatic, develop muscle weakness up to 17% of the time, and a third present cardiac abnormalities or cognitive impairment. Clinical features of DMD carriers during childhood are poorly known. We describe a cohort of pediatric DMD carriers, providing clinical, genetic, and histopathologic features, with a mean follow-up of 7 years. Fifteen females with a DMD mutation (age range 5 to 18 years) were included. Seven patients (46%) presented with clinically evident symptoms and signs such as limb girdle weakness, abnormal gait, and exercise intolerance. The other eight patients (53%) were evaluated because of an incidental finding of elevated level of creatine kinase. Creatine kinase level was elevated in all, ranging from 392 to 13,000 U/L. Calf hypertrophy was observed in eight patients (53%). No patient developed respiratory or cardiac involvement. The most frequent complication was scoliosis (46%). Four patients (29%) also presented minor learning disabilities or behavioral problems. We performed electromyography in half of patients, showing myopathic pattern in four (53%). Muscle biopsy revealed a mosaic reduction of dystrophin in nine available cases. DMD gene mutations were mostly deletions (71%), resulting in loss of reading frame in five patients (36%). The three patients who experienced the most severe disease course were affected either by a nonsense or frameshift mutation. Our analysis suggests that DMD gene mutations may be suspected in a female child with persistently elevated levels of creatine kinase. Evidence of scoliosis, calf hypertrophy, or myopathic pattern at electromyography may also be helpful, and muscle biopsy is always indicative. DMD carriers should be followed for subtle orthopedic and psychiatric complications during childhood. Copyright © 2016 Elsevier Inc. All rights reserved.

Behavioral phenomenology in Alzheimer's disease, frontotemporal dementia, and late-life depression: a retrospective analysis.

PubMed

Swartz, J R; Miller, B L; Lesser, I M; Booth, R; Darby, A; Wohl, M; Benson, D F

1997-04-01

Often patients in the early stages of Alzheimer's disease (AD), frontotemporal dementia (FTD), and late-life depression can be difficult to differentiate clinically. Although subtle cognitive distinctions exist between these disorders, noncognitive behavioral phenomenology may provide additional discriminating power. In 19 subjects with AD, 19 with FTD, 16 with late-life psychotic depression (LLPD), and 19 with late-life nonpsychotic depression (LLNPD), noncognitive behavioral symptoms were quantified retrospectively using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) and compared using both a one-way ANOVA and a multivariate stepwise discriminant analysis, which utilized a jackknife procedure. The FTD group showed the highest mean total SCAN score, while the AD group showed the lowest. ANOVA showed significant differences in the mean total SCAN scores between the four diagnostic groups (P < .0001). With the discriminant analysis, the four disorders demonstrated different clusters of behavioral abnormalities and were differentiated by these symptoms (P < .0001). A subset of 14 SCAN item group symptoms was identified that collectively classified the following percentages of subjects in each diagnostic category: AD 94.7%, FTD 100%, LLPD 87.5%, and LLNPD 100%. These results indicate that AD, FTD, LLPD, and LLNPD were distinguished retrospectively by the SCAN without using cognitive data. Better definition of the longitudinal course of noncognitive behavioral symptoms in different dementias and psychiatric disorders will be valuable both for diagnosis and to help define behavioral syndromes that are associated with selective neuroanatomic and neurochemical brain pathology.

Chronic mitochondrial energy impairment produces selective striatal degeneration and abnormal choreiform movements in primates.

PubMed Central

Brouillet, E; Hantraye, P; Ferrante, R J; Dolan, R; Leroy-Willig, A; Kowall, N W; Beal, M F

1995-01-01

Although the gene defect responsible for Huntington disease (HD) has recently been identified, the pathogenesis of the disease remains obscure. One potential mechanism is that the gene defect may lead to an impairment of energy metabolism followed by slow excitotoxic neuronal injury. In the present study we examined whether chronic administration of 3-nitropropionic acid (3-NP), an irreversible inhibitor of succinate dehydrogenase, can replicate the neuropathologic and clinical features of HD in nonhuman primates. After 3-6 weeks of 3-NP administration, apomorphine treatment induced a significant increase in motor activity as compared with saline-treated controls. Animals showed both choreiform movements, as well as foot and limb dystonia, which are characteristic of HD. More prolonged 3-NP treatment in two additional primates resulted in spontaneous dystonia and dyskinesia accompanied by lesions in the caudate and putamen seen by magnetic resonance imaging. Histologic evaluation showed that there was a depletion of calbindin neurons, astrogliosis, sparing of NADPH-diaphorase neurons, and growth-related proliferative changes in dendrites of spiny neurons similar to changes in HD. The striosomal organization of the striatum and the nucleus accumbens were spared. These findings show that chronic administration of 3-NP to nonhuman primates can replicate many of the characteristic motor and histologic features of HD, further strengthening the possibility that a subtle impairment of energy metabolism may play a role in its pathogenesis. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:7624378

Assessment of gait parameters and fatigue in MS patients during inpatient rehabilitation: a pilot trial.

PubMed

Sacco, Rosaria; Bussman, Rita; Oesch, Peter; Kesselring, Jürg; Beer, Serafin

2011-05-01

Gait impairment and fatigue are common and disabling problems in multiple sclerosis (MS). Characterisation of abnormal gait in MS patients has been done mainly using observational studies and simple walking tests providing only limited quantitative and no qualitative data, or using intricate and time-consuming assessment procedures. In addition, the correlation of gait impairments with fatigue is largely unknown. The aim of this study was to characterise spatio-temporal gait parameters by a simple and easy-to-use gait analysis system (GAITRite®) in MS patients compared with healthy controls, and to analyse changes and correlation with fatigue during inpatient rehabilitation. Twenty-four MS patients (EDSS <6.5) admitted for inpatient rehabilitation and 19 healthy subjects were evaluated using the GAITRite® Functional Ambulation System. Between-group differences and changes of gait parameters during inpatient rehabilitation were analysed, and correlation with fatigue, using the Wurzburg Fatigue Inventory for Multiple Sclerosis (WEIMuS), was determined. Compared to healthy controls MS patients showed significant impairments in different spatio-temporal gait parameters, which showed a significant improvement during inpatient rehabilitation. Different gait parameters were correlated with fatigue physical score, and change of gait parameters was correlated with improvement of fatigue. Spatio-temporal gait analysis is helpful to assess specific walking impairments in MS patients and subtle changes during rehabilitation. Correlation with fatigue may indicate a possible negative impact of fatigue on rehabilitation outcome.

Monoamine oxidase A and A/B knockout mice display autistic-like features

PubMed Central

Bortolato, Marco; Godar, Sean C.; Alzghoul, Loai; Zhang, Junlin; Darling, Ryan D.; Simpson, Kimberly L.; Bini, Valentina; Chen, Kevin; Wellman, Cara L.; Lin, Rick C. S.; Shih, Jean C.

2012-01-01

Converging lines of evidence show that a sizable subset of autism-spectrum disorders (ASDs) is characterized by increased blood levels of serotonin (5-hydroxytryptamine, 5-HT), yet the mechanistic link between these two phenomena remains unclear. The enzymatic degradation of brain 5-HT is mainly mediated by monoamine oxidase (MAO)A and, in the absence of this enzyme, by its cognate isoenzyme MAOB. MAOA and A/B knockout (KO) mice display high 5-HT levels, particularly during early developmental stages. Here we show that both mutant lines exhibit numerous behavioural hallmarks of ASDs, such as social and communication impairments, perseverative and stereotypical responses, behavioural inflexibility, as well as subtle tactile and motor deficits. Furthermore, both MAOA and A/B KO mice displayed neuropathological alterations reminiscent of typical ASD features, including reduced thickness of the corpus callosum, increased dendritic arborization of pyramidal neurons in the prefrontal cortex and disrupted microarchitecture of the cerebellum. The severity of repetitive responses and neuropathological aberrances was generally greater in MAOA/B KO animals. These findings suggest that the neurochemical imbalances induced by MAOAdeficiency (either by itself or in conjunction with lack of MAOB) may result in an array of abnormalities similar to those observed in ASDs. Thus, MAOA and A/B KO mice may afford valuable models to help elucidate the neurobiological bases of these disorders and related neurodevelopmental problems. PMID:22850464

The Effect of Product Placement Marketing on Effectiveness of Internet Advertising

NASA Astrophysics Data System (ADS)

Liao, Hsiu-Li; Liu, Su-Houn; Pi, Shih-Ming; Chen, Hui-Ju

Compared to the traditional way of doing advertising, such as ad Banners, internet product placement is now emerging as a promising strategy for advertisers to do their job effectively in this Web 2.0 era. Therefore, this study focuses on the effectiveness of product placement advertising on the Internet. The results show that product prominence (Subtle or Prominent) and presentation of the advertising (Video or Images) significantly impacts the effectiveness of product placement advertising on the Internet, including brand impression, advertising attitude, and intention to click. Product prominence and presentation of the advertisement have an interactive impact. Our findings indicated that presenting the product through videos will enhance higher levels of advertising attitude, brand impression, and intention to click than presenting it through still images. Subtle placements will increase the level of advertising attitude and intention to click more so than prominent placements. But prominent placements increase the brand impression more than the subtle placements.

Application of bacterial artificial chromosome array-based comparative genomic hybridization and spectral karyotyping to the analysis of glioblastoma multiforme.

PubMed

Cowell, John K; Matsui, Sei-Ichi; Wang, Yong D; LaDuca, Jeffrey; Conroy, Jeffrey; McQuaid, Devin; Nowak, Norma J

2004-05-01

Identification of genetic losses and gains is valuable in analysis of brain tumors. Locus-by-locus analyses have revealed correlations between prognosis and response to chemotherapy and loss or gain of specific genes and loci. These approaches are labor intensive and do not provide a global view of the genetic changes within the tumor cells. Bacterial artificial chromosome (BAC) arrays, which cover the genome with an average resolution of less than 1 MbP, allow defining the sum total of these genetic changes in a single comparative genomic hybridization (CGH) experiment. These changes are directly overlaid on the human genome sequence, thus providing the extent of the amplification or deletion, reflected by a megabase position, and gene content of the abnormal region. Although this array-based CGH approach (CGHa) seems to detect the extent of the genetic changes in tumors reliably, it has not been robustly tested. We compared genetic changes in four newly derived, early-passage glioma cell lines, using spectral karyotyping (SKY) and CGHa. Chromosome changes seen in cell lines under SKY analysis were also detected with CGHa. In addition, CGHa detected cryptic genetic gains and losses and resolved the nature of subtle marker chromosomes that could not be resolved with SKY, thus providing distinct advantages over previous technologies. There was remarkable general concordance between the CGHa results comparing the cell lines to the original tumor, except that the magnitude of the changes seen in the tumor sample was generally suppressed compared with the cell lines, a consequence of normal cells contaminating the tumor sample. CGHa revealed changes in cell lines that were not present in the original tumors and vice versa, even when analyzed at the earliest passage possible, which highlights the adaptation of the cells to in vitro culture. CGHa proved to be highly accurate and efficient for identifying genetic changes in tumor cells. This approach can accurately identify subtle, novel genetic abnormalities in tumors directly linked to the human genome sequence. CGHa far surpasses the resolution and information provided by conventional metaphase CGH, without relying on in vitro culture of tumors for metaphase spreads.

Dysmorphic features and developmental outcome of 2-year-old children.

PubMed

Seggers, Jorien; Haadsma, Maaike L; Bos, Arend F; Heineman, Maas Jan; Middelburg, Karin J; van den Heuvel, Edwin R; Hadders-Algra, Mijna

2014-11-01

The aim of this study was to assess the associations between dysmorphic features and neurological, mental, psychomotor, and behavioural development in order to improve our understanding of aetiological pathways leading to minor developmental problems. In our cross-sectional study, 272 generally healthy 2-year-olds (143 males, 129 females; median gestational age 39 weeks, [range 30-43wks]), born after a parental history of subfertility either with or without fertility treatment, were examined. Dysmorphic features were classified as abnormalities (clinically relevant or not), minor anomalies, or common variants according to Merks' classification system. Hempel's neurological assessment resulted in a neurological optimality score (NOS) and fluency score. Mental and psychomotor development were assessed with the Dutch version of the Bayley Scales of Infant Development and behavioural development with the Achenbach Child Behaviour Checklist. Of the different types of dysmorphic feature, clinically relevant abnormalities were most strongly associated with a lower NOS (difference -2.53, 95% confidence interval [CI] -4.23 to -0.83) and fluency score (difference -0.62, 95% CI -1.1 to -0.15). The presence of one or more abnormalities (clinically relevant or not) or one or more common variants was significantly associated with a lower NOS, and the presence of three or more minor anomalies was associated with lower fluency scores. Dysmorphic features were not associated with mental, psychomotor, or behavioural development. As dysmorphic features originate during the first trimester of pregnancy, the association between dysmorphic features and minor alterations in neurodevelopment may suggest an early ontogenetic origin of subtle neurological deviations. © 2014 Mac Keith Press.

Bull's eye and pigment maculopathy are further retinal manifestations of an abnormal Bruch's membrane in Alport syndrome.

PubMed

Savige, Judy; Wang, Yanyan; Crawford, Andrew; Smith, James; Symons, Andrew; Mack, Heather; Nicholls, Kathy; Wilson, Diane; Colville, Deb

2017-01-01

The retinal features of Alport syndrome include a central and peripheral fleck retinopathy, temporal retinal thinning, and a macular hole. Here we describe further retinal abnormalities. We identified a case of bull's eye maculopathy 20 years previously in a 68-year-old female, and reviewed archived retinal images from our cohort of X-linked (28 males, 28 females) or autosomal recessive (n = 13) Alport syndrome. All individuals had Alport syndrome confirmed on genetic testing or renal biopsy, were examined by an ophthalmologist, and underwent retinal imaging (KOWA non-mydriatic camera, Japan). The index case had the p.Q379X variant in COL4A5 and currently had renal impairment, (eGFR = 45 ml/min/1.73 m 2 ), bilateral hearing loss, and central and peripheral retinopathies. Her maculopathy had deteriorated, and she had a bilateral central visual field loss. Optical coherence tomography (Heidelberg Spectralis) demonstrated a disrupted retinal pigment epithelium and retinal atrophy. We identified a further early bull's eye maculopathy (1/69, 1.4%) from a female with autosomal recessive disease and normal renal function. We also noted a subtle pigment maculopathy associated with an abnormal retinal pigment epithelium in 27 (27/69, 39%) subjects with Alport syndrome, in both males (8/28, 29%) and females (13/28, 46%) with X-linked disease, and in autosomal recessive disease (6/13, 38%). The bull's eye and pigment maculopathies in Alport syndrome result mainly from the damaged Bruch's membrane and overlying retinal pigment epithelium. Bull's eye maculopathy affects vision and patients should undergo regular monitoring for retinal complications.

Subtle Hemorrhagic Brain Injury is Associated with Neurodevelopmental Impairment in Infants with Repaired Congenital Heart Disease

PubMed Central

Soul, Janet S.; Robertson, Richard L.; Wypij, David; Bellinger, David C.; Visconti, Karen J.; du Plessis, Adré J.; Kussman, Barry D.; Scoppettuolo, Lisa A.; Pigula, Frank; Jonas, Richard A.; Newburger, Jane W.

2009-01-01

Objective Perioperative stroke and periventricular leukomalacia have been reported to occur commonly in infants with congenital heart disease. We aimed to determine the incidence and type of brain injury in infants undergoing two-ventricle repair in infancy and to determine risk factors associated with such injury. Methods Forty-eight infants enrolled in a trial comparing two different hematocrits during surgical repair of congenital heart disease underwent brain MRI scans and neurodevelopmental testing at one year of age. Results Eighteen (38%) of our subjects had tiny foci of hemosiderin by susceptibility imaging, without evidence of abnormalities in corresponding regions on conventional MRI sequences. Subjects who had foci of hemosiderin had a significantly lower Psychomotor Developmental Index at one year of age (79.6 ± 16.5, mean ± SD) compared with subjects who did not have these foci (89.5 ± 15.3; p=0.04). Older age at surgery and diagnostic group were significantly associated with presence of hemosiderin foci. Only one subject had a small stroke (2%) and two had periventricular leukomalacia (4%). Conclusions Foci of hemosiderin without radiologic evidence of ischemic brain injury are an abnormality associated with adverse neurodevelopmental outcome not previously described in MRI studies of children with surgically repaired congenital heart disease. The association of hemosiderin foci with older age at surgery and cardiac diagnosis and not risk factors associated with brain injury in previous studies suggests that the etiology and pathogenesis of this abnormality is different from ischemic brain lesions reported previously. PMID:19619781

Asymmetric Meckel Cave Enlargement: A Potential Marker of PHACES Syndrome.

PubMed

Wright, J N; Wycoco, V

2017-06-01

PHACES syndrome is a complex of morphologic abnormalities of unknown cause and includes posterior fossa abnormalities; head and neck infantile hemangiomas; arterial, cardiac, and eye anomalies; and sternal or abdominal wall defects. Accurate identification of the syndrome is important for optimal treatment. The purpose of this study was to investigate the incidence of asymmetric Meckel cave enlargement, a potential novel imaging marker, in a population of patients referred for evaluation of possible PHACES syndrome. Eighty-five patients referred for neuroimaging evaluation of possible PHACES syndrome were identified and stratified on the basis of their ultimate clinical PHACES diagnosis categorization into PHACES, possible PHACES, or not PHACES. MR imaging studies were subsequently reviewed for the presence or absence of unilateral Meckel cave enlargement, with the reviewer blinded to the ultimate PHACES syndrome categorization. Twenty-five of 85 patients (29%) were ultimately categorized as having PHACES or possible PHACES according to consensus guidelines. Asymmetric Meckel cave enlargement was present in 76% (19/25) of these patients and in 82% (19/23) of only those patients with definite PHACES. This finding was present in none of the 60 patients determined not to have PHACES syndrome. In 7/19 patients (37%) with this finding, subtle MR imaging abnormalities consistent with PHACES were missed on the initial MR imaging interpretation. Asymmetric Meckel cave enlargement was a common feature of patients with PHACES in our cohort and may serve as a novel imaging marker. Increased awareness of this imaging feature has the potential to increase the diagnostic accuracy of PHACES. © 2017 by American Journal of Neuroradiology.

Familial isolated clubfoot is associated with recurrent chromosome 17q23.1q23.2 microduplications containing TBX4.

PubMed

Alvarado, David M; Aferol, Hyuliya; McCall, Kevin; Huang, Jason B; Techy, Matthew; Buchan, Jillian; Cady, Janet; Gonzales, Patrick R; Dobbs, Matthew B; Gurnett, Christina A

2010-07-09

Clubfoot is a common musculoskeletal birth defect for which few causative genes have been identified. To identify the genes responsible for isolated clubfoot, we screened for genomic copy-number variants with the Affymetrix Genome-wide Human SNP Array 6.0. A recurrent chromosome 17q23.1q23.2 microduplication was identified in 3 of 66 probands with familial isolated clubfoot. The chromosome 17q23.1q23.2 microduplication segregated with autosomal-dominant clubfoot in all three families but with reduced penetrance. Mild short stature was common and one female had developmental hip dysplasia. Subtle skeletal abnormalities consisted of broad and shortened metatarsals and calcanei, small distal tibial epiphyses, and thickened ischia. Several skeletal features were opposite to those described in the reciprocal chromosome 17q23.1q23.2 microdeletion syndrome associated with developmental delay and cardiac and limb abnormalities. Of note, during our study, we also identified a microdeletion at the locus in a sibling pair with isolated clubfoot. The chromosome 17q23.1q23.2 region contains the T-box transcription factor TBX4, a likely target of the bicoid-related transcription factor PITX1 previously implicated in clubfoot etiology. Our result suggests that this chromosome 17q23.1q23.2 microduplication is a relatively common cause of familial isolated clubfoot and provides strong evidence linking clubfoot etiology to abnormal early limb development. Copyright 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Mechanisms that Underlie Co-variation of the Brain and Face

PubMed Central

Marcucio, Ralph S.; Young, Nathan M.; Hu, Diane; Hallgrimsson, Benedikt

2011-01-01

The effect of the brain on the morphology of the face has long been recognized in both evolutionary biology and clinical medicine. In this paper we describe factors that are active between development of the brain and face and how these might impact craniofacial variation. First, there is the physical influence of the brain, which contributes to overall growth and morphology of the face through direct structural interactions. Second, there is the molecular influence of the brain, which signals to facial tissues to establish signaling centers that regulate patterned growth. Importantly, subtle alterations to these physical or molecular interactions may contribute to both normal and abnormal variation. These interactions are therefore critical to our understanding of how a diversity of facial morphologies can be generated both within species and across evolutionary time. PMID:21381182

[Qi as a materialist concept on the level of medical philosophy].

PubMed

Su, Zhan-Qing

2005-03-01

This paper has made a distinction between the materialist concept of qi on the medical philosophical level and its substantial existence, and illustrated the materiality and multiplicity of qi. Materiality refers to the objective reality, a summation of various things or phenomena related to human beings; while multiplicity refers to diversity of specific substances, each holding its individual essence. Based on two essential conceptions "xiang" and "xiangji", and combining the theories of traditional Chinese medicine and Western medicine, this paper has also made a preliminary study on the substantial existence of qi at macro- and micro-levels, and on physiological (normal) and pathological (abnormal) aspects. It is the author's argument that studies of the substantial existence of qi from different aspects, micro-dimension in particular, will push the syndrome differentiation of traditional Chinese medicine to a more subtle sphere.

Point-of-care ultrasound diagnosis and treatment of posterior shoulder dislocation.

PubMed

Beck, Sierra; Chilstrom, Mikaela

2013-02-01

Acute traumatic posterior shoulder dislocations are rare. The diagnosis is often missed or delayed, as radiologic abnormalities can be subtle. We report a case of a 37-year-old man who presented to the emergency department with severe right shoulder pain and inability to move his arm after a motor vehicle collision. Based on examination, he was initially thought to have an anterior dislocation; however, point-of-care (POC) ultrasound clearly demonstrated a posterior shoulder dislocation. Real-time ultrasound-guided intra-articular local anesthetic injection facilitated closed reduction in the emergency department without procedural sedation, and POC ultrasound confirmed successful reduction at the bedside after the procedure. This case demonstrates that POC ultrasound can be a useful diagnostic tool in the rapid assessment and treatment for patients with suspected posterior shoulder dislocation. Copyright © 2013 Elsevier Inc. All rights reserved.

Evolving hypopituitarism as a consequence of traumatic brain injury (TBI) in childhood - call for attention.

PubMed

Medic-Stojanoska, Milica; Pekic, Sandra; Curic, Nikola; Djilas-Ivanovic, Dragana; Popovic, Vera

2007-06-01

Hypopituitarism is a common complication of TBI in long-term survivors, more frequent than previously realized. It may be partial or complete, sometimes very subtle without visible lesions in hypothalamo-pituitary region and is diagnosed only by biochemical means. Neuroendocrine abnormalities caused by TBI may have significant implications for the recovery and rehabilitation of these patients. The subjects at risk are those who have suffered moderate to severe trauma, although mild intensity trauma may precede hypopituitarism also. Particular attention should be paid to this problem in children and adolescents. We describe a patient with hypopituitarism thought to be idiopathic due to mild head trauma which caused diabetes insipidus in childhood, gradual failure of pituitary hormones during the period of growth and development, and metabolic (dyslipidemia), physical (obesity), and cognitive impairments in the adult period.

Neurobiology of Schizophrenia: Search for the Elusive Correlation with Symptoms

PubMed Central

Mathalon, Daniel H.; Ford, Judith M.

2012-01-01

In the last half-century, human neuroscience methods provided a way to study schizophrenia in vivo, and established that it is associated with subtle abnormalities in brain structure and function. However, efforts to understand the neurobiological bases of the clinical symptoms that the diagnosis is based on have been largely unsuccessful. In this paper, we provide an overview of the conceptual and methodological obstacles that undermine efforts to link the severity of specific symptoms to specific neurobiological measures. These obstacles include small samples, questionable reliability and validity of measurements, medication confounds, failure to distinguish state and trait effects, correlation–causation ambiguity, and the absence of compelling animal models of specific symptoms to test mechanistic hypotheses derived from brain-symptom correlations. We conclude with recommendations to promote progress in establishing brain-symptom relationships. PMID:22654745

Thermal therapy techniques for skin and superficial tissue disease

NASA Astrophysics Data System (ADS)

Stauffer, Paul R.

2000-01-01

There are numerous diseases and abnormal growths and conditions that afflict the skin and underlying superficial tissues. In addition to cancers such as primary, recurrent, and metastatic melanomas and carcinomas, there are many non-malignant conditions such as psoriasis plaques, port wine stains, warts, and superficial cut and bum wounds. Many of these clinical conditions have been shown responsive to treatment with thermal therapy - either low temperature freezing (cryotherapy),. moderate temperature warming to about 41-45°C (hyperthermia), or high temperature (>50°C) ablation or coagulation necrosis therapy. Because both very low and very high temperature therapies are for the most part non-selectively destructive in nature, they normally are used for applications where therapy can be localized precisely in the desired target and some necrosis of adjacent normal tissues is acceptable. With the exception of precision controlled cryotherapy or laser surgery (e.g. wart, mole, tattoo and port wine stain removal) or focal thermal surgery of small deep-seated nodules, it is generally preferred to use moderate thermal therapy (hyperthermia) in the treatment of skin and subcutaneous tissue disease in order to preserve the protective barrier characteristic of intact skin within the target region while inducing more subtle long term therapeutic improvement in the disease condition. This type of subtle thermal therapy is usually administered in combination with one or more other therapies such as radiation or chemotherapy - something with a differential effect on the target and surrounding normal tissues that can be magnified by the adjuvant use of heat.

Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy: Progress and Pitfalls.

PubMed

Oomen, Ad W G J; Semsarian, Christopher; Puranik, Rajesh; Sy, Raymond W

2018-04-04

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy that predominantly affects the right ventricle. With a prevalence in the range of 1:5000 to 1:2000 persons, ARVC is one of the leading causes of sudden cardiac death in young people and in athletes. Although early detection and treatment is important, the diagnosis of ARVC remains challenging. There is no single pathognomonic diagnostic finding in ARVC; rather, current international task force criteria specify diagnostic major and minor criteria in six categories: right ventricular imaging (including echocardiography and cardiac magnetic resonance imaging (MRI)), histology, repolarisation abnormalities, depolarisation and conduction abnormalities, arrhythmias and family history (including genetic testing). Combining findings from differing diagnostic modalities can establish a "definite", "borderline" or "possible" diagnosis of ARVC. However, there are limitations inherent in the current task force criteria, including the lack of specificity for ARVC; future iterations may be improved, for example, by enhanced imaging protocols able to detect subtle changes in the structure and function of the right ventricle, incorporation of electro-anatomical data, response to adrenergic challenge, and validated criteria for interpreting genetic variants. Copyright © 2018 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Abnormal motor patterns in the framework of the equilibrium-point hypothesis: a cause for dystonic movements?

PubMed

Latash, M L; Gutman, S R

1994-01-01

Until now, the equilibrium-point hypothesis (lambda model) of motor control has assumed nonintersecting force-length characteristics of the tonic stretch reflex for individual muscles. Limited data from animal experiments suggest, however, that such intersections may occur. We have assumed the possibility of intersection of the characteristics of the tonic stretch reflex and performed a computer simulation of movement trajectories and electromyographic patterns. The simulation has demonstrated, in particular, that a transient change in the slope of the characteristic of an agonist muscle may lead to temporary movement reversals, hesitations, oscillations, and multiple electromyographic bursts that are typical of movements of patients with dystonia. The movement patterns of three patients with idiopathic dystonia during attempts at fast single-joint movements (in the elbow, wrist, and ankle) were recorded and compared with the results of the computer simulation. This approach considers that motor disorders in dystonia result from faulty control patterns that may not correlate with any morphological or neurophysiological changes. It provides a basis for the high variability of dystonic movements. The uniqueness of abnormal motor patterns in dystonia, that precludes statistical analysis across patients, may result from subtle differences in the patterns of intersecting characteristics of the tonic stretch reflex. The applicability of our analysis to disordered multijoint movement patterns is discussed.

High throughput image cytometry for detection of suspicious lesions in the oral cavity

NASA Astrophysics Data System (ADS)

MacAulay, Calum; Poh, Catherine F.; Guillaud, Martial; Michele Williams, Pamela; Laronde, Denise M.; Zhang, Lewei; Rosin, Miriam P.

2012-08-01

The successful management of oral cancer depends upon early detection, which relies heavily on the clinician's ability to discriminate sometimes subtle alterations of the infrequent premalignant lesions from the more common reactive and inflammatory conditions in the oral mucosa. Even among experienced oral specialists this can be challenging, particularly when using new wide field-of-view direct fluorescence visualization devices clinically introduced for the recognition of at-risk tissue. The objective of this study is to examine if quantitative cytometric analysis of oral brushing samples could facilitate the assessment of the risk of visually ambiguous lesions. About 369 cytological samples were collected and analyzed: (1) 148 samples from pathology-proven sites of SCC, carcinoma in situ or severe dysplasia; (2) 77 samples from sites with inflammation, infection, or trauma, and (3) 144 samples from normal sites. These were randomly separated into training and test sets. The best algorithm correctly recognized 92.5% of the normal samples, 89.4% of the abnormal samples, 86.2% of the confounders in the training set as well as 100% of the normal samples, and 94.4% of the abnormal samples in the test set. These data suggest that quantitative cytology could reduce by more than 85% the number of visually suspect lesions requiring further assessment by biopsy.

Reduced hippocampal and parahippocampal volumes in murderers with schizophrenia.

PubMed

Yang, Yaling; Raine, Adrian; Han, Chen-Bo; Schug, Robert A; Toga, Arthur W; Narr, Katherine L

2010-04-30

Evidence has accumulated to suggest that individuals with schizophrenia are at increased risk for violent offending. Furthermore, converging evidence suggests that abnormalities in the fronto-limbic system, including the prefrontal cortex, the hippocampus, and the parahippocampal gyrus, may contribute towards both neuropsychological disturbances in schizophrenia and violent behavior. Since the behavioral and clinical consequences of disturbed fronto-limbic circuitry appear to differ in schizophrenia and violence, it may be argued that patients with schizophrenia who exhibit violent behavior would demonstrate different structural abnormalities compared to their non-violent counterparts. However, the neurobiological basis underlying homicide offenders with schizophrenia remains unclear and little is known regarding the cross-cultural applicability of the findings. Using a 2 x 2 factorial design on a total Chinese sample of 92 males and females, we found reduced gray matter volume in the hippocampus and parahippocampal gyrus in murderers with schizophrenia, in the parahippocampal gyrus in murderers without schizophrenia, and in the prefrontal cortex in non-violent schizophrenia compared to normal controls. Results provide initial evidence demonstrating cross-cultural generalizability of prior fronto-limbic findings on violent schizophrenia. Future studies examining subtle morphological changes in frontal and limbic structures in association with clinical and behavioral characteristics may help further clarify the neurobiological basis of violent behavior. Copyright @ 2009 Elsevier Ireland Ltd. All rights reserved.

Reduced hippocampal and parahippocampal volumes in murderers with schizophrenia

PubMed Central

Raine, Adrian; Han, Chen-Bo; Schug, Robert A.; Toga, Arthur W.; Narr, Katherine L.

2010-01-01

Evidence has accumulated to suggest that individuals with schizophrenia are at increased risk for violent offending. Furthermore, converging evidence suggests that abnormalities in the fronto-limbic system, including the prefrontal cortex, hippocampus, and the parahippocampal gyrus, may contribute towards both neuropsychological disturbances in schizophrenia and violent behavior. Since the behavioral and clinical consequences of disturbed fronto-limbic circuitry appear to differ in schizophrenia and violence, it may be argued that patients with schizophrenia who exhibit violent behavior would demonstrate different structural abnormalities compared to their non-violent counterparts. However, the neurobiological basis underlying homicide offenders with schizophrenia remains unclear and little is known regarding the cross-cultural applicability of the findings. Using a 2 × 2 factorial design on a total Chinese sample of 92 males and females, we found reduced gray matter volume in the hippocampus and parahippocampal gyrus in murderers with schizophrenia, in the parahippocampal gyrus in murderers without schizophrenia, and in the prefrontal cortex in non-violent schizophrenia compared to normal controls. Results provide initial evidence demonstrating cross-cultural generalizability of prior fronto-limbic findings on violent schizophrenia. Future studies examining subtle morphological changes in frontal and limbic structures in association with clinical and behavioral characteristics may help further clarify the neurobiological basis of violent behavior. PMID:20227253

Core neuropathological abnormalities in progranulin-deficient mice are penetrant on multiple genetic backgrounds.

PubMed

Petkau, T L; Hill, A; Leavitt, B R

2016-02-19

Loss-of-function mutations in the progranulin gene (GRN) are a common cause of familial frontotemporal lobar degeneration (FTLD). A high degree of heterogeneity in the age-of-onset, duration of disease, and clinical presentation of FTLD, even among families carrying the same GRN mutation, suggests that additional modifying genes may be important to pathogenesis. Progranulin-knockout mice display subtle behavioral abnormalities and progressive neuropathological changes, as well as altered dendritic morphology and synaptic deficits in the hippocampus. In this study we evaluated multiple neuropathological endpoints in aged progranulin knockout mice and their wild-type littermates on two different genetic backgrounds: C57Bl/6 and 129/SvImJ. We find that in most brain regions, both strains are susceptible to progranulin-mediated neuropathological phenotypes, including astrogliosis, microgliosis, and highly accelerated deposition of the aging pigment lipofuscin. Neuroinflammation due to progranulin deficiency is exaggerated in the B6 strain and present, but less pronounced, in the 129 strain. Differences between the strains in hippocampal neuron counts and neuronal morphology suggest a complex role for progranulin in the hippocampus. We conclude that core progranulin-mediated neurodegenerative phenotypes are penetrant on multiple inbred mouse strains, but that genetic background modulates progranulin's role in neuroinflammation and hippocampal biology. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Specific loss of CatSper function is sufficient to compromise fertilizing capacity of human spermatozoa

PubMed Central

Williams, Hannah L.; Mansell, Steven; Alasmari, Wardah; Brown, Sean G.; Wilson, Stuart M.; Sutton, Keith A.; Miller, Melissa R.; Lishko, Polina V.; Barratt, Christopher L.R.; Publicover, Steven J.; Martins da Silva, Sarah

2015-01-01

STUDY QUESTION Are significant abnormalities of CatSper function present in IVF patients with normal sperm concentration and motility and if so what is their functional significance for fertilization success? SUMMARY ANSWER Sperm with a near absence of CatSper current failed to respond to activation of CatSper by progesterone and there was fertilization failure at IVF. WHAT IS KNOWN ALREADY In human spermatozoa, Ca2+ influx induced by progesterone is mediated by CatSper, a sperm-specific Ca2+ channel. A suboptimal Ca2+ influx is significantly associated with, and more prevalent in, men with abnormal semen parameters, and is associated with reduced fertilizing capacity. However, abnormalities in CatSper current can only be assessed directly using electrophysiology. There is only one report of a CatSper-deficient man who showed no progesterone potentiated CatSper current. A CatSper 2 genetic abnormality was present but there was no information on the [Ca2+]i response to CatSper activation by progesterone. Additionally, the semen samples had indicating significant abnormalities (oligoasthenoteratozoospermia) multiple suboptimal functional responses in the spermatozoon. As such it cannot be concluded that impaired CatSper function alone causes infertility or that CatSper blockade is a potential safe target for contraception. STUDY DESIGN, SIZE, DURATION Spermatozoa were obtained from donors and subfertile IVF patients attending a hospital assisted reproductive techniques clinic between January 2013 and December 2014. In total 134 IVF patients, 28 normozoospermic donors and 10 patients recalled due to a history of failed/low fertilization at IVF took part in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS Samples were primarily screened using the Ca2+ influx induced by progesterone and, if cell number was sufficient, samples were also assessed by hyperactivation and penetration into viscous media. A defective Ca2+ response to progesterone was defined using the 99% confidence interval from the distribution of response amplitudes in normozoospermic donors. Samples showing a defective Ca2+ response were further examined in order to characterize the potential CatSper abnormalities. In men where there was a consistent and robust failure of calcium signalling, a direct assessment of CatSper function was performed using electrophysiology (patch clamping), and a blood sample was obtained for genetic analysis. MAIN RESULTS AND THE ROLE OF CHANCE A total of 101/102 (99%) IVF patients and 22/23 (96%) donors exhibited a normal Ca2+ response. The mean (±SD) normalized peak response did not differ between donors and IVF patients (2.57 ± 0.68 [n = 34 ejaculates from 23 different donors] versus 2.66 ± 0.68 [n = 102 IVF patients], P = 0.63). In recall patients, 9/10 (90%) showed a normal Ca2+ response. Three men were initially identified with a defective Ca2+ influx. However, only one (Patient 1) had a defective response in repeat semen samples. Electrophysiology experiments on sperm from Patient 1 showed a near absence of CatSper current and exon screening demonstrated no mutations in the coding regions of the CatSper complex. There was no increase in penetration of viscous media when the spermatozoa were stimulated with progesterone and importantly there was failed fertilization at IVF. LIMITATIONS, REASONS FOR CAUTION A key limitation relates to working with a specific functional parameter (Ca2+ influx induced by progesterone) in fresh sperm samples from donors and patients that have limited viability. Therefore, for practical, technical and logistical reasons, some men (∼22% of IVF patients) could not be screened. As such the incidence of significant Ca2+ abnormalities induced by progesterone may be higher than the ∼1% observed here. Additionally, we used a strict definition of a defective Ca2+ influx such that only substantial abnormalities were selected for further study. Furthermore, electrophysiology was only performed on one patient with a robust and repeatable defective calcium response. This man had negligible CatSper current but more subtle abnormalities (e.g. currents present but significantly smaller) may have been present in men with either normal or below normal Ca2+ influx. WIDER IMPLICATIONS OF THE FINDINGS These data add significantly to the understanding of the role of CatSper in human sperm function and its impact on male fertility. Remarkably, these findings provide the first direct evidence that CatSper is a suitable and specific target for human male contraception. STUDY FUNDING/COMPETING INTEREST(S) Initial funding was from NHS Tayside, Infertility Research Trust, TENOVUS, Chief Scientist Office NRS Fellowship, the Wellcome Trust, University of Abertay. The majority of the data were obtained using funding from a MRC project grant (# 4190). The authors declare that there is no conflict of interest. TRIAL REGISTRATION NUMBER Not applicable. PMID:26453676

Body temperature patterns as a predictor of hospital-acquired sepsis in afebrile adult intensive care unit patients: a case-control study.

PubMed

Drewry, Anne M; Fuller, Brian M; Bailey, Thomas C; Hotchkiss, Richard S

2013-09-12

Early treatment of sepsis improves survival, but early diagnosis of hospital-acquired sepsis, especially in critically ill patients, is challenging. Evidence suggests that subtle changes in body temperature patterns may be an early indicator of sepsis, but data is limited. The aim of this study was to examine whether abnormal body temperature patterns, as identified by visual examination, could predict the subsequent diagnosis of sepsis in afebrile critically ill patients. Retrospective case-control study of 32 septic and 29 non-septic patients in an adult medical and surgical ICU. Temperature curves for the period starting 72 hours and ending 8 hours prior to the clinical suspicion of sepsis (for septic patients) and for the 72-hour period prior to discharge from the ICU (for non-septic patients) were rated as normal or abnormal by seven blinded physicians. Multivariable logistic regression was used to compare groups in regard to maximum temperature, minimum temperature, greatest change in temperature in any 24-hour period, and whether the majority of evaluators rated the curve to be abnormal. Baseline characteristics of the groups were similar except the septic group had more trauma patients (31.3% vs. 6.9%, p = .02) and more patients requiring mechanical ventilation (75.0% vs. 41.4%, p = .008). Multivariable logistic regression to control for baseline differences demonstrated that septic patients had significantly larger temperature deviations in any 24-hour period compared to control patients (1.5°C vs. 1.1°C, p = .02). An abnormal temperature pattern was noted by a majority of the evaluators in 22 (68.8%) septic patients and 7 (24.1%) control patients (adjusted OR 4.43, p = .017). This resulted in a sensitivity of 0.69 (95% CI [confidence interval] 0.50, 0.83) and specificity of 0.76 (95% CI 0.56, 0.89) of abnormal temperature curves to predict sepsis. The median time from the temperature plot to the first culture was 9.40 hours (IQR [inter-quartile range] 8.00, 18.20) and to the first dose of antibiotics was 16.90 hours (IQR 8.35, 34.20). Abnormal body temperature curves were predictive of the diagnosis of sepsis in afebrile critically ill patients. Analysis of temperature patterns, rather than absolute values, may facilitate decreased time to antimicrobial therapy.

Body temperature patterns as a predictor of hospital-acquired sepsis in afebrile adult intensive care unit patients: a case-control study

PubMed Central

2013-01-01

Introduction Early treatment of sepsis improves survival, but early diagnosis of hospital-acquired sepsis, especially in critically ill patients, is challenging. Evidence suggests that subtle changes in body temperature patterns may be an early indicator of sepsis, but data is limited. The aim of this study was to examine whether abnormal body temperature patterns, as identified by visual examination, could predict the subsequent diagnosis of sepsis in afebrile critically ill patients. Methods Retrospective case-control study of 32 septic and 29 non-septic patients in an adult medical and surgical ICU. Temperature curves for the period starting 72 hours and ending 8 hours prior to the clinical suspicion of sepsis (for septic patients) and for the 72-hour period prior to discharge from the ICU (for non-septic patients) were rated as normal or abnormal by seven blinded physicians. Multivariable logistic regression was used to compare groups in regard to maximum temperature, minimum temperature, greatest change in temperature in any 24-hour period, and whether the majority of evaluators rated the curve to be abnormal. Results Baseline characteristics of the groups were similar except the septic group had more trauma patients (31.3% vs. 6.9%, p = .02) and more patients requiring mechanical ventilation (75.0% vs. 41.4%, p = .008). Multivariable logistic regression to control for baseline differences demonstrated that septic patients had significantly larger temperature deviations in any 24-hour period compared to control patients (1.5°C vs. 1.1°C, p = .02). An abnormal temperature pattern was noted by a majority of the evaluators in 22 (68.8%) septic patients and 7 (24.1%) control patients (adjusted OR 4.43, p = .017). This resulted in a sensitivity of 0.69 (95% CI [confidence interval] 0.50, 0.83) and specificity of 0.76 (95% CI 0.56, 0.89) of abnormal temperature curves to predict sepsis. The median time from the temperature plot to the first culture was 9.40 hours (IQR [inter-quartile range] 8.00, 18.20) and to the first dose of antibiotics was 16.90 hours (IQR 8.35, 34.20). Conclusions Abnormal body temperature curves were predictive of the diagnosis of sepsis in afebrile critically ill patients. Analysis of temperature patterns, rather than absolute values, may facilitate decreased time to antimicrobial therapy. PMID:24028682

Use of internal control T-cell populations in the flow cytometric evaluation for T-cell neoplasms.

PubMed

Hunt, Alicia M; Shallenberger, Wendy; Ten Eyck, Stephen P; Craig, Fiona E

2016-09-01

Flow cytometry is an important tool for identification of neoplastic T-cells, but immunophenotypic abnormalities are often subtle and must be distinguished from nonneoplastic subsets. Use of internal control (IC) T-cells in the evaluation for T-cell neoplasms was explored, both as a quality measure and as a reference for evaluating abnormal antigen expression. All peripheral blood specimens (3-month period), or those containing abnormal T-cells (29-month period), stained with CD45 V500, CD2 V450, CD3 PE-Cy7, CD7 PE, CD4 Per-CP-Cy5.5, CD8 APC-H7, CD56 APC, CD16&57 FITC, were evaluated. IC T-cells were identified (DIVA, BD Biosciences) and median fluorescence intensity (MFI) recorded. Selected files were merged and reference templates generated (Infinicyt, Cytognos). IC T-cells were present in all specimens, including those with abnormal T-cells, but subsets were less well-represented. IC T-cell CD3 MFI differed between instruments (p = 0.0007) and subsets (p < 0.001), but not specimen categories, and served as a longitudinal process control. Merged files highlighted small unusual IC-T subsets: CD2+(dim) (0.25% total), CD2- (0.03% total). An IC reference template highlighted neoplastic T-cells, but was limited by staining variability (IC CD3 MFI reference samples different from test (p = 0.003)). IC T-cells present in the majority of specimens can serve as positive and longitudinal process controls. Use of IC T-cells as an internal reference is limited by variable representation of subsets. Analysis of merged IC T-cells from previously analyzed patient samples can alert the interpreter to less-well-recognized non-neoplastic subsets. However, application of a merged file IC reference template was limited by staining variability. © 2016 Clinical Cytometry Society. © 2016 International Clinical Cytometry Society.

Cortical thickness and surface area in neonates at high risk for schizophrenia.

PubMed

Li, Gang; Wang, Li; Shi, Feng; Lyall, Amanda E; Ahn, Mihye; Peng, Ziwen; Zhu, Hongtu; Lin, Weili; Gilmore, John H; Shen, Dinggang

2016-01-01

Schizophrenia is a neurodevelopmental disorder associated with subtle abnormal cortical thickness and cortical surface area. However, it is unclear whether these abnormalities exist in neonates associated with genetic risk for schizophrenia. To this end, this preliminary study was conducted to identify possible abnormalities of cortical thickness and surface area in the high-genetic-risk neonates. Structural magnetic resonance images were acquired from offspring of mothers (N = 21) who had schizophrenia (N = 12) or schizoaffective disorder (N = 9), and also matched healthy neonates of mothers who were free of psychiatric illness (N = 26). Neonatal cortical surfaces were reconstructed and parcellated as regions of interest (ROIs), and cortical thickness for each vertex was computed as the shortest distance between the inner and outer surfaces. Comparisons were made for the average cortical thickness and total surface area in each of 68 cortical ROIs. After false discovery rate (FDR) correction, it was found that the female high-genetic-risk neonates had significantly thinner cortical thickness in the right lateral occipital cortex than the female control neonates. Before FDR correction, the high-genetic-risk neonates had significantly thinner cortex in the left transverse temporal gyrus, left banks of superior temporal sulcus, left lingual gyrus, right paracentral cortex, right posterior cingulate cortex, right temporal pole, and right lateral occipital cortex, compared with the control neonates. Before FDR correction, in comparison with control neonates, male high-risk neonates had significantly thicker cortex in the left frontal pole, left cuneus cortex, and left lateral occipital cortex; while female high-risk neonates had significantly thinner cortex in the bilateral paracentral, bilateral lateral occipital, left transverse temporal, left pars opercularis, right cuneus, and right posterior cingulate cortices. The high-risk neonates also had significantly smaller cortical surface area in the right pars triangularis (before FDR correction), compared with control neonates. This preliminary study provides the first evidence that early development of cortical thickness and surface area might be abnormal in the neonates at genetic risk for schizophrenia.

The nature of combustion noise: Stochastic or chaotic?

NASA Astrophysics Data System (ADS)

Gupta, Vikrant; Lee, Min Chul; Li, Larry K. B.

2016-11-01

Combustion noise, which refers to irregular low-amplitude pressure oscillations, is conventionally thought to be stochastic. It has therefore been modeled using a stochastic term in the analysis of thermoacoustic systems. Recently, however, there has been a renewed interest in the validity of that stochastic assumption, with tests based on nonlinear dynamical theory giving seemingly contradictory results: some show combustion noise to be stochastic while others show it to be chaotic. In this study, we show that this contradiction arises because those tests cannot distinguish between noise amplification and chaos. We further show that although there are many similarities between noise amplification and chaos, there are also some subtle differences. It is these subtle differences, not the results of those tests, that should be the focus of analyses aimed at determining the true nature of combustion noise. Recognizing this is an important step towards improved understanding and modeling of combustion noise for the study of thermoacoustic instabilities. This work was supported by the Research Grants Council of Hong Kong (Project No. 16235716 and 26202815).

A new approach to the characterization of subtle errors in everyday action: implications for mild cognitive impairment.

PubMed

Seligman, Sarah C; Giovannetti, Tania; Sestito, John; Libon, David J

2014-01-01

Mild functional difficulties have been associated with early cognitive decline in older adults and increased risk for conversion to dementia in mild cognitive impairment, but our understanding of this decline has been limited by a dearth of objective methods. This study evaluated the reliability and validity of a new system to code subtle errors on an established performance-based measure of everyday action and described preliminary findings within the context of a theoretical model of action disruption. Here 45 older adults completed the Naturalistic Action Test (NAT) and neuropsychological measures. NAT performance was coded for overt errors, and subtle action difficulties were scored using a novel coding system. An inter-rater reliability coefficient was calculated. Validity of the coding system was assessed using a repeated-measures ANOVA with NAT task (simple versus complex) and error type (overt versus subtle) as within-group factors. Correlation/regression analyses were conducted among overt NAT errors, subtle NAT errors, and neuropsychological variables. The coding of subtle action errors was reliable and valid, and episodic memory breakdown predicted subtle action disruption. Results suggest that the NAT can be useful in objectively assessing subtle functional decline. Treatments targeting episodic memory may be most effective in addressing early functional impairment in older age.

IgD multiple myeloma: Clinical, biological features and prognostic value of the serum free light chain assay.

PubMed

Djidjik, R; Lounici, Y; Chergeulaïne, K; Berkouk, Y; Mouhoub, S; Chaib, S; Belhani, M; Ghaffor, M

2015-09-01

IgD multiple myeloma (MM) is a rare subtype of myeloma, it affects less than 2% of patients with MM. To evaluate the clinical and prognostic attributes of serum free light chains (sFLCs) analysis, we examined 17 cases of IgD MM. From 1998 to 2012, we obtained 1250 monoclonal gammapathies including 590 multiple myeloma and 17 patients had IgD MM. With preponderance of men patients with a mean age at diagnosis of: 59±12years. Patients with IgD MM have a short survival (Median survival=9months). The presenting features included: bone pain (75%), lymphadenopathy (16%), hepatomegaly (25%), splenomegaly (8%), associated AL amyloidosis (6%), renal impairment function (82%), infections (47%), hypercalcemia (37%) and anemia (93%). Serum electrophoresis showed a subtle M-spike (Mean=13.22±10g/L) in all patients associated to a hypogammaglobulinemia. There was an over-representation of Lambda light chain (65%); high serum β2-microglobulin in 91% and Bence Jones proteinuria was identified in 71%. The median rate of sFLCs κ was 19.05mg/L and 296.75mg/L for sFLCs λ. sFLCR was abnormal in 93% of patients and it showed concordance between baseline sFLCR and the survival (P=0.034). The contribution of FLC assay is crucial for the prognosis of patients with IgD MM. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Clinical and neuropathological features of X-linked spinal muscular atrophy (SMAX2) associated with a novel mutation in the UBA1 gene.

PubMed

Dlamini, Nomazulu; Josifova, Dragana J; Paine, Simon M L; Wraige, Elizabeth; Pitt, Matthew; Murphy, Amanda J; King, Andrew; Buk, Stefan; Smith, Frances; Abbs, Stephen; Sewry, Caroline; Jacques, Thomas S; Jungbluth, Heinz

2013-05-01

Infantile-onset X-linked spinal muscular atrophy (SMAX2) is a rare lethal disorder linked to mutations in the UBA1 (previously UBE1) gene, encoding ubiquitin-activating enzyme 1 that has an important role in the ubiquitin-proteasome pathway. Published pathological reports are scarce. Here we report a male infant who presented from birth with predominantly truncal hypotonia following an antenatal history of reduced fetal movements. He had a myopathic face, profound weakness, multiple contractures and areflexia. Creatine kinase was moderately raised. Brain MRI showed non-specific symmetrical periventricular white matter changes. Neurophysiology revealed evidence of motor and sensory involvement and muscle biopsy showed marked inflammatory changes with subtle features suggestive of acute denervation. UBA1 sequencing revealed a novel hemizygous missense mutation (c.1670A>T; p.Glu557Val). He died from progressive respiratory failure at 4 months. On post mortem assessment, in addition to severe ventral motor neuron pathology, there was widespread involvement of the sensory system, as well as developmental and degenerative cerebellar abnormalities. In contrast to typical SMN1-associated SMA, the thalamus was unaffected. These findings indicate that SMAX2 is more accurately classified as a motor sensory neuronopathy rather than a pure anterior horn cell disorder. Ubiquitin-proteasome pathway defects may not only cause neurodegeneration but also affect normal neuronal development. Copyright © 2013 Elsevier B.V. All rights reserved.

Lesbian mommy blogging in Canada: documenting subtle homophobia in Canadian society and building community online.

PubMed

Hunter, Andrea

2015-01-01

This article analyzes how lesbian mommy bloggers in Canada are using their blogs as forums for self-expression and a means to form community, as they record their unique experiences as queer parents. Further, it argues that lesbian mommy blogging is documenting a subtle form of homophobia that exists in Canada in terms of social acceptance. Although there is legal acceptance of queer families, society has not necessarily caught up with the law. These blogs show that lesbian parents in Canada still struggle with issues of equality, including difficulties being "out," invisibility, and having to advocate for the non-birth parent.

Nonhuman primate models of polycystic ovary syndrome

PubMed Central

Abbott, David H; Nicol, Lindsey E; Levine, Jon E; Xu, Ning; Goodarzi, Mark O; Dumesic, Daniel A

2013-01-01

With close genomic and phenotypic similarity to humans, nonhuman primate models provide comprehensive epigenetic mimics of polycystic ovary syndrome (PCOS), suggesting early life targeting for prevention. Fetal exposure to testosterone (T), of all nonhuman primate emulations, provides the closest PCOS-like phenotypes, with early-to-mid gestation T-exposed female rhesus monkeys exhibiting adult reproductive, endocrinological and metabolic dysfunctional traits that are co-pathologies of PCOS. Late gestational T exposure, while inducing adult ovarian hyperandrogenism and menstrual abnormalities, has less dysfunctional metabolic accompaniment. Fetal exposures to dihydrotestosterone (DHT) or diethylstilbestrol (DES) suggest androgenic and estrogenic aspects of fetal programming. Neonatal exposure to T produces no PCOS-like outcome, while continuous T treatment of juvenile females causes precocious weight gain and early menarche (high T), or high LH and weight gain (moderate T). Acute T exposure of adult females generates polyfollicular ovaries, while chronic T exposure induces subtle menstrual irregularities without metabolic dysfunction. PMID:23370180

Microstructural abnormalities in MEWDS demonstrated by ultrahigh resolution optical coherence tomography.

PubMed

Nguyen, My Hanh T; Witkin, Andre J; Reichel, Elias; Ko, Tony H; Fujimoto, James G; Schuman, Joel S; Duker, Jay S

2007-01-01

Histopathological studies of acute multiple evanescent white dot syndrome (MEWDS) have not been reported because of the transient and benign nature of the disease. Ultrahigh resolution optical coherence tomography (UHR-OCT), capable of high resolution in vivo imaging, offers a unique opportunity to visualize retinal microstructure in the disease. UHR-OCT images of the maculae of five patients with MEWDS were obtained and analyzed. Diagnosis was based on clinical presentation, examination, visual field testing, and angiography. UHR-OCT revealed disturbances in the photoreceptor inner/outer segment junction (IS/OS) in each of the five patients (six eyes) with MEWDS. In addition, thinning of the outer nuclear layer was seen in the case of recurrent MEWDS, suggesting that repeated episodes of MEWDS may result in photoreceptor atrophy. Subtle disruptions of the photoreceptor IS/OS are demonstrated in all eyes affected by MEWDS. UHR-OCT may be a useful adjunct to diagnosis and monitoring of MEWDS.

Novel PNKP mutation in siblings with ataxia-oculomotor apraxia type 4.

PubMed

Schiess, Nicoline; Zee, David S; Siddiqui, Khurram A; Szolics, Miklos; El-Hattab, Ayman W

The phenotypic and genetic spectrum of ataxia with oculomotor apraxia (AOA) disorders is rapidly evolving and new technologies such as genetic mapping using whole exome sequencing reveal subtle distinctions among the various subtypes. We report a novel PNKP mutation in two siblings with progressive ataxia, abnormal saccades, sensorimotor neuropathy and dystonia consistent with the AOA type 4 phenotype. Laboratory evaluation revealed hypoalbuminemia, hypercholesterolemia with elevated LDL, elevated IgE levels and normal α fetoprotein levels. Eye movement examination demonstrated a marked saccade initiation defect with profound hypometric horizontal saccades. Vertical saccades were also affected but less so. Also present were conspicuous thrusting head movements when attempting to change gaze, but rather than an apraxia these were an adaptive strategy to take advantage of an intact vestibulo-ocular reflex to carry the eyes to a new target of interest. This is demonstrated in accompanying videos.

Persistent dysphonia in two performers affecting the singing and projected speaking voice: a report on a collaborative approach to management.

PubMed

Baker, Janet

2002-01-01

The projected speaking voice and the singing voice are highly sensitive to external and internal influences, and teachers of spoken voice and singing are in a unique position to identify subtle and more serious vocal difficulties in their students. Persistent anomalies may herald early onset of changes in vocal fold structure, neurophysiological control, or emotional stability. Two cases are presented to illustrate the benefits of a collaborative approach to diagnosis and management. The first, a 21-year-old male drama and singing student with an abnormally high speaking voice and falsetto singing voice was found to have a psychogenic dysphonia referred to as "puberphonia" or "mutational falsetto". The second, a 34-year-old female alto with strained phonation and perceived stutter of the vocal folds was diagnosed with "adductor spasmodic dysphonia" or "focal laryngeal dystonia" of neurological origin.

Systematic chromosome examination of two families with schizophrenia and two families with manic depressive illness

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

Friedrich, U.; Mors, O.; Ewald, H.

1996-02-16

Systematic and detailed chromosome analysis, combined with a semistructured interview, was performed in 2 families with schizophrenia and in 2 families with manic depressive illness. Prometaphase technique did not reveal any subtle structural chromosome abnormalities. However, in standard techniques, gain and loss of sex chromosomes were observed. This occurred in patients at a younger age than in unaffected persons. This gives rise to the suspicion that sex chromosome aneuploidy may somehow be related to the development of psychosis. But since the data set is small, especially with respect to schizophrenia, further studies are needed to elucidate this observation. In onemore » family, cosegregation of the disease locus with a marker on chromosome 21 was seen. Therefore, further research should determine if chromosome 21 contains a gene for manic depressive illness. 10 refs., 3 figs., 2 tabs.« less

The layer concept: utilization in determining the pain generators, pathology and how structure determines treatment.

PubMed

Draovitch, Peter; Edelstein, Jaime; Kelly, Bryan T

2012-03-01

The level of understanding of pain in the non-arthritic hip has made significant strides in the last couple of decades beginning with the discoveries of Reinhold Ganz, MD. However, even with the detection of subtle bony abnormalities, including femoroacetabular impingement, a clinician's ability to differentiate pain generators in the hip has been ambiguous. Deciphering the etiology of the pathology versus the pain generator is essential in prescribing the proper treatment. The Layer Concept developed by Dr. Bryan Kelly, is a systematic means of determining which structures about the hip are the source of the pathology, which are the pain generators and how to then best implement treatment. Four layers will be discussed in this article. Layer I, the osseous layer, Layer II, the inert tissue layer, Layer III, the contractile layer and Layer IV, the neuromechanical layer.

Planar cell polarity genes control the connectivity of enteric neurons

PubMed Central

Sasselli, Valentina; Boesmans, Werend; Vanden Berghe, Pieter; Tissir, Fadel; Goffinet, André M.; Pachnis, Vassilis

2013-01-01

A highly complex network of intrinsic enteric neurons is required for the digestive and homeostatic functions of the gut. Nevertheless, the genetic and molecular mechanisms that regulate their assembly into functional neuronal circuits are currently unknown. Here we report that the planar cell polarity (PCP) genes Celsr3 and Fzd3 are required during murine embryogenesis to specifically control the guidance and growth of enteric neuronal projections relative to the longitudinal and radial gut axes. Ablation of these genes disrupts the normal organization of nascent neuronal projections, leading to subtle changes of axonal tract configuration in the mature enteric nervous system (ENS), but profound abnormalities in gastrointestinal motility. Our data argue that PCP-dependent modules of connectivity established at early stages of enteric neurogenesis control gastrointestinal function in adult animals and provide the first evidence that developmental deficits in ENS wiring may contribute to the pathogenesis of idiopathic bowel disorders. PMID:23478408

Allele related mutation specific-polymerase chain reaction for rapid diagnosis of Hb New York (beta 113 (G15) Val-->Glu, beta(CD113 GTG-->GAG)).

PubMed

Viprakasit, Vip; Tachavanich, Kalaya; Suwantol, Lerlugsn; Pung-Amritt, Parichat; Chinchang, Worawut; Tanphaichitr, Voravarn S

2002-08-01

Hemoglobin New York (beta 113 (G15) Val-->Glu), a beta-globin variant, was first reported in a Chinese family living in New York. Subsequently, this abnormal hemoglobin was reported in many Chinese descendants from several groups and it was also known as Hb Kaohsiung. The subtle change in alpha1beta1 contact region apart from the heme group connecting area by Val-->Glu substitution has minor changes in both the electrophoretic mobility and stability making this hemoglobin variant difficult to distinguish from Hb A using routine hemoglobin analysis. The authors described a case of heterozygosity of Hb New York diagnosed by a molecular technique and revealed a mutation in beta(CD113 GTG-->GAG). A novel Allele Related Mutation Specific-Polymerase Chain Reaction (ARMS-PCR) for rapid diagnosis of this mutation has been proposed.

The Mediational Effect of Weight Self-Stigma in the Relationship between Blatant and Subtle Discrimination and Depression and Anxiety.

PubMed

Magallares, Alejandro; Bolaños-Rios, Patricia; Ruiz-Prieto, Inmaculada; Benito de Valle, Pilar; Irles, Jose Antonio; Jáuregui-Lobera, Ignacio

2017-02-06

Obesity may be considered a social stigma. In addition, people with obesity are frequently aware of stigma directed at others who have a similar weight and come to think stigmatized thoughts about themselves. Our study focused specifically on how blatant and subtle discrimination and weight self-stigma are related to depression and anxiety in people with obesity. The sample comprised 170 participants from the Clinical Nutrition Unit of the "Hospital de Valme" (Seville, Spain). The Weight Self-Stigma Questionnaire, the Multidimensional Perceived Discrimination Scale, and the Hospital Anxiety and Depression Scale were used. It was found that blatant and subtle discrimination and weight self-stigma were positively related to depression (.31, .38, and .45 respectively) and anxiety (.30, .36, and .49 respectively; all ps < .01). The path analysis conducted showed that there was a mediational effect of weight self-stigma between blatant (β = .36) and subtle discrimination (β = .40) and depression (β = .24) and anxiety (β = .49; all ps < .01). According to these results, it can be said that weight self-stigma was a full mediator in the model found because the relationships between the independent and the dependent variables were non-significant. Finally, results are discussed in the frame of the obesity stigma literature, and some clinical implications of the results of the study are suggested.

Can Caring Create Prejudice? An Investigation of Positive and Negative Intergenerational Contact in Care Settings and the Generalisation of Blatant and Subtle Age Prejudice to Other Older People.

PubMed

Drury, Lisbeth; Abrams, Dominic; Swift, Hannah J; Lamont, Ruth A; Gerocova, Katarina

2017-01-01

Caring is a positive social act, but can it result in negative attitudes towards those cared for, and towards others from their wider social group? Based on intergroup contact theory, we tested whether care workers' (CWs) positive and negative contact with old-age care home residents (CHRs) predicts prejudiced attitudes towards that group, and whether this generalises to other older people. Fifty-six CWs were surveyed about their positive and negative contact with CHRs and their blatant and subtle attitudes (humanness attributions) towards CHRs and older adults. We tested indirect paths from contact with CHRs to attitudes towards older adults via attitudes towards CHRs. Results showed that neither positive nor negative contact generalised blatant ageism. However, the effect of negative, but not positive, contact on the denial of humanness to CHRs generalised to subtle ageism towards older adults. This evidence has practical implications for management of CWs' work experiences and theoretical implications, suggesting that negative contact with a subgroup generalises the attribution of humanness to superordinate groups. Because it is difficult to identify and challenge subtle prejudices such as dehumanisation, it may be especially important to reduce negative contact. © 2016 The Authors. Journal of Community & Applied Social Psychology Published by John Wiley & Sons Ltd.

Anaglyph, Yucatan Peninsula, Mexico

NASA Image and Video Library

2003-03-06

This anaglyph of Mexico Yucatan Peninsula was generated from NASA Shuttle Radar Topography Mission data, and shows a subtle but distinctive indication of the Chicxulub impact crater. 3D glasses are necessary to view this image.

Blocking Mimicry Makes True and False Smiles Look the Same

PubMed Central

Rychlowska, Magdalena; Cañadas, Elena; Wood, Adrienne; Krumhuber, Eva G.; Fischer, Agneta; Niedenthal, Paula M.

2014-01-01

Recent research suggests that facial mimicry underlies accurate interpretation of subtle facial expressions. In three experiments, we manipulated mimicry and tested its role in judgments of the genuineness of true and false smiles. Experiment 1 used facial EMG to show that a new mouthguard technique for blocking mimicry modifies both the amount and the time course of facial reactions. In Experiments 2 and 3, participants rated true and false smiles either while wearing mouthguards or when allowed to freely mimic the smiles with or without additional distraction, namely holding a squeeze ball or wearing a finger-cuff heart rate monitor. Results showed that blocking mimicry compromised the decoding of true and false smiles such that they were judged as equally genuine. Together the experiments highlight the role of facial mimicry in judging subtle meanings of facial expressions. PMID:24670316

Effects of carbamazepine and lamotrigine on functional magnetic resonance imaging cognitive networks.

PubMed

Xiao, Fenglai; Caciagli, Lorenzo; Wandschneider, Britta; Sander, Josemir W; Sidhu, Meneka; Winston, Gavin; Burdett, Jane; Trimmel, Karin; Hill, Andrea; Vollmar, Christian; Vos, Sjoerd B; Ourselin, Sebastien; Thompson, Pamela J; Zhou, Dong; Duncan, John S; Koepp, Matthias J

2018-06-13

To investigate the effects of sodium channel-blocking antiepileptic drugs (AEDs) on functional magnetic resonance imaging (fMRI) language network activations in patients with focal epilepsy. In a retrospective study, we identified patients who were treated at the time of language fMRI scanning with either carbamazepine (CBZ; n = 42) or lamotrigine (LTG; n = 42), but not another sodium channel-blocking AED. We propensity-matched 42 patients taking levetiracetam (LEV) as "patient-controls" and included further 42 age- and gender-matched healthy controls. After controlling for age, age at onset of epilepsy, gender, and antiepileptic comedications, we compared verbal fluency fMRI activations between groups and out-of-scanner psychometric measures of verbal fluency. Patients on CBZ performed less well on a verbal fluency tests than those taking LTG or LEV. Compared to either LEV-treated patients or controls, patients taking CBZ showed decreased activations in left inferior frontal gyrus and patients on LTG showed abnormal deactivations in frontal and parietal default mode areas. All patient groups showed fewer activations in the putamen bilaterally compared to controls. In a post hoc analysis, out-of-scanner fluency scores correlated positively with left putamen activation. Our study provides evidence of AED effects on the functional neuroanatomy of language, which might explain subtle language deficits in patients taking otherwise well-tolerated sodium channel-blocking agents. Patients on CBZ showed dysfunctional frontal activation and more pronounced impairment of performance than patients taking LTG, which was associated only with failure to deactivate task-negative networks. As previously shown for working memory, LEV treatment did not affect functional language networks. © 2018 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.

Relapsing bacteremia after blood transmission of Bartonella henselae to cats.

PubMed

Kordick, D L; Breitschwerdt, E B

1997-05-01

To determine persistence of bacteremia, pathogenicity, and immunoglobulin kinetics after blood transmission of Bartonella henselae in cats. 18 specific-pathogen-free (SPF) cats (16 weeks old) received blood or urine from 4 adult cats (2 SPF, 2 naturally infected with B henselae). SPF cats were inoculated with blood IV (n = 4), blood IM (n = 4), or urine sediment IM (n = 4) from 2 bacteremic cats (donors A and B). Control cats (2/route) received inoculum from culture-negative, seronegative SPF cats (donors C and D). 6 cats (5 blood, 1 urine) were transiently febrile during the 213-day observation period. Two bacteremic cats developed CNS abnormalities. Transient anemia was the only hematologic abnormality. Bacteremia was induced in 7 of 8 blood recipients by postinoculation day (PID) 11. Urine recipients (n = 6) did not become bacteremic or seroconvert by PID 108, but when challenge exposed IV with blood, 4 of 6 became infected. All infected cats developed relapsing bacteremia. Initially, colony counts for donor-A recipients were 10(3) greater than those for donor-B recipients; however, during relapses, counts were similar. Polymerase chain reaction-restriction fragment length polymorphism analysis of 16S rRNA gene and the intergenic spacer region revealed no differences among isolates derived from recipient cats. Bartonella henselae-specific antibodies were detected between PID 15 and 18 in donor-A, compared with PID 46 and 181 in donor-B recipients. The peak geometric mean titer of donor-A recipients was 1,448, versus 406 for donor-B recipients. Blood transmission of B henselae induced subtle clinical abnormalities; the biological behavior of the 2 donor strains differed; and relapsing bacteremia can persist in conjunction with variably high antibody titers.

Fetal, infant, adolescent and adult phenotypes of polycystic ovary syndrome in prenatally androgenized female rhesus monkeys

PubMed Central

Abbott, David H; Tarantal, Alice F; Dumesic, Daniel A

2010-01-01

Old World monkeys provide naturally-occurring and experimentally-induced phenotypes closely resembling the highly prevalent polycystic ovary syndrome (PCOS) in women. In particular, experimentally-induced fetal androgen excess in female rhesus monkeys produces a comprehensive adult PCOS-like phenotype that includes both reproductive and metabolic dysfunction found in PCOS women. Such a reliable experimental approach enables the use of the prenatally androgenized (PA) female rhesus monkey model to (1) examine fetal, infant and adolescent antecedents of adult pathophysiology, gaining valuable insight into early phenotypic expression of PCOS, and (2) to understand adult pathophysiology from a mechanistic perspective. Elevated circulating luteinizing hormone (LH) levels are the earliest indication of reproductive dysfunction in late gestation nonhuman primate fetuses and infants exposed to androgen excess during early (late first to second trimester) gestation. Such early gestation-exposed PA infants also are hyperandrogenic, with both LH hypersecretion and hyperandrogenism persisting in early gestation-exposed PA adults. Similarly, subtle metabolic abnormalities appearing in young nonhuman primate infants and adolescents precede the abdominal adiposity, hyperliplidemia, and increased incidence of type 2 diabetes that characterize early gestated-exposed PA adults. These new insights into the developmental origins of PCOS, and progression of the pathophysiology from infancy to adulthood, provide opportunities for clinical intervention to ameliorate the PCOS phenotype thus providing a preventive health care approach to PCOS-related abnormalities. For example, PCOS-like traits in PA monkeys, as in PCOS women, can improve with better insulin-glucose homeostasis, suggesting that lifestyle interventions preventing increased adiposity in adolescent daughters of PCOS mothers also may reduce their risk of acquiring many PCOS-related metabolic abnormalities in adulthood. PMID:19367587

SPECT/CT imaging in general orthopedic practice.

PubMed

Scharf, Stephen

2009-09-01

The availability of hybrid devices that combine the latest single-photon emission computed tomography (SPECT) imaging technology with multislice computed tomography (CT) scanning has allowed us to detect subtle, nonspecific abnormalities on bone scans and interpret them as specific focal areas of pathology. Abnormalities in the spine can be separated into those caused by pars fractures, facet joint arthritis, or osteophyte formation on vertebral bodies. Compression fractures can be distinguished from severe degenerative disease, both of which can cause intense activity across the spine on either planar or SPECT imaging. Localizing activity in patients who have had spinal fusion can provide tremendous insight into the causes of therapeutic failures. Infections of the spine now can be diagnosed with gallium SPECT/CT, despite the fact that gallium has long been abandoned because of its failure to detect spine infection on either planar or SPECT imaging. Small focal abnormalities in the feet and ankles can be localized well enough to make specific orthopedic diagnoses on the basis of their location. Moreover, when radiographic imaging provides equivocal or inadequate information, SPECT/CT can provide a road map for further diagnostic studies and has been invaluable in planning surgery. Our ability to localize activity within a bone or at an articular surface has allowed us to distinguish between fractures and joint disease. Increased activity associated with congenital anomalies, such as tarsal coalition and Bertolotti's syndrome have allowed us to understand the pathophysiology of these conditions, to confirm them as the cause of the patient's symptoms, and to provide information that is useful in determining appropriate clinical management. As our experience broadens, SPECT/CT will undoubtedly become an important tool in the evaluation and management of a wider variety of orthopedic patients.

Systolic Strain Abnormalities to Predict Hospital Readmission in Patients With Heart Failure and Normal Ejection Fraction

PubMed Central

Borer, Steven M.; Kokkirala, Aravind; O'Sullivan, David M.; Silverman, David I.

2011-01-01

Background Despite intensive investigation, the pathogenesis of heart failure with normal ejection fraction (HFNEF) remains unclear. We hypothesized that subtle abnormalities of systolic function might play a role, and that abnormal systolic strain and strain rate would provide a marker for adverse outcomes. Methods Patients of new CHF and left ventricular ejection fraction > 50% were included. Exclusion criteria were recent myocardial infarction, severe valvular heart disease, severe left ventricular hypertrophy (septum >1.8 cm), or a technically insufficient echocardiogram. Average peak systolic strain and strain rate were measured using an off-line grey scale imaging technique. Systolic strain and strain rate for readmitted patients were compared with those who remained readmission-free. Results One hundred consecutive patients with a 1st admission for HFNEF from January 1, 2004 through December 31, 2007, inclusive, were analyzed. Fifty two patients were readmitted with a primary diagnosis of heart failure. Systolic strain and strain rates were reduced in both study groups compared to controls. However, systolic strain did not differ significantly between the two groups (-11.7% for those readmitted compared with -12.9% for those free from readmission, P = 0.198) and systolic strain rates also were similar (-1.05 s-1 versus -1.09 s-1, P = 0.545). E/e’ was significantly higher in readmitted patients compared with those who remained free from readmission (14.5 versus 11.0, P = 0.013). E/e’ (OR 1.189, 95% CI 1.026-1.378; P = 0.021) was found to be an independent predictor for HFNEF readmission. Conclusions Among patients with new onset HFNEF, SS and SR rates are reduced compared with patients free of HFNEF, but do not predict hospital readmission. Elevated E/e’ is a predictor of readmission in these patients. PMID:28352395

Subtle abnormalities of gait detected early in vitamin B6 deficiency in aged and weanling rats with hind leg gait analysis.

PubMed

Schaeffer, M C; Cochary, E F; Sadowski, J A

1990-04-01

Motor abnormalities have been observed in every species made vitamin B6 deficient, and have been detected and quantified early in vitamin B6 deficiency in young adult female Long-Evans rats with hind leg gait analysis. Our objective was to determine if hind leg gait analysis could be used to detect vitamin B6 deficiency in weanling (3 weeks) and aged (23 months) Fischer 344 male rats. Rats (n = 10 per group) were fed: the control diet ad libitum (AL-CON); the control diet devoid of added pyridoxine hydrochloride (DEF); or the control diet pair-fed to DEF (PF-CON). At 10 weeks, plasma pyridoxal phosphate concentration confirmed deficiency in both age groups. Gait abnormalities were detected in the absence of gross motor disturbances in both aged and weanling DEF rats at 2-3 weeks. Width of step was significantly reduced (16%, p less than 0.003) in DEF aged rats compared to AL- and PF-CON. This pattern of response was similar to that reported previously in young adult rats. In weanling rats, pair feeding alone reduced mean width of step (+/- SEM) by 25% compared to ad libitum feeding (2.7 +/- 0.1 vs 3.6 +/- 0.1 cm for PF- vs AL-CON, respectively, p less than 0.05). In DEF weanling rats, width (3.0 +/- 0.1 cm) was increased compared to PF-CON (11%, p less than 0.05) but decreased compared to AL-CON (16%, p less than 0.05). Width of step was significantly altered early in B6 deficiency in rats of different ages and strains and in both sexes.(ABSTRACT TRUNCATED AT 250 WORDS)

A dysmorphology score system for assessing embryo abnormalities in rat whole embryo culture.

PubMed

Zhang, Cindy X; Danberry, Tracy; Jacobs, Mary Ann; Augustine-Rauch, Karen

2010-12-01

The rodent whole embryo culture (WEC) system is a well-established model for characterizing developmental toxicity of test compounds and conducting mechanistic studies. Laboratories have taken various approaches in describing type and severity of developmental findings of organogenesis-stage rodent embryos, but the Brown and Fabro morphological score system is commonly used as a quantitative approach. The associated score criteria is based upon developmental stage and growth parameters, where a series of embryonic structures are assessed and assigned respective scores relative to their gestational stage, with a Total Morphological Score (TMS) assigned to the embryo. This score system is beneficial because it assesses a series of stage-specific anatomical landmarks, facilitating harmonized evaluation across laboratories. Although the TMS provides a quantitative approach to assess growth and determine developmental delay, it is limited to its ability to identify and/or delineate subtle or structure-specific abnormalities. Because of this, the TMS may not be sufficiently sensitive for identifying compounds that induce structure or organ-selective effects. This study describes a distinct morphological score system called the "Dysmorphology Score System (DMS system)" that has been developed for assessing gestation day 11 (approximately 20-26 somite stage) rat embryos using numerical scores to differentiate normal from abnormal morphology and define the respective severity of dysmorphology of specific embryonic structures and organ systems. This method can also be used in scoring mouse embryos of the equivalent developmental stage. The DMS system enhances capabilities to rank-order compounds based upon teratogenic potency, conduct structure- relationships of chemicals, and develop statistical prediction models to support abbreviated developmental toxicity screens. © 2010 Wiley-Liss, Inc.

Psychosocial outcomes at three and nine months after good neurological recovery from aneurysmal subarachnoid haemorrhage: predictors and prognosis

PubMed Central

Powell, J; Kitchen, N; Heslin, J; Greenwood, R

2002-01-01

Objectives: To investigate (1) the prevalence of various aspects of cognitive and psychosocial dysfunction, including post-traumatic stress symptoms, over nine months after subarachnoid haemorrhage (SAH); (2) whether SAH is preceded by increased life stress; (3) to what extent adverse outcomes may be predicted from preillness life stress, early neurological impairment, age, and sex; and (4) relations between emotional and functional outcomes. Methods: 52 patients with good neurological recovery after surgery for SAH were each matched for age, sex, and occupation with a healthy control participant. SAH patients were assessed three and nine months postdischarge on measures of cognitive functioning, mood, and social functioning. Objective stressors and subjective life change during the preceding year were rated retrospectively. Controls completed measures of mood and social functioning once only. Results: Compared with controls, SAH patients showed increased mood disturbance, subtle cognitive impairment, and abnormally low independence and participation on measures of social functioning. 60% showed clinically significant post-traumatic stress symptomatology (intrusive thoughts or avoidance of reminders) at three months and 30% at nine months. Independence in activities of daily living was greatly reduced in half to a third of the sample at both three and nine months. Productive employment was below the 10th percentile of the control group for 75% of patients at three months and for 56% at nine months; this outcome could not be predicted from selected demographic, premorbid, or clinical variables but dependence on others for organisational activities was predicted by impaired prose recall. Mood at nine months was strongly predicted by prior mental health problems, poor physical health, dysphasia, and impaired prose recall at three months. There was no evidence of an abnormally high level of stressful life events in the year before SAH, although patients rated their subjective level of stress in this period slightly more highly than did the control participants. Conclusions: These findings highlight the need for structured support and treatment after surgery for SAH to reduce persisting mood disturbance and increase independence and participation. PMID:12023423

Fractal-dimension analysis detects cerebral changes in preterm infants with and without intrauterine growth restriction.

PubMed

Esteban, Francisco J; Padilla, Nelly; Sanz-Cortés, Magdalena; de Miras, Juan Ruiz; Bargalló, Núria; Villoslada, Pablo; Gratacós, Eduard

2010-12-01

In the search for a useful parameter to detect and quantify subtle brain abnormalities in infants with intrauterine growth restriction (IUGR), we hypothesised that the analysis of the structural complexity of grey matter (GM) and white matter (WM) using the fractal dimension (FD), a measurement of the topological complexity of an object, could be established as a useful tool for quantitative studies of infant brain morphology. We studied a sample of 18 singleton IUGR premature infants, (12.72 months corrected age (CA), range: 12 months-14 months), 15 preterm infants matched one-to-one for gestational age (GA) at delivery (12.6 months; range: 12 months-14 months), and 15 neonates born at term (12.4 months; range: 11 months-14 months). The neurodevelopmental outcome was assessed in all subjects at 18 months CA according to the Bayley Scale for Infant and Toddler Development - Third edition (BSID-III). For MRI acquisition and processing, the infants were scanned at 12 months CA, in a TIM TRIO 3T scanner, sleeping naturally. Images were pre-processed using the SPM5 toolbox, the GM and WM segmented under the VBM5 toolbox, and the box-counting method was applied for FD calculation of normal and skeletonized segmented images. The results showed a significant decrease of the FD of the brain GM and WM in the IUGR group when compared to the preterm or at-term controls. We also identified a significant linear tendency of both GM and WM FD from IUGR to preterm and term groups. Finally, multiple linear analyses between the FD of the GM or WM and the neurodevelopmental scales showed a significant regression of the language and motor scales with the FD of the GM. In conclusion, a decreased FD of the GM and WM in IUGR infants could be a sensitive indicator for the investigation of structural brain abnormalities in the IUGR population at 12 months of age, which can also be related to functional disorders. Copyright © 2010 Elsevier Inc. All rights reserved.

Significance of a diagnosis of atypical squamous cells of undetermined significance for Papanicolaou smears in perimenopausal and postmenopausal women.

PubMed

Keating, J T; Wang, H H

2001-04-25

The current study was conducted to determine the significance of a diagnosis of atypical squamous cells of undetermined significance (ASCUS) in perimenopausal and postmenopausal women. The reports for all Papanicolaou (Pap) smears viewed in the study institution's cytology laboratory over a 6-month period were reviewed. Women were divided into premenopausal (age < or = 45 years), perimenopausal (ages 46-54 years), and postmenopausal (age > or = 55 years) categories. Slide review and 2-year follow-up were obtained for selected cases diagnosed as ASCUS. ASCUS cases among the perimenopausal women were compared with an age-matched control group. The total number of abnormal Pap smears in the premenopausal, perimenopausal, and postmenopausal categories were 770 (6.8%), 104 (4.3%), and 67 (2.9%), with 482, 83, and 41 diagnoses of ASCUS, respectively. The ratio of ASCUS to squamous intraepithelial lesions (SIL) was 2.2 overall and 1.9, 7.5, and 4.1, respectively, for each group (P < 0.001). The positive predictive value for a diagnosis of SIL on subsequent Pap smears or biopsies was 22%, 12.2%, and 29.7%, respectively. Slide review showed that the premenopausal ASCUS cases appeared to have a higher percentage of nuclear-cytoplasmic ratio increase and nuclear membrane irregularities compared with the other categories (P = 0.03 and P = 0.02, respectively) and the perimenopausal group was found to have more ASCUS in metaplastic cells (P = 0.03). In perimenopausal women, slides diagnosed as ASCUS demonstrated more air-drying artifact than the control group (P = 0.004) but had less obvious atrophy (P = 0.01). Despite a decreased abnormality rate with increasing age, the results of the current study show that the perimenopausal and postmenopausal groups appear to have elevated ASCUS-to-SIL ratios. ASCUS appears to have a particularly low positive predictive value for SIL in perimenopausal women, and therefore most likely is overcalled in this age group. This may be attributable in part to air-drying artifact and subtle atrophic changes.

Kinematic analysis of handwriting movements in patients with obsessive-compulsive disorder

PubMed Central

Mavrogiorgou, P; Mergl, R; Tigges, P; El Husseini, J; Schroter, A; Juckel, G; Zaudig, M; Hegerl, U

2001-01-01

OBJECTIVES—Basal ganglia dysfunction is supposed to play a part in the pathophysiology of obsessive-compulsive disorder (OCD). A new computer aided technique for the analysis of hand movements, allowing the detection of subtle motor performance abnormalities, was applied in this study of patients with OCD and healthy controls.
METHODS—Using a digitising graphic tablet, hand motor performance was studied in 22 unmedicated patients with OCD and compared with 22 healthy controls. All subjects drew superimposed concentric circles with both the right and the left hand, in addition to writing a given sentence, their personal signature, and letter sequences in four different sizes. Kinematic parameters were calculated to quantify hand motion.
RESULTS—Patients with OCD had significant impairments of handwriting performance, reflected by lower peak velocity (sentence t=3.6; p=0.001; signature t=2.8; p=0.01) and micrographia (sentence t=3.4; p=0.002; signature t=2.5; p=0.02), compared with controls and shortened acceleration phases per stroke (sentence t=2.4; p=0.02; signature t=4.1; p=0.000). By contrast, in repetitive drawing, patients with OCD had higher peak velocity than healthy controls (group×task interaction p<0.01). There were no significant differences in left and right hand performance between groups. Patients with early versus late age of onset differed in handwriting parameters, such as handwriting consistency. Greater severity of obsessions and compulsions correlated with increasingly poor handwriting performance in patients with OCD.
CONCLUSIONS—A subtle motor dysfunction in OCD can be detected with a digitising tablet. The findings show handwriting impairments in patients with OCD, in line with the assumption that basal ganglia dysfunction is part of OCD pathophysiology. Repetitive motor pattern performance was not impaired, but rather tended to be even better in patients with OCD than in controls. The findings also support the concept that patients with OCD with early versus late age of onset differ in pathophysiological mechanisms and basal ganglia dysfunction.

 PMID:11309453

Shaded Relief with Height as Color, Yucatan Peninsula, Mexico

NASA Image and Video Library

2003-03-06

This shaded relief image of Mexico Yucatan Peninsula show a subtle, but unmistakable, indication of the Chicxulub impact crater. Most scientists now agree that this impact was the cause of the Cretatious-Tertiary Extinction.

Stressed hearts in children with obesity and diabetes: a cause for concern?

PubMed

Berry, C; Sattar, N

2011-04-01

Obesity in young people is an emerging public health problem, particularly because of its association with type 2 diabetes. Since obesity and diabetes contribute to the development of cardiovascular disease in adults, the question arises as to whether or not these conditions may be associated with cardiovascular abnormalities in children and adolescents. In this issue of Diabetologia, Shah et al. report the results of a cross-sectional study of heart structure and function in 612 adolescents and young adults (aged 10-24 years) subdivided into three groups: (1) those with obesity and type 2 diabetes; (2) those with type 2 diabetes but without obesity; and (3) lean healthy controls. Their results revealed that left ventricular mass (indexed to body surface area) was greater in the obese individuals than in lean controls. Left ventricular systolic function was more dynamic in obese participants and obese participants with type 2 diabetes compared with lean controls, whereas systolic function was comparable in obese patients with or without type 2 diabetes. Furthermore, compared with the healthy lean control participants, diastolic function was impaired in the obese group and further impaired in the obese individuals with diabetes. These results, and those of a few other similar studies, lend support to the notion that obesity and diabetes in children cause subtle abnormalities in cardiovascular structure and function. The present commentary discusses potential mechanisms and possible clinical ramifications for such findings.

RNAi silenced Dd-grp94 (Dictyostelium discoideum glucose-regulated protein 94 kDa) cell lines in Dictyostelium exhibit marked reduction in growth rate and delay in development.

PubMed

Baviskar, Sandhya N; Shields, Malcolm S

2010-01-01

Glucose-regulated 94 kDa protein (Grp94) is a resident of the endoplasmic reticulum (ER) of multicellular eukaryotes. It is a constitutively expressed protein that is overexpressed in certain abnormal conditions of the cell such as depletion of glucose and calcium, and low oxygen and pH. The protein is also implicated in diseased conditions like cancer and Alzheimer's disease. In this study, the consequences of downregulation of Grp94 were investigated at both unicellular and multicellular stages of Dictyostelium discoideum. Previous studies have shown the expression of Dd-Grp94 (Dictyostelium discoideum glucose-regulated 94 kDa protein) in wild-type cells varies during development, and overexpression of Dd-Grp94 leads to abnormal cell shape and inhibition of development (i.e., formation of fruiting bodies). Grp94 is a known calcium binding protein and an efficient calcium buffer. Therefore, in the present study we hypothesized that downregulation of Dd-Grp94 protein would affect Dictyostelium cell structure, growth, and development. We found that Dd-grp94 RNAi recombinants exhibited reduced growth rate, cell size, and a subtle change in cell motility compared to the parental cells. The recombinants also exhibited a delay in development and small fruiting bodies. These results establish that Dd-grp94 plays a crucial role in determining normal cell structure, growth and differentiation.

Disruption of Neurexin 1 Associated with Autism Spectrum Disorder

PubMed Central

Kim, Hyung-Goo; Kishikawa, Shotaro; Higgins, Anne W.; Seong, Ihn-Sik; Donovan, Diana J.; Shen, Yiping; Lally, Eric; Weiss, Lauren A.; Najm, Juliane; Kutsche, Kerstin; Descartes, Maria; Holt, Lynn; Braddock, Stephen; Troxell, Robin; Kaplan, Lee; Volkmar, Fred; Klin, Ami; Tsatsanis, Katherine; Harris, David J.; Noens, Ilse; Pauls, David L.; Daly, Mark J.; MacDonald, Marcy E.; Morton, Cynthia C.; Quade, Bradley J.; Gusella, James F.

2008-01-01

Autism is a neurodevelopmental disorder of complex etiology in which genetic factors play a major role. We have implicated the neurexin 1 (NRXN1) gene in two independent subjects who display an autism spectrum disorder (ASD) in association with a balanced chromosomal abnormality involving 2p16.3. In the first, with karyotype 46,XX,ins(16;2)(q22.1;p16.1p16.3)pat, NRXN1 is directly disrupted within intron 5. Importantly, the father possesses the same chromosomal abnormality in the absence of ASD, indicating that the interruption of α-NRXN1 is not fully penetrant and must interact with other factors to produce ASD. The breakpoint in the second subject, with 46,XY,t(1;2)(q31.3;p16.3)dn, occurs ∼750 kb 5′ to NRXN1 within a 2.6 Mb genomic segment that harbors no currently annotated genes. A scan of the NRXN1 coding sequence in a cohort of ASD subjects, relative to non-ASD controls, revealed that amino acid alterations in neurexin 1 are not present at high frequency in ASD. However, a number of rare sequence variants in the coding region, including two missense changes in conserved residues of the α-neurexin 1 leader sequence and of an epidermal growth factor (EGF)-like domain, respectively, suggest that even subtle changes in NRXN1 might contribute to susceptibility to ASD. PMID:18179900

Characterization of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in Shanghai, China: molecular and cytogenetic characteristics, IgV gene restriction and hypermutation patterns.

PubMed

Irons, Richard D; Le, Anh; Bao, Liming; Zhu, Xiongzeng; Ryder, John; Wang, Xiao Qin; Ji, Meirong; Chen, Yan; Wu, Xichun; Lin, Guowei

2009-12-01

The clinical, cytogenetic and molecular features of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), a disease previously considered to be rare in Asia, were examined in consecutive series of 70 cases diagnosed by our laboratory over a 30-month period. Clonal abnormalities were observed in 80% of CLL/SLL cases using a combination of conventional cytogenetic and fluorescence in situ hybridization (FISH) analysis. Those involving 14q32/IGH were the most frequent (24 cases), followed by trisomy 12 and 11q abnormalities. IgV(H) gene usage was non-random with over-representation of V(H)4-34, V(H)3-23 and a previously unreported increase in V(H)3-48 gene use. Somatic hypermutation (SHM) of IgV(H) germline sequences was observed in 56.5% of cases with stereotyped patterns of SHM observed in V(H)4-34 heavy chain complimentary-determining (HCDR1) and framework region CFR2 sequences. These findings in a Chinese population suggest subtle geographical differences in IgV(H) gene usage while the remarkably specific pattern of SHM suggest that a relatively limited set of antigens may be involved in the development of this disease worldwide. IgV(H) gene mutation status was a significant predictor of initial survival in CLL/SLL. However, an influence of karyotype on prognosis was not observed.

Clinical correlates of hypothalamic-pituitary-adrenal axis measures in individuals at risk for psychosis and with first-episode psychosis.

PubMed

Labad, Javier; Armario, Antonio; Nadal, Roser; Solé, Montse; Gutiérrez-Zotes, Alfonso; Montalvo, Itziar; Moreno-Samaniego, Lorena; Martorell, Lourdes; Sánchez-Gistau, Vanessa; Vilella, Elisabet

2018-07-01

Hypothalamic-pituitary-adrenal (HPA) axis alterations in at-risk mental states (ARMS) resemble those observed in established psychosis but are less consistent. We aimed to explore HPA axis abnormalities in both first-episode psychosis (FEP) and ARMS patients, while controlling for psychopathological symptoms. We studied 21 ARMS, 34 FEP patients and 34 healthy subjects. Clinical assessment included psychopathological symptoms (positive, negative, disorganized, excited and depressive symptoms) and stress measures. Saliva cortisol levels were determined at awakening, 30' and 60' post-awakening, 10:00 h, 23:00 h and 10:00 h on the day after the administration of 0.25 mg of dexamethasone, which occurred at 23:00 h. Three HPA axis measures were calculated: cortisol awakening response (CAR), cortisol diurnal slope and cortisol suppression ratio of the dexamethasone suppression test (DST). There were no significant differences between groups in HPA axis measures. However, when exploring the relationship between HPA axis measures and psychopathological symptoms, in ARMS subjects (but not FEP patients), a flatter cortisol slope was associated with more prominent negative symptoms, whereas a blunted CAR was associated with excited symptoms. Although no significant differences in HPA axis measures were found between diagnostic groups, subtle abnormalities in the CAR or circadian cortisol rhythmicity might be important for the phenotype of ARMS individuals. Copyright © 2018. Published by Elsevier B.V.

A Chip Off the Old Block: Parents’ Subtle Ethnic Prejudice Predicts Children’s Implicit Prejudice

PubMed Central

Pirchio, Sabine; Passiatore, Ylenia; Panno, Angelo; Maricchiolo, Fridanna; Carrus, Giuseppe

2018-01-01

The increasing flow of immigrants in many European countries and the growing presence of children from immigrant families in schools makes it relevant to study the development of prejudice in children. Parents play an important role in shaping children’s values and their attitudes toward members of other ethnic groups; an intergenerational transmission of prejudice has been found in a number of studies targeting adolescents. The present study aims to investigate the intergenerational transmission of ethnic prejudice in 3- to 9- year-old children and its relations to parenting styles. Parents’ blatant and subtle ethnic prejudice and parenting style are measured together with children’s explicit and implicit ethnic prejudice in pupils and parents of preschool and primary schools in the region of Rome, Italy (N = 318). Results show that parents’ subtle prejudice predicts children’s implicit prejudice regardless of the parenting style. Findings indicate that children might acquire prejudice by means of the parents’ implicit cognition and automatic behavior and educational actions. Implications for future studies and insights for possible applied interventions are discussed. PMID:29479328

Spectral mineral mapping for characterization of subtle geothermal prospects using ASTER data

NASA Astrophysics Data System (ADS)

Abubakar, A. J.; Hashim, M.; Pour, A. B.

2017-05-01

In this study, the performance of ASTER data is evaluated for mapping subtle geothermal prospects in an unexplored tropical region having a number of thermal springs. The study employed a simple Decorrelation stretch with specific absorptions to highlight possible alteration zones of interest related to Geothermal (GT) systems. Hydrothermal alteration minerals are subsequently mapped using Spectral Angle Mapper (SAM) and Linear Spectral Unmixing (LSU) algorithms to target representative minerals such as clays, carbonates and AL-OH minerals as indicators of GT activity. The results were validated through field GPS survey, rock sampling and laboratory analysis using latest smart lab X-Ray Diffractometer technology. The study indicates that ASTER broadband satellite data could be used to map subtle GT prospects with the aid of an in-situ verification. However, it also shows that ASTER could not discriminate within specie minerals especially for clays using SWIR bands. Subsequent studies are aimed at looking at both ASTER and Hyperion hyperspectral data in the same area as this could have significant implications for GT resource detection in unmapped aseismic and inaccessible tropical regions using available spaceborne data.

Virtual reality as a screening tool for sports concussion in adolescents.

PubMed

Nolin, Pierre; Stipanicic, Annie; Henry, Mylène; Joyal, Christian C; Allain, Philippe

2012-01-01

There is controversy surrounding the cognitive effects of sports concussion. This study aimed to verify whether the technique of virtual reality could aid in the identification of attention and inhibition deficits in adolescents. A prospective design was used to assess 25 sports-concussed and 25 non-sports-concussed adolescents enrolled in a sport and education programme. Participants were evaluated in immersive virtual reality via ClinicaVR: Classroom-CPT and in real life via the traditional VIGIL-CPT. The neuropsychological assessment using virtual reality showed greater sensitivity to the subtle effects of sports concussion compared to the traditional test, which showed no difference between groups. The results also demonstrated that the sports concussion group reported more symptoms of cybersickness and more intense cybersickness than the control group. Sports concussion was associated with subtle deficits in attention and inhibition. However, further studies are needed to support these results.

Sensitivity to differences in the motor origin of drawings: from human to robot.

PubMed

De Preester, Helena; Tsakiris, Manos

2014-01-01

This study explores the idea that an observer is sensitive to differences in the static traces of drawings that are due to differences in motor origin. In particular, our aim was to test if an observer is able to discriminate between drawings made by a robot and by a human in the case where the drawings contain salient kinematic cues for discrimination and in the case where the drawings only contain more subtle kinematic cues. We hypothesized that participants would be able to correctly attribute the drawing to a human or a robot origin when salient kinematic cues are present. In addition, our study shows that observers are also able to detect the producer behind the drawings in the absence of these salient kinematic cues. The design was such that in the absence of salient kinematic cues, the drawings are visually very similar, i.e. only differing in subtle kinematic differences. Observers thus had to rely on these subtle kinematic differences in the line trajectories between drawings. However, not only motor origin (human versus robot) but also motor style (natural versus mechanic) plays a role in attributing a drawing to the correct producer, because participants scored less high when the human hand draws in a relatively mechanical way. Overall, this study suggests that observers are sensitive to subtle kinematic differences between visually similar marks in drawings that have a different motor origin. We offer some possible interpretations inspired by the idea of "motor resonance".

Sensitivity to Differences in the Motor Origin of Drawings: From Human to Robot

PubMed Central

De Preester, Helena; Tsakiris, Manos

2014-01-01

This study explores the idea that an observer is sensitive to differences in the static traces of drawings that are due to differences in motor origin. In particular, our aim was to test if an observer is able to discriminate between drawings made by a robot and by a human in the case where the drawings contain salient kinematic cues for discrimination and in the case where the drawings only contain more subtle kinematic cues. We hypothesized that participants would be able to correctly attribute the drawing to a human or a robot origin when salient kinematic cues are present. In addition, our study shows that observers are also able to detect the producer behind the drawings in the absence of these salient kinematic cues. The design was such that in the absence of salient kinematic cues, the drawings are visually very similar, i.e. only differing in subtle kinematic differences. Observers thus had to rely on these subtle kinematic differences in the line trajectories between drawings. However, not only motor origin (human versus robot) but also motor style (natural versus mechanic) plays a role in attributing a drawing to the correct producer, because participants scored less high when the human hand draws in a relatively mechanical way. Overall, this study suggests that observers are sensitive to subtle kinematic differences between visually similar marks in drawings that have a different motor origin. We offer some possible interpretations inspired by the idea of “motor resonance”. PMID:25014198

Gently does it: Humans outperform a software classifier in recognizing subtle, nonstereotypical facial expressions.

PubMed

Yitzhak, Neta; Giladi, Nir; Gurevich, Tanya; Messinger, Daniel S; Prince, Emily B; Martin, Katherine; Aviezer, Hillel

2017-12-01

According to dominant theories of affect, humans innately and universally express a set of emotions using specific configurations of prototypical facial activity. Accordingly, thousands of studies have tested emotion recognition using sets of highly intense and stereotypical facial expressions, yet their incidence in real life is virtually unknown. In fact, a commonplace experience is that emotions are expressed in subtle and nonprototypical forms. Such facial expressions are at the focus of the current study. In Experiment 1, we present the development and validation of a novel stimulus set consisting of dynamic and subtle emotional facial displays conveyed without constraining expressers to using prototypical configurations. Although these subtle expressions were more challenging to recognize than prototypical dynamic expressions, they were still well recognized by human raters, and perhaps most importantly, they were rated as more ecological and naturalistic than the prototypical expressions. In Experiment 2, we examined the characteristics of subtle versus prototypical expressions by subjecting them to a software classifier, which used prototypical basic emotion criteria. Although the software was highly successful at classifying prototypical expressions, it performed very poorly at classifying the subtle expressions. Further validation was obtained from human expert face coders: Subtle stimuli did not contain many of the key facial movements present in prototypical expressions. Together, these findings suggest that emotions may be successfully conveyed to human viewers using subtle nonprototypical expressions. Although classic prototypical facial expressions are well recognized, they appear less naturalistic and may not capture the richness of everyday emotional communication. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Staging of Macular Telangiectasia: Power-Doppler Optical Coherence Tomography and Macular Pigment Optical Density

PubMed Central

Chin, Eric K.; Kim, Dae Yu; Hunter, Allan A.; Pilli, Suman; Wilson, Machelle; Zawadzki, Robert J.; Werner, John S.; Park, Susanna S.

2013-01-01

Purpose. Two methods were used to study the stages of macular telangiectasia (MacTel): Power-Doppler optical coherence tomography (PD-OCT), which allows imaging of the retinal circulation in three dimensions, and macular pigment optical density (MPOD), which quantifies the distribution of macular carotenoids. Methods. Among 49 patients with MacTel identified, 12 eyes (6 patients) with MacTel and 7 age-matched control eyes (7 patients) were imaged with a custom-built Fourier-domain OCT instrument to acquire PD-OCT images. MPOD was measured using heterochromatic flicker photometry in 10 eyes (5 patients) with MacTel and compared with 44 age-matched control eyes (44 patients). Clinical staging of MacTel was based on best-corrected visual acuity, fundus biomicroscopy, fluorescein angiography, and OCT. Results. Stage 1 eyes (n = 2) had subtle punctate vascular signal confined to the inner portion of the outer plexiform layer (OPL) on PD-OCT. Stage 2 (n = 2) showed larger oblique vascular signal extending into deeper OPL. Stage 3 (n = 5) had disruption of outer retinal layers with abnormal vasculature extending into the outer nuclear layer. Stage 4 (n = 3) showed diffuse blurring of the retinal layers with vascular channels extending the full thickness of the retina. MPOD values in four eyes with stage 1 or 2 MacTel correlated well with age-matched controls. Six eyes with stage 3 or 4 MacTel had loss of MPOD especially at the fovea. Conclusions. PD-OCT shows penetration of the retinal capillaries into the deeper retinal layers in early stages of MacTel, with full thickness vascular proliferation in advanced disease. MPOD is commonly depleted but may appear normal in early stage MacTel. PMID:23716628

Patterns of Gray Matter Abnormalities in Schizophrenia Based on an International Mega-analysis.

PubMed

Gupta, Cota Navin; Calhoun, Vince D; Rachakonda, Srinivas; Chen, Jiayu; Patel, Veena; Liu, Jingyu; Segall, Judith; Franke, Barbara; Zwiers, Marcel P; Arias-Vasquez, Alejandro; Buitelaar, Jan; Fisher, Simon E; Fernandez, Guillen; van Erp, Theo G M; Potkin, Steven; Ford, Judith; Mathalon, Daniel; McEwen, Sarah; Lee, Hyo Jong; Mueller, Bryon A; Greve, Douglas N; Andreassen, Ole; Agartz, Ingrid; Gollub, Randy L; Sponheim, Scott R; Ehrlich, Stefan; Wang, Lei; Pearlson, Godfrey; Glahn, David C; Sprooten, Emma; Mayer, Andrew R; Stephen, Julia; Jung, Rex E; Canive, Jose; Bustillo, Juan; Turner, Jessica A

2015-09-01

Analyses of gray matter concentration (GMC) deficits in patients with schizophrenia (Sz) have identified robust changes throughout the cortex. We assessed the relationships between diagnosis, overall symptom severity, and patterns of gray matter in the largest aggregated structural imaging dataset to date. We performed both source-based morphometry (SBM) and voxel-based morphometry (VBM) analyses on GMC images from 784 Sz and 936 controls (Ct) across 23 scanning sites in Europe and the United States. After correcting for age, gender, site, and diagnosis by site interactions, SBM analyses showed 9 patterns of diagnostic differences. They comprised separate cortical, subcortical, and cerebellar regions. Seven patterns showed greater GMC in Ct than Sz, while 2 (brainstem and cerebellum) showed greater GMC for Sz. The greatest GMC deficit was in a single pattern comprising regions in the superior temporal gyrus, inferior frontal gyrus, and medial frontal cortex, which replicated over analyses of data subsets. VBM analyses identified overall cortical GMC loss and one small cluster of increased GMC in Sz, which overlapped with the SBM brainstem component. We found no significant association between the component loadings and symptom severity in either analysis. This mega-analysis confirms that the commonly found GMC loss in Sz in the anterior temporal lobe, insula, and medial frontal lobe form a single, consistent spatial pattern even in such a diverse dataset. The separation of GMC loss into robust, repeatable spatial patterns across multiple datasets paves the way for the application of these methods to identify subtle genetic and clinical cohort effects. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Early gestational exposure to moderate concentrations of ethanol alters adult behaviour in C57BL/6J mice.

PubMed

Sanchez Vega, Michelle C; Chong, Suyinn; Burne, Thomas H J

2013-09-01

Alcohol consumption during pregnancy has deleterious effects on the developing foetus ranging from subtle physical deficits to severe behavioural abnormalities and is encompassed under a broad umbrella term, foetal alcohol spectrum disorders (FASD). High levels of exposure show distinct effects, whereas the consequences of moderate exposures have been less well studied. The aim of this study was to examine the effects of a moderate dose ethanol exposure using an ad libitum drinking procedure during the first eight days of gestation in mice on the behavioural phenotype of adult offspring. Adult female C57Bl/6J mice were mated and exposed to either 10% (v/v) ethanol or water for the first 8 days of gestation (GD 0-8), and then offered water for the rest of gestation. Early developmental milestone achievement was assessed in offspring at postnatal days (P) 7, 14 and 21. Adult offspring underwent a comprehensive battery of behavioural tests to examine a range of behavioural domains including locomotion, exploration, anxiety, social behaviour, learned helplessness, sensorimotor gating, and nociception, as well as spatial memory in a water maze. Ethanol-exposed mice had similar postnatal developmental trajectories to water-exposed mice. However, the ethanol-exposed mice showed increased hyperlocomotion at P 14, 21 and 70 (p<0.05). Increased exploration and heightened motivation were also observed in adult mice. Furthermore, ethanol-exposed mice showed a significant improvement in memory in the water maze. The main findings were that mice had persistent and long lasting alterations in behaviour, including hyperactivity and enhanced spatial memory. These data suggest that even moderate dose ethanol exposure in early gestation has long term consequences on brain function and behaviour in mice. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Aversive Disablism: Subtle Prejudice toward Disabled People

ERIC Educational Resources Information Center

Deal, Mark

2007-01-01

Blatant forms of prejudice towards disabled people appear to be disappearing in the UK. However, subtle forms of prejudice remain and may be highly damaging to the achievement of the vision of disabled people being "respected and included as equal members of society". In order to assist placing subtle forms of prejudice within a…

Subtle Alterations in Brain Anatomy May Change an Individual’s Personality in Chronic Pain

PubMed Central

Gustin, Sylvia M.; McKay, Jamie G.; Petersen, Esben T.; Peck, Chris C.; Murray, Greg M.; Henderson, Luke A.

2014-01-01

It is well established that gross prefrontal cortex damage can affect an individual’s personality. It is also possible that subtle prefrontal cortex changes associated with conditions such as chronic pain, and not detectable until recent advances in human brain imaging, may also result in subtle changes in an individual’s personality. In an animal model of chronic neuropathic pain, subtle prefrontal cortex changes including altered basal dendritic length, resulted in altered decision making ability. Using multiple magnetic resonance imaging techniques, we found in humans, although gray matter volume and on-going activity were unaltered, chronic neuropathic pain was associated with reduced free and bound proton movement, indicators of subtle anatomical changes, in the medial prefrontal cortex, anterior cingulate cortex and mediodorsal thalamus. Furthermore, proton spectroscopy revealed an increase in neural integrity in the medial prefrontal cortex in neuropathic pain patients, the degree of which was significantly correlated to the personality temperament of novelty seeking. These data reveal that even subtle changes in prefrontal cortex anatomy may result in a significant change in an individual’s personality. PMID:25291361

Retinal pigment epithelial changes in chronic Vogt-Koyanagi-Harada disease: fundus autofluorescence and spectral domain optical coherence tomography findings

PubMed Central

Vasconcelos-Santos, Daniel V.; Sohn, Elliott H.; Sadda, Srinivas; Rao, Narsing A.

2009-01-01

Purpose To determine whether fundus autofluorescence (FAF) and spectral-domain optical coherence tomography (SD-OCT) imaging allows better assessment of RPE and outer retina (OR) in subjects with chronic VKH compared to examination and angiography alone. Methods Cross-sectional analysis of a series of seven consecutive patients with chronic VKH undergoing FAF and SD-OCT. Chronic VKH was defined as during >3 months. Color fundus photographs were correlated to FAF and SD-OCT images. The images were later correlated to fluorescein angiography (FA) and indocyanine green angiography (ICG-A). Results All patients had sunset glow fundus, which resulted in no apparent corresponding abnormality on FAF or SD-OCT. Lesions with decreased autofluorescence signal were observed in 11 eyes (85%), being associated with loss of the RPE and involvement of OR on SD-OCT. In 5 eyes (38%) some of these lesions were very subtle on clinical examination but easily detected by FAF. Lesions with increased autofluorescence signal were seen in 8 eyes (61.5%), showing variable involvement of the OR on SD-OCT and corresponding clinically to areas of RPE proliferation and cystoid macular edema. Conclusion Combined use of FAF and SD-OCT imaging allowed noninvasive delineation of RPE/OR changes in patients with chronic VKH, which were consistent with previous histopathological reports. Some of these changes were not apparent on clinical examination. PMID:20010321

Nutrition in brain development and aging: role of essential fatty acids.

PubMed

Uauy, Ricardo; Dangour, Alan D

2006-05-01

The essential fatty acids (EFAs), particularly the n-3 long-chain polyunsaturated fatty acids (LCPs), are important for brain development during both the fetal and postnatal period. They are also increasingly seen to be of value in limiting the cognitive decline during aging. EFA deficiency was first shown over 75 years ago, but the more subtle effects of the n-3 fatty acids in terms of skin changes, a poor response to linoleic acid supplementation, abnormal visual function, and peripheral neuropathy were only discovered later. Both n-3 and n-6 LCPs play important roles in neuronal growth, development of synaptic processing of neural cell interaction, and expression of genes regulating cell differentiation and growth. The fetus and placenta are dependent on maternal EFA supply for their growth and development, with docosahexaenomic acid (DHA)-supplemented infants showing significantly greater mental and psychomotor development scores (breast-fed children do even better). Dietary DHA is needed for the optimum functional maturation of the retina and visual cortex, with visual acuity and mental development seemingly improved by extra DHA. Aging is also associated with decreased brain levels of DHA: fish consumption is associated with decreased risk of dementia and Alzheimer's disease, and the reported daily use of fish-oil supplements has been linked to improved cognitive function scores, but confirmation of these effects is needed.

Repressive but not activating epigenetic modifications are aberrant on the inactive X chromosome in live cloned cattle.

PubMed

Geng-Sheng, Cao; Yu, Gao; Kun, Wang; Fang-Rong, Ding; Ning, Li

2009-08-01

X inactivation is the process of a chromosome-wide silencing of the majority of genes on the X chromosome during early mammalian development. This process may be aberrant in cloned animals. Here we show that repressive modifications, such as methylation of DNA, and the presence of methylated histones, H3K9me2 and H3K27me3, exhibit distinct aberrance on the inactive X chromosome in live clones. In contrast, H3K4me3, an active gene marker, is obviously missing from the inactive X chromosome in all cattle studied. This suggests that the disappearance of active histone modifications (H3K4me3) seems to be more important for X inactivation than deposition of marks associated with heterochromatin (DNA methylation, H3K27me3 and H3K9me2). It also implies that even apparently normal clones may have subtle abnormalities in repressive, but not activating epigenetic modifications on the inactive X when they survive to term. We also found that the histone H3 methylations were enriched and co-localized at q21-31 of the active X chromosome, which may be associated with an abundance of LINE1 repeat elements. © 2009 The Authors. Journal compilation © 2009 Japanese Society of Developmental Biologists.

Track-based event recognition in a realistic crowded environment

NASA Astrophysics Data System (ADS)

van Huis, Jasper R.; Bouma, Henri; Baan, Jan; Burghouts, Gertjan J.; Eendebak, Pieter T.; den Hollander, Richard J. M.; Dijk, Judith; van Rest, Jeroen H.

2014-10-01

Automatic detection of abnormal behavior in CCTV cameras is important to improve the security in crowded environments, such as shopping malls, airports and railway stations. This behavior can be characterized at different time scales, e.g., by small-scale subtle and obvious actions or by large-scale walking patterns and interactions between people. For example, pickpocketing can be recognized by the actual snatch (small scale), when he follows the victim, or when he interacts with an accomplice before and after the incident (longer time scale). This paper focusses on event recognition by detecting large-scale track-based patterns. Our event recognition method consists of several steps: pedestrian detection, object tracking, track-based feature computation and rule-based event classification. In the experiment, we focused on single track actions (walk, run, loiter, stop, turn) and track interactions (pass, meet, merge, split). The experiment includes a controlled setup, where 10 actors perform these actions. The method is also applied to all tracks that are generated in a crowded shopping mall in a selected time frame. The results show that most of the actions can be detected reliably (on average 90%) at a low false positive rate (1.1%), and that the interactions obtain lower detection rates (70% at 0.3% FP). This method may become one of the components that assists operators to find threatening behavior and enrich the selection of videos that are to be observed.

big bang gene modulates gut immune tolerance in Drosophila.

PubMed

Bonnay, François; Cohen-Berros, Eva; Hoffmann, Martine; Kim, Sabrina Y; Boulianne, Gabrielle L; Hoffmann, Jules A; Matt, Nicolas; Reichhart, Jean-Marc

2013-02-19

Chronic inflammation of the intestine is detrimental to mammals. Similarly, constant activation of the immune response in the gut by the endogenous flora is suspected to be harmful to Drosophila. Therefore, the innate immune response in the gut of Drosophila melanogaster is tightly balanced to simultaneously prevent infections by pathogenic microorganisms and tolerate the endogenous flora. Here we describe the role of the big bang (bbg) gene, encoding multiple membrane-associated PDZ (PSD-95, Discs-large, ZO-1) domain-containing protein isoforms, in the modulation of the gut immune response. We show that in the adult Drosophila midgut, BBG is present at the level of the septate junctions, on the apical side of the enterocytes. In the absence of BBG, these junctions become loose, enabling the intestinal flora to trigger a constitutive activation of the anterior midgut immune response. This chronic epithelial inflammation leads to a reduced lifespan of bbg mutant flies. Clearing the commensal flora by antibiotics prevents the abnormal activation of the gut immune response and restores a normal lifespan. We now provide genetic evidence that Drosophila septate junctions are part of the gut immune barrier, a function that is evolutionarily conserved in mammals. Collectively, our data suggest that septate junctions are required to maintain the subtle balance between immune tolerance and immune response in the Drosophila gut, which represents a powerful model to study inflammatory bowel diseases.

Your visual system provides all the information you need to make moral judgments about generic visual events.

PubMed

De Freitas, Julian; Alvarez, George A

2018-05-28

To what extent are people's moral judgments susceptible to subtle factors of which they are unaware? Here we show that we can change people's moral judgments outside of their awareness by subtly biasing perceived causality. Specifically, we used subtle visual manipulations to create visual illusions of causality in morally relevant scenarios, and this systematically changed people's moral judgments. After demonstrating the basic effect using simple displays involving an ambiguous car collision that ends up injuring a person (E1), we show that the effect is sensitive on the millisecond timescale to manipulations of task-irrelevant factors that are known to affect perceived causality, including the duration (E2a) and asynchrony (E2b) of specific task-irrelevant contextual factors in the display. We then conceptually replicate the effect using a different paradigm (E3a), and also show that we can eliminate the effect by interfering with motion processing (E3b). Finally, we show that the effect generalizes across different kinds of moral judgments (E3c). Combined, these studies show that obligatory, abstract inferences made by the visual system influence moral judgments. Copyright © 2018 Elsevier B.V. All rights reserved.

The Destiny of Cells: Mechanisms and Implications of Senescence.

ERIC Educational Resources Information Center

Cristofalo, Vincent J.

1985-01-01

Approaches the regulation of aging by perturbing the rate of senescent changes in studying how the modulating agent exerts its effects. Shows that very subtle molecular changes may be involved in the overall regulation of cellular aging. (Author/BL)

Shaded Relief with Height as Color and Landsat, Yucatan Peninsula, Mexico

NASA Image and Video Library

2003-03-06

The top picture is a shaded relief image of the northwest corner of Mexico Yucatan Peninsula generated from NASA Shuttle Radar Topography Mission SRTM data, and shows a subtle, but unmistakable, indication of the Chicxulub impact crater.

Clinical and cytogenetic features of a Potocki-Lupski syndrome with the shortest 0.25Mb microduplication in 17p11.2 including RAI1.

PubMed

Lee, Cha Gon; Park, Sang-Jin; Yim, Shin-Young; Sohn, Young Bae

2013-08-01

Potocki-Lupski syndrome (PTLS [MIM 610883]) is a recently recognized microduplication syndrome associated with 17p11.2. It is characterized by mild facial dysmorphic features, hypermetropia, infantile hypotonia, failure to thrive, mental retardation, autistic spectrum disorders, behavioral abnormalities, sleep apnea, and cardiovascular anomalies. In several studies, the critical PTLS region was deduced to be 1.3Mb in length, and included RAI1 and 17 other genes. We report a 3-year-old Korean boy with the smallest duplication in 17p11.2 and a milder phenotype. He had no family history of neurologic disease or developmental delay and no history of seizure, autistic features, or behavior problems. He showed subtle facial dysmorphic features (dolichocephaly and a mildly asymmetric smile) and flat feet. All laboratory tests were normal and he had no evidence of internal organ anomalies. He was found to have mild intellectual disabilities (full scale IQ 65 on K-WPPSI) and language developmental delay (age of 2.2year-old on PRESS). Array comparative genomic hybridization (CGH) showed about a 0.25Mb microduplication on chromosome 17p11.2 containing four Refseq (NCBI reference sequence) genes, including RAI1 [arr 17p11.2(17,575,978-17,824,623)×3]. When compared with previously reported cases, the milder phenotype of our patient may be associated with the smallest duplication in 17p11.2, 0.25Mb in length. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Synchrony of corticostriatal-midbrain activation enables normal inhibitory control and conflict processing in recovering alcoholic men.

PubMed

Schulte, Tilman; Müller-Oehring, Eva M; Sullivan, Edith V; Pfefferbaum, Adolf

2012-02-01

Alcohol dependence is associated with inhibitory control deficits, possibly related to abnormalities in frontoparietal cortical and midbrain function and connectivity. We examined functional connectivity and microstructural fiber integrity between frontoparietal and midbrain structures using a Stroop Match-to-Sample task with functional magnetic resonance imaging and diffusion tensor imaging in 18 alcoholic and 17 control subjects. Manipulation of color cues and response repetition sequences modulated cognitive demands during Stroop conflict. Despite similar lateral frontoparietal activity and functional connectivity in alcoholic and control subjects when processing conflict, control subjects deactivated the posterior cingulate cortex (PCC), whereas alcoholic subjects did not. Posterior cingulum fiber integrity predicted the degree of PCC deactivation in control but not alcoholic subjects. Also, PCC activity was modulated by executive control demands: activated during response switching and deactivated during response repetition. Alcoholics showed the opposite pattern: activation during repetition and deactivation during switching. Here, in alcoholic subjects, greater deviations from the normal PCC activity correlated with higher amounts of lifetime alcohol consumption. A functional dissociation of brain network connectivity between the groups further showed that control subjects exhibited greater corticocortical connectivity among middle cingulate, posterior cingulate, and medial prefrontal cortices than alcoholic subjects. In contrast, alcoholic subjects exhibited greater midbrain-orbitofrontal cortical network connectivity than control subjects. Degree of microstructural fiber integrity predicted robustness of functional connectivity. Thus, even subtle compromise of microstructural connectivity in alcoholism can influence modulation of functional connectivity and underlie alcohol-related cognitive impairment. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Changes in cognitive control in pre-manifest Huntington's disease examined using pre-saccadic EEG potentials - a longitudinal study.

PubMed

Ness, Vanessa; Bestgen, Anne-Kathrin; Saft, Carsten; Beste, Christian

2014-01-01

It is well-known that Huntington's disease (HD) affects saccadic processing. However, saccadic dysfunctions in HD may be seen as a result of dysfunctional processes occurring at the oculomotor level prior to the execution of saccades, i.e., at a pre-saccadic level. Virtually nothing is known about possible changes in pre-saccadic processes in HD. This study examines pre-saccadic processing in pre-manifest HD gene mutation carriers (pre-HDs) by using clinically available EEG measures. Error rates, pre-saccadic EEG potentials and saccade onset EEG potentials were measured in 14 pre-HDs and case-matched controls performing prosaccades and antisaccades in a longitudinal study over a 15-month period. The results show that pre-saccadic potentials were changed in pre-HDs, relative to controls and also revealed changes across the 15-month longitudinal period. In particular, pre-saccadic ERP in pre-HDs were characterized by lower amplitudes and longer latencies, which revealed longitudinal changes. These changes were observed for anti-saccades, but not for pro-saccades. Overt saccadic trajectories (potentials) were not different to those in controls, showing that pre-saccadic processes are sensitive to subtle changes in fronto-striatal networks in pre-HDs. Deficits in pre-saccadic processes prior the execution of an erroneous anti-saccade can be seen as an effect of dysfunctional cognitive control in HD. This may underlie saccadic abnormalities and hence a major phenotype of HD. Pre-saccadic EEG potentials preceding erroneous anti-saccades are sensitive to pre-manifest disease progression in HD.

Male sex interspecies divergence and down regulation of expression of spermatogenesis genes in Drosophila sterile hybrids.

PubMed

Sundararajan, Vignesh; Civetta, Alberto

2011-01-01

Male sex genes have shown a pattern of rapid interspecies divergence at both the coding and gene expression level. A common outcome from crosses between closely-related species is hybrid male sterility. Phenotypic and genetic studies in Drosophila sterile hybrid males have shown that spermatogenesis arrest is postmeiotic with few exceptions, and that most misregulated genes are involved in late stages of spermatogenesis. Comparative studies of gene regulation in sterile hybrids and parental species have mainly used microarrays providing a whole genome representation of regulatory problems in sterile hybrids. Real-time PCR studies can reject or reveal differences not observed in microarray assays. Moreover, differences in gene expression between samples can be dependant on the source of RNA (e.g., whole body vs. tissue). Here we survey expression in D. simulans, D. mauritiana and both intra and interspecies hybrids using a real-time PCR approach for eight genes expressed at the four main stages of sperm development. We find that all genes show a trend toward under expression in the testes of sterile hybrids relative to parental species with only the two proliferation genes (bam and bgcn) and the two meiotic class genes (can and sa) showing significant down regulation. The observed pattern of down regulation for the genes tested can not fully explain hybrid male sterility. We discuss the down regulation of spermatogenesis genes in hybrids between closely-related species within the contest of rapid divergence experienced by the male genome, hybrid sterility and possible allometric changes due to subtle testes-specific developmental abnormalities.

Glucose Metabolic Profile by Visual Assessment Combined with Statistical Parametric Mapping Analysis in Pediatric Patients with Epilepsy.

PubMed

Zhu, Yuankai; Feng, Jianhua; Wu, Shuang; Hou, Haifeng; Ji, Jianfeng; Zhang, Kai; Chen, Qing; Chen, Lin; Cheng, Haiying; Gao, Liuyan; Chen, Zexin; Zhang, Hong; Tian, Mei

2017-08-01

PET with 18 F-FDG has been used for presurgical localization of epileptogenic foci; however, in nonsurgical patients, the correlation between cerebral glucose metabolism and clinical severity has not been fully understood. The aim of this study was to evaluate the glucose metabolic profile using 18 F-FDG PET/CT imaging in patients with epilepsy. Methods: One hundred pediatric epilepsy patients who underwent 18 F-FDG PET/CT, MRI, and electroencephalography examinations were included. Fifteen age-matched controls were also included. 18 F-FDG PET images were analyzed by visual assessment combined with statistical parametric mapping (SPM) analysis. The absolute asymmetry index (|AI|) was calculated in patients with regional abnormal glucose metabolism. Results: Visual assessment combined with SPM analysis of 18 F-FDG PET images detected more patients with abnormal glucose metabolism than visual assessment only. The |AI| significantly positively correlated with seizure frequency ( P < 0.01) but negatively correlated with the time since last seizure ( P < 0.01) in patients with abnormal glucose metabolism. The only significant contributing variable to the |AI| was the time since last seizure, in patients both with hypometabolism ( P = 0.001) and with hypermetabolism ( P = 0.005). For patients with either hypometabolism ( P < 0.01) or hypermetabolism ( P = 0.209), higher |AI| values were found in those with drug resistance than with seizure remission. In the post-1-y follow-up PET studies, a significant change of |AI| (%) was found in patients with clinical improvement compared with those with persistence or progression ( P < 0.01). Conclusion: 18 F-FDG PET imaging with visual assessment combined with SPM analysis could provide cerebral glucose metabolic profiles in nonsurgical epilepsy patients. |AI| might be used for evaluation of clinical severity and progress in these patients. Patients with a prolonged period of seizure freedom may have more subtle (or no) metabolic abnormalities on PET. The clinical value of PET might be enhanced by timing the scan closer to clinical seizures. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Complex networks: Effect of subtle changes in nature of randomness

NASA Astrophysics Data System (ADS)

Goswami, Sanchari; Biswas, Soham; Sen, Parongama

2011-03-01

In two different classes of network models, namely, the Watts Strogatz type and the Euclidean type, subtle changes have been introduced in the randomness. In the Watts Strogatz type network, rewiring has been done in different ways and although the qualitative results remain the same, finite differences in the exponents are observed. In the Euclidean type networks, where at least one finite phase transition occurs, two models differing in a similar way have been considered. The results show a possible shift in one of the phase transition points but no change in the values of the exponents. The WS and Euclidean type models are equivalent for extreme values of the parameters; we compare their behaviour for intermediate values.

Gender effects in alcohol dependence: an fMRI pilot study examining affective processing.

PubMed

Padula, Claudia B; Anthenelli, Robert M; Eliassen, James C; Nelson, Erik; Lisdahl, Krista M

2015-02-01

Alcohol dependence (AD) has global effects on brain structure and function, including frontolimbic regions regulating affective processing. Preliminary evidence suggests alcohol blunts limbic response to negative affective stimuli and increases activation to positive affective stimuli. Subtle gender differences are also evident during affective processing. Fourteen abstinent AD individuals (8 F, 6 M) and 14 healthy controls (9 F, 5 M), ages 23 to 60, were included in this facial affective processing functional magnetic resonance imaging pilot study. Whole-brain linear regression analyses were performed, and follow-up analyses examined whether AD status significantly predicted depressive symptoms and/or coping. Fearful Condition-The AD group demonstrated reduced activation in the right medial frontal gyrus, compared with controls. Gender moderated the effects of AD in bilateral inferior frontal gyri. Happy Condition-AD individuals had increased activation in the right thalamus. Gender moderated the effects of AD in the left caudate, right middle frontal gyrus, left paracentral lobule, and right lingual gyrus. Interactive AD and gender effects for fearful and happy faces were such that AD men activated more than control men, but AD women activated less than control women. Enhanced coping was associated with greater activation in right medial frontal gyrus during fearful condition in AD individuals. Abnormal affective processing in AD may be a marker of alcoholism risk or a consequence of chronic alcoholism. Subtle gender differences were observed, and gender moderated the effects of AD on neural substrates of affective processing. AD individuals with enhanced coping had brain activation patterns more similar to controls. Results help elucidate the effects of alcohol, gender, and their interaction on affective processing. Copyright © 2015 by the Research Society on Alcoholism.

Orientation Discrimination with Macular Changes Associated with Early AMD

PubMed Central

Bedell, Harold E.; Tong, Jianliang; Woo, Stanley Y.; House, Jon R.; Nguyen, Tammy

2010-01-01

Purpose Age-related macular degeneration (AMD) is a condition that progressively reduces central vision in elderly individuals, resulting in a reduced capacity to perform many daily activities and a diminished quality of life. Recent studies identified clinical treatments that can slow or reverse the progression of exudative (wet) AMD and ongoing research is evaluating earlier interventions. Because early diagnosis is critical for an optimal outcome, the goal of this study is to assess psychophysical orientation discrimination for randomly positioned short line segments as a potential indicator of subtle macular changes in eyes with early AMD. Methods Orientation discrimination was measured in a sample of 74 eyes of patients aged 47 to 82 years old, none of which had intermediate or advanced AMD. Amsler-grid testing was performed as well. A masked examiner graded each eye as level 0, 1, 2, or 3 on a streamlined version of the Age-Related Eye Disease Study (AREDS) scale for AMD, based on the presence and extent of macular drusen or retinal pigment epithelium (RPE) changes. Visual acuity in the 74 eyes ranged from 20/15 to 20/40+1, with no significant differences among the grading levels. Humphrey 10–2 and Nidek MP-1 micro-perimetry were used to assess retinal sensitivity at test locations 1° from the locus of fixation. Results Average orientation-discrimination thresholds increased systematically from 7.4° to 11.3° according to the level of macular changes. In contrast, only 3 of 74 eyes exhibited abnormalities on the Amsler grid and central-field perimetric defects occurred with approximately equal probability at all grading levels. Conclusions In contrast to Amsler grid and central-visual-field testing, psychophysical orientation discrimination has the capability to distinguish between eyes with and without subtle age-related macular changes. PMID:19319009

Integrating magnetic resonance imaging postprocessing results into neuronavigation for electrode implantation and resection of subtle focal cortical dysplasia in previously cryptogenic epilepsy.

PubMed

Wellmer, Jörg; Parpaley, Yaroslav; von Lehe, Marec; Huppertz, Hans-Jürgen

2010-01-01

Focal cortical dysplasias (FCDs) are highly epileptogenic lesions. Surgical removal is frequently the best treatment option for pharmacoresistant epilepsy. However, subtle FCDs may remain undetected even after high-resolution magnetic resonance imaging (MRI). Morphometric MRI analysis, which compares the individual brain with a normal database, can facilitate the detection of FCDs. We describe how the results of normal database-based MRI postprocessing can be used to guide stereotactic electrode implantation and subsequent resection of lesions that are suspected to be FCDs. A presurgical evaluation was conducted on a 19-year-old woman with pharmacoresistant hypermotor seizures. Conventional high-resolution MRI was classified as negative for epileptogenic lesions. However, morphometric analysis of the spatially normalized MRI revealed abnormal gyration and blurring of the gray-white matter junction, which was suggestive of a small and deeply seated FCD in the left frontal lobe. The brain region highlighted by morphometric analysis was marked as a region of interest, transferred back to the original dimension of the individual MRI, and imported into a neuronavigation system. This allowed the region of interest-targeted stereotactic implantation of 2 depth electrodes, by which seizure onset was confirmed in the lesion. The electrodes also guided the final resection, which rendered the patient seizure-free. The lesion was histologically classified as FCD Palmini and Lüders IIB. Transferring normal database-based MRI postprocessing results into a neuronavigation system is a new and worthwhile extension of multimodal neuronavigation. The combination of resulting regions of interest with functional and anatomic data may facilitate planning of electrode implantation for invasive electroencephalographic recordings and the final resection of small or deeply seated FCDs.

Gender Effects in Alcohol Dependence: An fMRI Pilot Study Examining Affective Processing

PubMed Central

Padula, Claudia B.; Anthenelli, Robert M.; Eliassen, James C.; Nelson, Erik; Lisdahl, Krista M.

2017-01-01

Background Alcohol dependence (AD) has global effects on brain structure and function, including frontolimbic regions regulating affective processing. Preliminary evidence suggests alcohol blunts limbic response to negative affective stimuli and increases activation to positive affective stimuli. Subtle gender differences are also evident during affective processing. Methods Fourteen abstinent AD individuals (8 F, 6 M) and 14 healthy controls (9 F, 5 M), ages 23 to 60, were included in this facial affective processing functional magnetic resonance imaging pilot study. Whole-brain linear regression analyses were performed, and follow-up analyses examined whether AD status significantly predicted depressive symptoms and/or coping. Results Fearful Condition—The AD group demonstrated reduced activation in the right medial frontal gyrus, compared with controls. Gender moderated the effects of AD in bilateral inferior frontal gyri. Happy Condition—AD individuals had increased activation in the right thalamus. Gender moderated the effects of AD in the left caudate, right middle frontal gyrus, left paracentral lobule, and right lingual gyrus. Interactive AD and gender effects for fearful and happy faces were such that AD men activated more than control men, but AD women activated less than control women. Enhanced coping was associated with greater activation in right medial frontal gyrus during fearful condition in AD individuals. Conclusions Abnormal affective processing in AD may be a marker of alcoholism risk or a consequence of chronic alcoholism. Subtle gender differences were observed, and gender moderated the effects of AD on neural substrates of affective processing. AD individuals with enhanced coping had brain activation patterns more similar to controls. Results help elucidate the effects of alcohol, gender, and their interaction on affective processing. PMID:25684049

Mars-Flyby Comet in False Color

NASA Image and Video Library

2014-11-07

This frame from a movie sequence of images from NASA Mars Reconnaissance Orbiter MRO shows comet C/2013 A1 Siding Spring before and after its close pass by Mars in October 2014. False color enhances subtle variations in brightness in the comet coma.

Efficient subtle motion detection from high-speed video for sound recovery and vibration analysis using singular value decomposition-based approach

NASA Astrophysics Data System (ADS)

Zhang, Dashan; Guo, Jie; Jin, Yi; Zhu, Chang'an

2017-09-01

High-speed cameras provide full field measurement of structure motions and have been applied in nondestructive testing and noncontact structure monitoring. Recently, a phase-based method has been proposed to extract sound-induced vibrations from phase variations in videos, and this method provides insights into the study of remote sound surveillance and material analysis. An efficient singular value decomposition (SVD)-based approach is introduced to detect sound-induced subtle motions from pixel intensities in silent high-speed videos. A high-speed camera is initially applied to capture a video of the vibrating objects stimulated by sound fluctuations. Then, subimages collected from a small region on the captured video are reshaped into vectors and reconstructed to form a matrix. Orthonormal image bases (OIBs) are obtained from the SVD of the matrix; available vibration signal can then be obtained by projecting subsequent subimages onto specific OIBs. A simulation test is initiated to validate the effectiveness and efficiency of the proposed method. Two experiments are conducted to demonstrate the potential applications in sound recovery and material analysis. Results show that the proposed method efficiently detects subtle motions from the video.

Detection of subtle nocturnal motor activity from 3-D accelerometry recordings in epilepsy patients.

PubMed

Nijsen, Tamara M E; Cluitmans, Pierre J M; Arends, Johan B A M; Griep, Paul A M

2007-11-01

This paper presents a first step towards reliable detection of nocturnal epileptic seizures based on 3-D accelerometry (ACM) recordings. The main goal is to distinguish between data with and without subtle nocturnal motor activity, thus reducing the amount of data that needs further (more complex) analysis for seizure detection. From 15 ACM signals (measured on five positions on the body), two features are computed, the variance and the jerk. In the resulting 2-D feature space, a linear threshold function is used for classification. For training and testing, the algorithm ACM data along with video data is used from nocturnal registrations in seven mentally retarded patients with severe epilepsy. Per patient, the algorithm detected 100% of the periods of motor activity that are marked in video recordings and the ACM signals by experts. From all the detections, 43%-89% was correct (mean =65%). We were able to reduce the amount of data that need to be analyzed considerably. The results show that our approach can be used for detection of subtle nocturnal motor activity. Furthermore, our results indicate that our algorithm is robust for fluctuations across patients. Consequently, there is no need for training the algorithm for each new patient.

High-resolution axial MR imaging of tibial stress injuries

PubMed Central

2012-01-01

Purpose To evaluate the relative involvement of tibial stress injuries using high-resolution axial MR imaging and the correlation with MR and radiographic images. Methods A total of 33 patients with exercise-induced tibial pain were evaluated. All patients underwent radiograph and high-resolution axial MR imaging. Radiographs were taken at initial presentation and 4 weeks later. High-resolution MR axial images were obtained using a microscopy surface coil with 60 × 60 mm field of view on a 1.5T MR unit. All images were evaluated for abnormal signals of the periosteum, cortex and bone marrow. Results Nineteen patients showed no periosteal reaction at initial and follow-up radiographs. MR imaging showed abnormal signals in the periosteal tissue and partially abnormal signals in the bone marrow. In 7 patients, periosteal reaction was not seen at initial radiograph, but was detected at follow-up radiograph. MR imaging showed abnormal signals in the periosteal tissue and entire bone marrow. Abnormal signals in the cortex were found in 6 patients. The remaining 7 showed periosteal reactions at initial radiograph. MR imaging showed abnormal signals in the periosteal tissue in 6 patients. Abnormal signals were seen in the partial and entire bone marrow in 4 and 3 patients, respectively. Conclusions Bone marrow abnormalities in high-resolution axial MR imaging were related to periosteal reactions at follow-up radiograph. Bone marrow abnormalities might predict later periosteal reactions, suggesting shin splints or stress fractures. High-resolution axial MR imaging is useful in early discrimination of tibial stress injuries. PMID:22574840

CryoEM structure of the human SLC4A4 sodium-coupled acid-base transporter NBCe1.

PubMed

Huynh, Kevin W; Jiang, Jiansen; Abuladze, Natalia; Tsirulnikov, Kirill; Kao, Liyo; Shao, Xuesi; Newman, Debra; Azimov, Rustam; Pushkin, Alexander; Zhou, Z Hong; Kurtz, Ira

2018-03-02

Na + -coupled acid-base transporters play essential roles in human biology. Their dysfunction has been linked to cancer, heart, and brain disease. High-resolution structures of mammalian Na + -coupled acid-base transporters are not available. The sodium-bicarbonate cotransporter NBCe1 functions in multiple organs and its mutations cause blindness, abnormal growth and blood chemistry, migraines, and impaired cognitive function. Here, we have determined the structure of the membrane domain dimer of human NBCe1 at 3.9 Å resolution by cryo electron microscopy. Our atomic model and functional mutagenesis revealed the ion accessibility pathway and the ion coordination site, the latter containing residues involved in human disease-causing mutations. We identified a small number of residues within the ion coordination site whose modification transformed NBCe1 into an anion exchanger. Our data suggest that symporters and exchangers utilize comparable transport machinery and that subtle differences in their substrate-binding regions have very significant effects on their transport mode.

mir-125a-5p-mediated Regulation of Lfng is Essential for the Avian Segmentation Clock

PubMed Central

Riley, Maurisa F.; Bochter, Matthew S.; Wahi, Kanu; Nuovo, Gerard J.; Cole, Susan E.

2013-01-01

Summary Somites are embryonic precursors of the axial skeleton and skeletal muscles, and establish the segmental vertebrate body plan. Somitogenesis is controlled in part by a segmentation clock that requires oscillatory expression of genes including Lunatic fringe (Lfng). Oscillatory genes must be tightly regulated both at the transcriptional and post-transcriptional levels for proper clock function. Here we demonstrate that microRNA-mediated regulation of Lfng is essential for proper segmentation during chick somitogenesis. We find that mir-125a-5p targets evolutionarily conserved sequences in the Lfng 3′UTR, and that preventing interactions between mir-125a-5p and Lfng transcripts in vivo causes abnormal segmentation and perturbs clock activity. This provides strong evidence that miRNAs function in the post-transcriptional regulation of oscillatory genes in the segmentation clock. Further, this demonstrates that the relatively subtle effects of miRNAs on target genes can have broad effects in developmental situations that have critical requirements for tight post-transcriptional regulation. PMID:23484856

Abnormal origins of the long head of the biceps tendon can lead to rotator cuff pathology: a report of two cases.

PubMed

Zhang, Alan L; Gates, Cameron H; Link, Thomas M; Ma, C Benjamin

2014-11-01

Previous case reports have highlighted various anomalous origins of the long head of the biceps tendon (LHBT) that do not originate from the superior glenoid labrum or supraglenoid tubercle. Yet, these cases were all reported as incidental findings and were not thought to cause any significant shoulder pathology. We present the magnetic resonance (MR) imaging and clinical treatment of two cases where aberrant intra-articular origins of the long head of the biceps tendon from the anterior edge of the supraspinatus tendon may have contributed to symptomatic rotator cuff pathology. Arthroscopy confirmed MR findings of partial articular-sided supraspinatus lesions in close proximity to the anomalous origins and treatment with tenodesis of the LHBT successfully relieved symptoms. Although rare occurrences with subtle and potentially misleading imaging findings, it is important to be aware of aberrant origins of the LHBT that may contribute to concomitant rotator cuff pathology.

What is regressive autism and why does it occur? Is it the consequence of multi-systemic dysfunction affecting the elimination of heavy metals and the ability to regulate neural temperature?

PubMed Central

Ewing, Graham E.

2009-01-01

There is a compelling argument that the occurrence of regressive autism is attributable to genetic and chromosomal abnormalities, arising from the overuse of vaccines, which subsequently affects the stability and function of the autonomic nervous system and physiological systems. That sense perception is linked to the autonomic nervous system and the function of the physiological systems enables us to examine the significance of autistic symptoms from a systemic perspective. Failure of the excretory system influences elimination of heavy metals and facilitates their accumulation and subsequent manifestation as neurotoxins: the long-term consequences of which would lead to neurodegeneration, cognitive and developmental problems. It may also influence regulation of neural hyperthermia. This article explores the issues and concludes that sensory dysfunction and systemic failure, manifested as autism, is the inevitable consequence arising from subtle DNA alteration and consequently from the overuse of vaccines. PMID:22666668

MICROSTRUCTURAL ABNORMALITIES IN MEWDS DEMONSTRATED BY ULTRAHIGH RESOLUTION OPTICAL COHERENCE TOMOGRAPHY

PubMed Central

NGUYEN, MY HANH T.; WITKIN, ANDRE J.; REICHEL, ELIAS; KO, TONY H.; FUJIMOTO, JAMES G.; SCHUMAN, JOEL S.; DUKER, JAY S.

2007-01-01

Background Histopathological studies of acute multiple evanescent white dot syndrome (MEWDS) have not been reported because of the transient and benign nature of the disease. Ultrahigh resolution optical coherence tomography (UHR-OCT), capable of high resolution in vivo imaging, offers a unique opportunity to visualize retinal microstructure in the disease. Methods UHR-OCT images of the maculae of five patients with MEWDS were obtained and analyzed. Diagnosis was based on clinical presentation, examination, visual field testing, and angiography. Results UHR-OCT revealed disturbances in the photoreceptor inner/outer segment junction (IS/OS) in each of the five patients (six eyes) with MEWDS. In addition, thinning of the outer nuclear layer was seen in the case of recurrent MEWDS, suggesting that repeated episodes of MEWDS may result in photoreceptor atrophy. Conclusions Subtle disruptions of the photoreceptor IS/OS are demonstrated in all eyes affected by MEWDS. UHR-OCT may be a useful adjunct to diagnosis and monitoring of MEWDS. PMID:17420691

[Contribution of animal models to the study of reproduction, assisted reproductive technologies and of development].

PubMed

Jammes, Hélène; Fauque, Patricia; Jouannet, Pierre

2010-02-01

Children conceived through assisted reproductive technologies (ART) now account for a noteworthy proportion (-2.4%) of births in France. Considerable attention is being paid to the outcome of ART pregnancies. The vast majority of these children are apparently normal. However, they are at an increased risk of minor birth defects, low birth weight, and rare imprinting disorders such as Beckwith-Wiedemann syndrome (BWS), Angelman syndrome (AS) and Silver Russel syndrome (SRS). Animal models are important for investigating the possible role of each step of ART (ovarian stimulation, gamete manipulation, in vitro fertilization, embryo culture and embryo transfer) in epigenetic reprogramming This review discusses these issues in the context of epigenetic and developmental abnormalities observed in animals following ART More research is needed on ART-induced errors, focusing not only on genomic imprinting but also on non-imprinted loci, which may help explain some of the more subtle longer-term health effects emerging from studies with animal models.

Value and limitations of auscultation in the management of congenital heart disease.

PubMed

McNamara, D G

1990-02-01

With advances in technology, especially that of ultrasonography, the art and science of auscultation could become relegated to that of an obsolete technique. Physicians in a cardiovascular training program involved in learning modern instrumentation diagnostic techniques often become expert in these areas before they have mastered the use of the stethoscope. Although the technology of ultrasonic examination, cardiac catheterization, and angiocardiography must be learned, the value of auscultation of the heart cannot be ignored. Many highly competent physicians who are responsible for diagnosis and treatment of the pediatric patient, including some pediatric cardiologists, may not be aware that they have not yet become experts at auscultation. The skill of auscultation of the heart must be learned by supervised experience with patients in whom a wide variety of normal and abnormal heart sounds and murmurs can be heard. Once learned, the skill can be maintained only by frequent practice in hearing and evaluating both subtle and obvious sounds emanating from the heart and from the pulmonary and systemic blood vessels.

Gigantism due to growth hormone excess in a boy with optic glioma.

PubMed

Drimmie, F M; MacLennan, A C; Nicoll, J A; Simpson, E; McNeill, E; Donaldson, M D

2000-10-01

True gigantism is rare in early childhood and is usually due to excess GH secretion from a pituitary adenoma. We report a case in which the endocrine abnormality is secondary to an optic glioma. Careful endocrine evaluation has shown that GH peak amplitude was not increased but rather there was failure of GH levels to suppress to baseline and a lack of pulsatility. There is no evidence of a direct secretory role for the tumour and we postulate that the tumour is affecting GH secretion through an effect on somatostatin tone. Specific tumour therapy is not indicated for this patient in the absence of mass effect or visual disturbance. The GH excess is being treated with somatostatin analogue (Octreotide) and as he has developed precocious puberty he is also receiving long acting GnRH analogue (Zoladex). This boy appears likely to have neurofibromatosis type 1 (NF1) which raises the question of subtle GH excess in NF1 patients with tall stature.

Antiepileptic drugs and brain maturation: fetal exposure to lamotrigine generates cortical malformations in rats.

PubMed

Manent, Jean-Bernard; Jorquera, Isabel; Franco, Valentina; Ben-Ari, Yehezkel; Perucca, Emilio; Represa, Alfonso

2008-02-01

Intake of antiepileptic drugs (AEDs) during pregnancy can provoke severe and subtle fetal malformations associated with deleterious sequelae, reflecting the need for experimental investigations on the comparative teratogenic potential of these agents. We recently reported that prenatal exposure to vigabatrin and valproate, two AEDs which act through GABAergic mechanisms, induces hippocampal and cortical dysplasias in rodents. We have now investigated the effects of phenobarbital (PB, 30 mg/kg day) i.p.), a drug also endowed with GABAergic effects, and the new generation AEDs lamotrigine (LTG, 5-20mg/kg/day i.p.), topiramate (TPM, 10mg/kg/day i.p.), and levetiracetam (LEV, 50mg/kg/day i.p.) on brain development. Prenatal exposure to LTG induced hippocampal and cortical malformations in a dose-dependent manner, at maternal plasma concentrations within the clinically occurring range. These abnormalities were not observed after exposure to PB, TP and LEV. These observations raise concerns about potential clinical correlates and call for detailed comparative investigations on the consequences of AED use during pregnancy.

Continuous noninvasive monitoring in the neonatal ICU.

PubMed

Sahni, Rakesh

2017-04-01

Standard hemodynamic monitoring such as heart rate and systemic blood pressure may only provide a crude estimation of organ perfusion during neonatal intensive care. Pulse oximetry monitoring allows for continuous noninvasive monitoring of hemoglobin oxygenation and thus provides estimation of end-organ oxygenation. This review aims to provide an overview of pulse oximetry and discuss its current and potential clinical use during neonatal intensive care. Technological advances in continuous assessment of dynamic changes in systemic oxygenation with pulse oximetry during transition to extrauterine life and beyond provide additional details about physiological interactions among the key hemodynamic factors regulating systemic blood flow distribution along with the subtle changes that are frequently transient and undetectable with standard monitoring. Noninvasive real-time continuous systemic oxygen monitoring has the potential to serve as biomarkers for early-organ dysfunction, to predict adverse short-term and long-term outcomes in critically ill neonates, and to optimize outcomes. Further studies are needed to establish values predicting adverse outcomes and to validate targeted interventions to normalize abnormal values to improve outcomes.

Insular subdivisions functional connectivity dysfunction within major depressive disorder.

PubMed

Peng, Xiaolong; Lin, Pan; Wu, Xiaoping; Gong, Ruxue; Yang, Rui; Wang, Jue

2018-02-01

Major depressive disorder (MDD) is a mental disorder characterized by cognitive and affective deficits. Previous studies suggested that insula is a crucial node of the salience network for initiating network switching, and dysfunctional connection to this region may be related to the mechanism of MDD. In this study, we systematically investigated and quantified the altered functional connectivity (FC) of the specific insular subdivisions and its relationship to psychopathology of MDD. Resting-state FC of insular subdivisions, including bilateral ventral/dorsal anterior insula and posterior insula, were estimated in 19 MDD patients and 19 healthy controls. Abnormal FC was quantified between groups. Additionally, we investigated the relationships between insular connectivity and depressive symptom severity. MDD patients demonstrated aberrant FC for insular subdivisions to superior temporal sulcus, inferior prefrontal gyrus, amygdala and posterior parietal cortex. Moreover, depression symptoms (Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale scorers) were associated with the FC values of insular subdivisions. First, the sample size of our current study is relatively small, which may affect the statistic power. Second, using standardized insular subdivision seeds for FC analyses may neglect subtle natural differences in size and location of functional area across individuals and may thus affect connectivity maps. Abnormal FC of insular subdivisions to default network and central executive network may represent impaired intrinsic networks switching which may affect the underlying emotional and sensory disturbances in MDD. And our findings can help to understand the pathophysiology and underlying neural mechanisms of MDD. Copyright © 2017 Elsevier B.V. All rights reserved.

Atlas-based analysis of cardiac shape and function: correction of regional shape bias due to imaging protocol for population studies.

PubMed

Medrano-Gracia, Pau; Cowan, Brett R; Bluemke, David A; Finn, J Paul; Kadish, Alan H; Lee, Daniel C; Lima, Joao A C; Suinesiaputra, Avan; Young, Alistair A

2013-09-13

Cardiovascular imaging studies generate a wealth of data which is typically used only for individual study endpoints. By pooling data from multiple sources, quantitative comparisons can be made of regional wall motion abnormalities between different cohorts, enabling reuse of valuable data. Atlas-based analysis provides precise quantification of shape and motion differences between disease groups and normal subjects. However, subtle shape differences may arise due to differences in imaging protocol between studies. A mathematical model describing regional wall motion and shape was used to establish a coordinate system registered to the cardiac anatomy. The atlas was applied to data contributed to the Cardiac Atlas Project from two independent studies which used different imaging protocols: steady state free precession (SSFP) and gradient recalled echo (GRE) cardiovascular magnetic resonance (CMR). Shape bias due to imaging protocol was corrected using an atlas-based transformation which was generated from a set of 46 volunteers who were imaged with both protocols. Shape bias between GRE and SSFP was regionally variable, and was effectively removed using the atlas-based transformation. Global mass and volume bias was also corrected by this method. Regional shape differences between cohorts were more statistically significant after removing regional artifacts due to imaging protocol bias. Bias arising from imaging protocol can be both global and regional in nature, and is effectively corrected using an atlas-based transformation, enabling direct comparison of regional wall motion abnormalities between cohorts acquired in separate studies.

Neurological abnormalities in recent-onset schizophrenia and asperger-syndrome.

PubMed

Hirjak, Dusan; Wolf, Robert Christian; Koch, Sabine C; Mehl, Laura; Kelbel, Janna K; Kubera, Katharina Maria; Traeger, Tanja; Fuchs, Thomas; Thomann, Philipp Arthur

2014-01-01

Neurological abnormalities including a variety of subtle deficits such as discrete impairments in sensory integration, motor coordination (MOCO), and sequencing of complex motor acts are frequently found in patients with schizophrenia (SZ) and commonly referred to as neurological soft signs (NSS). Asperger-syndrome (AS) is characterized by sensory-motor difficulties as well. However, the question whether the two disorders share a common or a disease-specific pattern of NSS remains unresolved. A total of 78 age- and education-matched participants [26 patients with recent-onset SZ, 26 individuals with AS, and 26 healthy controls (HC)] were recruited for the study. Analyses of covariance (ANCOVAs), with age, years of education, and medication included as covariates, were used to examine group differences on total NSS and the five subscale scores. Discriminant analyses were employed to identify the NSS subscales that maximally discriminate between the three groups. Significant differences among the three groups were found in NSS total score and on the five NSS subscales. The clinical groups differed significantly in the NSS subscale MOCO. The correct discriminant rate between patients with SZ and individuals with AS was 61.5%. The correct discriminant rate was 92.3% between individuals with AS and HC, and 80.8% between SZ patients and HC, respectively. Our findings provide new evidence for the presence of NSS in AS and lend further support to previously reported difficulties in movement control in this disorder. According to the present results, SZ and AS seem to be characterized by both quantitative and qualitative NSS expression.

Thyroid function abnormalities and cognitive impairment in elderly people: results of the Invecchiare in Chianti study.

PubMed

Ceresini, Graziano; Lauretani, Fulvio; Maggio, Marcello; Ceda, Gian Paolo; Morganti, Simonetta; Usberti, Elisa; Chezzi, Carlo; Valcavi, Rita; Bandinelli, Stefania; Guralnik, Jack M; Cappola, Anne R; Valenti, Giorgio; Ferrucci, Luigi

2009-01-01

To investigate thyroid function testing abnormalities in older persons and to explore the relationship between thyroid dysfunction and cognition. Cross-sectional. Community-based. One thousand one hundred seventy-one men and women aged 23 to 102. Thyroid function was evaluated by measuring plasma concentrations of thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3). Cognition was evaluated using the Mini-Mental State Examination (MMSE). Prevalence of overt and subclinical thyroid dysfunction was evaluated in different age groups (<65 vs > or =65). Age trends in TSH, FT4, and FT3 were examined in euthyroid participants. The cross-sectional association between thyroid dysfunction and MMSE score was evaluated adjusting for confounders. Subclinical hypothyroidism and subclinical hyperthyroidism were more prevalent in older than in younger participants (subclinical hypothyroidism, 3.5% vs 0.4%, P<.03; subclinical hyperthyroidism, 7.8% vs 1.9%, P<.002). In euthyroid participants, TSH and FT3 declined with age, whereas FT4 increased. Older participants with subclinical hyperthyroidism had lower MMSE scores than euthyroid subjects (22.61+/-6.88 vs 24.72+/-4.52, P<.03). In adjusted analyses, participants with subclinical hyperthyroidism were significantly more likely to have cognitive dysfunction (hazard rate=2.26, P=.003). Subtle age-related changes in FT3, FT4, and TSH occur in individuals who remain euthyroid. Subclinical hyperthyroidism is the most prevalent thyroid dysfunction in Italian older persons and is associated with cognitive impairment.

Drugs of abuse in pregnancy, poor neonatal development, and future neurodegeneration. Is oxidative stress the culprit?

PubMed

Neri, Margherita; Bello, Stefania; Turillazzi, Emanuela; Riezzo, Irene

2015-01-01

The abuse of licit and illicit drugs is a worldwide issue that is a cause for concern in pregnant women. It may lead to complications in pregnancy that may affect the mother, fetus, and /or neonate. The effects of any substance on the developing embryo and fetus are dependent upon dosing, timing, duration of drug exposure, and the extent of drug distribution. Teratogenic effects have been described when exposure takes place during the embryonic stage; however drugs have subtle effects, including abnormal growth and/or maturation, alterations in neurotransmitters and their receptors, and brain organization. The mechanisms by which intrauterine exposure to many substances may result in neuronal injury have not been completely elucidated. Oxidative stress and epigenetic changes have been recently implicated in the pathogenesis of long - term adverse health sequelae, and neuro-developmental impairment in the offspring of addicted mothers. Transgenerational epigenetics may also explain the alarming datum that developmental abnormalities, impairment in learning and memory, and attention deficit can occur even in the absence of direct fetal exposure, when drugs are consumed prior to conception. There is a growing body of evidence demonstrating a link between redox state unbalance, epigenetic markers, developmental anomalies, and neurodegeneration. The reviewed literature data uphold redox homeostasis disruption as an important factor in the pathogenesis of drug of abuse- induced neurodegeneration, and highlight the potential for new therapies that could prevent neurodegeneration through antioxidant and epigenetic modulatory mechanisms. This therefore reveals important targets for novel neuroprotective strategies.

Cardiac structure and function in the obese: a cardiovascular magnetic resonance imaging study.

PubMed

Danias, Peter G; Tritos, Nicholas A; Stuber, Matthias; Kissinger, Kraig V; Salton, Carol J; Manning, Warren J

2003-07-01

Obesity is a major health problem in the Western world. Among obese subjects cardiac pathology is common, but conventional noninvasive imaging modalities are often suboptimal for detailed evaluation of cardiac structure and function. We investigated whether cardiovascular magnetic resonance imaging (CMR) can better characterize possible cardiac abnormalities associated with obesity, in the absence of other confounding comorbidities. In this prospective cross-sectional study, CMR was used to quantify left and right ventricular volumes, ejection fraction, mass, cardiac output, and apical left ventricular rotation in 25 clinically healthy obese men and 25 age-matched lean controls. Obese subjects had higher left ventricular mass (203 +/- 38 g vs. 163 +/- 22 g, p < 0.001), end-diastolic volume (176 +/- 29 mL vs. 156 +/- 25 mL, p < 0.05), and cardiac output (8.2 +/- 1.2 L/min vs. 6.4 +/- 1.3 L/min, p < 0.001). The obese also had increased right ventricular mass (105 +/- 25 g vs. 87 +/- 18 g, p < 0.005) and end-diastolic volume (179 +/- 36 mL vs. 155 +/- 28 mL, p < 0.05). When indexed for height, differences in left and right ventricular mass, and left ventricular end-diastolic volume remained significant. Apical left ventricular rotation and rotational velocity patterns were also different between obese and lean subjects. Obesity is independently associated with remodeling of the heart. Cardiovascular magnetic resonance imaging identifies subtle cardiac abnormalities and may be the preferred imaging technique to evaluate cardiac structure and function in the obese.

Mutagen-induced fetal anomalies and death following treatment of females within hours after mating.

PubMed

Generoso, W M; Rutledge, J C; Cain, K T; Hughes, L A; Downing, D J

1988-05-01

In an earlier study (Generoso et al., 1987), it was observed that the mutagen, ethylene oxide (EtO), produced remarkable increases in the incidence of developmental abnormalities and death of fetuses when early zygotic stages were exposed. This is a major finding in experimental induction of embryopathy, implicating genetic damage to the zygotes as the likely cause. In the subsequent study reported here, 3 other mutagens--ethyl methanesulfonate (EMS), ethyl nitrosourea (ENU), and triethylene melamine (TEM), were studied for embryopathic effects following exposure of dictyate oocytes, prefertilization oviducal eggs and sperm, early pronuclear zygotes, zygotes undergoing pronuclear DNA synthesis, and two-cell embryos. All 4 mutagens produced developmental abnormalities among living fetuses following exposure of early pronuclear zygotes (the only stage studied for this endpoint in this report). With respect to stage specificity and gestational timing of death of conceptuses, EMS and EtO on one hand and ENU and TEM on the other, are very similar to one another. EMS, like EtO, produced a high incidence of midgestation and late fetal deaths only in prefertilization oviducal eggs and sperm and in early pronuclear eggs. In contrast, ENU and TEM produced high losses of conceptuses in all postmating stages studied but death occurred primarily prior to or around the time of implantation. Thus, the frequency of induction and the expression of embryopathy, which ranged from early embryonic preimplantation and late fetal deaths to subtle fetal anomalies, are dependent upon the stage exposed and the mutagen used.

X-Ray and UV Photoelectron Spectroscopy | Materials Science | NREL

Science.gov Websites

backsheet material, showing excellent quantitative agreement between measured and predicted peak area ratios quantitative agreement between measured and predicted peak area ratios. Subtle differences in polymer functionality are assessed by deviations from stoichiometry. Elemental Analysis Uses quantitative identification

Abnormal Selective Attention Normalizes P3 Amplitudes in PDD

ERIC Educational Resources Information Center

Hoeksma, Marco R.; Kemner, Chantal; Kenemans, J. Leon; van Engeland, Herman

2006-01-01

This paper studied whether abnormal P3 amplitudes in PDD are a corollary of abnormalities in ERP components related to selective attention in visual and auditory tasks. Furthermore, this study sought to clarify possible age differences in such abnormalities. Children with PDD showed smaller P3 amplitudes than controls, but no abnormalities in…

Wearable Wide-Range Strain Sensors Based on Ionic Liquids and Monitoring of Human Activities

PubMed Central

Zhang, Shao-Hui; Wang, Feng-Xia; Li, Jia-Jia; Peng, Hong-Dan; Yan, Jing-Hui; Pan, Ge-Bo

2017-01-01

Wearable sensors for detection of human activities have encouraged the development of highly elastic sensors. In particular, to capture subtle and large-scale body motion, stretchable and wide-range strain sensors are highly desired, but still a challenge. Herein, a highly stretchable and transparent stain sensor based on ionic liquids and elastic polymer has been developed. The as-obtained sensor exhibits impressive stretchability with wide-range strain (from 0.1% to 400%), good bending properties and high sensitivity, whose gauge factor can reach 7.9. Importantly, the sensors show excellent biological compatibility and succeed in monitoring the diverse human activities ranging from the complex large-scale multidimensional motions to subtle signals, including wrist, finger and elbow joint bending, finger touch, breath, speech, swallow behavior and pulse wave. PMID:29135928

IgG4-related Hypophysitis with Subtle Hypopituitarism in an Elderly Diabetic Patient: Is Treatment or Observation Preferable?

PubMed Central

Kawasaki, Motoki; Tsujino, Motoyoshi; Sato, Fuminori; Sakurada, Maya; Nishida, Kenji; Kise, Takayasu; Hijioka, Yuko; Ishizawa, Mitsugu; Enatsu, Kazuaki; Ogawa, Yoshihiro

2017-01-01

A 70-year-old man with diabetes mellitus presented with an enlarged pituitary stalk in 2014. IgG4-related parotitis and submandibular sialoadenitis were diagnosed in 2012. He denied any symptoms related to a pituitary mass. His visual field was intact, and his hypopituitarism was subtle. The serum IgG4 level was elevated. A lip biopsy revealed strong fibrosis and hyper-infiltration of IgG4-positive plasma cells. Based on these findings, IgG4-related hypophysitis was diagnosed. The patient was carefully followed without specific intervention. His clinical condition showed no change until December 2016, suggesting a stable, natural course. Care should be taken when considering glucocorticoid therapy, especially for elderly diabetic patients, given possible side effects. PMID:28924128

IgG4-related Hypophysitis with Subtle Hypopituitarism in an Elderly Diabetic Patient: Is Treatment or Observation Preferable?

PubMed

Kawasaki, Motoki; Tsujino, Motoyoshi; Sato, Fuminori; Sakurada, Maya; Nishida, Kenji; Kise, Takayasu; Hijioka, Yuko; Ishizawa, Mitsugu; Enatsu, Kazuaki; Ogawa, Yoshihiro

2017-10-15

A 70-year-old man with diabetes mellitus presented with an enlarged pituitary stalk in 2014. IgG4-related parotitis and submandibular sialoadenitis were diagnosed in 2012. He denied any symptoms related to a pituitary mass. His visual field was intact, and his hypopituitarism was subtle. The serum IgG4 level was elevated. A lip biopsy revealed strong fibrosis and hyper-infiltration of IgG4-positive plasma cells. Based on these findings, IgG4-related hypophysitis was diagnosed. The patient was carefully followed without specific intervention. His clinical condition showed no change until December 2016, suggesting a stable, natural course. Care should be taken when considering glucocorticoid therapy, especially for elderly diabetic patients, given possible side effects.

Overt and Subtle Racial Discrimination and Mental Health: Preliminary Findings for Korean Immigrants

PubMed Central

Noh, Samuel; Kaspar, Violet; Wickrama, K.A.S.

2007-01-01

Objectives. We examined differential effects of overt and subtle forms of racial discrimination on 2 dimensions of mental health—positive affect and depressive symptoms, and explored the mediating roles of emotional arousal and cognitive appraisal. Methods. Cross-sectional survey data were collected through face-to-face interviews with a sample (N=180) of adult Korean immigrants living in Toronto, Ontario. Maximum likelihood estimates of path coefficients were obtained using structural equation models. Results. Perceived racial discrimination was associated with both the erosion of positive affect and depressive symptoms. Overt discrimination was associated with the erosion of positive affect, and subtle discrimination was associated with depressive symptoms. Effects of subtle discrimination on depressive symptoms were mediated through cognitive appraisal. Conclusions. The results emphasize the salience of subtle discrimination for the mental health of Asian immigrants. Experiences of overt racial bias seemed to be of little importance for the levels of depressive symptoms among those in our sample, although the experience of blatant discrimination tended to reduce positive mood. PMID:17538066

Forms of ethnic prejudice: assessing the dimensionality of a Spanish-language version of the Blatant and Subtle Prejudice Scale.

PubMed

Cárdenas Castro, Manuel

2010-02-01

The main purpose of this study was to investigate the dimensionality of a Spanish-language version of the Blatant and Subtle Prejudice Scale via exploratory (EFA) and confirmatory factor analysis (CFA). No research has confirmed the hypothesized factor structure in Latin American countries. Using data from a random and probability survey in population of the northern area of Chile (N= 896), four models were specified: single factor model (global prejudice factor), correlated two-factor model (subtle and blatant prejudice), correlated two-factor second-order model, and single-factor second-order model. The findings indicated that the two-factor second-order model had the best fit. The corresponding alpha coefficients were .82 (subtle prejudice) and .76 (blatant prejudice). Lastly, differences were examined between , , and regarding their feelings toward immigrants, their feelings about their beliefs concerning the state aid received by these out-groups, and their feelings about their beliefs regarding future policies for them.

Study of the incidence and nature of "very subtle epidermal melasma" in relation to intense pulsed light treatment.

PubMed

Negishi, Kei; Kushikata, Nobuharu; Tezuka, Yukiko; Takeuchi, Kaori; Miyamoto, Eiko; Wakamatsu, Shingo

2004-06-01

Skin rejuvenation with intense pulsed light (IPL) is effective for clearing epidermal pigment disorders. Complications are mild and limited to epidermal burns caused by excessive settings. Some patients, however, experience IPL-induced melasma-like hyperpigmentation despite the appearance of normal skin. These patients seem to have very subtle epidermal melasma not visible to the naked eye. Ultraviolet photography has been useful in identifying these patients and preventing complications. The study investigated the incidence of very subtle melasma in patients using UV photography, and assessed this tool in identifying high-risk patients. 223 Japanese women, 30-69 years old, participated in the study. Very subtle melasma invisible to the naked eye under normal light was diagnosed by UV photography by two physicians, and any relationship among the disease incidence, age, and regular sunscreen use was examined. Sixty-three cases of very subtle melasma (28.3%) were identified among the 223 subjects, with a significantly lower incidence in sunscreen users. Patients diagnosed with subtle epidermal melasma and treated with mild IPL parameters did not suffer induced secondary hyperpigmentaion. To help avoid complications after treatment, IPL users should be aware of the age and sunscreen-related incidence of this phenomenon in Asian patients.

Automated impedance-manometry analysis detects esophageal motor dysfunction in patients who have non-obstructive dysphagia with normal manometry.

PubMed

Nguyen, N Q; Holloway, R H; Smout, A J; Omari, T I

2013-03-01

Automated integrated analysis of impedance and pressure signals has been reported to identify patients at risk of developing dysphagia post fundoplication. This study aimed to investigate this analysis in the evaluation of patients with non-obstructive dysphagia (NOD) and normal manometry (NOD/NM). Combined impedance-manometry was performed in 42 patients (27F : 15M; 56.2 ± 5.1 years) and compared with that of 24 healthy subjects (8F : 16M; 48.2 ± 2.9 years). Both liquid and viscous boluses were tested. MATLAB-based algorithms defined the median intrabolus pressure (IBP), IBP slope, peak pressure (PP), and timing of bolus flow relative to peak pressure (TNadImp-PP). An index of pressure and flow (PFI) in the distal esophagus was derived from these variables. Diagnoses based on conventional manometric assessment: diffuse spasm (n = 5), non-specific motor disorders (n = 19), and normal (n = 11). Patients with achalasia (n = 7) were excluded from automated impedance-manometry (AIM) analysis. Only 2/11 (18%) patients with NOD/NM had evidence of flow abnormality on conventional impedance analysis. Several variables derived by integrated impedance-pressure analysis were significantly different in patients as compared with healthy: higher PNadImp (P < 0.01), IBP (P < 0.01) and IBP slope (P < 0.05), and shorter TNadImp_PP (P = 0.01). The PFI of NOD/NM patients was significantly higher than that in healthy (liquid: 6.7 vs 1.2, P = 0.02; viscous: 27.1 vs 5.7, P < 0.001) and 9/11 NOD/NM patients had abnormal PFI. Overall, the addition of AIM analysis provided diagnoses and/or a plausible explanation in 95% (40/42) of patients who presented with NOD. Compared with conventional pressure-impedance assessment, integrated analysis is more sensitive in detecting subtle abnormalities in esophageal function in patients with NOD and normal manometry. © 2012 Blackwell Publishing Ltd.

Primordial dwarfism: overview of clinical and genetic aspects.

PubMed

Khetarpal, Preeti; Das, Satrupa; Panigrahi, Inusha; Munshi, Anjana

2016-02-01

Primordial dwarfism is a group of genetic disorders which include Seckel Syndrome, Silver-Russell Syndrome, Microcephalic Osteodysplastic Primordial Dwarfism types I/III, II and Meier-Gorlin Syndrome. This genetic disorder group is characterized by intra-uterine growth retardation and post-natal growth abnormalities which occur as a result of disorganized molecular and genomic changes in embryonic stage and, thus, it represents a unique area to study growth and developmental abnormalities. Lot of research has been carried out on different aspects; however, a consolidated review that discusses an overall spectrum of this disorder is not accessible. Recent research in this area points toward important molecular and cellular mechanisms in human body that regulate the complexity of growth process. Studies have emerged that have clearly associated with a number of abnormal chromosomal, genetic and epigenetic alterations that can predispose an embryo to develop PD-associated developmental defects. Finding and associating such fundamental changes to its subtypes will help in re-examination of alleged functions at both cellular and developmental levels and thus reveal the intrinsic mechanism that leads to a balanced growth. Although such findings have unraveled a subtle understanding of growth process, we further require active research in terms of identification of reliable biomarkers for different subtypes as an immediate requirement for clinical utilization. It is hoped that further study will advance the understanding of basic mechanisms regulating growth relevant to human health. Therefore, this review has been written with an aim to present an overview of chromosomal, molecular and epigenetic modifications reported to be associated with different subtypes of this heterogenous disorder. Further, latest findings with respect to clinical and molecular genetics research have been summarized to aid the medical fraternity in their clinical utility, for diagnosing disorders where there are overlapping physical attributes and simultaneously inform about the latest developments in PD biology.

Association between renal function and cardiovascular structure and function in heart failure with preserved ejection fraction.

PubMed

Gori, Mauro; Senni, Michele; Gupta, Deepak K; Charytan, David M; Kraigher-Krainer, Elisabeth; Pieske, Burkert; Claggett, Brian; Shah, Amil M; Santos, Angela B S; Zile, Michael R; Voors, Adriaan A; McMurray, John J V; Packer, Milton; Bransford, Toni; Lefkowitz, Martin; Solomon, Scott D

2014-12-21

Renal dysfunction is a common comorbidity in patients with heart failure and preserved ejection fraction (HFpEF). We sought to determine whether renal dysfunction was associated with measures of cardiovascular structure/function in patients with HFpEF. We studied 217 participants from the PARAMOUNT study with HFpEF who had echocardiography and measures of kidney function. We evaluated the relationships between renal dysfunction [estimated glomerular filtration rate (eGFR) >30 and <60 mL/min/1.73 m(2) and/or albuminuria] and cardiovascular structure/function. The mean age of the study population was 71 years, 55% were women, 94% hypertensive, and 40% diabetic. Impairment of at least one parameter of kidney function was present in 62% of patients (16% only albuminuria, 23% only low eGFR, 23% both). Renal dysfunction was associated with abnormal LV geometry (defined as concentric hypertrophy, or eccentric hypertrophy, or concentric remodelling) (adjusted P = 0.048), lower midwall fractional shortening (MWFS) (P = 0.009), and higher NT-proBNP (P = 0.006). Compared with patients without renal dysfunction, those with low eGFR and no albuminuria had a higher prevalence of abnormal LV geometry (P = 0.032) and lower MWFS (P < 0.01), as opposed to those with only albuminuria. Conversely, albuminuria alone was associated with greater LV dimensions (P < 0.05). Patients with combined renal impairment had mixed abnormalities (higher LV wall thicknesses, NT-proBNP; lower MWFS). Renal dysfunction, as determined by both eGFR and albuminuria, is highly prevalent in HFpEF, and associated with cardiac remodelling and subtle systolic dysfunction. The observed differences in cardiac structure/function between each type of renal damage suggest that both parameters of kidney function might play a distinct role in HFpEF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Multi-centre diagnostic classification of individual structural neuroimaging scans from patients with major depressive disorder.

PubMed

Mwangi, Benson; Ebmeier, Klaus P; Matthews, Keith; Steele, J Douglas

2012-05-01

Quantitative abnormalities of brain structure in patients with major depressive disorder have been reported at a group level for decades. However, these structural differences appear subtle in comparison with conventional radiologically defined abnormalities, with considerable inter-subject variability. Consequently, it has not been possible to readily identify scans from patients with major depressive disorder at an individual level. Recently, machine learning techniques such as relevance vector machines and support vector machines have been applied to predictive classification of individual scans with variable success. Here we describe a novel hybrid method, which combines machine learning with feature selection and characterization, with the latter aimed at maximizing the accuracy of machine learning prediction. The method was tested using a multi-centre dataset of T(1)-weighted 'structural' scans. A total of 62 patients with major depressive disorder and matched controls were recruited from referred secondary care clinical populations in Aberdeen and Edinburgh, UK. The generalization ability and predictive accuracy of the classifiers was tested using data left out of the training process. High prediction accuracy was achieved (~90%). While feature selection was important for maximizing high predictive accuracy with machine learning, feature characterization contributed only a modest improvement to relevance vector machine-based prediction (~5%). Notably, while the only information provided for training the classifiers was T(1)-weighted scans plus a categorical label (major depressive disorder versus controls), both relevance vector machine and support vector machine 'weighting factors' (used for making predictions) correlated strongly with subjective ratings of illness severity. These results indicate that machine learning techniques have the potential to inform clinical practice and research, as they can make accurate predictions about brain scan data from individual subjects. Furthermore, machine learning weighting factors may reflect an objective biomarker of major depressive disorder illness severity, based on abnormalities of brain structure.

Cluster analysis of behavioural and event-related potentials during a contingent negative variation paradigm in remitting-relapsing and benign forms of multiple sclerosis

PubMed Central

2011-01-01

Background Event-related potentials (ERPs) may be used as a highly sensitive way of detecting subtle degrees of cognitive dysfunction. On the other hand, impairment of cognitive skills is increasingly recognised as a hallmark of patients suffering from multiple sclerosis (MS). We sought to determine the psychophysiological pattern of information processing among MS patients with the relapsing-remitting form of the disease and low physical disability considered as two subtypes: 'typical relapsing-remitting' (RRMS) and 'benign MS' (BMS). Furthermore, we subjected our data to a cluster analysis to determine whether MS patients and healthy controls could be differentiated in terms of their psychophysiological profile. Methods We investigated MS patients with RRMS and BMS subtypes using event-related potentials (ERPs) acquired in the context of a Posner visual-spatial cueing paradigm. Specifically, our study aimed to assess ERP brain activity in response preparation (contingent negative variation -CNV) and stimuli processing in MS patients. Latency and amplitude of different ERP components (P1, eN1, N1, P2, N2, P3 and late negativity -LN) as well as behavioural responses (reaction time -RT; correct responses -CRs; and number of errors) were analyzed and then subjected to cluster analysis. Results Both MS groups showed delayed behavioural responses and enhanced latency for long-latency ERP components (P2, N2, P3) as well as relatively preserved ERP amplitude, but BMS patients obtained more important performance deficits (lower CRs and higher RTs) and abnormalities related to the latency (N1, P3) and amplitude of ERPs (eCNV, eN1, LN). However, RRMS patients also demonstrated abnormally high amplitudes related to the preparation performance period of CNV (cCNV) and post-processing phase (LN). Cluster analyses revealed that RRMS patients appear to make up a relatively homogeneous group with moderate deficits mainly related to ERP latencies, whereas BMS patients appear to make up a rather more heterogeneous group with more severe information processing and attentional deficits. Conclusions Our findings are suggestive of a slowing of information processing for MS patients that may be a consequence of demyelination and axonal degeneration, which also seems to occur in MS patients that show little or no progression in the physical severity of the disease over time. PMID:21635741

Psoriasis and Diabetes Millitus.

PubMed

Sundharam, J A; Singh, Ratan; Agarwal, P S

1980-01-01

Twenty uncomplicated cases of psoriasis and an equal number of matched controls were evaluated using the oral and steroid primed glucose tolerance test. Six of the twenty psoriatics (30%) studied showed an abnormal glucose tolerancewhereas only one of the twenty control subjects (5 %) showed abnormality (p < 0.05). A relationship was found between abnormal glucose tolerance and surface area involved by psoriasis.

Glioblastoma entities express subtle differences in molecular composition and response to treatment

PubMed Central

Balça-Silva, Joana; Matias, Diana; Do Carmo, Anália; Dubois, Luiz Gustavo; Gonçalves, Ana Cristina; Girão, Henrique; Silva Canedo, Nathalie Henriques; Correia, Ana Helena; De Souza, Jorge Marcondes; Sarmento-Ribeiro, Ana Bela; Lopes, Maria Celeste; Moura-Neto, Vivaldo

2017-01-01

Glioblastoma (GBM) is a grade IV astrocytoma. GBM patients show resistance to chemotherapy such as temozolomide (TMZ), the gold standard treatment. In order to simulate the molecular mechanisms behind the different chemotherapeutic responses in GBM patients we compared the cellular heterogeneity and chemotherapeutic resistance mechanisms in different GBM cell lines. We isolated and characterized a human GBM cell line obtained from a GBM patient, named GBM11. We studied the GBM11 behaviour when treated with Tamoxifen (TMX) that, among other functions, is a protein kinase C (PKC) inhibitor, alone and in combination with TMZ in comparison with the responses of U87 and U118 human GBM cell lines. We evaluated the cell death, cell cycle arrest and cell proliferation, mainly through PKC expression, by flow cytometry and western blot analysis and, ultimately, cell migration capability and F-actin filament disorganization by fluorescence microscopy. We demonstrated that the constitutive activation of p-PKC seems to be one of the main metabolic implicated on GBM malignancy. Despite of its higher resistance, possibly due to the overexpression of P-glycoprotein and stem-like cell markers, GBM11 cells presented a subtle different chemotherapeutic response compared to U87 and U118 cells. The GBM11, U87, U118 cell lines show subtle molecular differences, which clearly indicate the characterization of GBM heterogeneity, one of the main reasons for tumor resistance. The adding of cellular heterogeneity in molecular behaviour constitutes a step closer in the understanding of resistant molecular mechanisms in GBM, and can circumvents the eventual impaired therapy. PMID:28714013

Technetium-99m-HMPAO SPECT in the evaluation of patients with a remote history of traumatic brain injury: a comparison with x-ray computed tomography.

PubMed

Gray, B G; Ichise, M; Chung, D G; Kirsh, J C; Franks, W

1992-01-01

The functional imaging modality has potential for demonstrating parenchymal abnormalities not detectable by traditional morphological imaging. Fifty-three patients with a remote history of traumatic brain injury (TBI) were studied with SPECT using 99mTc-hexamethylpropyleneamineoxime (HMPAO) and x-ray computed tomography (CT). Overall, 42 patients (80%) showed regional cerebral blood flow (rCBF) deficits by HMPAO SPECT, whereas 29 patients (55%) showed morphological abnormalities by CT. Out of 20 patients with minor head injury, 12 patients (60%) showed rCBF deficits and 5 patients (25%) showed CT abnormalities. Of 33 patients with major head injury, 30 patients (90%) showed rCBF deficits and 24 patients (72%) showed CT abnormalities. Thus, HMPAO SPECT was more sensitive than CT in detecting abnormalities in patients with a history of TBI, particularly in the minor head injury group. In the major head injury group, three patients showed localized cortical atrophy by CT and normal rCBF by HMPAO SPECT. In the evaluation of TBI patients, HMPAO SPECT is a useful technique to demonstrate regional brain dysfunction in the presence of morphological integrity as assessed by CT.

A Curious Reality: Exploring the Paintings of Philip C. Curtis

ERIC Educational Resources Information Center

Stephens, Pamela; Walkup, Nancy

2011-01-01

Many of the paintings of 20th-century American artist Philip C. Curtis defy clear classification. Curtis's artworks often show dreamlike and fantastical qualities and are therefore frequently pigeonholed as Surrealistic. While this classification is not completely erroneous, it fails to acknowledge some subtle differences between Curtis's artwork…

Directing Diplomacy: Creating the Best Experience for Everyone in the Show.

ERIC Educational Resources Information Center

Mulcahy, Lisa

2003-01-01

Discusses the subtle psychological strategies good directors know how to employ with actors. Contends that if a director demonstrates a diplomatic attitude toward every student involved in a production, a perfect working atmosphere is created. Explores diplomacy basics; first impressions; rehearsal problems; personality issues; and talking points.…

Detailed Magnetic Resonance Imaging (MRI) Analysis in Infantile Spasms.

PubMed

Harini, Chellamani; Sharda, Sonal; Bergin, Ann Marie; Poduri, Annapurna; Yuskaitis, Christopher J; Peters, Jurriaan M; Rakesh, Kshitiz; Kapur, Kush; Pearl, Phillip L; Prabhu, Sanjay P

2018-05-01

To evaluate initial magnetic resonance imaging (MRI) abnormalities in infantile spasms, correlate them to clinical characteristics, and describe repeat imaging findings. A retrospective review of infantile spasm patients was conducted, classifying abnormal MRI into developmental, acquired, and nonspecific subgroups. MRIs were abnormal in 52 of 71 infantile spasm patients (23 developmental, 23 acquired, and 6 nonspecific) with no correlation to the clinical infantile spasm characteristics. Both developmental and acquired subgroups exhibited cortical gray and/or white matter abnormalities. Additional abnormalities of deep gray structures, brain stem, callosum, and volume loss occurred in the structural acquired subgroup. Repeat MRI showed better definition of the extent of existing malformations. In structural infantile spasms, developmental/acquired subgroups showed differences in pattern of MRI abnormalities but did not correlate with clinical characteristics.

[Neurological soft signs in schizophrenia: correlations with age, sex, educational status and psychopathology].

PubMed

Panagiotidis, P; Kaprinis, G; Iacovides, A; Fountoulakis, K

2013-01-01

Though the pathobiology of schizophrenia can be examined in multiple levels, the organic notion of brain disease suggests that neurological features will be present. One straightforward, inexpensive method of investigating brain dysfunction in schizophrenia is thought the bedside assessment of neurological abnormalities with a standard neurological examination. Neurological abnormalities are traditionally classified as "hard signs" (impairments in basic motor, sensory, and reflex behaviors, which do not appear to be affected in schizophrenia) and "soft signs", which refer to more complex phenomena such as abnormalities in motor control, integrative sensory function, sensorimotor integration, and cerebral laterality. Additionally, neurological soft signs (NSS) are minor motor and sensory abnormalities that are considered to be normal in the course of early development but abnormal when elicited in later life or persist beyond childhood. Soft signs also, have no definitive localizing significance but are indicative of subtle brain dysfunction. Most authors believe that they are a reflection not only of deficient integration between the sensory and motor systems, but also of dysfunctional neuronal circuits linking subcortical brain structures such as the basal ganglia, the brain stem, and the limbic system. Throughout the last four decades, studies have consistently shown that NSS are more frequently present in patients with schizophrenia than in normal subjects and non-psychotic psychiatric patients. However, the functional relevance of NSS remains unclear and their specificity has often been challenged, even though there is indication for a relative specificity with regard to diagnosis, or symptomatology. Many studies have considered soft signs as categorical variables thus hampering the evaluation of fluctuation with symptomatology and/or treatment, whereas other studies included insufficient number of assessed signs, or lacked a comprehensive assessment of extrapyramidal symptomatology. Factors such as sex, age or family history of schizophrenia, are said to influence the performance of neurological examination, whereas relative few studies have provided longitudinal follow-up data on neurological soft signs in a sufficient number of patients, in order to address a possible deterioration of neurological functions. Finally, one additional difficulty when analyzing the NSS literature lies in the diversity of symptoms that are evaluated in the studies and/or non-standardized procedures or scoring. We will review some basic issues concerning recurrent difficulties in the measurement and definition of soft signs, as well as controversies on the significance of these signs with respect to clinical subtyping of schizophrenia, and social and demographic variables.

The sensitivity of auditory-motor representations to subtle changes in auditory feedback while singing

PubMed Central

Keough, Dwayne; Jones, Jeffery A.

2009-01-01

Singing requires accurate control of the fundamental frequency (F0) of the voice. This study examined trained singers’ and untrained singers’ (nonsingers’) sensitivity to subtle manipulations in auditory feedback and the subsequent effect on the mapping between F0 feedback and vocal control. Participants produced the consonant-vowel ∕ta∕ while receiving auditory feedback that was shifted up and down in frequency. Results showed that singers and nonsingers compensated to a similar degree when presented with frequency-altered feedback (FAF); however, singers’ F0 values were consistently closer to the intended pitch target. Moreover, singers initiated their compensatory responses when auditory feedback was shifted up or down 6 cents or more, compared to nonsingers who began compensating when feedback was shifted up 26 cents and down 22 cents. Additionally, examination of the first 50 ms of vocalization indicated that participants commenced subsequent vocal utterances, during FAF, near the F0 value on previous shift trials. Interestingly, nonsingers commenced F0 productions below the pitch target and increased their F0 until they matched the note. Thus, singers and nonsingers rely on an internal model to regulate voice F0, but singers’ models appear to be more sensitive in response to subtle discrepancies in auditory feedback. PMID:19640048

The sensitivity of auditory-motor representations to subtle changes in auditory feedback while singing.

PubMed

Keough, Dwayne; Jones, Jeffery A

2009-08-01

Singing requires accurate control of the fundamental frequency (F0) of the voice. This study examined trained singers' and untrained singers' (nonsingers') sensitivity to subtle manipulations in auditory feedback and the subsequent effect on the mapping between F0 feedback and vocal control. Participants produced the consonant-vowel /ta/ while receiving auditory feedback that was shifted up and down in frequency. Results showed that singers and nonsingers compensated to a similar degree when presented with frequency-altered feedback (FAF); however, singers' F0 values were consistently closer to the intended pitch target. Moreover, singers initiated their compensatory responses when auditory feedback was shifted up or down 6 cents or more, compared to nonsingers who began compensating when feedback was shifted up 26 cents and down 22 cents. Additionally, examination of the first 50 ms of vocalization indicated that participants commenced subsequent vocal utterances, during FAF, near the F0 value on previous shift trials. Interestingly, nonsingers commenced F0 productions below the pitch target and increased their F0 until they matched the note. Thus, singers and nonsingers rely on an internal model to regulate voice F0, but singers' models appear to be more sensitive in response to subtle discrepancies in auditory feedback.

The subtle body: an interoceptive map of central nervous system function and meditative mind-brain-body integration.

PubMed

Loizzo, Joseph J

2016-06-01

Meditation research has begun to clarify the brain effects and mechanisms of contemplative practices while generating a range of typologies and explanatory models to guide further study. This comparative review explores a neglected area relevant to current research: the validity of a traditional central nervous system (CNS) model that coevolved with the practices most studied today and that provides the first comprehensive neural-based typology and mechanistic framework of contemplative practices. The subtle body model, popularly known as the chakra system from Indian yoga, was and is used as a map of CNS function in traditional Indian and Tibetan medicine, neuropsychiatry, and neuropsychology. The study presented here, based on the Nalanda tradition, shows that the subtle body model can be cross-referenced with modern CNS maps and challenges modern brain maps with its embodied network model of CNS function. It also challenges meditation research by: (1) presenting a more rigorous, neural-based typology of contemplative practices; (2) offering a more refined and complete network model of the mechanisms of contemplative practices; and (3) serving as an embodied, interoceptive neurofeedback aid that is more user friendly and complete than current teaching aids for clinical and practical applications of contemplative practice. © 2016 New York Academy of Sciences.

[INDIVIDUAL EVALUATION OF LORETA ABNORMALITIES IN IDIOPATHIC GENERALIZED EPILEPSY].

PubMed

Clemens, Béla; Puskás, Szilvia; Besenyei, Mónika; Kondákor, István; Hollódy, Katalin; Fogarasi, Andrós; Bense, Katalin; Emri, Miklós; Opposits Gábor; Kovács, Noémi Zsuzsanna; Fekete, István

2016-03-30

Contemporary neuroimaging methods disclosed structural and functional cerebral abnormalities in idiopathic generalized epilepsies (IGEs). However, individual electrical (EEG) abnormalities have not been evaluated yet in IGE patients. IGE patients were investigated in the drug-free condition and after 3-6 month of antiepileptic treatment. To estimate the reproducibility of qEEG variables a retrospective recruited cohort of IGE patients was investigated. 19-channel resting state EEG activity was recorded. For each patient a total of 2 minutes EEG activity was analyzed by LORETA (Low Resolution Electromagnetic Tomography). Raw LORETA values were Z-transformed and projected to a MRI template. Z-values outside within the [+3Z] to [-3Z] range were labelled as statistically abnormal. 1. In drug-free condition, 41-50% of IGE patients showed abnormal LORETA values. 2. Abnormal LORETA findings showed great inter-individual variability. 3. Most abnormal LORETA-findings were symmetrical. 4. Most maximum Z-values were localized to frontal or temporal cortex. 5. Succesfull treatment was mostly coupled with disappearence of LORETA-abnormality, persistent seizures were accompanied by persistent LORETA abnormality. 1. LORETA abnormalities detected in the untreated condition reflect seizure-generating property of the cortex in IGE patients. 2. Maximum LORETA-Z abnormalities were topographically congruent with structural abnormalities reported by other research groups. 3. LORETA might help to investigate drug effects at the whole-brain level.

Sleep-like behavior and 24-h rhythm disruption in the Tc1 mouse model of Down syndrome.

PubMed

Heise, I; Fisher, S P; Banks, G T; Wells, S; Peirson, S N; Foster, R G; Nolan, P M

2015-02-01

Down syndrome is a common disorder associated with intellectual disability in humans. Among a variety of severe health problems, patients with Down syndrome exhibit disrupted sleep and abnormal 24-h rest/activity patterns. The transchromosomic mouse model of Down syndrome, Tc1, is a trans-species mouse model for Down syndrome, carrying most of human chromosome 21 in addition to the normal complement of mouse chromosomes and expresses many of the phenotypes characteristic of Down syndrome. To date, however, sleep and circadian rhythms have not been characterized in Tc1 mice. Using both circadian wheel-running analysis and video-based sleep scoring, we showed that these mice exhibited fragmented patterns of sleep-like behaviour during the light phase of a 12:12-h light/dark (LD) cycle with an extended period of continuous wakefulness at the beginning of the dark phase. Moreover, an acute light pulse during night-time was less effective in inducing sleep-like behaviour in Tc1 animals than in wild-type controls. In wheel-running analysis, free running in constant light (LL) or constant darkness (DD) showed no changes in the circadian period of Tc1 animals although they did express subtle behavioural differences including a reduction in total distance travelled on the wheel and differences in the acrophase of activity in LD and in DD. Our data confirm that Tc1 mice express sleep-related phenotypes that are comparable with those seen in Down syndrome patients with moderate disruptions in rest/activity patterns and hyperactive episodes, while circadian period under constant lighting conditions is essentially unaffected. © 2015 Medical Research Council. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.

T1 and T2 mapping for evaluation of myocardial involvement in patients with ANCA-associated vasculitides.

PubMed

Greulich, Simon; Mayr, Agnes; Kitterer, Daniel; Latus, Joerg; Henes, Joerg; Steubing, Hannah; Kaesemann, Philipp; Patrascu, Alexandru; Greiser, Andreas; Groeninger, Stefan; Braun, Niko; Alscher, M Dominik; Sechtem, Udo; Mahrholdt, Heiko

2017-01-06

Myocardial involvement in AAV patients might be silent, presenting with no or nonspecific symptoms, normal ECG, and preserved left-ventricular ejection fraction (LV-EF). Since up to 50% of deaths in these patients may be due to myocardial involvement, a reliable diagnostic tool is warranted. In contrast to LGE-CMR, which has its strengths in detecting focal inflammatory or fibrotic processes, recent mapping techniques are able to detect even subtle, diffuse inflammatory or fibrotic processes. Our study sought to investigate ANCA (antineutrophil cytoplasmic antibody) associated vasculitides (AAV) patients for myocardial involvement by a cardiovascular magnetic resonance (CMR) protocol, including late gadolinium enhancement (LGE) and mapping sequences. Thirty seven AAV patients were prospectively enrolled and underwent CMR imaging. Twenty healthy volunteers served as controls. Mean LV-EF was 64%; LGE prevalence of the AAV patients was 43%. AAV patients had higher median native T1 (988 vs. 952 ms, p < 0.001), lower post-contrast T1 (488 vs. 524 ms, p = 0.03), expanded extracellular volume (ECV) (27.5 vs. 24.5%, p < 0.001), and higher T2 (53 vs. 49 ms, p < 0.001) compared to controls, with most parameters independent of the LGE status. Native T1 and T2 in AAV patients showed the highest prevalence of abnormally increased values beyond the 95% percentile of controls. AAV patients demonstrated increased T1, ECV, and T2 values, with native T1 and T2 showing the highest prevalence of values beyond the 95% percentile of normal. Since these findings seem to be independent of LGE, mapping techniques may provide complementary information to LGE-CMR in the assessment of myocardial involvement in patients with AAV.

[Fabry nephropathy in a female with superposed IgA glomerulonephritis].

PubMed

Pisani, A; Sessa, A; Sabbatini, M; Andreucci, M V; Fusco, C; Balletta, M; Cianciaruso, B

2005-01-01

In Anderson-Fabry disease (AFd), the kidney is affected in all hemizygous males and in some heterozygous females. Female carriers can present subtle renal abnormalities due to glycosphingolipid (GSL) accumulation within renal cells. Renal biopsy is rarely performed in female Fabry patients because clinical renal manifestations are usually lacking. However, female carriers can accumulate GSL in their renal cells despite the absence of clinically evident kidney disease. We performed a kidney biopsy in a 52-year-old female patient, a Fabry disease carrier. The patient showed normal glomerular filtration rate, persistent microhematuria and proteinuria (about 1.7 g/24 hr), cornea "verticillata", and evident left ventricular hypertrophy. The molecular study documented a missense mutation R227Q in exon 5 of the alpha-galactosidase A gene. Optical microscopy showed electron-dense mesangial deposits due IgA glomerulonephritis, as confirmed by immunofluorescence. We decided to start therapy with angiotensin-converting enzyme inhibitors (ACE-I). After 8 months of treatment, the patient demonstrated proteinuria of 0.9 g/24 hr. To decide when to start treatment using enzyme replacement therapy (ERT) with human recombinant GAL A (Fabrazyme), we decided to perform an electron microscopy study of the renal biopsy. The renal ultrastructural findings were typical GSL inclusions in all kinds of glomerular cells, in tubular epithelial cells and in endothelial cells of interstitial capillaries, confirming the hypothesis of Fabry nephropathy. Consequently, Fabrazyme was given at a standard dose of 1 mg/kg every 2 weeks. After 24 months of combined treatment (ACE-I-Fabrazyme), proteinuria decreased to 0.2 g/24 hr. The importance of performing the ultrastructural examination of the kidney biopsy is stressed, especially in heterozygous Fabry patients to evaluate the need to treat them with ERT and to evaluate the degree of renal involvement.

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

PubMed

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

2013-08-01

An insertional translocation (IT) can result in pure segmental aneusomy for the inserted genomic segment allowing to define a more accurate clinical phenotype. Here, we report on two siblings sharing an unbalanced IT inherited from the mother with a history of learning difficulty. An 8-year-old girl with developmental delay, speech disability, and attention-deficit hyperactivity disorder (ADHD), showed by GTG banding analysis a subtle interstitial alteration in 21q21. Oligonucleotide array comparative genomic hybridization (array-CGH) analysis showed a 4q13.1-q13.3 duplication spanning 8.6 Mb. Fluorescence in situ hybridization (FISH) with bacterial artificial chromosome (BAC) clones confirmed the rearrangement, a der(21)ins(21;4)(q21;q13.1q13.3). The duplication described involves 50 RefSeq genes including the EPHA5 gene that encodes for the EphA5 receptor involved in embryonic development of the brain and also in synaptic remodeling and plasticity thought to underlie learning and memory. The same rearrangement was observed in a younger brother with behavioral problems and also exhibiting ADHD. ADHD is among the most heritable of neuropsychiatric disorders. There are few reports of patients with duplications involving the proximal region of 4q and a mild phenotype. To the best of our knowledge this is the first report of a duplication restricted to band 4q13. This abnormality could be easily missed in children who have nonspecific cognitive impairment. The presence of this behavioral disorder in the two siblings reinforces the hypothesis that the region involved could include genes involved in ADHD. Copyright © 2013 Wiley Periodicals, Inc.

Normal radial migration and lamination are maintained in dyslexia-susceptibility candidate gene homolog Kiaa0319 knockout mice.

PubMed

Martinez-Garay, Isabel; Guidi, Luiz G; Holloway, Zoe G; Bailey, Melissa A G; Lyngholm, Daniel; Schneider, Tomasz; Donnison, Timothy; Butt, Simon J B; Monaco, Anthony P; Molnár, Zoltán; Velayos-Baeza, Antonio

2017-04-01

Developmental dyslexia is a common disorder with a strong genetic component, but the underlying molecular mechanisms are still unknown. Several candidate dyslexia-susceptibility genes, including KIAA0319, DYX1C1, and DCDC2, have been identified in humans. RNA interference experiments targeting these genes in rat embryos have shown impairments in neuronal migration, suggesting that defects in radial cortical migration could be involved in the disease mechanism of dyslexia. Here we present the first characterisation of a Kiaa0319 knockout mouse line. Animals lacking KIAA0319 protein do not show anatomical abnormalities in any of the layered structures of the brain. Neurogenesis and radial migration of cortical projection neurons are not altered, and the intrinsic electrophysiological properties of Kiaa0319-deficient neurons do not differ from those of wild-type neurons. Kiaa0319 overexpression in cortex delays radial migration, but does not affect final neuronal position. However, knockout animals show subtle differences suggesting possible alterations in anxiety-related behaviour and in sensorimotor gating. Our results do not reveal a migration disorder in the mouse model, adding to the body of evidence available for Dcdc2 and Dyx1c1 that, unlike in the rat in utero knockdown models, the dyslexia-susceptibility candidate mouse homolog genes do not play an evident role in neuronal migration. However, KIAA0319 protein expression seems to be restricted to the brain, not only in early developmental stages but also in adult mice, indicative of a role of this protein in brain function. The constitutive and conditional knockout lines reported here will be useful tools for further functional analyses of Kiaa0319.

Slc25a12 disruption alters myelination and neurofilaments: a model for a hypomyelination syndrome and childhood neurodevelopmental disorders.

PubMed

Sakurai, Takeshi; Ramoz, Nicolas; Barreto, Marta; Gazdoiu, Mihaela; Takahashi, Nagahide; Gertner, Michael; Dorr, Nathan; Gama Sosa, Miguel A; De Gasperi, Rita; Perez, Gissel; Schmeidler, James; Mitropoulou, Vivian; Le, H Carl; Lupu, Mihaela; Hof, Patrick R; Elder, Gregory A; Buxbaum, Joseph D

2010-05-01

SLC25A12, a susceptibility gene for autism spectrum disorders that is mutated in a neurodevelopmental syndrome, encodes a mitochondrial aspartate-glutamate carrier (aspartate-glutamate carrier isoform 1 [AGC1]). AGC1 is an important component of the malate/aspartate shuttle, a crucial system supporting oxidative phosphorylation and adenosine triphosphate production. We characterized mice with a disruption of the Slc25a12 gene, followed by confirmatory in vitro studies. Slc25a12-knockout mice, which showed no AGC1 by immunoblotting, were born normally but displayed delayed development and died around 3 weeks after birth. In postnatal day 13 to 14 knockout brains, the brains were smaller with no obvious alteration in gross structure. However, we found a reduction in myelin basic protein (MBP)-positive fibers, consistent with a previous report. Furthermore, the neocortex of knockout mice contained abnormal neurofilamentous accumulations in neurons, suggesting defective axonal transport and/or neurodegeneration. Slice cultures prepared from knockout mice also showed a myelination defect, and reduction of Slc25a12 in rat primary oligodendrocytes led to a cell-autonomous reduction in MBP expression. Myelin deficits in slice cultures from knockout mice could be reversed by administration of pyruvate, indicating that reduction in AGC1 activity leads to reduced production of aspartate/N-acetylaspartate and/or alterations in the dihydronicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide(+) ratio, resulting in myelin defects. Our data implicate AGC1 activity in myelination and in neuronal structure and indicate that while loss of AGC1 leads to hypomyelination and neuronal changes, subtle alterations in AGC1 expression could affect brain development, contributing to increased autism susceptibility. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Leg Movement Activity During Sleep in Adults With Attention-Deficit/Hyperactivity Disorder.

PubMed

Garbazza, Corrado; Sauter, Cornelia; Paul, Juliane; Kollek, Jenny; Dujardin, Catharine; Hackethal, Sandra; Dorn, Hans; Peter, Anita; Hansen, Marie-Luise; Manconi, Mauro; Ferri, Raffaele; Danker-Hopfe, Heidi

2018-01-01

Objectives: To conduct a first detailed analysis of the pattern of leg movement (LM) activity during sleep in adult subjects with Attention-Deficit/Hyperactivity Disorder (ADHD) compared to healthy controls. Methods: Fifteen ADHD patients and 18 control subjects underwent an in-lab polysomnographic sleep study. The periodic character of LMs was evaluated with established markers of "periodicity," i.e., the periodicity index, intermovement intervals, and time distribution of LM during sleep, in addition to standard parameters such as the periodic leg movement during sleep index (PLMSI) and the periodic leg movement during sleep arousal index (PLMSAI). Subjective sleep and psychiatric symptoms were assessed using several, self-administered, screening questionnaires. Results: Objective sleep parameters from the baseline night did not significantly differ between ADHD and control subjects, except for a longer sleep latency (SL), a longer duration of the periodic leg movements during sleep (PLMS) in REM sleep and a higher PLMSI also in REM sleep. Data from the sleep questionnaires showed perception of poor sleep quality in ADHD patients. Conclusions: Leg movements during sleep in ADHD adults are not significantly more frequent than in healthy controls and the nocturnal motor events do not show an increased periodicity in these patients. The non-periodic character of LMs in ADHD has already been shown in children and seems to differentiate ADHD from other pathophysiological related conditions like restless legs syndrome (RLS) or periodic limb movement disorder (PLMD). The reduced subjective sleep quality reported by ADHD adults contrasted with the normal objective polysomnographic parameters, which could suggest a sleep-state misperception in these individuals or more subtle sleep abnormalities not picked up by the traditional sleep staging.

Alterations of resting state networks and structural connectivity in relation to the prefrontal and anterior cingulate cortices in late prematurity.

PubMed

Degnan, Andrew J; Wisnowski, Jessica L; Choi, SoYoung; Ceschin, Rafael; Bhushan, Chitresh; Leahy, Richard M; Corby, Patricia; Schmithorst, Vincent J; Panigrahy, Ashok

2015-01-07

Late preterm birth is increasingly recognized as a risk factor for cognitive and social deficits. The prefrontal cortex is particularly vulnerable to injury in late prematurity because of its protracted development and extensive cortical connections. Our study examined children born late preterm without access to advanced postnatal care to assess structural and functional connectivity related to the prefrontal cortex. Thirty-eight preadolescents [19 born late preterm (34-36 /7 weeks gestational age) and 19 at term] were recruited from a developing community in Brazil. Participants underwent neuropsychological testing. Individuals underwent three-dimensional T1-weighted, diffusion-weighted, and resting state functional MRI. Probabilistic tractography and functional connectivity analyses were carried out using unilateral seeds combining the medial prefrontal cortex and the anterior cingulate cortex. Late preterm children showed increased functional connectivity within regions of the default mode, salience, and central-executive networks from both right and left frontal cortex seeds. Decreased functional connectivity was observed within the right parahippocampal region from left frontal seeding. Probabilistic tractography showed a pattern of decreased streamlines in frontal white matter pathways and the corpus callosum, but also increased streamlines in the left orbitofrontal white matter and the right frontal white matter when seeded from the right. Late preterm children and term control children scored similarly on neuropsychological testing. Prefrontal cortical connectivity is altered in late prematurity, with hyperconnectivity observed in key resting state networks in the absence of neuropsychological deficits. Abnormal structural connectivity indicated by probabilistic tractography suggests subtle changes in white matter development, implying disruption of normal maturation during the late gestational period.

Phase shift in the 24-hour rhythm of hippocampal EEG spiking activity in a rat model of temporal lobe epilepsy

PubMed Central

Stanley, David A.; Talathi, Sachin S.; Parekh, Mansi B.; Cordiner, Daniel J.; Zhou, Junli; Mareci, Thomas H.; Ditto, William L.

2013-01-01

For over a century epileptic seizures have been known to cluster at specific times of the day. Recent studies have suggested that the circadian regulatory system may become permanently altered in epilepsy, but little is known about how this affects neural activity and the daily pattern of seizures. To investigate, we tracked long-term changes in the rate of spontaneous hippocampal EEG spikes (SPKs) in a rat model of temporal lobe epilepsy. In healthy animals, SPKs oscillated with near 24-h period; however, after injury by status epilepticus, a persistent phase shift of ∼12 h emerged in animals that later went on to develop chronic spontaneous seizures. Additional measurements showed that global 24-h rhythms, including core body temperature and theta state transitions, did not phase shift. Instead, we hypothesized that locally impaired circadian input to the hippocampus might be responsible for the SPK phase shift. This was investigated with a biophysical computer model in which we showed that subtle changes in the relative strengths of circadian input could produce a phase shift in hippocampal neural activity. MRI provided evidence that the medial septum, a putative circadian relay center for the hippocampus, exhibits signs of damage and therefore could contribute to local circadian impairment. Our results suggest that balanced circadian input is critical to maintaining natural circadian phase in the hippocampus and that damage to circadian relay centers, such as the medial septum, may disrupt this balance. We conclude by discussing how abnormal circadian regulation may contribute to the daily rhythms of epileptic seizures and related cognitive dysfunction. PMID:23678009

Nucleus Accumbens Invulnerability to Methamphetamine Neurotoxicity

PubMed Central

Kuhn, Donald M.; Angoa-Pérez, Mariana; Thomas, David M.

2016-01-01

Methamphetamine (Meth) is a neurotoxic drug of abuse that damages neurons and nerve endings throughout the central nervous system. Emerging studies of human Meth addicts using both postmortem analyses of brain tissue and noninvasive imaging studies of intact brains have confirmed that Meth causes persistent structural abnormalities. Animal and human studies have also defined a number of significant functional problems and comorbid psychiatric disorders associated with long-term Meth abuse. This review summarizes the salient features of Meth-induced neurotoxicity with a focus on the dopamine (DA) neuronal system. DA nerve endings in the caudate-putamen (CPu) are damaged by Meth in a highly delimited manner. Even within the CPu, damage is remarkably heterogeneous, with ventral and lateral aspects showing the greatest deficits. The nucleus accumbens (NAc) is largely spared the damage that accompanies binge Meth intoxication, but relatively subtle changes in the disposition of DA in its nerve endings can lead to dramatic increases in Meth-induced toxicity in the CPu and overcome the normal resistance of the NAc to damage. In contrast to the CPu, where DA neuronal deficiencies are persistent, alterations in the NAc show a partial recovery. Animal models have been indispensable in studies of the causes and consequences of Meth neurotoxicity and in the development of new therapies. This research has shown that increases in cytoplasmic DA dramatically broaden the neurotoxic profile of Meth to include brain structures not normally targeted for damage. The resistance of the NAc to Meth-induced neurotoxicity and its ability to recover reveal a fundamentally different neuroplasticity by comparison to the CPu. Recruitment of the NAc as a target of Meth neurotoxicity by alterations in DA homeostasis is significant in light of the numerous important roles played by this brain structure. PMID:23382149

Nucleus accumbens invulnerability to methamphetamine neurotoxicity.

PubMed

Kuhn, Donald M; Angoa-Pérez, Mariana; Thomas, David M

2011-01-01

Methamphetamine (Meth) is a neurotoxic drug of abuse that damages neurons and nerve endings throughout the central nervous system. Emerging studies of human Meth addicts using both postmortem analyses of brain tissue and noninvasive imaging studies of intact brains have confirmed that Meth causes persistent structural abnormalities. Animal and human studies have also defined a number of significant functional problems and comorbid psychiatric disorders associated with long-term Meth abuse. This review summarizes the salient features of Meth-induced neurotoxicity with a focus on the dopamine (DA) neuronal system. DA nerve endings in the caudate-putamen (CPu) are damaged by Meth in a highly delimited manner. Even within the CPu, damage is remarkably heterogeneous, with ventral and lateral aspects showing the greatest deficits. The nucleus accumbens (NAc) is largely spared the damage that accompanies binge Meth intoxication, but relatively subtle changes in the disposition of DA in its nerve endings can lead to dramatic increases in Meth-induced toxicity in the CPu and overcome the normal resistance of the NAc to damage. In contrast to the CPu, where DA neuronal deficiencies are persistent, alterations in the NAc show a partial recovery. Animal models have been indispensable in studies of the causes and consequences of Meth neurotoxicity and in the development of new therapies. This research has shown that increases in cytoplasmic DA dramatically broaden the neurotoxic profile of Meth to include brain structures not normally targeted for damage. The resistance of the NAc to Meth-induced neurotoxicity and its ability to recover reveal a fundamentally different neuroplasticity by comparison to the CPu. Recruitment of the NAc as a target of Meth neurotoxicity by alterations in DA homeostasis is significant in light of the numerous important roles played by this brain structure.

Neuromotor outcomes at school age after extremely low birth weight: early detection of subtle signs.

PubMed

Gidley Larson, Jennifer C; Baron, Ida Sue; Erickson, Kristine; Ahronovich, Margot D; Baker, Robin; Litman, Fern R

2011-01-01

Motor impairments are prevalent in children born at extremely low birth weight (ELBW; <1,000 g). Rarely studied are subtle motor deficits that indicate dysfunction or delay in neural systems critical for optimal cognitive, academic, and behavioral function. We aimed to examine quantifiable signs of subtle neuromotor dysfunction in an early school-aged ELBW cohort that coincidentally had age-appropriate cognition and design copying. We studied 97 participants born between 1998 and 2001; 74 ELBW (6.7 years ± 0.75) compared with 23 term-born (6.6 years ± 0.29). Neuromotor outcomes were assessed using the Physical and Neurological Examination of Subtle Signs-Revised, and measures of dexterity/coordination and visual-motor integration. ELBW participants performed worse than term-born on design-copying and dexterity, were age-appropriate compared to normative data, and had slower timed movements and more subtle overflow movements. Those ELBW born <26 weeks performed most poorly compared with those born 26-34 weeks and term-born. Subtle motor dysfunctions are detectable and quantifiable in ELBW children by school age, even in the presence of average cognition. Early age assessment of incoordination, motor speed, and overflow movements should aid initiation of timely therapies to prepare at-risk ELBW children for subsequent school entry and facilitate design of optimal early treatment strategies. (c) 2010 APA, all rights reserved.

Treatment with sodium benzoate leads to malformation of zebrafish larvae.

PubMed

Tsay, Huey-Jen; Wang, Yun-Hsin; Chen, Wei-Li; Huang, Mei-Yun; Chen, Yau-Hung

2007-01-01

Sodium benzoate (SB) is a commonly used food preservative and anti-microbial agent in many foods from soup to cereals. However, little is known about the SB-induced toxicity and teratogenicity during early embryonic development. Here, we used zebrafish as a model to test the toxicity and teratogenicity because of their transparent eggs; therefore, the organogenesis of zebrafish embryos is easy to observe. After low dosages of SB (1-1000 ppm) treatment, the zebrafish embryos exhibited a 100% survival rate. As the exposure dosages increased, the survival rates decreased. No embryos survived after treatment with 2000 ppm SB. The 50% lethal dose (LD(50)) of zebrafish is found to be in the range of 1400-1500 ppm. Gut abnormalities, malformation of pronephros, defective hatching gland and edema in pericardial sac were observed after treatment with SB. Compared to untreated littermates (vehicle-treated control), SB-treated embryos exhibited significantly reduced tactile sensitivity frequencies of touch-induced movement (vehicle-treated control: 27.60+/-1.98 v.s. 1000 ppm SB: 7.89+/-5.28; N=30). Subtle changes are easily observed by staining with specific monoclonal antibodies F59, Znp1 and alpha6F to detect morphology changes in muscle fibers, motor axons and pronephros, respectively. Our data showed that the treatment of SB led to misalignment of muscle fibers, motor neuron innervations, excess acetyl-choline receptor cluster and defective pronephric tubes. On the basis of these observations, we suggest that sodium benzoate is able to induce neurotoxicity and nephrotoxicity of zebrafish larvae.

A trend toward smaller optical angles and medial-ocular distance in schizophrenia spectrum, but not in bipolar and major depressive disorders.

PubMed

Wang, Yi; Deng, Yi; Li, Zhi; Li, Xu; Zhang, Chen-Yuan; Jin, Zhen; Fan, Ming-Xia; Compton, Michael T; Cheung, Eric F C; Lim, Kelvin O; Chan, Raymond C K

2016-12-01

Minor physical anomalies (MPAs) are subtle signs of fetal developmental abnormalities that have been considered to be among the most replicated risk markers for schizophrenia-spectrum disorders. However, quantitative approaches are needed to measure craniofacial MPAs. The present study adopted an imaging-based quantitative approach to examine craniofacial MPAs across the spectrum of schizophrenia and affective disorders, to address their sensitivity and specificity. We sampled 31 patients with schizophrenia, 30 of their unaffected relatives, and 30 individuals with schizotypal personality traits, as well as 37 non-schizotypal controls. We also examined 17 patients with bipolar disorder and 19 patients with major depressive disorder. Five craniofacial MPAs were measured on anterior-posterior commissure-aligned T1-weighted images of an individual's native brain space: medial-ocular distance, lateral-ocular distance, optical angle, maximum skull length, and skull-base width. Compared to non-schizotypal controls, patients with schizophrenia and their relatives showed a trend toward having smaller optical angles and medial-ocular distance, while no difference was found in patients with bipolar or major depressive disorders, suggesting some degree of specificity to schizophrenia. Our approach may benefit future research on craniofacial MPAs as risk markers for schizophrenia-spectrum disorders, and may eventually be useful in strategies to enhance risk stratification using multiple risk markers. © 2016 The Institute of Psychology, Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

Use magnetic resonance imaging to assess articular cartilage

PubMed Central

Wang, Yuanyuan; Wluka, Anita E.; Jones, Graeme; Ding, Changhai

2012-01-01

Magnetic resonance imaging (MRI) enables a noninvasive, three-dimensional assessment of the entire joint, simultaneously allowing the direct visualization of articular cartilage. Thus, MRI has become the imaging modality of choice in both clinical and research settings of musculoskeletal diseases, particular for osteoarthritis (OA). Although radiography, the current gold standard for the assessment of OA, has had recent significant technical advances, radiographic methods have significant limitations when used to measure disease progression. MRI allows accurate and reliable assessment of articular cartilage which is sensitive to change, providing the opportunity to better examine and understand preclinical and very subtle early abnormalities in articular cartilage, prior to the onset of radiographic disease. MRI enables quantitative (cartilage volume and thickness) and semiquantitative assessment of articular cartilage morphology, and quantitative assessment of cartilage matrix composition. Cartilage volume and defects have demonstrated adequate validity, accuracy, reliability and sensitivity to change. They are correlated to radiographic changes and clinical outcomes such as pain and joint replacement. Measures of cartilage matrix composition show promise as they seem to relate to cartilage morphology and symptoms. MRI-derived cartilage measurements provide a useful tool for exploring the effect of modifiable factors on articular cartilage prior to clinical disease and identifying the potential preventive strategies. MRI represents a useful approach to monitoring the natural history of OA and evaluating the effect of therapeutic agents. MRI assessment of articular cartilage has tremendous potential for large-scale epidemiological studies of OA progression, and for clinical trials of treatment response to disease-modifying OA drugs. PMID:22870497

Future Perspectives for Management of Stage A Heart Failure.

PubMed

Tanaka, Hidekazu

2018-05-07

Patients with Stage A heart failure (HF) show no HF symptoms but have related comorbid diseases with a high risk of progressing to HF. Screening for comorbid diseases warrants closer attention because of the growing interest in addressing Stage A HF as the best means of preventing eventual progression to overt HF such as Stages C and D. The identification of individuals of Stage A HF is potentially useful for the implementation of HF-prevention strategies; however, not all Stage A HF patients develop left ventricular (LV) structural heart disease or symptomatic HF, which lead to advanced HF stages. Therefore, Stage A HF requires management with the long-term goal of avoiding HF development; likewise, Stage B HF patients are ideal targets for HF prevention. Although the early detection of subclinical LV dysfunction is, thus, essential for delaying the progression to HF, the assessment of subclinical LV dysfunction can be challenging. Global longitudinal strain (GLS) as assessed by speckle-tracking echocardiography has recently been reported to be a sensitive marker of early subtle LV myocardial abnormalities, helpful for the prediction of the outcomes for various cardiac diseases, and superior to conventional echocardiographic indices. GLS reflects LV longitudinal myocardial systolic function, and can be assessed usually by means of two-dimensional speckle-tracking. This article reviews the importance of the assessment of subclinical LV dysfunction in Stage A HF patients by means of GLS, and its current potential to prevent progression to later stage HF.

The Mechanism of Speech Processing in Congenital Amusia: Evidence from Mandarin Speakers

PubMed Central

Liu, Fang; Jiang, Cunmei; Thompson, William Forde; Xu, Yi; Yang, Yufang; Stewart, Lauren

2012-01-01

Congenital amusia is a neuro-developmental disorder of pitch perception that causes severe problems with music processing but only subtle difficulties in speech processing. This study investigated speech processing in a group of Mandarin speakers with congenital amusia. Thirteen Mandarin amusics and thirteen matched controls participated in a set of tone and intonation perception tasks and two pitch threshold tasks. Compared with controls, amusics showed impaired performance on word discrimination in natural speech and their gliding tone analogs. They also performed worse than controls on discriminating gliding tone sequences derived from statements and questions, and showed elevated thresholds for pitch change detection and pitch direction discrimination. However, they performed as well as controls on word identification, and on statement-question identification and discrimination in natural speech. Overall, tasks that involved multiple acoustic cues to communicative meaning were not impacted by amusia. Only when the tasks relied mainly on pitch sensitivity did amusics show impaired performance compared to controls. These findings help explain why amusia only affects speech processing in subtle ways. Further studies on a larger sample of Mandarin amusics and on amusics of other language backgrounds are needed to consolidate these results. PMID:22347374

The mechanism of speech processing in congenital amusia: evidence from Mandarin speakers.

PubMed

Liu, Fang; Jiang, Cunmei; Thompson, William Forde; Xu, Yi; Yang, Yufang; Stewart, Lauren

2012-01-01

Congenital amusia is a neuro-developmental disorder of pitch perception that causes severe problems with music processing but only subtle difficulties in speech processing. This study investigated speech processing in a group of Mandarin speakers with congenital amusia. Thirteen Mandarin amusics and thirteen matched controls participated in a set of tone and intonation perception tasks and two pitch threshold tasks. Compared with controls, amusics showed impaired performance on word discrimination in natural speech and their gliding tone analogs. They also performed worse than controls on discriminating gliding tone sequences derived from statements and questions, and showed elevated thresholds for pitch change detection and pitch direction discrimination. However, they performed as well as controls on word identification, and on statement-question identification and discrimination in natural speech. Overall, tasks that involved multiple acoustic cues to communicative meaning were not impacted by amusia. Only when the tasks relied mainly on pitch sensitivity did amusics show impaired performance compared to controls. These findings help explain why amusia only affects speech processing in subtle ways. Further studies on a larger sample of Mandarin amusics and on amusics of other language backgrounds are needed to consolidate these results.

Oxytocin enhances pupil dilation and sensitivity to ‘hidden’ emotional expressions

PubMed Central

Wessberg, Johan; Ellingsen, Dan-Mikael; Chelnokova, Olga; Olausson, Håkan; Laeng, Bruno

2013-01-01

Sensing others’ emotions through subtle facial expressions is a highly important social skill. We investigated the effects of intranasal oxytocin treatment on the evaluation of explicit and ‘hidden’ emotional expressions and related the results to individual differences in sensitivity to others’ subtle expressions of anger and happiness. Forty healthy volunteers participated in this double-blind, placebo-controlled crossover study, which shows that a single dose of intranasal oxytocin (40 IU) enhanced or ‘sharpened’ evaluative processing of others’ positive and negative facial expression for both explicit and hidden emotional information. Our results point to mechanisms that could underpin oxytocin’s prosocial effects in humans. Importantly, individual differences in baseline emotional sensitivity predicted oxytocin’s effects on the ability to sense differences between faces with hidden emotional information. Participants with low emotional sensitivity showed greater oxytocin-induced improvement. These participants also showed larger task-related pupil dilation, suggesting that they also allocated the most attentional resources to the task. Overall, oxytocin treatment enhanced stimulus-induced pupil dilation, consistent with oxytocin enhancement of attention towards socially relevant stimuli. Since pupil dilation can be associated with increased attractiveness and approach behaviour, this effect could also represent a mechanism by which oxytocin increases human affiliation. PMID:22648957

Oxytocin enhances pupil dilation and sensitivity to 'hidden' emotional expressions.

PubMed

Leknes, Siri; Wessberg, Johan; Ellingsen, Dan-Mikael; Chelnokova, Olga; Olausson, Håkan; Laeng, Bruno

2013-10-01

Sensing others' emotions through subtle facial expressions is a highly important social skill. We investigated the effects of intranasal oxytocin treatment on the evaluation of explicit and 'hidden' emotional expressions and related the results to individual differences in sensitivity to others' subtle expressions of anger and happiness. Forty healthy volunteers participated in this double-blind, placebo-controlled crossover study, which shows that a single dose of intranasal oxytocin (40 IU) enhanced or 'sharpened' evaluative processing of others' positive and negative facial expression for both explicit and hidden emotional information. Our results point to mechanisms that could underpin oxytocin's prosocial effects in humans. Importantly, individual differences in baseline emotional sensitivity predicted oxytocin's effects on the ability to sense differences between faces with hidden emotional information. Participants with low emotional sensitivity showed greater oxytocin-induced improvement. These participants also showed larger task-related pupil dilation, suggesting that they also allocated the most attentional resources to the task. Overall, oxytocin treatment enhanced stimulus-induced pupil dilation, consistent with oxytocin enhancement of attention towards socially relevant stimuli. Since pupil dilation can be associated with increased attractiveness and approach behaviour, this effect could also represent a mechanism by which oxytocin increases human affiliation.

Relevant signs of stable and unstable thoracolumbar vertebral column trauma

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

Gehweiler, J.A.; Daffner, R.H.; Osborne, R.L.

1981-12-01

One-hundred and seventeen patients with acute thoracolumbar vertebral column fracture or fracture-dislocations were analyzed and classified into stable (36%) and unstable (64%). Eight helpful roentgen signs were observed that may serve to direct attention to serious underlying, often occult, fractures and dislocations. The changes fall into four principal groups: abnormal soft tissues, abnormal vertebral alignment, abnormal joints, and widened vertebral canal. All stable and unstable lesions showed abnormal soft tissues, while 70% demonstrated kyphosis and/or scoliosis, and an abnormal adjacent intervertebral disk space. All unstable lesions showed one or more of the following signs: displaced vertebra, widened interspinous space, abnormalmore » apophyseal joint(s), and widened vertebral canal.« less

Awareness of subtle emotional feelings: a comparison of long-term meditators and nonmeditators.

PubMed

Nielsen, Lisbeth; Kaszniak, Alfred W

2006-08-01

The authors explored whether meditation training to enhance emotional awareness improves discrimination of subtle emotional feelings hypothesized to guide decision-making. Long-term meditators and nonmeditators were compared on measures of self-reported valence and arousal, skin conductance response (SCR), and facial electromyography (EMG) to masked and nonmasked emotional pictures, and on measures of heartbeat detection and self-reported emotional awareness. Groups responded similarly to nonmasked pictures. In the masked condition, only controls showed discrimination in valence self-reports. However, meditators reported greater emotional clarity than controls, and meditators with higher clarity had reduced arousal and improved valence discrimination in the masked condition. These findings provide qualified support for the somatic marker hypothesis and suggest that meditation may influence how emotionally ambiguous information is processed, regulated, and represented in conscious awareness. (c) 2006 APA, all rights reserved

Age-related differences in responses to thoughts of one's own death: mortality salience and judgments of moral transgressions.

PubMed

Maxfield, Molly; Pyszczynski, Tom; Kluck, Benjamin; Cox, Cathy R; Greenberg, Jeff; Solomon, Sheldon; Weise, David

2007-06-01

Two experiments explored age differences in response to reminders of death. Terror management research has shown that death reminders lead to increased adherence to and defense of one's cultural worldview. In Study 1, the effect of mortality salience (MS) on evaluations of moral transgressions made by younger and older adults was compared. Whereas younger adults showed the typical pattern of harsher judgments in response to MS, older adults did not. Study 2 compared younger and older adults' responses to both the typical MS induction and a more subtle death reminder. Whereas younger adults responded to both MS inductions with harsher evaluations, older adults made significantly less harsh evaluations after the subtle MS induction. Explanations for this developmental shift in responses to reminders of death are discussed. ((c) 2007 APA, all rights reserved).

Wernicke-Korsakoff syndrome

MedlinePlus

... cause leg tremor Vision changes such as abnormal eye movements (back and forth movements called nystagmus), double vision , ... may show damage to many nerve systems: Abnormal eye movement Decreased or abnormal reflexes Fast pulse (heart rate) ...

Semi-quantitative Assessment of Brain Maturation by Conventional Magnetic Resonance Imaging in Neonates with Clinically Mild Hypoxic-ischemic Encephalopathy

PubMed Central

Gao, Jie; Sun, Qin-Li; Zhang, Yu-Miao; Li, Yan-Yan; Li, Huan; Hou, Xin; Yu, Bo-Lang; Zhou, Xi-Hui; Yang, Jian

2015-01-01

Background: Mild hypoxic-ischemic encephalopathy (HIE) injury is becoming the major type in neonatal brain diseases. The aim of this study was to assess brain maturation in mild HIE neonatal brains using total maturation score (TMS) based on conventional magnetic resonance imaging (MRI). Methods: Totally, 45 neonates with clinically mild HIE and 45 matched control neonates were enrolled. Gestated age, birth weight, age after birth and postmenstrual age at magnetic resonance (MR) scan were homogenous in the two groups. According to MR findings, mild HIE neonates were divided into three subgroups: Pattern I, neonates with normal MR appearance; Pattern II, preterm neonates with abnormal MR appearance; Pattern III, full-term neonates with abnormal MR appearance. TMS and its parameters, progressive myelination (M), cortical infolding (C), involution of germinal matrix tissue (G), and glial cell migration bands (B), were employed to assess brain maturation and compare difference between HIE and control groups. Results: The mean of TMS was significantly lower in mild HIE group than it in the control group (mean ± standard deviation [SD] 11.62 ± 1.53 vs. 12.36 ± 1.26, P < 0.001). In four parameters of TMS scores, the M and C scores were significantly lower in mild HIE group. Of the three patterns of mild HIE, Pattern I (10 cases) showed no significant difference of TMS compared with control neonates, while Pattern II (22 cases), III (13 cases) all had significantly decreased TMS than control neonates (mean ± SD 10.56 ± 0.93 vs. 11.48 ± 0.55, P < 0.05; 12.59 ± 1.28 vs. 13.25 ± 1.29, P < 0.05). It was M, C, and GM scores that significantly decreased in Pattern II, while for Pattern III, only C score significantly decreased. Conclusions: The TMS system, based on conventional MRI, is an effective method to detect delayed brain maturation in clinically mild HIE. The conventional MRI can reveal the different retardations in subtle structures and development processes among the different patterns of mild HIE. PMID:25698186

Patients with mild cognitive impairment have an abnormal upper-alpha event-related desynchronization/synchronization (ERD/ERS) during a task of temporal attention.

PubMed

Caravaglios, Giuseppe; Muscoso, Emma Gabriella; Di Maria, Giulia; Costanzo, Erminio

2015-03-01

There are several evidences indicating that an impairment in attention-executive functions is present in prodromal Alzheimer's disease and predict future global cognitive decline. In particular, the issue of temporal orienting of attention in patients with mild cognitive impairment (MCI) due to Alzheimer's disease has been overlooked. The present research aimed to explore whether subtle deficits of cortical activation are present in these patients early in the course of the disease. We studied the upper-alpha event-related synchronization/desynchronization phenomenon during a paradigm of temporal orientation of attention. MCI patients (n = 27) and healthy elderly controls (n = 15) performed a task in which periodically omitted tones had to be predicted and their virtual onset time had to be marked by pressing a button. Single-trial responses were measured, respectively, before and after the motor response. Then, upper-alpha responses were compared to upper-alpha power during eyes-closed resting state. The time course of the task was characterized by two different behavioral conditions: (1) a pre-event epoch, in which the subject awaited the virtual onset of the omitted tone, (2) a post-event epoch (after button pressing), in which the subject was in a post-motor response condition. The principal findings are: (1) during the waiting epoch, only healthy elderly had an upper-alpha ERD at the level of both temporal and posterior brain regions; (2) during the post-motor epoch, the aMCI patients had a weaker upper-alpha ERS on prefrontal regions; (3) only healthy elderly showed a laterality effect: (a) during the waiting epoch, the upper-alpha ERD was greater at the level of the right posterior-temporal lead; during the post-motor epoch, the upper alpha ERS was greater on the left prefrontal lead. The relevance of these findings is that the weaker upper-alpha response observed in aMCI patients is evident even if the accuracy of the behavioral performance (i.e., button pressing) is still spared. This abnormal upper-alpha response might represent an early biomarker of the attention-executive network impairment in MCI due to Alzheimer's disease.

Investigating Subtle Colors on Iapetus

NASA Image and Video Library

2015-04-06

NASA Cassini spacecraft stared toward Saturn two-toned moon Iapetus for about a week in early 2015, in a campaign motivated in part to investigate subtle color differences within the moon bright terrain.

Using impedance cardiography with postural change to stratify patients with hypertension.

PubMed

DeMarzo, Arthur P

2011-06-01

Early detection of cardiovascular disease in patients with hypertension could initiate appropriate treatment to control blood pressure and prevent the progression of cardiovascular disease. The goal of this study was to show how impedance cardiography waveform analysis with postural change can be used to detect subclinical cardiovascular disease in patients with high blood pressure. Patients with high blood pressure had impedance cardiography data obtained in two positions, standing upright and supine. In 50 adults, impedance cardiography indicated that all patients had abnormal data, with 44 (88%) having multiple abnormalities. Impedance cardiography showed 32 (64%) had ventricular dysfunction, 48 (96%) had vascular load abnormalities, 34 (68%) had hemodynamic abnormalities, 2 (4%) had hypovolemia, and 3 (6%) had hypervolemia. Hypertensive patients have diverse cardiovascular abnormalities that can be quantified by impedance cardiography. By stratifying patients with ventricular, vascular, and hemodynamic abnormalities, treatment could be customized based on the abnormal underlying mechanisms with the potential to rapidly control blood pressure, prevent progression of cardiovascular disease, and possibly reverse remodeling.

The Many Faces of Constructivist Discussion

ERIC Educational Resources Information Center

Golding, Clinton

2011-01-01

Although constructivist discussions in the classroom are often treated as if they were all of the same kind, in this paper I argue that there are subtle but important distinctions that need to be made. An analysis of these distinctions shows that there is a continuum of different constructivist discussions. At one extreme are teacher-directed…

Values in Principals' Thinking when Solving Problems

ERIC Educational Resources Information Center

Lazaridou, Angeliki

2007-01-01

The values that school principals use when solving organisational problems were studied. Data were collected by a think aloud procedure, in which the participants verbalised their thoughts while working on a set of five administrative problems. The results show that the principals referred to seven values that had subtle but important sub-texts:…

Subtleties in Energy Calculations in the Image Method

ERIC Educational Resources Information Center

Taddei, M. M.; Mendes, T. N. C.; Farina, C.

2009-01-01

In this pedagogical work, we point out a subtle mistake that can be made by undergraduate or graduate students in the computation of the electrostatic energy of a system containing charges and perfect conductors if they naively use the image method. Specifically, we show that naive expressions for the electrostatic energy for these systems…

Rightward Collisions and Their Association with Pseudoneglect

ERIC Educational Resources Information Center

Nicholls, Michael E. R.; Loftus, Andrea M.; Orr, Catherine A.; Barre, Natalie

2008-01-01

Whereas right parietal damage can result in left hemineglect, the general population shows a subtle neglect of the right hemispace--known as pseudoneglect. A recent study has demonstrated that people collide to the right more often and attributed this bias to pseudoneglect. [Nicholls, M. E. R., Loftus, A., Meyer, K., & Mattingley, J.B. (2007).…

Solvent friction changes the folding pathway of the tryptophan zipper TZ2.

PubMed

Narayanan, Ranjani; Pelakh, Leslie; Hagen, Stephen J

2009-07-17

Because the rate of a diffusional process such as protein folding is controlled by friction encountered along the reaction pathway, the speed of folding is readily tunable through adjustment of solvent viscosity. The precise relationship between solvent viscosity and the rate of diffusion is complex and even conformation-dependent, however, because both solvent friction and protein internal friction contribute to the total reaction friction. The heterogeneity of the reaction friction along the folding pathway may have subtle consequences. For proteins that fold on a multidimensional free-energy surface, an increase in solvent friction may drive a qualitative change in folding trajectory. Our time-resolved experiments on the rapidly and heterogeneously folding beta-hairpin TZ2 show a shift in the folding pathway as viscosity increases, even though the energetics of folding is unaltered. We also observe a nonlinear or saturating behavior of the folding relaxation time with rising solvent viscosity, potentially an experimental signature of the shifting pathway for unfolding. Our results show that manipulations of solvent viscosity in folding experiments and simulations may have subtle and unexpected consequences on the folding dynamics being studied.

Neurological Abnormalities in Recent-Onset Schizophrenia and Asperger-Syndrome

PubMed Central

Hirjak, Dusan; Wolf, Robert Christian; Koch, Sabine C.; Mehl, Laura; Kelbel, Janna K.; Kubera, Katharina Maria; Traeger, Tanja; Fuchs, Thomas; Thomann, Philipp Arthur

2014-01-01

Background: Neurological abnormalities including a variety of subtle deficits such as discrete impairments in sensory integration, motor coordination (MOCO), and sequencing of complex motor acts are frequently found in patients with schizophrenia (SZ) and commonly referred to as neurological soft signs (NSS). Asperger-syndrome (AS) is characterized by sensory-motor difficulties as well. However, the question whether the two disorders share a common or a disease-specific pattern of NSS remains unresolved. Method: A total of 78 age- and education-matched participants [26 patients with recent-onset SZ, 26 individuals with AS, and 26 healthy controls (HC)] were recruited for the study. Analyses of covariance (ANCOVAs), with age, years of education, and medication included as covariates, were used to examine group differences on total NSS and the five subscale scores. Discriminant analyses were employed to identify the NSS subscales that maximally discriminate between the three groups. Results: Significant differences among the three groups were found in NSS total score and on the five NSS subscales. The clinical groups differed significantly in the NSS subscale MOCO. The correct discriminant rate between patients with SZ and individuals with AS was 61.5%. The correct discriminant rate was 92.3% between individuals with AS and HC, and 80.8% between SZ patients and HC, respectively. Conclusion: Our findings provide new evidence for the presence of NSS in AS and lend further support to previously reported difficulties in movement control in this disorder. According to the present results, SZ and AS seem to be characterized by both quantitative and qualitative NSS expression. PMID:25147527

Heart rate dynamics before spontaneous onset of ventricular fibrillation in patients with healed myocardial infarcts

NASA Technical Reports Server (NTRS)

Makikallio, T. H.; Koistinen, J.; Jordaens, L.; Tulppo, M. P.; Wood, N.; Golosarsky, B.; Peng, C. K.; Goldberger, A. L.; Huikuri, H. V.

1999-01-01

The traditional methods of analyzing heart rate (HR) variability have failed to predict imminent ventricular fibrillation (VF). We sought to determine whether new methods of analyzing RR interval variability based on nonlinear dynamics and fractal analysis may help to detect subtle abnormalities in RR interval behavior before the onset of life-threatening arrhythmias. RR interval dynamics were analyzed from 24-hour Holter recordings of 15 patients who experienced VF during electrocardiographic recording. Thirty patients without spontaneous or inducible arrhythmia events served as a control group in this retrospective case control study. Conventional time- and frequency-domain measurements, the short-term fractal scaling exponent (alpha) obtained by detrended fluctuation analysis, and the slope (beta) of the power-law regression line (log power - log frequency, 10(-4)-10(-2) Hz) of RR interval dynamics were determined. The short-term correlation exponent alpha of RR intervals (0.64 +/- 0.19 vs 1.05 +/- 0.12; p <0.001) and the power-law slope beta (-1.63 +/- 0.28 vs -1.31 +/- 0.20, p <0.001) were lower in the patients before the onset of VF than in the control patients, but the SD and the low-frequency spectral components of RR intervals did not differ between the groups. The short-term scaling exponent performed better than any other measurement of HR variability in differentiating between the patients with VF and controls. Altered fractal correlation properties of HR behavior precede the spontaneous onset of VF. Dynamic analysis methods of analyzing RR intervals may help to identify abnormalities in HR behavior before VF.

Gait analysis in patients with chronic obstructive pulmonary disease: a systematic review.

PubMed

Zago, Matteo; Sforza, Chiarella; Bonardi, Daniela Rita; Guffanti, Enrico Eugenio; Galli, Manuela

2018-03-01

Gait instability is a major fall-risk factor in patients with chronic obstructive pulmonary disease (COPD). Clinical gait analysis is a reliable tool to predict fall onsets. However, controversy still exists on gait impairments associated with COPD. Thus, the aims of this review were to evaluate the current understanding of spatiotemporal, kinematic and kinetic gait features in patients with COPD. In line with PRISMA guidelines, a systematic literature search was performed throughout Web of Science, PubMed Medline, Scopus, PEDro and Scielo databases. We considered observational cross-sectional studies evaluating gait features in patients with COPD as their primary outcome. Risk of bias and applicability of these papers were assessed according to the QUADAS-2 tool. Seven articles, cross-sectional studies published from 2011 to 2017, met the inclusion criteria. Sample size of patients with COPD ranged 14-196 (mean age range: 64-75 years). The main reported gait abnormalities were reduced step length and cadence, and altered variability of spatiotemporal parameters. Only subtle biomechanical changes were reported at the ankle level. A convincing mechanistic link between such gait impairments and falls in patients with COPD is still lacking. The paucity of studies, small sample sizes, gender and disease status pooling were the main risk of biases affecting the results uncertainty. Two research directions emerged: stricter cohorts characterization in terms of COPD phenotype and longitudinal studies. Quantitative assessment of gait would identify abnormalities and sensorimotor postural deficiencies that in turn may lead to better falling prevention strategies in COPD. Copyright © 2018 Elsevier B.V. All rights reserved.

Thyroid Function Abnormalities and Cognitive Impairment in the Elderly. Results of the InCHIANTI Study

PubMed Central

Ceresini, Graziano; Lauretani, Fulvio; Maggio, Marcello; Ceda, Gian Paolo; Morganti, Simonetta; Usberti, Elisa; Chezzi, Carlo; Valcavi, Rita; Bandinelli, Stefania; Guralnik, Jack M.; Cappola, Anne R.; Valenti, Giorgio; Ferrucci, Luigi

2008-01-01

Objectives To investigate thyroid function testing abnormalities in older persons and to explore the relationship between thyroid dysfunction and cognition. Design Cross-sectional study Setting Community-based Participants 1171 men and women aged 23-102 yrs Measurements Thyroid function was evaluated by measuring plasma concentrations of thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3). Cognition was evaluated by the Mini Mental State Examination (MMSE). Prevalence of overt and subclinical thyroid dysfunction was evaluated in different age groups (<65 versus ≥65 years). Age trends in TSH, FT4, and FT3 were examined in euthyroid participants. The cross-sectional association of thyroid dysfunction with MMSE score was evaluated adjusting for confounders. Results Both subclinical hypothyroidism and subclinical hyperthyroidism were more prevalent in older than in younger participants (Subclinical hypothyroidism, 0.4 % vs 3.5 % in younger vs older participants, respectively, P<.03 Subclinical hyperthyroidism, 1.9 % vs 7.8 % in younger vs older participants, respectively, P<.002). In euthyroid participants TSH and FT3 declined with age while FT4 increased. Old participants with subclinical hyperthyroidism had a lower MMSE score than euthyroid subjects (22.61 ± 6.88 vs 24.72 ± 4.52, P<.03). In adjusted analyses, participants with subclinical hyperthyroidism were significantly more likely to have cognitive dysfunction (HR: 2.26, P= .003). Conclusion Subtle age-related changes in FT3, FT4 and TSH occur in individuals who remain euthyroid. Subclinical hyperthyroidism is the most prevalent thyroid dysfunction in Italian older persons and is associated with cognitive impairment. PMID:19054181

Congenital portosystemic shunt: characterization of a multisystem disease.

PubMed

Sokollik, Christiane; Bandsma, Robert H J; Gana, Juan C; van den Heuvel, Meta; Ling, Simon C

2013-06-01

Congenital portosystemic shunts (CPSSs) are rare but increasingly recognized as a cause of important multisystem morbidity. We present new cases and a systematic literature review and propose an algorithm for the identification and care of affected patients. We reviewed the charts of consecutive patients seen in our pediatric liver clinic between 2003 and 2010 and systematically reviewed the literature of cases with CPSS. We identified 316 published cases and 12 patients in our own clinic. Of the published cases (177 male), 185 had an extrahepatic and 131 an intrahepatic portosystemic shunt. Diagnosis was made at any age, from prenatal to late adulthood. Cardiac anomalies were found in 22% of patients. The main complications were hyperammonemia/neurological abnormalities (35%), liver tumors (26%), and pulmonary hypertension or hepatopulmonary syndrome (18%). The spectrum of neurological involvement ranged from changes in brain imaging, subtle abnormalities on neuropsychological testing, through learning disabilities to overt encephalopathy. Spontaneous shunt closure occurred mainly in infants with intrahepatic shunts. Therapeutic interventions included shunt closure by surgery or interventional radiology techniques (35%) and liver transplantation (10%) leading to an improvement of symptoms in the majority. These findings mirror the observations in our own patients. In this largest review of the reported clinical experience, we identify that children with CPSS may present with otherwise unexplained developmental delay, encephalopathy, pulmonary hypertension, hypoxemia, or liver tumors. When CPSS is diagnosed, children should be screened for all of these complications. Spontaneous closure of intrahepatic shunts may occur in infancy. Closure of the shunt is indicated in symptomatic patients and is associated with a favorable outcome.

Investigation of human multiple sclerosis lesions using high resolution spectrally unmixed CARS microscopy

NASA Astrophysics Data System (ADS)

Poon, Kelvin W.; Brideau, Craig; Teo, Wulin; Schenk, Geert J.; Klaver, Roel; Klauser, Antoine M.; Kawasoe, Jean H.; Geurts, Jeroen J. G.; Stys, Peter K.

2013-03-01

The pathology of multiple sclerosis (MS) involves both the gray and white matter regions of the brain and spinal cord. It is characterized by various combinations of demyelination, inflammatory infiltration, axonal degeneration, and later gliosis in chronic lesions. While acute and chronic white matter plaques are well characterized and easily identified, evidence indicates that the CNS of MS patients may be globally altered, with subtle abnormalities found in grossly normal appearing white matter (NAWM) and in diffusely abnormal white matter (DAWM) where histochemical stains and advanced magnetic resonance imaging indicate altered tissue composition. Thus, the prototypical acute inflammatory lesion may merely represent the most obvious manifestation of a chronic widespread involvement of the CNS, which is difficult to examine reliably. The current study deals with the microstructure and biochemistry of demyelination, remyelination and axonal loss in various regions of post-mortem human MS brain, including NAWM, areas of remyelination and more typical acute and chronic lesions. The myelin sheath, neuroglia and perivascular spaces were investigated using a novel Coherent Anti-Stokes Raman Scattering (CARS) microscope with simultaneous Two-Photon Excited Fluorescence (TPEF) imaging. The active CH stretching region between 2800 and 3000 cm-1 was probed to provide chemically specific, high resolution, label-free imaging pertaining to the progression of the disease. CARS data were correlated with TPEF and conventional histochemical and immunohistochemical stains. Our novel CARS microscopy system provides detailed morphological and biochemical information regarding CNS pathology in MS and that may be applicable to a broad range of other human brain and spinal cord disorders.

Disrupted functional and structural networks in cognitively normal elderly subjects with the APOE ɛ4 allele.

PubMed

Chen, Yaojing; Chen, Kewei; Zhang, Junying; Li, Xin; Shu, Ni; Wang, Jun; Zhang, Zhanjun; Reiman, Eric M

2015-03-13

As the Apolipoprotein E (APOE) ɛ4 allele is a major genetic risk factor for sporadic Alzheimer's disease (AD), which has been suggested as a disconnection syndrome manifested by the disruption of white matter (WM) integrity and functional connectivity (FC), elucidating the subtle brain structural and functional network changes in cognitively normal ɛ4 carriers is essential for identifying sensitive neuroimaging based biomarkers and understanding the preclinical AD-related abnormality development. We first constructed functional network on the basis of resting-state functional magnetic resonance imaging and a structural network on the basis of diffusion tensor image. Using global, local and nodal efficiencies of these two networks, we then examined (i) the differences of functional and WM structural network between cognitively normal ɛ4 carriers and non-carriers simultaneously, (ii) the sensitivity of these indices as biomarkers, and (iii) their relationship to behavior measurements, as well as to cholesterol level. For ɛ4 carriers, we found reduced global efficiency significantly in WM and marginally in FC, regional FC dysfunctions mainly in medial temporal areas, and more widespread for WM network. Importantly, the right parahippocampal gyrus (PHG.R) was the only region with simultaneous functional and structural damage, and the nodal efficiency of PHG.R in WM network mediates the APOE ɛ4 effect on memory function. Finally, the cholesterol level correlated with WM network differently than with the functional network in ɛ4 carriers. Our results demonstrated ɛ4-specific abnormal structural and functional patterns, which may potentially serve as biomarkers for early detection before the onset of the disease.

Wanting to Be Different Predicts Nonmotivated Change: Actual-Desired Self-Discrepancies and Susceptibility to Subtle Change Inductions.

PubMed

DeMarree, Kenneth G; Rios, Kimberly; Randell, J Adam; Wheeler, S Christian; Reich, Darcy A; Petty, Richard E

2016-12-01

Actual-desired discrepancies in people's self-concepts represent structural incongruities in their self-representations that can lead people to experience subjective conflict. Theory and research suggest that structural incongruities predict susceptibility to subtle influences like priming and conditioning. Although typically examined for their motivational properties, we hypothesized that because self-discrepancies represent structural incongruities in people's self-concepts, they should also predict susceptibility to subtle influences on people's active self-views. Across three studies, we found that subtle change inductions (self-evaluative conditioning and priming) exerted greater impact on active self-perceptions and behavior as actual-desired self-discrepancies increased in magnitude. Exploratory analyses suggested that these changes occurred regardless of the compatibility of the change induction with individuals' desired self-views. © 2016 by the Society for Personality and Social Psychology, Inc.

Sequential involvement of the nervous system in subacute combined degeneration.

PubMed

Minn, Yang-Ki; Kim, Seung-Min; Kim, Se-Hoon; Kwon, Ki-Han; Sunwoo, Il-Nam

2012-03-01

Subacute combined degeneration (SCD) involves progressive degeneration of the spinal cord, optic nerve, and peripheral nerves. Vitamin B12 (VB12) is a co-factor in myelin synthesis. Because each cell that constitutes the myelin component in the central nervous system and peripheral nervous system is different, it is improbable that these cells undergo simultaneous degeneration. However, the sequence of degeneration in SCD has not been established. In this study, we analysed medical records and electrophysiological data of patients who showed neurological symptoms and whose serum VB12 levels were lower than 200 pg/mL. We enrolled 49 patients in this study. Their mean VB12 level was 68.3 pg/mL. Somatosensory evoked potential (SEP) study showed abnormal findings in 38 patients. Of the 40 patients who underwent visual evoked potential (VEP) study, 14 showed abnormal responses. Eighteen patients showed abnormal findings on a nerve conduction study (NCS). In this study, abnormal posterior tibial nerve SEPs only were seen in 16 patients, median nerve SEPs only were seen in 3 patients, abnormal VEPs only in two, and abnormal NCS responses in one patient. No patient complained of cognitive symptoms. In SCD, degeneration appears to progress in the following order: lower spinal cord, cervical spinal cord, peripheral nerve/optic nerve, and finally, the brain.

Asymmetry in auditory and spatial attention span in normal elderly genetically at risk for Alzheimer's disease.

PubMed

Jacobson, Mark W; Delis, Dean C; Bondi, Mark W; Salmon, David P

2005-02-01

Some studies of elderly individuals with the ApoE-e4 genotype noted subtle deficits on tests of attention such as the WAIS-R Digit Span subtest, but these findings have not been consistently reported. One possible explanation for the inconsistent results could be the presence of subgroups of e4+ individuals with asymmetric cognitive profiles (i.e., significant discrepancies between verbal and visuospatial skills). Comparing genotype groups with individual, modality-specific tests might obscure subtle differences between verbal and visuospatial attention in these asymmetric subgroups. In this study, we administered the WAIS-R Digit Span and WMS-R Visual Memory Span subtests to 21 nondemented elderly e4+ individuals and 21 elderly e4- individuals matched on age, education, and overall cognitive ability. We hypothesized that a) the e4+ group would show a higher incidence of asymmetric cognitive profiles when comparing Digit Span/Visual Memory Span performance relative to the e4- group; and (b) an analysis of individual test performance would fail to reveal differences between the two subject groups. Although the groups' performances were comparable on the individual attention span tests, the e4+ group showed a significantly larger discrepancy between digit span and spatial span scores compared to the e4- group. These findings suggest that contrast measures of modality-specific attentional skills may be more sensitive to subtle group differences in at-risk groups, even when the groups do not differ on individual comparisons of standardized test means. The increased discrepancy between verbal and visuospatial attention may reflect the presence of "subgroups" within the ApoE-e4 group that are qualitatively similar to asymmetric subgroups commonly associated with the earliest stages of AD.

Abnormal pressures as hydrodynamic phenomena

USGS Publications Warehouse

Neuzil, C.E.

1995-01-01

So-called abnormal pressures, subsurface fluid pressures significantly higher or lower than hydrostatic, have excited speculation about their origin since subsurface exploration first encountered them. Two distinct conceptual models for abnormal pressures have gained currency among earth scientists. The static model sees abnormal pressures generally as relict features preserved by a virtual absence of fluid flow over geologic time. The hydrodynamic model instead envisions abnormal pressures as phenomena in which flow usually plays an important role. This paper develops the theoretical framework for abnormal pressures as hydrodynamic phenomena, shows that it explains the manifold occurrences of abnormal pressures, and examines the implications of this approach. -from Author

The incidence and influence of abnormal styloid conditions on the etiology of craniomandibular functional disorders.

PubMed

Krennmair, G; Piehslinger, E

1999-10-01

This study aimed to examine the incidence and influence of craniomandibular functional disorders caused by abnormal styloid-stylohyoid chains. Seven hundred sixty-five patients with temporomandibular joint (TMJ) disorders were divided into two groups (with and without radiographically visible abnormal styloid conditions). In the group with abnormal stylohyoid conditions, the etiology of TMJ disorders was further subdivided into poly-, oligo- and monoetiological factors, and, after this classification, evaluated regarding a clear, possible or unlikely involvement of abnormal stylohyoid conditions in TMJ disorders. One hundred thirty-six out of 765 patients presented abnormal styloid-stylohyoid chains. One hundred five of the patients (77.2%) demonstrated polyetiological causes of TMJ symptoms with an unlikely involvement of the abnormal styloid-stylohyoid chain. Twenty-nine of the patients (21.3%) showed oligoetiological causes with possible involvement of the abnormal styloid-stylohyoid chain. In two patients (1.5%), the abnormal styloid conditions showed up as the only definite cause of TMJ symptoms (monoetiological). Detailed knowledge of variations and possible effects of suprahyoid structures is important for an accurate diagnosis of TMJ disorders. All in all, the incidence of a stylohyoid involvement in TMJ disorders is very low. However, after an initial subdivision into abnormal and normal stylohyoid conditions, the incidence of pathological stylohyoid chains gains significant importance in the etiology of TMJ disorders.

Tuning and Freezing Disorder in Photonic Crystals using Percolation Lithography.

PubMed

Burgess, Ian B; Abedzadeh, Navid; Kay, Theresa M; Shneidman, Anna V; Cranshaw, Derek J; Lončar, Marko; Aizenberg, Joanna

2016-01-21

Although common in biological systems, synthetic self-assembly routes to complex 3D photonic structures with tailored degrees of disorder remain elusive. Here we show how liquids can be used to finely control disorder in porous 3D photonic crystals, leading to complex and hierarchical geometries. In these optofluidic crystals, dynamically tunable disorder is superimposed onto the periodic optical structure through partial wetting or evaporation. In both cases, macroscopic symmetry breaking is driven by subtle sub-wavelength variations in the pore geometry. These variations direct site-selective infiltration of liquids through capillary interactions. Incorporating cross-linkable resins into our liquids, we developed methods to freeze in place the filling patterns at arbitrary degrees of partial wetting and intermediate stages of drying. These percolation lithography techniques produced permanent photonic structures with adjustable disorder. By coupling strong changes in optical properties to subtle differences in fluid behavior, optofluidic crystals may also prove useful in rapid analysis of liquids.

Do subtle reminders of money change people's political views?

PubMed

Rohrer, Doug; Pashler, Harold; Harris, Christine R

2015-08-01

A number of researchers have reported studies showing that subtle reminders of money can alter behaviors and beliefs that are seemingly unrelated to money. In 1 set of studies published in this journal, Caruso, Vohs, Baxter, and Waytz (2013) found that incidental exposures to money led subjects to indicate greater support for inequality, socioeconomic differences, group-based discrimination, and free market economies. We conducted high-powered replication attempts of these 4 money priming effects and found no evidence of priming (weighted Cohen's d = 0.03). We later learned that Caruso et al. also found several null effects in their line of research that were not reported in the original article. In addition, the money priming effect observed in the first study of Caruso et al. was included in the Many Labs Replication Project (Klein et al., 2014), and only 1 of the 36 labs was able to find the effect. (c) 2015 APA, all rights reserved).

Implicit Age Cues in Resumes: Subtle Effects on Hiring Discrimination

PubMed Central

Derous, Eva; Decoster, Jeroen

2017-01-01

Anonymous resume screening, as assumed, does not dissuade age discriminatory effects. Building on job market signaling theory, this study investigated whether older applicants may benefit from concealing explicitly mentioned age signals on their resumes (date of birth) or whether more implicit/subtle age cues on resumes (older-sounding names/old-fashioned extracurricular activities) may lower older applicants’ hirability ratings. An experimental study among 610 HR professionals using a mixed factorial design showed hiring discrimination of older applicants based on implicit age cues in resumes. This effect was more pronounced for older raters. Concealing one’s date of birth led to overall lower ratings. Study findings add to the limited knowledge on the effects of implicit age cues on hiring discrimination in resume screening and the usefulness of anonymous resume screening in the context of age. Implications for research and practice are discussed. PMID:28848463

Words That Move Us. The Effects of Sentences on Body Sway

PubMed Central

Stins, John F.; Marmolejo-Ramos, Fernando; Hulzinga, Femke; Wenker, Eric; Cañal-Bruland, Rouwen

2017-01-01

According to the embodied cognition perspective, cognitive systems and perceptuo-motor systems are deeply intertwined and exert a causal effect on each other. A prediction following from this idea is that cognitive activity can result in subtle changes in observable movement. In one experiment, we tested whether reading various sentences resulted in changes in postural sway. Sentences symbolized various human activities involving high, low, or no physical effort. Dutch participants stood upright on a force plate, measuring the body center of pressure, while reading a succession of sentences. High physical effort sentences resulted in more postural sway (greater SD) than low physical effort sentences. This effect only showed up in medio-lateral sway but not anterio-posterior sway. This suggests that sentence comprehension was accompanied by subtle motoric activity, likely mirroring the various activities symbolized in the sentences. We conclude that semantic processing reaches the motor periphery, leading to increased postural activity. PMID:28713451

A Review of Magnetic Resonance Imaging and Diffusion Tensor Imaging Findings in Mild Traumatic Brain Injury

PubMed Central

Shenton, ME; Hamoda, HM; Schneiderman, JS; Bouix, S; Pasternak, O; Rathi, Y; M-A, Vu; Purohit, MP; Helmer, K; Koerte, I; Lin, AP; C-F, Westin; Kikinis, R; Kubicki, M; Stern, RA; Zafonte, R

2013-01-01

Mild traumatic brain injury (mTBI), also referred to as concussion, remains a controversial diagnosis because the brain often appears quite normal on conventional computed tomography (CT) and magnetic resonance imaging (MRI) scans. Such conventional tools, however, do not adequately depict brain injury in mTBI because they are not sensitive to detecting diffuse axonal injuries (DAI), also described as traumatic axonal injuries (TAI), the major brain injuries in mTBI. Furthermore, for the 15 to 30% of those diagnosed with mTBI on the basis of cognitive and clinical symptoms, i.e., the “miserable minority,” the cognitive and physical symptoms do not resolve following the first three months post-injury. Instead, they persist, and in some cases lead to long-term disability. The explanation given for these chronic symptoms, i.e., postconcussive syndrome, particularly in cases where there is no discernible radiological evidence for brain injury, has led some to posit a psychogenic origin. Such attributions are made all the easier since both post-traumatic stress disorder (PTSD) and depression are frequently co-morbid with mTBI. The challenge is thus to use neuroimaging tools that are sensitive to DAI/TAI, such as diffusion tensor imaging (DTI), in order to detect brain injuries in mTBI. Of note here, recent advances in neuroimaging techniques, such as DTI, make it possible to characterize better extant brain abnormalities in mTBI. These advances may lead to the development of biomarkers of injury, as well as to staging of reorganization and reversal of white matter changes following injury, and to the ability to track and to characterize changes in brain injury over time. Such tools will likely be used in future research to evaluate treatment efficacy, given their enhanced sensitivity to alterations in the brain. In this article we review the incidence of mTBI and the importance of characterizing this patient population using objective radiological measures. Evidence is presented for detecting brain abnormalities in mTBI based on studies that use advanced neuroimaging techniques. Taken together, these findings suggest that more sensitive neuroimaging tools improve the detection of brain abnormalities (i.e., diagnosis) in mTBI. These tools will likely also provide important information relevant to outcome (prognosis), as well as play an important role in longitudinal studies that are needed to understand the dynamic nature of brain injury in mTBI. Additionally, summary tables of MRI and DTI findings are included. We believe that the enhanced sensitivity of newer and more advanced neuroimaging techniques for identifying areas of brain damage in mTBI will be important for documenting the biological basis of postconcussive symptoms, which are likely associated with subtle brain alterations, alterations that have heretofore gone undetected due to the lack of sensitivity of earlier neuroimaging techniques. Nonetheless, it is noteworthy to point out that detecting brain abnormalities in mTBI does not mean that other disorders of a more psychogenic origin are not co-morbid with mTBI and equally important to treat. They arguably are. The controversy of psychogenic versus physiogenic, however, is not productive because the psychogenic view does not carefully consider the limitations of conventional neuroimaging techniques in detecting subtle brain injuries in mTBI, and the physiogenic view does not carefully consider the fact that PTSD and depression, and other co-morbid conditions, may be present in those suffering from mTBI. Finally, we end with a discussion of future directions in research that will lead to the improved care of patients diagnosed with mTBI. PMID:22438191

Effects of Early Motor Intervention in the Prone Position of Full-Term Infants through the First Year of Life.

ERIC Educational Resources Information Center

Douret, L.

1993-01-01

Full-term infants who had slept in the prone position since birth were followed to detect early postural abnormalities and differentiate potential peripheral abnormality from abnormalities of a central origin. Results showed that disappearance of initial signs of abnormality appeared to be muscular, and symptoms disappeared faster when a motor…

Self-adapted and tunable graphene strain sensors for detecting both subtle and large human motions.

PubMed

Tao, Lu-Qi; Wang, Dan-Yang; Tian, He; Ju, Zhen-Yi; Liu, Ying; Pang, Yu; Chen, Yuan-Quan; Yang, Yi; Ren, Tian-Ling

2017-06-22

Conventional strain sensors rarely have both a high gauge factor and a large strain range simultaneously, so they can only be used in specific situations where only a high sensitivity or a large strain range is required. However, for detecting human motions that include both subtle and large motions, these strain sensors can't meet the diverse demands simultaneously. Here, we come up with laser patterned graphene strain sensors with self-adapted and tunable performance for the first time. A series of strain sensors with either an ultrahigh gauge factor or a preferable strain range can be fabricated simultaneously via one-step laser patterning, and are suitable for detecting all human motions. The strain sensors have a GF of up to 457 with a strain range of 35%, or have a strain range of up to 100% with a GF of 268. Most importantly, the performance of the strain sensors can be easily tuned by adjusting the patterns of the graphene, so that the sensors can meet diverse demands in both subtle and large motion situations. The graphene strain sensors show significant potential in applications such as wearable electronics, health monitoring and intelligent robots. Furthermore, the facile, fast and low-cost fabrication method will make them possible and practical to be used for commercial applications in the future.

Time dependent neural network models for detecting changes of state in complex processes: applications in earth sciences and astronomy.

PubMed

Valdés, Julio J; Bonham-Carter, Graeme

2006-03-01

A computational intelligence approach is used to explore the problem of detecting internal state changes in time dependent processes; described by heterogeneous, multivariate time series with imprecise data and missing values. Such processes are approximated by collections of time dependent non-linear autoregressive models represented by a special kind of neuro-fuzzy neural network. Grid and high throughput computing model mining procedures based on neuro-fuzzy networks and genetic algorithms, generate: (i) collections of models composed of sets of time lag terms from the time series, and (ii) prediction functions represented by neuro-fuzzy networks. The composition of the models and their prediction capabilities, allows the identification of changes in the internal structure of the process. These changes are associated with the alternation of steady and transient states, zones with abnormal behavior, instability, and other situations. This approach is general, and its sensitivity for detecting subtle changes of state is revealed by simulation experiments. Its potential in the study of complex processes in earth sciences and astrophysics is illustrated with applications using paleoclimate and solar data.

Brain-specific Foxp1 deletion impairs neuronal development and causes autistic-like behaviour.

PubMed

Bacon, C; Schneider, M; Le Magueresse, C; Froehlich, H; Sticht, C; Gluch, C; Monyer, H; Rappold, G A

2015-05-01

Neurodevelopmental disorders are multi-faceted and can lead to intellectual disability, autism spectrum disorder and language impairment. Mutations in the Forkhead box FOXP1 gene have been linked to all these disorders, suggesting that it may play a central role in various cognitive and social processes. To understand the role of Foxp1 in the context of neurodevelopment leading to alterations in cognition and behaviour, we generated mice with a brain-specific Foxp1 deletion (Nestin-Cre(Foxp1-/-)mice). The mutant mice were viable and allowed for the first time the analysis of pre- and postnatal neurodevelopmental phenotypes, which included a pronounced disruption of the developing striatum and more subtle alterations in the hippocampus. More detailed analysis in the CA1 region revealed abnormal neuronal morphogenesis that was associated with reduced excitability and an imbalance of excitatory to inhibitory input in CA1 hippocampal neurons in Nestin-Cre(Foxp1-/-) mice. Foxp1 ablation was also associated with various cognitive and social deficits, providing new insights into its behavioural importance.

Scurvy in the present times: vitamin C allergy leading to strict fast food diet.

PubMed

Shaath, Tarek; Fischer, Ryan; Goeser, Megan; Rajpara, Anand; Aires, Daniel

2016-01-15

Scurvy results from a deficiency of vitamin C, a nutrient otherwise known as ascorbic acid. Today, scurvy is rare yet emerges in select patients. The patient reported herein developed scurvy secondary to deliberate avoidance of vitamin C-rich foods. Classic cutaneous manifestations of scurvy include follicular hyperkeratosis and perifollicular hemorrhage encompassing coiled "corkscrew" hairs and hairs bent into "swan-neck" deformities. Ecchymoses, purpura, and petechiae are also characteristically prominent. Classic oral abnormalities include erythematous, swollen gingivae that hemorrhage from subtle microtrauma.Subungual linear splinter hemorrhages may also manifest as a sign of the disease. To establish the diagnosis requirements include characteristic physical exam findings, evidence of inadequate dietary intake, and rapid reversal of symptoms upon supplementation. Although unnecessary for diagnosis, histological findings demonstrate perifollicular inflammation and hemorrhage, fibrosis, and hyperkeratosis, amongst dilated hair follicles and keratin plugging. Although citrus fruit allergies have been historically documented, ascorbic acid has not been previously reported as an allergen. Although lacking absolute certainty, this report suggests a presumed case of ascorbic acid allergy based on patient history and favorable response to ascorbic acid desensitization therapy.

Embryologic and Fetal Development of the Human Eyelid

PubMed Central

Abdulhafez, Mohamed H.; Fouad, Yousef A.; Dutton, Jonathan J.

2016-01-01

Purpose: To review the recent data about eyelid morphogenesis, and outline a timeline for eyelid development from the very early stages during embryonic life till final maturation of the eyelid late in fetal life. Methods: The authors extensively review major studies detailing human embryologic and fetal eyelid morphogenesis. These studies span almost a century and include some more recent cadaver studies. Numerous studies in the murine model have helped to better understand the molecular signals that govern eyelid embryogenesis. The authors summarize the current findings in molecular biology, and highlight the most significant studies in mice regarding the multiple and interacting signaling pathways involved in regulating normal eyelid morphogenesis. Results: Eyelid morphogenesis involves a succession of subtle yet strictly regulated morphogenetic episodes of tissue folding, proliferation, contraction, and even migration, which may occur simultaneously or in succession. Conclusions: Understanding the extraordinary process of building eyelid tissue in embryonic life, and deciphering its underlying signaling machinery has far reaching clinical implications beyond understanding the developmental abnormalities involving the eyelids, and may pave the way for achieving scar-reducing therapies in adult mammalian wounds, or control the spread of malignancies. PMID:27124372

The Mechanisms of Movement Control and Time Estimation in Cervical Dystonia Patients

PubMed Central

Lungu, Ovidiu V.; Shaw, Daniel J.; Kasparek, Tomas; Bareš, Martin

2013-01-01

Traditionally, the pathophysiology of cervical dystonia has been regarded mainly in relation to neurochemical abnormities in the basal ganglia. Recently, however, substantial evidence has emerged for cerebellar involvement. While the absence of neurological “cerebellar signs” in most dystonia patients may be considered at least provoking, there are more subtle indications of cerebellar dysfunction in complex, demanding tasks. Specifically, given the role of the cerebellum in the neural representation of time, in the millisecond range, dysfunction to this structure is considered to be of greater importance than dysfunction of the basal ganglia. In the current study, we investigated the performance of cervical dystonia patients on a computer task known to engage the cerebellum, namely, the interception of a moving target with changing parameters (speed, acceleration, and angle) with a simple response (pushing a button). The cervical dystonia patients achieved significantly worse results than a sample of healthy controls. Our results suggest that the cervical dystonia patients are impaired at integrating incoming visual information with motor responses during the prediction of upcoming actions, an impairment we interpret as evidence of cerebellar dysfunction. PMID:24198973

Advances in Cochlear Implant Telemetry: Evoked Neural Responses, Electrical Field Imaging, and Technical Integrity

PubMed Central

Mens, Lucas H. M.

2007-01-01

During the last decade, cochlear implantation has evolved into a well-established treatment of deafness, predominantly because of many improvements in speech processing and the controlled excitation of the auditory nerve. Cochlear implants now also feature telemetry, which is highly useful to monitor the proper functioning of the implanted electronics and electrode contacts. Telemetry can also support the clinical management in young children and difficult cases where neural unresponsiveness is suspected. This article will review recent advances in the telemetry of the electrically evoked compound action potential that have made these measurements simple and routine procedures in most cases. The distribution of the electrical stimulus itself sampled by “electrical field imaging” reveals general patterns of current flow in the normal cochlea and gross abnormalities in individual patients; models have been developed to derive more subtle insights from an individual electrical field imaging. Finally, some thoughts are given to the extended application of telemetry, for example, in monitoring the neural responses or in combination with other treatments of the deaf ear. PMID:17709572

Ambiguity domain-based identification of altered gait pattern in ALS disorder

NASA Astrophysics Data System (ADS)

Sugavaneswaran, L.; Umapathy, K.; Krishnan, S.

2012-08-01

The onset of a neurological disorder, such as amyotrophic lateral sclerosis (ALS), is so subtle that the symptoms are often overlooked, thereby ruling out the option of early detection of the abnormality. In the case of ALS, over 75% of the affected individuals often experience awkwardness when using their limbs, which alters their gait, i.e. stride and swing intervals. The aim of this work is to suitably represent the non-stationary characteristics of gait (fluctuations in stride and swing intervals) in order to facilitate discrimination between normal and ALS subjects. We define a simple-yet-representative feature vector space by exploiting the ambiguity domain (AD) to achieve efficient classification between healthy and pathological gait stride interval. The stride-to-stride fluctuations and the swing intervals of 16 healthy control and 13 ALS-affected subjects were analyzed. Three features that are representative of the gait signal characteristics were extracted from the AD-space and are fed to linear discriminant analysis and neural network classifiers, respectively. Overall, maximum accuracies of 89.2% (LDA) and 100% (NN) were obtained in classifying the ALS gait.

Analysis of motor fan radiated sound and vibration waveform by automatic pattern recognition technique using "Mahalanobis distance"

NASA Astrophysics Data System (ADS)

Toma, Eiji

2018-06-01

In recent years, as the weight of IT equipment has been reduced, the demand for motor fans for cooling the interior of electronic equipment is on the rise. Sensory test technique by inspectors is the mainstream for quality inspection of motor fans in the field. This sensory test requires a lot of experience to accurately diagnose differences in subtle sounds (sound pressures) of the fans, and the judgment varies depending on the condition of the inspector and the environment. In order to solve these quality problems, development of an analysis method capable of quantitatively and automatically diagnosing the sound/vibration level of a fan is required. In this study, it was clarified that the analysis method applying the MT system based on the waveform information of noise and vibration is more effective than the conventional frequency analysis method for the discrimination diagnosis technology of normal and abnormal items. Furthermore, it was found that due to the automation of the vibration waveform analysis system, there was a factor influencing the discrimination accuracy in relation between the fan installation posture and the vibration waveform.

Array-CGH in children with mild intellectual disability: a population-based study.

PubMed

Coutton, Charles; Dieterich, Klaus; Satre, Véronique; Vieville, Gaëlle; Amblard, Florence; David, Marie; Cans, Christine; Jouk, Pierre-Simon; Devillard, Francoise

2015-01-01

Intellectual disability (ID) is characterized by limitation in intellectual function and adaptive behavior, with onset in childhood. Frequent identifiable causes of ID originate from chromosomal imbalances. During the last years, array-CGH has successfully contributed to improve the diagnostic detection rate of genetic abnormalities in patients with ID. Most array-CGH studies focused on patients with moderate or severe intellectual disability. Studies on genetic etiology in children with mild intellectual disability (ID) are very rare. We performed array-CGH analysis in 66 children with mild intellectual disability assessed in a population-based study and for whom no genetic etiology was identified. We found one or more copy number variations (CNVs) in 20 out of 66 (~30 %) patients with a mild ID. In eight of them (~12 %), the CNVs were certainly responsible for the phenotype and in six they were potentially pathogenic for ID. Altogether, array-CGH helped to determine the etiology of ID in 14 patients (~21 %). Our results underscore the clinical relevance of array-CGH to investigate the etiology of isolated idiopathic mild ID in patients or associated with even subtle dysmorphic features or congenital malformations.

Diffusion tensor imaging of the inferior colliculus and brainstem auditory-evoked potentials in preterm infants.

PubMed

Reiman, Milla; Parkkola, Riitta; Johansson, Reijo; Jääskeläinen, Satu K; Kujari, Harry; Lehtonen, Liisa; Haataja, Leena; Lapinleimu, Helena

2009-08-01

Preterm and low-birth-weight infants have an increased risk of sensorineural hearing loss. Brainstem auditory-evoked potentials (BAEP) are an effective method to detect subtle deficits in impulse conduction in the auditory pathway. Abnormalities on diffusion tensor imaging (DTI) have been shown to be associated with perinatal white-matter injury and reduced fractional anisotropy (FA) has been reported in patients with sensorineural hearing loss. To evaluate the possibility of a correlation between BAEP and DTI of the inferior colliculus in preterm infants. DTI at term age and BAEP measurements were performed on all very-low-birth-weight or very preterm study infants (n=56). FA and apparent diffusion coefficient (ADC) of the inferior colliculus were measured from the DTI. Shorter BAEP wave I, III, and V latencies and I-III and I-V intervals and higher wave V amplitude correlated with higher FA of the inferior colliculus. The association between the DTI findings of the inferior colliculus and BAEP responses suggests that DTI can be used to assess the integrity of the auditory pathway in preterm infants.

Depression in Parkinson's disease: impediments to recognition and treatment options.

PubMed

Poewe, W; Luginger, E

1999-01-01

By some estimates, nearly half of patients with PD also suffer depression. Because features of PD frequently overlap with typical manifestations of major affective disorder (or mild dysthymia), both diagnosis and treatment of this comorbidity are challenging. Some of these interactive features include cognitive and speech deficits and impairments in emotional expression (e.g., PD-related facial masking) or processing. Parkinsonian depression probably is caused by an independent abnormality rather than as a maladaptive response to disease, in that the degree of depression is not correlated with PD severity. Prognostically, depressive features (e.g., introversion, inflexibility) may represent a subtle premorbid state heralding the onset of PD or an accelerated cognitive decline thereafter. Therapeutic mainstays for parkinsonian depression include psychosocial counseling at the time of PD diagnosis (and during advanced stages of PD) as well as appropriate medication regimens, the relative clinical efficacy of which remain a matter of ongoing clinical inquiry: levodopa, dopamine agonists, selegilene, tricyclic antidepressants, and selective serotonin reuptake inhibitors). This review formulates a rational treatment algorithm to assist in clinical management of parkinsonian depression, an enormously complex clinical entity.

Intelligent Process Abnormal Patterns Recognition and Diagnosis Based on Fuzzy Logic.

PubMed

Hou, Shi-Wang; Feng, Shunxiao; Wang, Hui

2016-01-01

Locating the assignable causes by use of the abnormal patterns of control chart is a widely used technology for manufacturing quality control. If there are uncertainties about the occurrence degree of abnormal patterns, the diagnosis process is impossible to be carried out. Considering four common abnormal control chart patterns, this paper proposed a characteristic numbers based recognition method point by point to quantify the occurrence degree of abnormal patterns under uncertain conditions and a fuzzy inference system based on fuzzy logic to calculate the contribution degree of assignable causes with fuzzy abnormal patterns. Application case results show that the proposed approach can give a ranked causes list under fuzzy control chart abnormal patterns and support the abnormity eliminating.

Scene and human face recognition in the central vision of patients with glaucoma

PubMed Central

Aptel, Florent; Attye, Arnaud; Guyader, Nathalie; Boucart, Muriel; Chiquet, Christophe; Peyrin, Carole

2018-01-01

Primary open-angle glaucoma (POAG) firstly mainly affects peripheral vision. Current behavioral studies support the idea that visual defects of patients with POAG extend into parts of the central visual field classified as normal by static automated perimetry analysis. This is particularly true for visual tasks involving processes of a higher level than mere detection. The purpose of this study was to assess visual abilities of POAG patients in central vision. Patients were assigned to two groups following a visual field examination (Humphrey 24–2 SITA-Standard test). Patients with both peripheral and central defects and patients with peripheral but no central defect, as well as age-matched controls, participated in the experiment. All participants had to perform two visual tasks where low-contrast stimuli were presented in the central 6° of the visual field. A categorization task of scene images and human face images assessed high-level visual recognition abilities. In contrast, a detection task using the same stimuli assessed low-level visual function. The difference in performance between detection and categorization revealed the cost of high-level visual processing. Compared to controls, patients with a central visual defect showed a deficit in both detection and categorization of all low-contrast images. This is consistent with the abnormal retinal sensitivity as assessed by perimetry. However, the deficit was greater for categorization than detection. Patients without a central defect showed similar performances to the controls concerning the detection and categorization of faces. However, while the detection of scene images was well-maintained, these patients showed a deficit in their categorization. This suggests that the simple loss of peripheral vision could be detrimental to scene recognition, even when the information is displayed in central vision. This study revealed subtle defects in the central visual field of POAG patients that cannot be predicted by static automated perimetry assessment using Humphrey 24–2 SITA-Standard test. PMID:29481572

Cerebellar abnormalities typical of methylmercury poisoning in a fledged saltmarsh sparrow, Ammodramus caudacutus.

PubMed

Scoville, Sheila A; Lane, Oksana P

2013-05-01

A fledged, 12-15 day-old saltmarsh sparrow, Ammodramus caudacutus, was collected from an accidental kill on Cinder Island, Long Island, NY, USA. The sparrow was assessed for feather mercury levels and the brain analyzed for cerebellar abnormalities by microscopic examination. In humans, fetal Minamata disease is caused by maternal ingestion of mercury. It is characterized by disrupted and disordered cerebellar neuronal migration in the fetus or infant. Results from this sparrow show cerebellar abnormalities typical of Minamata disease. It is the first known avian or mammalian specimen taken from the wild to show the abnormalities typical of the human fetal syndrome.

The association between discrimination and health: findings on Russian, Somali and Kurdish origin populations in Finland.

PubMed

Rask, Shadia; Elo, Irma T; Koskinen, Seppo; Lilja, Eero; Koponen, Päivikki; Castaneda, Anu E

2018-06-06

The Second European Union Minorities and Discrimination Survey recently demonstrated widespread discrimination across EU countries, with high discrimination rates observed in countries like Finland. Discrimination is known to negatively impact health, but fewer studies have examined how different types of perceived discrimination are related to health. This study examines (i) the prevalence of different types of perceived discrimination among Russian, Somali and Kurdish origin populations in Finland, and (ii) the association between different types of perceived discrimination (no experiences; subtle discrimination only; overt or subtle and overt discrimination) and health (self-rated health; limiting long-term illness (LLTI) or disability; mental health symptoms). Data are from the Finnish Migrant Health and Wellbeing Study (n = 1795). Subtle discrimination implies reporting being treated with less courtesy and/or treated with less respect than others, and overt discrimination being called names or insulted and/or threatened or harassed. The prevalence of discrimination and the associations between discrimination and health were calculated with predicted margins and logistic regression. Experiences of subtle discrimination were more common than overt discrimination in all the studied groups. Subtle discrimination was reported by 29% of Somali origin persons and 35% Russian and Kurdish origin persons. The prevalence of overt discrimination ranged between 22% and 24%. Experiences of discrimination increased the odds for poor self-reported health, LLTI and mental health symptoms, particularly among those reporting subtle discrimination only. To promote the health of diverse populations, actions against racism and discrimination are highly needed, including initiatives that promote shared belonging.

42 CFR 37.53 - Notification of abnormal roentgenographic findings.

Code of Federal Regulations, 2012 CFR

2012-10-01

... suggesting, enlarged heart, tuberculosis, lung cancer, or any other significant abnormal findings other than... files and the most recent examination was interpreted to show enlarged heart, tuberculosis, cancer... findings suggesting, abnormality of cardiac shape or size, tuberculosis, lung cancer, or any other...

A review of MRI findings in schizophrenia

PubMed Central

Shenton, Martha E.; Dickey, Chandlee C.; Frumin, Melissa; McCarley, Robert W.

2009-01-01

After more than 100 years of research, the neuropathology of schizophrenia remains unknown and this is despite the fact that both Kraepelin (1919/1971: Kraepelin,E., 1919/1971. Dementia praecox. Churchill Livingston Inc., New York) and Bleuler (1911/1950: Bleuler, E., 1911/1950. Dementia praecox or the group of schizophrenias. International Universities Press, New York), who first described ‘dementia praecox’ and the ‘ schizophrenias’, were convinced that schizophrenia would ultimately be linked to an organic brain disorder. Alzheimer (1897: Alzheimer, A., 1897. Beitrage zur pathologischen anatomie der hirnrinde und zur anatomischen grundlage einiger psychosen. Monatsschrift fur Psychiarie und Neurologie. 2, 82–120) was the first to investigate the neuropathology of schizophrenia, though he went on to study more tractable brain diseases. The results of subsequent neuropathological studies were disappointing because of conflicting findings. Research interest thus waned and did not flourish again until 1976, following the pivotal computer assisted tomography (CT) finding of lateral ventricular enlargement in schizophrenia by Johnstone and colleagues. Since that time significant progress has been made in brain imaging, particularly with the advent of magnetic resonance imaging (MRI), beginning with the first MRI study of schizophrenia by Smith and coworkers in 1984 (Smith, R.C., Calderon, M., Ravichandran, G.K., et al. (1984). Nuclear magnetic resonance in schizophrenia: A preliminary study. Psychiatry Res. 12, 137–147). MR in vivo imaging of the brain now confirms brain abnormalities in schizophrenia. The 193 peer reviewed MRI studies reported in the current review span the period from 1988 to August, 2000. This 12 year period has witnessed a burgeoning of MRI studies and has led to more definitive findings of brain abnormalities in schizophrenia than any other time period in the history of schizophrenia research. Such progress in defining the neuropathology of schizophrenia is largely due to advances in in vivo MRI techniques. These advances have now led to the identification of a number of brain abnormalities in schizophrenia. Some of these abnormalities confirm earlier post-mortem findings, and most are small and subtle, rather than large, thus necessitating more advanced and accurate measurement tools. These findings include ventricular enlargement (80% of studies reviewed) and third ventricle enlargement (73% of studies reviewed). There is also preferential involvement of medial temporal lobe structures (74% of studies reviewed), which include the amygdala, hippocampus, and parahippocampal gyrus, and neocortical temporal lobe regions (superior temporal gyrus) (100% of studies reviewed). When gray and white matter of superior temporal gyrus was combined, 67% of studies reported abnormalities. There was also moderate evidence for frontal lobe abnormalities (59% of studies reviewed), particularly prefrontal gray matter and orbitofrontal regions. Similarly, there was moderate evidence for parietal lobe abnormalities (60% of studies reviewed), particularly of the inferior parietal lobule which includes both supramarginal and angular gyri. Additionally, there was strong to moderate evidence for subcortical abnormalities (i.e. cavum septi pellucidi—92% of studies reviewed, basal ganglia—68% of studies reviewed, corpus callosum—63% of studies reviewed, and thalamus—42% of studies reviewed), but more equivocal evidence for cerebellar abnormalities (31% of studies reviewed). The timing of such abnormalities has not yet been determined, although many are evident when a patient first becomes symptomatic. There is, however, also evidence that a subset of brain abnormalities may change over the course of the illness. The most parsimonious explanation is that some brain abnormalities are neurodevelopmental in origin but unfold later in development, thus setting the stage for the development of the symptoms of schizophrenia. Or there may be additional factors, such as stress or neurotoxicity, that occur during adolescence or early adulthood and are necessary for the development of schizophrenia, and may be associated with neurodegenerative changes. Importantly, as several different brain regions are involved in the neuropathology of schizophrenia, new models need to be developed and tested that explain neural circuitry abnormalities effecting brain regions not necessarily structurally proximal to each other but nonetheless functionally interrelated. Future studies will likely benefit from: (1) studying more homogeneous patient groups so that the relationship between MRI findings and clinical symptoms become more meaningful; (2) studying at risk populations such as family members of patients diagnosed with schizophrenia and subjects diagnosed with schizotypal personality disorder in order to define which abnormalities are specific to schizophrenia spectrum disorders, which are the result of epiphenomena such as medication effects and chronic institutionalization, and which are needed for the development of frank psychosis; (3) examining shape differences not detectable from measuring volume alone; (4) applying newer methods such as diffusion tensor imaging to investigate abnormalities in brain connectivity and white matter fiber tracts; and, (5) using methods that analyze brain function (fMRI) and structure simultaneously. PMID:11343862

"Atypical" chronic wasting disease in PRNP genotype 225FF mule deer.

PubMed

Wolfe, Lisa L; Fox, Karen A; Miller, Michael W

2014-07-01

We compared mule deer (Odocoileus hemionus) of two different PRNP genotypes (225SS, 225FF) for susceptibility to chronic wasting disease (CWD) in the face of environmental exposure to infectivity. All three 225SS deer had immunohistochemistry (IHC)-positive tonsil biopsies by 710 days postexposure (dpe), developed classic clinical signs by 723-1,200 dpe, and showed gross and microscopic pathology, enzyme-linked immunosorbent assay (ELISA) results, and IHC staining typical of prion disease in mule deer. In contrast, although all three 225FF deer also became infected, the two individuals surviving >720 dpe had consistently negative biopsies, developed more-subtle clinical signs of CWD, and died 924 or 1,783 dpe. The 225FF deer were "suspect" by ELISA postmortem but showed negative or equivocal IHC staining of lymphoid tissues; both clinically affected 225FF deer had spongiform encephalopathy in the absence of IHC staining in the brain tissue. The experimental cases resembled three cases encountered among five additional captive 225FF deer that were not part of our experiment but also died from CWD. Aside from differences in clinical disease presentation and detection, 225FF mule deer also showed other, more-subtle, atypical traits that may help to explain the rarity of this genotype in natural populations, even in the presence of enzootic CWD.

Discrepancy between fluorescein angiography and optical coherence tomography in detection of macular disease.

PubMed

Kozak, Igor; Morrison, Victoria L; Clark, Thomas M; Bartsch, Dirk-Uwe; Lee, Byung Ro; Falkenstein, Iryna; Tammewar, Ajay M; Mojana, Francesca; Freeman, William R

2008-04-01

To compare high-resolution optical coherence tomography (OCT) and fluorescein angiography (FA) in detection of macular edema (ME) of various etiologies. In a retrospective study over a 12-month period at one retina center, data for consecutive eyes that had undergone simultaneous conventional FA (HRA; Heidelberg Engineering, Vista, CA) and StratusOCT (Carl Zeiss Meditec, Dublin, CA) to rule out ME were reviewed. A subset of patients underwent additional examination with extremely high-resolution (6-microm)/ultrahigh-speed spectral OCT/scanning laser ophthalmoscopy (OTI, Inc., Toronto, Ontario, Canada). Of 1,272 eyes, 1,208 (94.97%) had the finding of ME or subretinal fluid confirmed by both techniques. There were 49 eyes (3.86%) for which FA showed dye leakage in the macular area and OCT showed normal foveal contour. Of 10 eyes in this group that underwent imaging with ultrahigh-speed spectral OCT/scanning laser ophthalmoscopy, 8 had subtle diffuse lucencies in the retina. For 15 eyes (1.17%), OCT showed intraretinal and subretinal fluid, which was missed by FA. Both FA and high-resolution OCT are highly sensitive techniques and correlate well in detection of ME. However, there is a small chance that when performed alone they might miss existing subtle ME.

Failure to thrive as primary feature in two patients with subtle chromosomal aneuploidy: Interstitial deletion 2q33

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

Grace, K.; Mulla, W.; Stump, T.

1994-09-01

It is well known that patients with chromosomal aneuploidy present with multiple congenital anomalies and dysmorphia, and that they may have associated failure to thrive. However, rarely is failure to thrive the predominant presenting feature. We report two such patients. Patient 1 had a marked history of failure to thrive, (weight 50% for 5 1/2 months at 20 months, length 50% for 15 months at 20 months). Patient 2 was noted to be growth retarded at 2 months upon presenting to the hospital with respiratory symptoms (weight 50% for a newborn, length 50% for 36 weeks gestation). There was relativemore » head sparing in both patients. Chromosome analysis in patient 1, prompted by a negative work-up for the failure to thrive, and emerging evidence of developmental delay, revealed a 46,XY,del(2)(q32.2q33) karyotype. Chromosome analysis in patient 2, done as part of a complete workup for the failure to thrive, revealed a 46,XX,del(2)(q33.2q33.2 or q33.2q33.3) karyotype. On careful examination, subtle dysmorphic features were seen. In both patients these included a long flat philtrum, thin upper lip and high arched palate. Patient 1 also had a small posterior cleft of the palate. These patients have the smallest interstitial deletions of chromosome 2 so far reported. Their deletions overlap within 2q33 although they are not identical. Review of the literature reveals 15 patients with interstitial deletions which include 2q33. Marked growth retardation is reported in 14 of these cases. Cleft palate/abnormal uvula were frequently associated. These cases illustrate the need to include high resolution chromosomal studies as part of a complete work-up for unexplained failure to thrive.« less

Comparison of In Vivo and Ex Vivo MRI for the Detection of Structural Abnormalities in a Mouse Model of Tauopathy

PubMed Central

Holmes, Holly E.; Powell, Nick M.; Ma, Da; Ismail, Ozama; Harrison, Ian F.; Wells, Jack A.; Colgan, Niall; O'Callaghan, James M.; Johnson, Ross A.; Murray, Tracey K.; Ahmed, Zeshan; Heggenes, Morten; Fisher, Alice; Cardoso, M. Jorge; Modat, Marc; O'Neill, Michael J.; Collins, Emily C.; Fisher, Elizabeth M. C.; Ourselin, Sébastien; Lythgoe, Mark F.

2017-01-01

With increasingly large numbers of mouse models of human disease dedicated to MRI studies, compromises between in vivo and ex vivo MRI must be fully understood in order to inform the choice of imaging methodology. We investigate the application of high resolution in vivo and ex vivo MRI, in combination with tensor-based morphometry (TBM), to uncover morphological differences in the rTg4510 mouse model of tauopathy. The rTg4510 mouse also offers a novel paradigm by which the overexpression of mutant tau can be regulated by the administration of doxycycline, providing us with a platform on which to investigate more subtle alterations in morphology with morphometry. Both in vivo and ex vivo MRI allowed the detection of widespread bilateral patterns of atrophy in the rTg4510 mouse brain relative to wild-type controls. Regions of volume loss aligned with neuronal loss and pathological tau accumulation demonstrated by immunohistochemistry. When we sought to investigate more subtle structural alterations in the rTg4510 mice relative to a subset of doxycycline-treated rTg4510 mice, ex vivo imaging enabled the detection of more regions of morphological brain changes. The disadvantages of ex vivo MRI may however mitigate this increase in sensitivity: we observed a 10% global shrinkage in brain volume of the post-mortem tissues due to formalin fixation, which was most notable in the cerebellum and olfactory bulbs. However, many central brain regions were not adversely affected by the fixation protocol, perhaps due to our “in-skull” preparation. The disparity between our TBM findings from in vivo and ex vivo MRI underlines the importance of appropriate study design, given the trade-off between these two imaging approaches. We support the utility of in vivo MRI for morphological phenotyping of mouse models of disease; however, for subtler phenotypes, ex vivo offers enhanced sensitivity to discrete morphological changes. PMID:28408879

Comparison of In Vivo and Ex Vivo MRI for the Detection of Structural Abnormalities in a Mouse Model of Tauopathy.

PubMed

Holmes, Holly E; Powell, Nick M; Ma, Da; Ismail, Ozama; Harrison, Ian F; Wells, Jack A; Colgan, Niall; O'Callaghan, James M; Johnson, Ross A; Murray, Tracey K; Ahmed, Zeshan; Heggenes, Morten; Fisher, Alice; Cardoso, M Jorge; Modat, Marc; O'Neill, Michael J; Collins, Emily C; Fisher, Elizabeth M C; Ourselin, Sébastien; Lythgoe, Mark F

2017-01-01

With increasingly large numbers of mouse models of human disease dedicated to MRI studies, compromises between in vivo and ex vivo MRI must be fully understood in order to inform the choice of imaging methodology. We investigate the application of high resolution in vivo and ex vivo MRI, in combination with tensor-based morphometry (TBM), to uncover morphological differences in the rTg4510 mouse model of tauopathy. The rTg4510 mouse also offers a novel paradigm by which the overexpression of mutant tau can be regulated by the administration of doxycycline, providing us with a platform on which to investigate more subtle alterations in morphology with morphometry. Both in vivo and ex vivo MRI allowed the detection of widespread bilateral patterns of atrophy in the rTg4510 mouse brain relative to wild-type controls. Regions of volume loss aligned with neuronal loss and pathological tau accumulation demonstrated by immunohistochemistry. When we sought to investigate more subtle structural alterations in the rTg4510 mice relative to a subset of doxycycline-treated rTg4510 mice, ex vivo imaging enabled the detection of more regions of morphological brain changes. The disadvantages of ex vivo MRI may however mitigate this increase in sensitivity: we observed a 10% global shrinkage in brain volume of the post-mortem tissues due to formalin fixation, which was most notable in the cerebellum and olfactory bulbs. However, many central brain regions were not adversely affected by the fixation protocol, perhaps due to our "in-skull" preparation. The disparity between our TBM findings from in vivo and ex vivo MRI underlines the importance of appropriate study design, given the trade-off between these two imaging approaches. We support the utility of in vivo MRI for morphological phenotyping of mouse models of disease; however, for subtler phenotypes, ex vivo offers enhanced sensitivity to discrete morphological changes.

Long-term follow-up of two patients with oligocone trichromacy.

PubMed

Smirnov, Vasily; Drumare, Isabelle; Bouacha, Ikram; Puech, Bernard; Defoort-Dhellemmes, Sabine

2015-10-01

Oligocone trichromacy (OT) is an uncommon cone dysfunction disorder, the mechanism of which remains poorly understood. OT has been thought to be non-progressive, but its long-term visual outcome has been seldom reported in the literature. Our aim was to present two OT patients followed at our institution over 18 years. Complete ocular examination, color vision, visual fields, and full-field electroretinography (ERG) were performed at initial presentation and follow-up. Spectral-domain optical coherence tomography (OCT) was performed during follow-up when available at our institution. Initial ocular examination showed satisfactory visual acuities with normal fundus examination and near-to-normal color vision. However, computerized perimetry demonstrated a ring-shaped scotoma around fixation, and ERG showed a profound cone dysfunction. The discrepancy between preserved color vision and profound cone dysfunction leads to the diagnosis of OT. Subsequent follow-ups over 18 years showed subtle degradation of visual acuities along with progression of the myopia in both patients and slight worsening of color vision in one patient. Initial OCT revealed a focal interruption of the ellipsoid line along with decreased thickness of the perifoveal macula. Subsequent OCT imaging performed 2 years later did not show any macular changes. Although OT is known to be a non-progressive cone dysfunction, our results suggest that subtle degradation of the visual function might happen over time.

Sequential Involvement of the Nervous System in Subacute Combined Degeneration

PubMed Central

Minn, Yang-Ki; Kim, Seung-Min; Kim, Se-Hoon; Kwon, Ki-Han

2012-01-01

Purpose Subacute combined degeneration (SCD) involves progressive degeneration of the spinal cord, optic nerve, and peripheral nerves. Vitamin B12 (VB12) is a co-factor in myelin synthesis. Because each cell that constitutes the myelin component in the central nervous system and peripheral nervous system is different, it is improbable that these cells undergo simultaneous degeneration. However, the sequence of degeneration in SCD has not been established. Materials and Methods In this study, we analysed medical records and electrophysiological data of patients who showed neurological symptoms and whose serum VB12 levels were lower than 200 pg/mL. Results We enrolled 49 patients in this study. Their mean VB12 level was 68.3 pg/mL. Somatosensory evoked potential (SEP) study showed abnormal findings in 38 patients. Of the 40 patients who underwent visual evoked potential (VEP) study, 14 showed abnormal responses. Eighteen patients showed abnormal findings on a nerve conduction study (NCS). In this study, abnormal posterior tibial nerve SEPs only were seen in 16 patients, median nerve SEPs only were seen in 3 patients, abnormal VEPs only in two, and abnormal NCS responses in one patient. No patient complained of cognitive symptoms. Conclusion In SCD, degeneration appears to progress in the following order: lower spinal cord, cervical spinal cord, peripheral nerve/optic nerve, and finally, the brain. PMID:22318813

Mutations in KIAA0586 Cause Lethal Ciliopathies Ranging from a Hydrolethalus Phenotype to Short-Rib Polydactyly Syndrome

PubMed Central

Alby, Caroline; Piquand, Kevin; Huber, Céline; Megarbané, André; Ichkou, Amale; Legendre, Marine; Pelluard, Fanny; Encha-Ravazi, Ferechté; Abi-Tayeh, Georges; Bessières, Bettina; El Chehadeh-Djebbar, Salima; Laurent, Nicole; Faivre, Laurence; Sztriha, László; Zombor, Melinda; Szabó, Hajnalka; Failler, Marion; Garfa-Traore, Meriem; Bole, Christine; Nitschké, Patrick; Nizon, Mathilde; Elkhartoufi, Nadia; Clerget-Darpoux, Françoise; Munnich, Arnold; Lyonnet, Stanislas; Vekemans, Michel; Saunier, Sophie; Cormier-Daire, Valérie; Attié-Bitach, Tania; Thomas, Sophie

2015-01-01

KIAA0586, the human ortholog of chicken TALPID3, is a centrosomal protein that is essential for primary ciliogenesis. Its disruption in animal models causes defects attributed to abnormal hedgehog signaling; these defects include polydactyly and abnormal dorsoventral patterning of the neural tube. Here, we report homozygous mutations of KIAA0586 in four families affected by lethal ciliopathies ranging from a hydrolethalus phenotype to short-rib polydactyly. We show defective ciliogenesis, as well as abnormal response to SHH-signaling activation in cells derived from affected individuals, consistent with a role of KIAA0586 in primary cilia biogenesis. Whereas centriolar maturation seemed unaffected in mutant cells, we observed an abnormal extended pattern of CEP290, a centriolar satellite protein previously associated with ciliopathies. Our data show the crucial role of KIAA0586 in human primary ciliogenesis and subsequent abnormal hedgehog signaling through abnormal GLI3 processing. Our results thus establish that KIAA0586 mutations cause lethal ciliopathies. PMID:26166481

Cluster structure in the correlation coefficient matrix can be characterized by abnormal eigenvalues

NASA Astrophysics Data System (ADS)

Nie, Chun-Xiao

2018-02-01

In a large number of previous studies, the researchers found that some of the eigenvalues of the financial correlation matrix were greater than the predicted values of the random matrix theory (RMT). Here, we call these eigenvalues as abnormal eigenvalues. In order to reveal the hidden meaning of these abnormal eigenvalues, we study the toy model with cluster structure and find that these eigenvalues are related to the cluster structure of the correlation coefficient matrix. In this paper, model-based experiments show that in most cases, the number of abnormal eigenvalues of the correlation matrix is equal to the number of clusters. In addition, empirical studies show that the sum of the abnormal eigenvalues is related to the clarity of the cluster structure and is negatively correlated with the correlation dimension.

Clozapine-induced EEG abnormalities and clinical response to clozapine.

PubMed

Risby, E D; Epstein, C M; Jewart, R D; Nguyen, B V; Morgan, W N; Risch, S C; Thrivikraman, K V; Lewine, R L

1995-01-01

The authors hypothesized that patients who develop gross EEG abnormalities during clozapine treatment would have a less favorable outcome than patients who did not develop abnormal EEGs. The clinical EEGs and the Brief Psychiatric Rating Scale (BPRS) scores of 12 patients with schizophrenia and 4 patients with schizoaffective disorder were compared before and during treatment with clozapine. Eight patients developed significant EEG abnormalities on clozapine; 1 showed worsening of an abnormal pre-clozapine EEG; none of these subjects had clinical seizures. BPRS scores improved significantly in the group of patients who developed abnormal EEGs but not in the group who did not. Findings are consistent with previous reports of a high incidence of clozapine-induced EEG abnormalities and a positive association between these abnormalities and clinical improvement.

The usefulness of MR defecography in the evaluation of pelvic floor dysfunction: our experience using 3T MRI.

PubMed

Al-Najar, Mahasen S; Ghanem, Ahmed F; AlRyalat, Saif Aldeen S; Al-Ryalat, Nosaiba T; Alhajahjeh, Sultan O

2017-09-01

To assess the usefulness of MR defecography in evaluating pelvic floor dysfunction, and to correlate several pelvic organ abnormalities with each other and with patients' symptoms and characteristics. MR defecographic examinations performed in 3T MRI machine of 95 patients (70 females, 25 males; mean age 48) were retrospectively reviewed. Pelvic organ abnormalities from all three compartments were recorded, including the anorectal junction descent, anterior rectocele, and cystocele. These were graded according to the known HMO system in relation to the pubococcygeal line. The correlation between these different abnormalities and their relation to patient symptoms and characteristics were evaluated. Anorectal junction descent and anterior rectocele were most commonly observed, predominantly manifesting in female patients. Both were associated with abnormalities from all compartments. The middle compartment was the least affected, and its abnormality of uterine/vaginal descent tended to occur in association with the anterior compartment abnormality (cystocele). Anismus was low in incidence, and was not associated with other compartments abnormalities. Both enterocele/peritoneocele and intussusception were uncommon. MR defecography is the modality of choice in assessing pelvic floor dysfunction, because it can neatly show various pelvic organ abnormalities from all compartments in a dynamic fashion, which are frequently coexistent. It can even show clinically silent or unsuspected abnormalities which can impact the management of patients.

Pyrosequencing reveals the microbial communities in the Red Sea sponge Carteriospongia foliascens and their impressive shifts in abnormal tissues.

PubMed

Gao, Zhao-Ming; Wang, Yong; Lee, On On; Tian, Ren-Mao; Wong, Yue Him; Bougouffa, Salim; Batang, Zenon; Al-Suwailem, Abdulaziz; Lafi, Feras F; Bajic, Vladimir B; Qian, Pei-Yuan

2014-10-01

Abnormality and disease in sponges have been widely reported, yet how sponge-associated microbes respond correspondingly remains inconclusive. Here, individuals of the sponge Carteriospongia foliascens under abnormal status were collected from the Rabigh Bay along the Red Sea coast. Microbial communities in both healthy and abnormal sponge tissues and adjacent seawater were compared to check the influences of these abnormalities on sponge-associated microbes. In healthy tissues, we revealed low microbial diversity with less than 100 operational taxonomic units (OTUs) per sample. Cyanobacteria, affiliated mainly with the sponge-specific species "Candidatus Synechococcus spongiarum," were the dominant bacteria, followed by Bacteroidetes and Proteobacteria. Intraspecies dynamics of microbial communities in healthy tissues were observed among sponge individuals, and potential anoxygenic phototrophic bacteria were found. In comparison with healthy tissues and the adjacent seawater, abnormal tissues showed dramatic increase in microbial diversity and decrease in the abundance of sponge-specific microbial clusters. The dominated cyanobacterial species Candidatus Synechococcus spongiarum decreased and shifted to unspecific cyanobacterial clades. OTUs that showed high similarity to sequences derived from diseased corals, such as Leptolyngbya sp., were found to be abundant in abnormal tissues. Heterotrophic Planctomycetes were also specifically enriched in abnormal tissues. Overall, we revealed the microbial communities of the cyanobacteria-rich sponge, C. foliascens, and their impressive shifts under abnormality.

Migraine patients consistently show abnormal vestibular bedside tests.

PubMed

Maranhão, Eliana Teixeira; Maranhão-Filho, Péricles; Luiz, Ronir Raggio; Vincent, Maurice Borges

2016-01-01

Migraine and vertigo are common disorders, with lifetime prevalences of 16% and 7% respectively, and co-morbidity around 3.2%. Vestibular syndromes and dizziness occur more frequently in migraine patients. We investigated bedside clinical signs indicative of vestibular dysfunction in migraineurs. To test the hypothesis that vestibulo-ocular reflex, vestibulo-spinal reflex and fall risk (FR) responses as measured by 14 bedside tests are abnormal in migraineurs without vertigo, as compared with controls. Cross-sectional study including sixty individuals - thirty migraineurs, 25 women, 19-60 y-o; and 30 gender/age healthy paired controls. Migraineurs showed a tendency to perform worse in almost all tests, albeit only the Romberg tandem test was statistically different from controls. A combination of four abnormal tests better discriminated the two groups (93.3% specificity). Migraine patients consistently showed abnormal vestibular bedside tests when compared with controls.

Chromosomal abnormalities as a cause of recurrent abortions in Egypt

PubMed Central

El-Dahtory, Faeza Abdel Mogib

2011-01-01

BACKGROUND: In 4%-8% of couples with recurrent abortion, at least one of the partners has chromosomal abnormality. Most spontaneous miscarriages which happen in the first and second trimesters are caused by chromosomal abnormalities. These chromosomal abnormalities may be either numerical or structural. MATERIAL AND METHODS: Cytogenetic study was done for 73 Egyptian couples who presented with recurrent abortion at Genetic Unit of Children Hospital, Mansoura University. RESULTS: We found that the frequency of chromosomal abnormalities was not significantly different from that reported worldwide. Chromosomal abnormalities were detected in 9 (6.1%) of 73 couples. Seven of chromosomal abnormalities were structural and two of them were numerical. CONCLUSION: Our results showed that 6.1% of the couples with recurrent abortion had chromosomal abnormalities, with no other abnormalities. We suggest that it is necessary to perform cytogenetic in vestigation for couples who have recurrent abortion. PMID:22090718

Subtle Messages.

ERIC Educational Resources Information Center

Tamplin de Poinsot, Nan

1999-01-01

Describes a self-portrait assignment inspired by the work of Frida Kahlo. Discusses Frida Kahlo's artwork and use of surrealist and symbolist views. States that each student had to incorporate personal symbolism in the portrait to convey a message about him or herself in a subtle manner. (CMK)

Retinal pigment epithelial changes in chronic Vogt-Koyanagi-Harada disease: fundus autofluorescence and spectral domain-optical coherence tomography findings.

PubMed

Vasconcelos-Santos, Daniel V; Sohn, Elliott H; Sadda, Srinivas; Rao, Narsing A

2010-01-01

The purpose of this study was to determine whether fundus autofluorescence (FAF) and spectral domain-optical coherence tomography (SD-OCT) imaging allow better assessment of retinal pigment epithelium and the outer retina in subjects with chronic Vogt-Koyanagi-Harada disease compared with examination and angiography alone. A cross-sectional analysis of a series of seven consecutive patients with chronic Vogt-Koyanagi-Harada disease undergoing FAF and SD-OCT was conducted. Chronic disease was defined as duration of intraocular inflammation >3 months. Color fundus photographs were correlated to FAF and SD-OCT images. The images were later correlated to fluorescein angiography and indocyanine green angiography. All patients had sunset glow fundus, which resulted in no apparent corresponding abnormality on FAF or SD-OCT. Lesions with decreased autofluorescence signal were observed in 11 eyes (85%), being associated with loss of the retinal pigment epithelium and involvement of the outer retina on SD-OCT. In 5 eyes (38%), some of these lesions were very subtle on clinical examination but easily detected by FAF. Lesions with increased autofluorescence signal were seen in 8 eyes (61.5%), showing variable involvement of the outer retina on SD-OCT and corresponding clinically to areas of retinal pigment epithelium proliferation and cystoid macular edema. Combined use of FAF and SD-OCT imaging allowed noninvasive delineation of retinal pigment epithelium/outer retina changes in patients with chronic Vogt-Koyanagi-Harada disease, which were consistent with previous histopathologic reports. Some of these changes were not apparent on clinical examination.

Marginal Iodine Deficiency Affects Dendritic Spine Development by Disturbing the Function of Rac1 Signaling Pathway on Cytoskeleton.

PubMed

Min, Hui; Dong, Jing; Wang, Yi; Wang, Yuan; Yu, Ye; Shan, Zhongyan; Xi, Qi; Teng, Weiping; Chen, Jie

2017-01-01

Iodine deficiency (ID)-induced thyroid hormone (TH) insufficient during development leads to impairments of brain function, such as learning and memory. Marginal ID has been defined as subtle insufficiency of TH, characterized as low thyroxine (T 4 ) levels, whether marginal ID potentially had adverse effects on the development of hippocampus and the underlying mechanisms remain unclear. Thus, in the present study, we established Wistar rat models with ID diet during pregnancy and lactation. The effects of marginal ID on long-term potentiation (LTP) were investigated in the hippocampal CA1 region. To study the development of dendritic spines in pyramidal cells, Golgi-Cox staining was conducted on postnatal day (PN) 7, PN14, PN21, and PN28. The activation of Rac1 signaling pathway, which is essential for dendritic spine development by regulating actin cytoskeleton, was also investigated. Our results showed that marginal ID slightly reduced the field-excitatory postsynaptic potential (f-EPSP) slope and the population spike (PS) amplitude. Besides, the density of dendritic spines during the critical period of rat postnatal development was mildly decreased, and we found no significant change of spine morphology in marginal ID group. We also observed decreased activation of the Rac1 signaling pathway in pups subjected to maternal marginal ID. Our study may support the hypothesis that decreased T 4 induced by marginal ID results in slight impairments of LTP and leads to mild damage of dendritic spine development, which may be due to abnormal regulation of Rac1 signaling pathway on cytoskeleton.

Transcription and methylation analyses of preleukemic promyelocytes indicate a dual role for PML/RARA in leukemia initiation

PubMed Central

Gaillard, Coline; Tokuyasu, Taku A.; Rosen, Galit; Sotzen, Jason; Vitaliano-Prunier, Adeline; Roy, Ritu; Passegué, Emmanuelle; de Thé, Hugues; Figueroa, Maria E.; Kogan, Scott C.

2015-01-01

Acute promyelocytic leukemia is an aggressive malignancy characterized by the accumulation of promyelocytes in the bone marrow. PML/RARA is the primary abnormality implicated in this pathology, but the mechanisms by which this chimeric fusion protein initiates disease are incompletely understood. Identifying PML/RARA targets in vivo is critical for comprehending the road to pathogenesis. Utilizing a novel sorting strategy, we isolated highly purified promyelocyte populations from normal and young preleukemic animals, carried out microarray and methylation profiling analyses, and compared the results from the two groups of animals. Surprisingly, in the absence of secondary lesions, PML/RARA had an overall limited impact on both the transcriptome and methylome. Of interest, we did identify down-regulation of secondary and tertiary granule genes as the first step engaging the myeloid maturation block. Although initially not sufficient to arrest terminal granulopoiesis in vivo, such alterations set the stage for the later, complete differentiation block seen in leukemia. Further, gene set enrichment analysis revealed that PML/RARA promyelocytes exhibit a subtle increase in expression of cell cycle genes, and we show that this leads to both increased proliferation of these cells and expansion of the promyelocyte compartment. Importantly, this proliferation signature was absent from the poorly leukemogenic p50/RARA fusion model, implying a critical role for PML in the altered cell-cycle kinetics and ability to initiate leukemia. Thus, our findings challenge the predominant model in the field and we propose that PML/RARA initiates leukemia by subtly shifting cell fate decisions within the promyelocyte compartment. PMID:26088929

Tubulin perturbation leads to unexpected cell wall modifications and affects stomatal behaviour in Populus

DOE PAGES

Swamy, Prashant S.; Hu, Hao; Pattathil, Sivakumar; ...

2015-08-05

Cortical microtubules are integral to plant morphogenesis, cell wall synthesis, and stomatal behaviour, presumably by governing cellulose microfibril orientation. Genetic manipulation of tubulins often leads to abnormal plant development, making it difficult to probe additional roles of cortical microtubules in cell wall biogenesis. Here, it is shown that expressing post-translational C-terminal modification mimics of α-tubulin altered cell wall characteristics and guard cell dynamics in transgenic Populus tremula x alba that otherwise appear normal. 35S promoter-driven transgene expression was high in leaves but unusually low in xylem, suggesting high levels of tubulin transgene expression were not tolerated in wood-forming tissues duringmore » regeneration of transformants. Cellulose, hemicellulose, and lignin contents were unaffected in transgenic wood, but expression of cell wall-modifying enzymes, and extractability of lignin-bound pectin and xylan polysaccharides were increased in developing xylem. The results suggest that pectin and xylan polysaccharides deposited early during cell wall biogenesis are more sensitive to subtle tubulin perturbation than cellulose and matrix polysaccharides deposited later. Tubulin perturbation also affected guard cell behaviour, delaying drought-induced stomatal closure as well as light-induced stomatal opening in leaves. Pectins have been shown to confer cell wall flexibility critical for reversible stomatal movement, and results presented here are consistent with microtubule involvement in this process. In conclusion, taken together, the data show the value of growth-compatible tubulin perturbations for discerning microtubule functions, and add to the growing body of evidence for microtubule involvement in non-cellulosic polysaccharide assembly during cell wall biogenesis.« less

Connectivity-based parcellation reveals distinct cortico-striatal connectivity fingerprints in Autism Spectrum Disorder.

PubMed

Balsters, Joshua H; Mantini, Dante; Wenderoth, Nicole

2018-04-15

Autism Spectrum Disorder (ASD) has been associated with abnormal synaptic development causing a breakdown in functional connectivity. However, when measured at the macro scale using resting state fMRI, these alterations are subtle and often difficult to detect due to the large heterogeneity of the pathology. Recently, we outlined a novel approach for generating robust biomarkers of resting state functional magnetic resonance imaging (RS-fMRI) using connectivity based parcellation of gross morphological structures to improve single-subject reproducibility and generate more robust connectivity fingerprints. Here we apply this novel approach to investigating the organization and connectivity strength of the cortico-striatal system in a large sample of ASD individuals and typically developed (TD) controls (N=130 per group). Our results showed differences in the parcellation of the striatum in ASD. Specifically, the putamen was found to be one single structure in ASD, whereas this was split into anterior and posterior segments in an age, IQ, and head movement matched TD group. An analysis of the connectivity fingerprints revealed that the group differences in clustering were driven by differential connectivity between striatum and the supplementary motor area, posterior cingulate cortex, and posterior insula. Our approach for analysing RS-fMRI in clinical populations has provided clear evidence that cortico-striatal circuits are organized differently in ASD. Based on previous task-based segmentations of the striatum, we believe that the anterior putamen cluster present in TD, but not in ASD, likely contributes to social and language processes. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Correlation analysis of tree growth, climate, and acid deposition in the Lake States.

Treesearch

Margaret R. Holdaway

1990-01-01

Describes research designed to detect subtle regional tree growth trends related to sulfate (SO4) deposition in the Lake States. Correlation methods were used to analyze climatic and SO4 deposition. Effects of SO4 deposition are greater on climatically stressed trees, especially pine species on dry sites, than on unstressed trees. Jack pine growth shows the...

Leadership Characteristics and Training Needs of Women and Men in Charge of Spanish Universities

ERIC Educational Resources Information Center

Sánchez-Moreno, Marita; López-Yáñez, Julián; Altopiedi, Mariana

2015-01-01

This article discusses the results obtained by two consecutive enquiries into the leadership styles and training needs of women and men leading higher education organisations. It compares the findings of the first stage of two studies, based on ad hoc questionnaires responded to by 136 women and 129 men. Results showed only subtle differences…

The biological impacts of the Fukushima nuclear accident on the pale grass blue butterfly

PubMed Central

Hiyama, Atsuki; Nohara, Chiyo; Kinjo, Seira; Taira, Wataru; Gima, Shinichi; Tanahara, Akira; Otaki, Joji M.

2012-01-01

The collapse of the Fukushima Dai-ichi Nuclear Power Plant caused a massive release of radioactive materials to the environment. A prompt and reliable system for evaluating the biological impacts of this accident on animals has not been available. Here we show that the accident caused physiological and genetic damage to the pale grass blue Zizeeria maha, a common lycaenid butterfly in Japan. We collected the first-voltine adults in the Fukushima area in May 2011, some of which showed relatively mild abnormalities. The F1 offspring from the first-voltine females showed more severe abnormalities, which were inherited by the F2 generation. Adult butterflies collected in September 2011 showed more severe abnormalities than those collected in May. Similar abnormalities were experimentally reproduced in individuals from a non-contaminated area by external and internal low-dose exposures. We conclude that artificial radionuclides from the Fukushima Nuclear Power Plant caused physiological and genetic damage to this species. PMID:22880161

The biological impacts of the Fukushima nuclear accident on the pale grass blue butterfly.

PubMed

Hiyama, Atsuki; Nohara, Chiyo; Kinjo, Seira; Taira, Wataru; Gima, Shinichi; Tanahara, Akira; Otaki, Joji M

2012-01-01

The collapse of the Fukushima Dai-ichi Nuclear Power Plant caused a massive release of radioactive materials to the environment. A prompt and reliable system for evaluating the biological impacts of this accident on animals has not been available. Here we show that the accident caused physiological and genetic damage to the pale grass blue Zizeeria maha, a common lycaenid butterfly in Japan. We collected the first-voltine adults in the Fukushima area in May 2011, some of which showed relatively mild abnormalities. The F₁ offspring from the first-voltine females showed more severe abnormalities, which were inherited by the F₂ generation. Adult butterflies collected in September 2011 showed more severe abnormalities than those collected in May. Similar abnormalities were experimentally reproduced in individuals from a non-contaminated area by external and internal low-dose exposures. We conclude that artificial radionuclides from the Fukushima Nuclear Power Plant caused physiological and genetic damage to this species.

Morphological alterations in the freshwater rotifer Brachionus calyciflorus Pallas 1766 (Rotifera: Monogononta) caused by vinclozolin chronic exposure.

PubMed

Alvarado-Flores, Jesús; Rico-Martínez, Roberto; Adabache-Ortíz, Araceli; Silva-Briano, Marcelo

2015-05-01

Vinclozolin (VZ) is a dicarboximide fungicide widely used on fruits, vegetables and wines, effective against fungi plagues. In this study we characterized the effects of VZ using a 4-day reproductive chronic assay with the freshwater rotifer Brachionus calyciflorus. The assay included observations of several features of asexual and sexual reproduction. Our results indicate that VZ: (a) increased asexual and sexual reproduction, (b) caused severe abnormality in females and (c) these abnormalities were inherited by sexual and asexual reproduction. At 1.2 mg/L three abnormal females were found out of 457 total females (0.66 %). This low percentage is consistent and reproducible according to further analysis, where we increased the number of replicates and total females exposed to 1.2 mg/L of VZ, and found 18 abnormal females out of 2868 total females (0.63 % abnormality). Interestingly, abnormal females found at 5.6 mg/L VZ exposure, were able to show mating behavior. Our results suggest that VZ behaves as a strong endocrine disruptor whose effects show the characteristic inverted-U-shape exposure concentration response curve regarding the intrinsic population increase and the percentage of abnormalities as endpoints.

Moving Faces

ERIC Educational Resources Information Center

Journal of College Science Teaching, 2005

2005-01-01

A recent study by Zara Ambadar and Jeffrey F. Cohn of the University of Pittsburgh and Jonathan W. Schooler of the University of British Columbia, examined how motion affects people's judgment of subtle facial expressions. Two experiments demonstrated robust effects of motion in facilitating the perception of subtle facial expressions depicting…

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

Voylov, D. N.; Griffin, P. J.; Mercado, B.

In this detailed analysis of the static structure factor S(Q) in several glass-forming liquids we show that the temperature variations of the width of the main diffraction peak Q(T ) correlate with the fragility of these liquids. Our observation suggests a direct connection between rather subtle structural changes and sharp slowing down of structural relaxation in glass-forming liquids. We also show that this observation can be rationalized using the Adam-Gibbs approach, through a connection between temperature variations of structural correlation length, lc 2 /Q, and the size of cooperatively rearranging regions.

Neural conduction abnormality in the brain stem and prevalence of the abnormality in late preterm infants with perinatal problems.

PubMed

Jiang, Ze Dong

2013-08-01

Neurodevelopment in late preterm infants has recently attracted considerable interest. The prevalence of brain stem conduction abnormality remains unknown. We examined maximum length sequence brain stem auditory evoked response in 163 infants, born at 33-36 weeks gestation, who had various perinatal problems. Compared with 49 normal term infants without problems, the late preterm infants showed a significant increase in III-V and I-V interpeak intervals at all 91-910/s clicks, particularly at 455 and 910/s (p < 0.01-0.001). The I-III interval was slightly increased, without statistically significant difference from the controls at any click rates. These results suggest that neural conduction along the, mainly more central or rostral part of, auditory brain stem is abnormal in late preterm infants with perinatal problems. Of the 163 late preterm infant, the number (and percentage rate) of infants with abnormal I-V interval at 91, 227, 455, and 910/s clicks was, respectively, 11 (6.5%), 17 (10.2%), 37 (22.3%), and 31 (18.7%). The number (and percentage rate) of infants with abnormal III-V interval at these rates was, respectively, 10 (6.0%), 17 (10.2%), 28 (16.9), and 36 (21.2%). Apparently, the abnormal rates were much higher at 455 and 910/s clicks than at lower rates 91 and 227/s. In total, 42 (25.8%) infants showed abnormal I-V and/or III-V intervals. Conduction in, mainly in the more central part, the brain stem is abnormal in late preterm infants with perinatal problems. The abnormality is more detectable at high- than at low-rate sensory stimulation. A quarter of late preterm infants with perinatal problems have brain stem conduction abnormality.

Abnormalities in amphibian populations inhabiting agroecosystems in Northeastern Buenos Aires Province, Argentina.

PubMed

Agostini, M G; Kacoliris, F; Demetrio, P; Natale, G S; Bonetto, C; Ronco, A E

2013-05-27

The occurrence of abnormalities in amphibians has been reported in many populations, and its increase could be related to environmental pollution and habitat degradation. We evaluated the type and prevalence of abnormalities in 5 amphibian populations from agroecosystems with different degrees of agricultural disturbance (cultivated and reference areas). We detected 9 types of abnormalities, of which the most frequent were those occurring in limbs. The observed prevalence of abnormality in assessed populations from cultivated and reference areas was as follows: Rhinella fernandezae (37.1 and 10.2%, respectively), Leptodactylus latrans adults (28.1 and 9.2%) and juveniles (32.9 and 15.3%), and Hypsiboas pulchellus (11.6 and 2.8%). Scinax granulatus populations did not show abnormalities. Pseudis minuta, which was only detected in the reference area, exhibited a prevalence of 13.3%. For R. fernandezae, L. latrans, and H. pulchellus, generalized linear mixed models showed that prevalence of abnormalities was significantly higher (p < 0.05) in cultivated than in reference areas. L. latrans juveniles were more vulnerable to abnormalities than adults (p < 0.05). The presence of abnormalities in some species inhabiting different agroecosystems suggests that environmental stress factors might be responsible for their occurrence. While we detected pesticides (endosulfan, cypermethrin, and chlorpyrifos) and lower dissolved oxygen levels in ponds of the cultivated area, no data are currently available on how other factors, such as injuries from predators and parasite infections, vary by land use. Further research will be necessary to evaluate possible causes of abnormalities detected in the present study mainly in the context of factor interactions.

[MRI in Duane retraction syndrome: Preliminary results].

PubMed

Denis, D; Cousin, M; Zanin, E; Toesca, E; Girard, N

2011-09-01

Duane retraction syndrome (DRS) is a congenital ocular motility disorder with innervational dysgenesis. MRI improves our understanding of this disease by providing in vivo access to nerves and oculomotor muscles. The goal of this prospective study (2000-2008) was to analyze DRS clinically and neuroradiologically. Twenty-four patients (27 eyes) received a complete ophthalmologic evaluation and a brain-orbital MRI. The average age was 6.1 years. MRI was performed with 3D T2 CISS-weighted images through the brainstem to visualize the cisternal segments of the cranial nerves and the orbit (lateral and medial recti muscles). MRI anomalies were classified according to type I, II, and III and depending on their condition in the posterior fossa (absence, hypoplasia) and in the orbit (muscle anomalies). Of 27 eyes, 70% were type I, 19% type II, and 11% type III. MRI showed abducens nerve abnormalities in 93% of the cases (78% absence) and muscle abnormalities in 57.5% of the cases. A detailed description showed 100% abducens nerve abnormalities and 58% abnormal lateral rectus muscle in type I, 60% abducens nerve abnormalities and 60% abnormal lateral rectus muscle in type II, and 100% abducens nerve abnormalities and 66% abnormal lateral rectus in type III. This study presents two major findings: detection of abducens nerve abnormalities in most cases of DRS whatever the type, associated with muscle abnormalities, and the confirmation that this absence may exist in type II (2/5). Thus MRI proved to be a valuable tool for investigating these patients, improving the comprehension of the physiopathogenics of this disease. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Increased technetium uptake is not equivalent to muscle necrosis: scintigraphic, morphological and intramuscular pressure analyses of sore muscles after exercise

NASA Technical Reports Server (NTRS)

Crenshaw, A. G.; Friden, J.; Hargens, A. R.; Lang, G. H.; Thornell, L. E.

1993-01-01

A scintigraphic technique employing technetium pyrophosphate uptake was used to identify the area of skeletal muscle damage in the lower leg of four runners 24 h after an ultramarathon footrace (160 km). Most of the race had been run downhill which incorporated an extensive amount of eccentric work. Soreness was diffuse throughout the posterior region of the lower leg. In order to interpret what increased technetium uptake reflects and to express extreme endurance related damages, a biopsy was taken from the 3-D position of abnormal uptake. In addition, intramuscular pressures were determined in the deep posterior compartment. Scintigraphs revealed increased technetium pyrophosphate uptake in the medial portion of the gastrocnemius muscle. For 3698 fibres analysed, 33 fibres (1%) were necrotic, while a few other fibres were either atrophic or irregular shaped. A cluster of necrotic fibres occurred at the fascicular periphery for one subject and fibre type grouping occurred for another. Ultrastructural analysis revealed Z-line streaming near many capillaries and variously altered subsarcolemmal mitochondria including some with paracrystalline inclusions. The majority of the capillaries included thickened and irregular shaped endothelial cells. Intramuscular pressures of the deep posterior compartment were slightly elevated (12-15 mmHg) for three of the four subjects. Increased technetium uptake following extreme endurance running does not just reflect muscle necrosis but also subtle fibre abnormalities. Collectively, these pathological findings are attributed to relative ischaemia occurring during the race and during pre-race training, whereas, intramuscular pressure elevations associated with muscle soreness are attributed to mechanical stress caused by extensive eccentric work during the race.

PINK1 heterozygous mutations induce subtle alterations in dopamine-dependent synaptic plasticity

PubMed Central

Madeo, G.; Schirinzi, T.; Martella, G.; Latagliata, E.C.; Puglisi, F.; Shen, J.; Valente, E.M.; Federici, M.; Mercuri, N.B.; Puglisi-Allegra, S.; Bonsi, P.; Pisani, A.

2014-01-01

Background Homozygous or compound heterozygous mutations in the PTEN-induced kinase 1 (PINK1) gene are causative of autosomal recessive, early onset PD. Single heterozygous mutations have been repeatedly detected in a subset of patients as well as in non-affected subjects, and their significance has long been debated. Several neurophysiological studies from non-manifesting PINK1 heterozygotes have shown the existence of neural plasticity abnormalities, indicating the presence of specific endophenotypic traits in the heterozygous state. Methods In the present study, we performed a functional analysis of corticostriatal synaptic plasticity in heterozygous PINK1 knock-out (PINK1+/−) mice by a multidisciplinary approach. Results We found that, despite a normal motor behavior, repetitive activation of cortical inputs to striatal neurons failed to induce long-term potentiation (LTP), whereas long-term depression (LTD) was normal. Although nigral dopaminergic neurons exhibited normal morphological and electrophysiological properties with normal responses to dopamine receptor activation, we measured a significantly lower dopamine release in the striatum of PINK1+/−, compared to control mice, suggesting that a decrease in stimulus-evoked dopamine overflow acts as a major determinant for the LTP deficit. Accordingly, pharmacological agents capable of increasing the availability of dopamine in the synaptic cleft restored a normal LTP in heterozygous mice. Moreover, MAO-B inhibitors rescued a physiological LTP and a normal dopamine release. Conclusions Our results provide novel evidence for striatal plasticity abnormalities even in the heterozygous disease state. These alterations might be considered an endophenotype to this monogenic form of PD, and a valid tool to characterize early disease stage and design possible disease-modifying therapies. PMID:24167038

Right precordial-directed electrocardiographical markers identify arrhythmogenic right ventricular cardiomyopathy in the absence of conventional depolarization or repolarization abnormalities.

PubMed

Cortez, Daniel; Svensson, Anneli; Carlson, Jonas; Graw, Sharon; Sharma, Nandita; Brun, Francesca; Spezzacatene, Anita; Mestroni, Luisa; Platonov, Pyotr G

2017-10-13

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) carries a risk of sudden death. We aimed to assess whether vectorcardiographic (VCG) parameters directed toward the right heart and a measured angle of the S-wave would help differentiate ARVD/C with otherwise normal electrocardiograms from controls. Task Force 2010 definite ARVD/C criteria were met for all patients. Those who did not fulfill Task Force depolarization or repolarization criteria (-ECG) were compared with age and gender-matched control subjects. Electrocardiogram measures of a 3-dimentional spatial QRS-T angle, a right-precordial-directed orthogonal QRS-T (RPD) angle, a root mean square of the right sided depolarizing forces (RtRMS-QRS), QRS duration (QRSd) and the corrected QT interval (QTc), and a measured angle including the upslope and downslope of the S-wave (S-wave angle) were assessed. Definite ARVD/C was present in 155 patients by 2010 Task Force criteria (41.7 ± 17.6 years, 65.2% male). -ECG ARVD/C patients (66 patients) were compared to 66 control patients (41.7 ± 17.6 years, 65.2% male). All parameters tested except the QRSd and QTc significantly differentiated -ECG ARVD/C from control patients (p < 0.004 to p < 0.001). The RPD angle and RtRMS-QRS best differentiated the groups. Combined, the 2 novel criteria gave 81.8% sensitivity, 90.9% specificity and odds ratio of 45.0 (95% confidence interval 15.8 to 128.2). ARVD/C disease process may lead to development of subtle ECG abnormalities that can be distinguishable using right-sided VCG or measured angle markers better than the spatial QRS-T angle, the QRSd or QTc, in the absence of Taskforce ECG criteria.

Nonpeptide corticotropin-releasing hormone receptor type 1 antagonists and their applications in psychosomatic disorders.

PubMed

Contoreggi, Carlo; Rice, Kenner C; Chrousos, George

2004-01-01

Overproduction of corticotropin-releasing hormone (CRH) and stress system abnormalities are seen in psychiatric diseases such as depression, anxiety, eating disorders, and addiction. Investigations of CRH type 1 receptor (CRHR1) nonpeptide antagonists suggest therapeutic potential for treatment of these and other neuropsychiatric diseases. However, overproduction of CRH in the brain and on its periphery and disruption of the hypothalamic-pituitary-adrenal axis are also found in 'somatic' disorders. Some rare forms of Cushing's disease and related pituitary/adrenal disorders are obvious applications for CRHR1 antagonists. In addition, however, these antagonists may also be effective in treating more common somatic diseases. Patients with obesity and metabolic syndrome who often have subtle, but chronic hypothalamic-pituitary-adrenal hyperactivity, which may reflect central dysregulation of CRH and consequently glucocorticoid hypersecretion, could possibly be treated by administration of CRHR1 antagonists. Hormonal, autonomic, and immune aberrations are also present in chronic inflammatory, autoimmune, and allergic diseases, with considerable evidence linking CRH with the observed abnormalities. Furthermore, autonomic dysregulation is a prominent feature of common gastrointestinal disorders, such as irritable bowel syndrome and peptic ulcer disease. Patients with irritable bowel syndrome and other gastrointestinal disorders frequently develop altered pain perception and affective symptoms. CRH acts peripherally to modulate bowel activity both directly through the autonomic system and centrally by processing viscerosensory and visceromotor neural signals. This review presents clinical and preclinical evidence for the role of CRH in the pathophysiology of these disorders and for potential diagnostic and therapeutic applications of CRHR1 antagonists. Recognition of a dysfunctional stress system in these and other diseases will alter the understanding and treatment of 'psychosomatic' disorders.

The role of imaging in early hip OA.

PubMed

Siebelt, M; Agricola, R; Weinans, H; Kim, Y J

2014-10-01

Hip osteoarthritis (OA) is characterized by cartilage degradation, subchondral bone sclerosis and osteophyte formation. Nowadays, OA is thought to develop via different etiologies that all lead to a similar form of end stage joint degradation. One of these subtypes is related to an abnormal shaped hip joint, like acetabular dysplasia and a cam deformity. These bony abnormalities are highly predictive for development of hip OA, but they are likely to already be present from childhood. This suggests that these deformations induce OA changes in the hip, well before extensive hip degradation becomes present three to four decades later. Accurate detection and successful characterization of these early OA events might lead to better treatment options for hip OA besides nowadays available invasive joint replacement surgery. However, current diagnostic imaging techniques like radiographs or plain magnetic resonance imaging (MRI), are not sensitive enough to detect these subtle early OA changes. Nor are they able to disentangle intertwined and overlapping cascades from different OA subtypes, and neither can they predict OA progression. New and more sensitive imaging techniques might enable us to detect first OA changes on a cellular level, providing us with new opportunities for early intervention. In this respect, shape analysis using radiography, MRI, computed tomography (CT), single photon emission computed tomography (SPECT)/CT, and positron emission tomography (PET) might prove promising techniques and be more suited to detect early pathological changes in the hip joint. A broad application of these techniques might give us more understanding what can be considered physiological adaptation of the hip, or when early OA really starts. With a more clear definition of early OA, more homogenous patient populations can be selected and help with the development of new disease modifying OA interventions. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Attenuated variants of Lesch-Nyhan disease

PubMed Central

Ceballos-Picot, Irene; Torres, Rosa J.; Visser, Jasper E.; Schretlen, David J.; Verdu, Alfonso; Laróvere, Laura E.; Chen, Chung-Jen; Cossu, Antonello; Wu, Chien-Hui; Sampat, Radhika; Chang, Shun-Jen; de Kremer, Raquel Dodelson; Nyhan, William; Harris, James C.; Reich, Stephen G.; Puig, Juan G.

2010-01-01

Lesch–Nyhan disease is a neurogenetic disorder caused by deficiency of the enzyme hypoxanthine–guanine phosphoribosyltransferase. The classic form of the disease is described by a characteristic syndrome that includes overproduction of uric acid, severe generalized dystonia, cognitive disability and self-injurious behaviour. In addition to the classic disease, variant forms of the disease occur wherein some clinical features are absent or unusually mild. The current studies provide the results of a prospective and multi-centre international study focusing on neurological manifestations of the largest cohort of Lesch–Nyhan disease variants evaluated to date, with 46 patients from 3 to 65 years of age coming from 34 families. All had evidence for overproduction of uric acid. Motor abnormalities were evident in 42 (91%), ranging from subtle clumsiness to severely disabling generalized dystonia. Cognitive function was affected in 31 (67%) but it was never severe. Though none exhibited self-injurious behaviours, many exhibited behaviours that were maladaptive. Only three patients had no evidence of neurological dysfunction. Our results were compared with a comprehensive review of 78 prior reports describing a total of 127 Lesch–Nyhan disease variants. Together these results define the spectrum of clinical features associated with hypoxanthine–guanine phosphoribosyltransferase deficiency. At one end of the spectrum are patients with classic Lesch–Nyhan disease and the full clinical phenotype. At the other end of the spectrum are patients with overproduction of uric acid but no apparent neurological or behavioural deficits. Inbetween are patients with varying degrees of motor, cognitive, or behavioural abnormalities. Recognition of this spectrum is valuable for understanding the pathogenesis and diagnosis of all forms of hypoxanthine–guanine phosphoribosyltransferase deficiency. PMID:20176575

Age-related differences in autism: The case of white matter microstructure.

PubMed

Koolschijn, P Cédric M P; Caan, Matthan W A; Teeuw, Jalmar; Olabarriaga, Sílvia D; Geurts, Hilde M

2017-01-01

Autism spectrum disorder (ASD) is typified as a brain connectivity disorder in which white matter abnormalities are already present early on in life. However, it is unknown if and to which extent these abnormalities are hard-wired in (older) adults with ASD and how this interacts with age-related white matter changes as observed in typical aging. The aim of this first cross-sectional study in mid- and late-aged adults with ASD was to characterize white matter microstructure and its relationship with age. We utilized diffusion tensor imaging with head motion control in 48 adults with ASD and 48 age-matched controls (30-74 years), who also completed a Flanker task. Intra-individual variability of reaction times (IIVRT) measures based on performance on the Flanker interference task were used to assess IIVRT-white matter microstructure associations. We observed primarily higher mean and radial diffusivity in white matter microstructure in ASD, particularly in long-range fibers, which persisted after taking head motion into account. Importantly, group-by-age interactions revealed higher age-related mean and radial diffusivity in ASD, in projection and association fiber tracts. Subtle dissociations were observed in IIVRT-white matter microstructure relations between groups, with the IIVRT-white matter association pattern in ASD resembling observations in cognitive aging. The observed white matter microstructure differences are lending support to the structural underconnectivity hypothesis in ASD. These reductions seem to have behavioral percussions given the atypical relationship with IIVRT. Taken together, the current results may indicate different age-related patterns of white matter microstructure in adults with ASD. Hum Brain Mapp 38:82-96, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Self-Disturbances as a Possible Premorbid Indicator of Schizophrenia Risk: A Neurodevelopmental Perspective

PubMed Central

Brent, Benjamin K.; Seidman, Larry J.; Thermenos, Heidi W.; Holt, Daphne J.; Keshavan, Matcheri S.

2013-01-01

Self-disturbances (SDs) are increasingly identified in schizophrenia and are theorized to confer vulnerability to psychosis. Neuroimaging research has shed some light on the neural correlates of SDs in schizophrenia. But, the onset and trajectory of the neural alterations underlying SDs in schizophrenia remain incompletely understood. We hypothesize that the aberrant structure and function of brain areas (e.g., prefrontal, lateral temporal, and parietal cortical structures) comprising the “neural circuitry of self” may represent an early, premorbid (i.e., pre-prodromal) indicator of schizophrenia risk. Consistent with neurodevelopmental models, we argue that “early” (i.e., perinatal) dysmaturational processes (e.g., abnormal cortical neural cell migration and mini-columnar formation) affecting key prefrontal (e.g., medial prefrontal cortex), lateral temporal cortical (e.g., superior temporal sulcus), parietal (e.g., inferior parietal lobule) structures involved in self-processing may lead to subtle disruptions of “self” during childhood in persons at risk for schizophrenia. During adolescence, progressive neurodevelopmental alterations (e.g., aberrant synaptic pruning) affecting the neural circuitry of self may contribute to worsening of SDs. This could result in the emergence of prodromal symptoms and, eventually, full-blown psychosis. To highlight why adolescence may be a period of heightened risk for SDs, we first summarize the literature regarding the neural correlates of self in typically developing children. Next, we present evidence from neuroimaging studies in genetic high-risk youth suggesting that fronto-temporal-parietal structures mediating self-reflection may be abnormal in the premorbid period. Our goal is that the ideas presented here might provide future directions for research into the neurobiology of SDs during the pre-psychosis development of youth at risk for schizophrenia. PMID:23932148

Perturbations in reward-related decision-making induced by reduced prefrontal cortical GABA transmission: Relevance for psychiatric disorders.

PubMed

Piantadosi, Patrick T; Khayambashi, Shahin; Schluter, Magdalen G; Kutarna, Agnes; Floresco, Stan B

2016-02-01

The prefrontal cortex (PFC) is critical for higher-order cognitive functions, including decision-making. In psychiatric conditions such as schizophrenia, prefrontal dysfunction co-occurs with pronounced alterations in decision-making ability. These alterations include a diminished ability to utilize probabilistic reinforcement in guiding future choice, and a reduced willingness to expend effort to receive reward. Among the neurochemical abnormalities observed in the PFC of individuals with schizophrenia are alterations in the production and function of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). To probe how PFC GABA hypofunction may contribute to alterations in cost/benefit decision-making, we assessed the effects GABAA-receptor antagonist bicuculline (BIC; 50 ng in 0.5 μl saline/hemisphere) infusion in the medial PFC of rats during performance on a series of well-validated cost/benefit decision-making tasks. Intra-PFC BIC reduced risky choice and reward sensitivity during probabilistic discounting and decreased the preference for larger rewards associated with a greater effort cost, similar to the behavioral sequelae observed in schizophrenia. Additional experiments revealed that these treatments did not alter instrumental responding on a progressive ratio schedule, nor did they impair the ability to discriminate between reward and no reward. However, BIC induced a subtle but consistent impairment in preference for larger vs. smaller rewards of equal cost. BIC infusion also increased decision latencies and impaired the ability to "stay on task" as indexed by reduced rates of instrumental responding. Collectively, these results implicate prefrontal GABAergic dysfunction as a key contributing factor to abnormal decision-making observed in schizophrenia and other neuropsychiatric conditions with similar neurobiological and behavioral alterations. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prognostic significance of ventricular late potentials in patients with pulmonary sarcoidosis.

PubMed

Yodogawa, Kenji; Seino, Yoshihiko; Ohara, Toshihiko; Iwasaki, Yu-Ki; Hayashi, Meiso; Miyauchi, Yasushi; Azuma, Arata; Shimizu, Wataru

2018-06-01

Early detection of cardiac involvement in sarcoidosis is difficult but essential to achieve optimal treatment. Signal-averaged electrocardiography (SAECG) can detect subtle cardiac electrical abnormalities termed late potentials (LPs) and would be useful for the early diagnosis of cardiac involvement. This study aims to investigate the prognostic significance of LP in patients with pulmonary sarcoidosis. We prospectively studied 74 patients with pulmonary sarcoidosis without overt electrocardiographic abnormalities. All participants underwent SAECG, cardiac echocardiography, and 24-hour ambulatory Holter monitoring. Serum angiotensin-converting enzyme and B-type natriuretic peptide levels were also evaluated. We followed these patients for the evaluation of incidence of cardiac events including cardiac death, arrhythmias, and heart failure requiring hospital admission. Of the studied population, 29 patients (39.2%) had detectable LP. During a mean follow-up period of 9.8 years, 8 patients with LPs had cardiovascular events, including development of complete atrioventricular block (n = 4), ventricular tachycardia (n = 2), and heart failure (n = 2). Meanwhile, only 1 of 45 patients without LP developed cardiac event (heart failure). Multivariate analyses revealed that LPs were associated with an increased risk of developing cardiac events (hazard ratio 9.66; 95% confidence interval 1.20-78.01; P = .033) whereas age, sex, serum angiotensin-converting enzyme and B-type natriuretic peptide levels, number of premature ventricular contractions on 24-hour Holter monitoring, and echocardiographic parameters were not associated with subsequent cardiac events. SAECG might possibly be useful for the early detection of cardiac sarcoidosis and, if independently validated, could eventually be considered as a screening test for further risk stratification. Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Morphometric Brain Abnormalities in Boys with Conduct Disorder

ERIC Educational Resources Information Center

Huebner, Thomas; Vloet, Timo D.; Marx, Ivo; Konrad, Kerstin; Fink, Gereon R.; Herpertz, Sabine C.; Herpertz-Dahlmann, Beate

2008-01-01

Conduct disorder (CD) is associated with antisocial personality behavior that violates the basic rights of others. Results, on examining the structural brain aberrations in boys' CD, show that boys with CD and cormobid attention-deficit/hyperactivity disorder showed abnormalities in frontolimbic areas that could contribute to antisocial…

Ultrastructural examination of skin biopsies may assist in diagnosing mitochondrial cytopathy when muscle biopsies yield negative results.

PubMed

McAfee, John L; Warren, Christine B; Prayson, Richard A

2017-08-01

Ultrastructural evaluation of skin biopsies has been utilized for diagnosis of mitochondrial disease. This study investigates how frequently skin biopsies reveal mitochondrial abnormalities, correlates skin and muscle biopsy findings, and describes clinical diagnoses rendered following the evaluation. A retrospective review of surgical pathology reports from 1990 to 2015 identified skin biopsies examined by electron microscopy for suspected metabolic disease. A total of 630 biopsies were included from 615 patients. Of these patients, 178 also underwent a muscle biopsy. Of the 630 skin biopsies, 75 (12%) showed ultrastructural abnormalities and 34 (5%) specifically showed mitochondrial abnormalities including increased size (n=27), reduced or abnormal cristae (n=23), dense matrices (n=20), and increased number (n=8). Additional findings included lysosomal abnormalities (n=13), lipid accumulation (n=2) or glycogen accumulation (n=1). Of the 34 patients with mitochondrial abnormalities on skin biopsy, 20 also had muscle biopsies performed and nine showed abnormalities suggestive of a mitochondrial disorder including absent cytochrome oxidase staining (n=2), increased subsarcolemmal NADH, SDH, or cytochrome oxidase staining (n=1), or ultrastructural findings including large mitochondrial size (n=5), abnormal mitochondrial structure (n=5), and increased mitochondrial number (n=4). The most common presenting symptoms were intellectual disability (n=13), seizures (n=12), encephalopathy (n=9), and gastrointestinal disturbances (n=9). At last known follow-up, 12 patients had a definitive diagnosis of a mitochondrial disorder. One patient each had Complex I deficiency, Complex III deficiency, Charcot-Marie-Tooth disease, pyruvate dehydrogenase deficiency, and Phelan-McDermid syndrome. Our results suggest that skin biopsy sometimes yields diagnostic clues suggestive of a mitochondrial cytopathy in cases with a negative muscle biopsy. Copyright © 2017 Elsevier Inc. All rights reserved.

Ocular screening tests of elementary school children

NASA Technical Reports Server (NTRS)

Richardson, J.

1983-01-01

This report presents an analysis of 507 abnormal retinal reflex images taken of Huntsville kindergarten and first grade students. The retinal reflex images were obtained by using an MSFC-developed Generated Retinal Reflex Image System (GRRIS) photorefractor. The system uses a 35 mm camera with a telephoto lens with an electronic flash attachment. Slide images of the eyes were examined for abnormalities. Of a total of 1835 students screened for ocular abnormalities, 507 were found to have abnormal retinal reflexes. The types of ocular abnormalities detected were hyperopia, myopia, astigmatism, esotropia, exotropia, strabismus, and lens obstuctions. The report shows that the use of the photorefractor screening system is an effective low-cost means of screening school children for abnormalities.

Dysphagia lusorium in elderly: A case report

PubMed Central

Kantarceken, Bulent; Bulbuloglu, Ertan; Yuksel, Murvet; Cetinkaya, Ali

2004-01-01

AIM: Late unset of dysphagia due to vascular abnormalities is a rare condition. We aimed to present a case of right subclavian artery abnormalities caused dysphagia in the elderly. METHODS: A 68-year-old female was admitted with dysphagia seven months ago. Upper endoscopic procedures and routine examinations could not demonstrate any etiology. Multislice computed thorax tomography was performed for probable extra- esophagial lesions. RESULTS: Multislice computed thorax tomography showed right subclavian artery abnormality and esophagial compression with this aberrant artery. CONCLUSION: Causes of dysphagia in the elderly are commonly malignancies, strictures and/or motility disorders. If routine examinations and endoscopic procedures fail to show any etiology, rare vascular abnormalities can be considered in such patients. Multislice computed tomography is a usefull choice in such conditions. PMID:15285045

Magnetic resonance imaging in stress fractures and shin splints.

PubMed

Aoki, Yoshimitsu; Yasuda, Kazunori; Tohyama, Harukazu; Ito, Hirokazu; Minami, Akio

2004-04-01

The purpose of the current study was to determine whether stress fractures and shin splints could be discriminated with MRI in the early phase. Twenty-two athletes, who had pain in the middle or distal part of their leg during or after sports activity, were evaluated with radiographs and MRI scans. Stress fractures were diagnosed when consecutive radiographs showed local periosteal reaction or a fracture line, and shin splints were diagnosed in all the other cases. In all eight patients with stress fractures, an abnormally wide high signal in the localized bone marrow was the most detectable in the coronal fat-suppressed MRI scan. In 11 patients with shin splints, the coronal fat-suppressed MRI scans showed a linear abnormally high signal along the medial posterior surface of the tibia, and in seven patients with shin splints, the MRI scans showed a linear abnormally high signal along the medial bone marrow. No MRI scans of shin splints showed an abnormally wide high signal in the bone marrow as observed on MRI scans of stress fractures. This study showed that fat-suppressed MRI is useful for discrimination between stress fracture and shin splints before radiographs show a detectable periosteal reaction in the tibia.

Abnormalities at chromosome region 3p12-14 characterize clear cell renal carcinoma.

PubMed

Carroll, P R; Murty, V V; Reuter, V; Jhanwar, S; Fair, W R; Whitmore, W F; Chaganti, R S

1987-06-01

In an effort to determine whether or not any characteristic chromosomal abnormalities exist in renal cancer, cytogenetic findings were correlated with tumor histology in nine cases of renal adenocarcinoma. Metaphase preparations adequate for analysis were obtained from cultures harvested between day 3 and day 21. Model chromosome number was diploid in three cases, hypodiploid in three, and hyperdiploid in the remaining three. One clear cell adenocarcinoma failed to reveal any chromosomal abnormality. Two tumors, a tubular/papillary carcinoma and an acinar/papillary carcinoma, showed the clonal abnormalities del(1)(p2l),+2,+7,+8,+12,+13,+16,+17,-21 and t(2;10)(q14-21;q26),+7q,+11q,-18, respectively. Interestingly, five of six clear cell tumors studied had clonal abnormalities affecting the short arm of chromosome #3 in the 3p12-21 region, and in the remaining case, of 15 karyotyped metaphases suitable for interpretation, one showed a deletion in 3p. These data indicate that clear cell carcinoma of the kidney may be associated with a nonrandom chromosomal abnormality involving the 3p12-14 region.

Mutations in KIAA0586 Cause Lethal Ciliopathies Ranging from a Hydrolethalus Phenotype to Short-Rib Polydactyly Syndrome.

PubMed

Alby, Caroline; Piquand, Kevin; Huber, Céline; Megarbané, André; Ichkou, Amale; Legendre, Marine; Pelluard, Fanny; Encha-Ravazi, Ferechté; Abi-Tayeh, Georges; Bessières, Bettina; El Chehadeh-Djebbar, Salima; Laurent, Nicole; Faivre, Laurence; Sztriha, László; Zombor, Melinda; Szabó, Hajnalka; Failler, Marion; Garfa-Traore, Meriem; Bole, Christine; Nitschké, Patrick; Nizon, Mathilde; Elkhartoufi, Nadia; Clerget-Darpoux, Françoise; Munnich, Arnold; Lyonnet, Stanislas; Vekemans, Michel; Saunier, Sophie; Cormier-Daire, Valérie; Attié-Bitach, Tania; Thomas, Sophie

2015-08-06

KIAA0586, the human ortholog of chicken TALPID3, is a centrosomal protein that is essential for primary ciliogenesis. Its disruption in animal models causes defects attributed to abnormal hedgehog signaling; these defects include polydactyly and abnormal dorsoventral patterning of the neural tube. Here, we report homozygous mutations of KIAA0586 in four families affected by lethal ciliopathies ranging from a hydrolethalus phenotype to short-rib polydactyly. We show defective ciliogenesis, as well as abnormal response to SHH-signaling activation in cells derived from affected individuals, consistent with a role of KIAA0586 in primary cilia biogenesis. Whereas centriolar maturation seemed unaffected in mutant cells, we observed an abnormal extended pattern of CEP290, a centriolar satellite protein previously associated with ciliopathies. Our data show the crucial role of KIAA0586 in human primary ciliogenesis and subsequent abnormal hedgehog signaling through abnormal GLI3 processing. Our results thus establish that KIAA0586 mutations cause lethal ciliopathies. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Joint imaging in polymyalgia rheumatica

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

O'Duffy, J.D.; Wahner, H.W.; Hunder, G.G.

1976-08-01

Technetium pertechnetate joint scintigrams were abnormal in 24 of 25 patients with polymyalgia rheumatica, in all 16 with rheumatoid arthritis, in 4 of 13 with nonarticular rheumatism, but in none of 26 control patients. Abnormal uptake in polymyalgia patients was commonest in shoulders and was less likely to be symmetric than in patients with rheumatoid arthritis, in whom distal joint abnormalities predominated. The pattern of abnormal uptake in polymyalgia rheumatica was not different in those with biopsy-proved giant cell arteritis. Correlation between symptoms and abnormal scintigrams was 72%, and abnormal uptake was present in 81% of joints of patients havingmore » physical abnormalities. Biopsy showed lymphocytic synovitis in the knee of one patient. After treatment the number of abnormal joints declined. These findings suggest that synovitis is common in polymyalgia rheumatica, and that it may account for some or most of the symptoms in this condition.« less

Validating the Adolescent Form of the Substance Abuse Subtle Screening Inventory.

ERIC Educational Resources Information Center

Risberg, Richard A.; And Others

1995-01-01

Tests validity of the Substance Abuse Subtle Screening Inventory (SASSI) in detecting chemical dependency in adolescents (n=107), when compared to the Minnesota Multiphasic Personality Inventory (MMPI) results. Further validation for the SASSI was obtained. Treatment implications and suggestions for further research are provided. (SNR)

EPR: how subtle is the Lord and how is the Lord subtle?

NASA Astrophysics Data System (ADS)

Plotnitsky, Arkady

The article offers a counterargument to the argument of A. Einstein, B. Podolsky and N. Rosen (EPR) concerning the incompleteness, or else nonlocality, of quantum mechanics, based on Bohr's reply to EPR's article. The article also relates argument to the impossibility of exact repetition of quantum events.

SUBTLE: Situation Understanding Bot through Language and Environment

DTIC Science & Technology

2016-01-06

a 4 day “hackathon” by Stuart Young’s small robots group which successfully ported the SUBTLE MURI NLP robot interface to the Packbot platform they...null element restoration, a step typically ig- nored in NLP systems, allows for correct parsing of im- peratives and questions, critical structures

T-Wave Abnormality as Electrocardiographic Signature of Myocardial Edema in Non-ST-Elevation Acute Coronary Syndromes.

PubMed

Cardona, Andrea; Zareba, Karolina M; Nagaraja, Haikady N; Schaal, Stephen F; Simonetti, Orlando P; Ambrosio, Giuseppe; Raman, Subha V

2018-01-26

T-wave abnormalities are common during the acute phase of non-ST-segment elevation acute coronary syndromes, but mechanisms underlying their occurrence are unclear. We hypothesized that T-wave abnormalities in the presentation of non-ST-segment elevation acute coronary syndromes correspond to the presence of myocardial edema. Secondary analysis of a previously enrolled prospective cohort of patients presenting with non-ST-segment elevation acute coronary syndromes was conducted. Twelve-lead electrocardiography (ECG) and cardiac magnetic resonance with T2-weighted imaging were acquired before invasive coronary angiography. ECGs were classified dichotomously (ie, ischemic versus normal/nonischemic) and nominally according to patterns of presentation: no ST- or T-wave abnormalities, isolated T-wave abnormality, isolated ST depression, ST depression+T-wave abnormality. Myocardial edema was determined by expert review of T2-weighted images. Of 86 subjects (65% male, 59.4 years), 36 showed normal/nonischemic ECG, 25 isolated T-wave abnormalities, 11 isolated ST depression, and 14 ST depression+T-wave abnormality. Of 30 edema-negative subjects, 24 (80%) had normal/nonischemic ECGs. Isolated T-wave abnormality was significantly more prevalent in edema-positive versus edema-negative subjects (41.1% versus 6.7%, P =0.001). By multivariate analysis, an ischemic ECG showed a strong association with myocardial edema (odds ratio 12.23, 95% confidence interval 3.65-40.94, P <0.0001). Among individual ECG profiles, isolated T-wave abnormality was the single strongest predictor of myocardial edema (odds ratio 23.84, 95% confidence interval 4.30-132, P <0.0001). Isolated T-wave abnormality was highly specific (93%) but insensitive (43%) for detecting myocardial edema. T-wave abnormalities in the setting of non-ST-segment elevation acute coronary syndromes are related to the presence of myocardial edema. High specificity of this ECG alteration identifies a change in ischemic myocardium associated with worse outcomes that is potentially reversible. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Probing Implicit Learning in Obsessive-Compulsive Disorder: Moderating Role of Medication on the Weather Prediction Task

PubMed Central

Kelmendi, Benjamin; Adams, Thomas; Jakubovski, Ewgeni; Hawkins, Keith A.; Coric, Vladimir; Pittenger, Christopher

2016-01-01

Deficits in implicit learning, a process by which knowledge is acquired accretively through practice independent of conscious awareness, have been implicated in Obsessive-Compulsive Disorder (OCD). The weather-prediction task (WPT) was used to assess implicit learning in 26 unmedicated patients with OCD and 23 healthy controls. An additional analysis compared these two groups with 25 medicated patients with OCD. In the comparison of unmedicated patients with healthy controls there was a subtle but statistically significant group-by-block interaction. Patients with OCD showed slower improvement in performance during the middle phase of learning. In a three-group comparison, there was no main effect of group; in post-hoc tests, medicated patients with OCD differed from unmedicated patients and were not different from healthy controls. Unmedicated patients with OCD have a subtle deficit in implicit learning in the WPT. This may be mitigated by pharmacotherapy, although prospective studies would be required to confirm this conclusion. PMID:27134820

Tuning and Freezing Disorder in Photonic Crystals using Percolation Lithography

PubMed Central

Burgess, Ian B.; Abedzadeh, Navid; Kay, Theresa M.; Shneidman, Anna V.; Cranshaw, Derek J.; Lončar, Marko; Aizenberg, Joanna

2016-01-01

Although common in biological systems, synthetic self-assembly routes to complex 3D photonic structures with tailored degrees of disorder remain elusive. Here we show how liquids can be used to finely control disorder in porous 3D photonic crystals, leading to complex and hierarchical geometries. In these optofluidic crystals, dynamically tunable disorder is superimposed onto the periodic optical structure through partial wetting or evaporation. In both cases, macroscopic symmetry breaking is driven by subtle sub-wavelength variations in the pore geometry. These variations direct site-selective infiltration of liquids through capillary interactions. Incorporating cross-linkable resins into our liquids, we developed methods to freeze in place the filling patterns at arbitrary degrees of partial wetting and intermediate stages of drying. These percolation lithography techniques produced permanent photonic structures with adjustable disorder. By coupling strong changes in optical properties to subtle differences in fluid behavior, optofluidic crystals may also prove useful in rapid analysis of liquids. PMID:26790372

For love or money? What motivates people to know the minds of others?

PubMed

Harkness, Kate L; Jacobson, Jill A; Sinclair, Brooke; Chan, Emilie; Sabbagh, Mark A

2012-01-01

Mood affects social cognition and "theory of mind", such that people in a persistent negative mood (i.e., dysphoria) have enhanced abilities at making subtle judgements about others' mental states. Theorists have argued that this hypersensitivity to subtle social cues may have adaptive significance in terms of solving interpersonal problems and/or minimising social risk. We tested whether increasing the social salience of a theory of mind task would preferentially increase dyspshoric individuals' performance on the task. Forty-four dysphoric and 51 non-dysphoric undergraduate women participated in a theory of mind decoding task following one of three motivational manipulations: (i) social motivation (ii) monetary motivation, or (iii) no motivation. Social motivation was associated with the greatest accuracy of mental state decoding for the dysphoric group, whereas the non-dysphoric group showed the highest accuracy in the monetary motivation condition. These results suggest that dysphoric individuals may be especially, and preferentially, motivated to understand the mental states of others.

The Synapse as a Central Target for Neurodevelopmental Susceptibility to Pesticides

PubMed Central

Vester, Aimee; Caudle, W. Michael

2016-01-01

The developmental period of the nervous system is carefully orchestrated and highly vulnerable to alterations. One crucial factor of a properly-functioning nervous system is the synapse, as synaptic signaling is critical for the formation and maturation of neural circuits. Studies show that genetic and environmental impacts can affect diverse components of synaptic function. Importantly, synaptic dysfunction is known to be associated with neurologic and psychiatric disorders, as well as more subtle cognitive, psychomotor, and sensory defects. Given the importance of the synapse in numerous domains, we wanted to delineate the effects of pesticide exposure on synaptic function. In this review, we summarize current epidemiologic and molecular studies that demonstrate organochlorine, organophosphate, and pyrethroid pesticide exposures target the developing synapse. We postulate that the synapse plays a central role in synaptic vulnerability to pesticide exposure during neurodevelopment, and the synapse is a worthy candidate for investigating more subtle effects of chronic pesticide exposure in future studies. PMID:29051423

Computed tomographic (CT) neuroradiological evaluation of intra-axial and extra-axial lesions: a receiver operating characteristic (ROC) study of film and 1K workstation

NASA Astrophysics Data System (ADS)

El-Saden, Suzie; Hademenos, George J.; Zhu, Wei; Sayre, James W.; Glenn, Brad; Steidler, Jim; Kode, L.; King, Brian; Quinones, Diana; Valentino, Daniel J.; Bentsen, John R.

1995-04-01

Digital display workstations are now commonly used for cross-sectional image viewing; however, few receiver operating characteristic (ROC) studies have been performed to evaluate the diagnostic efficiency of hard copy versus a workstation display for neuroradiology applications. We have performed an ROC study of film and 1K workstation based on the diagnostic performance of neuroradiology fellows to detect subtle intra- axial (high density (HD) and low density (LD)) and extra-axial (fluid, blood) lesions presented on computed tomographic (CT) images. An ROC analysis of the interpretation of approximately 200 CT images (1/2 normals and 1/2 abnormals) was performed by five experienced observers. The total number of abnormal images were equally divided among the three represented types of lesions (HD, LD, and extra-axial lesions). The images comprising the extra-axial lesion group were further subdivided into the following three distinct types: subdural hemorrhage, subarachnoid hemorrhage, and epidural hemorrhage. A fraction of the abnormal images were represented by more than one type of lesion, e.g., one abnormal image could contain both a HD and LD lesion. The digitized CT images were separated into four groups and read on the standard light box and a 1K workstation monitor equipped with simple image processing functions. Confidence ratings were scaled on a range from 0 (least confident) to 4 (most confident). Reader order sequences were randomized for each reader and for each modality. Each observer read from a total of eight different groups with a four-week intermission following the fourth group. The randomly assigned image number, lesion type and approximate location, incidental findings and comments, and confidence ratings were reported in individual worksheets for each image. ROC curves that were generated and analyzed for the various subgroups are presented in addition to the overall generalized jackknifed estimates of the grouped data. Also, 95% confidence intervals are presented for the differences in the area under the ROC curves. Although there were no statistically significant differences in the diagnostic accuracy between the original CT slice with HD and LD lesions viewed on the light box and on the 1K display workstation, the observers tended to record extra- axial lesions more frequently and with more confidence on the 1K display in comparison to the light box primarily due to the added advantage of adjusting the display window levels.

Context Preexposure Prevents Forgetting of a Contextual Fear Memory: Implication for Regional Changes in Brain Activation Patterns Associated with Recent and Remote Memory Tests

ERIC Educational Resources Information Center

Biedenkapp, Joseph C.; Rudy, Jerry W.

2007-01-01

Contextual fear conditioning was maintained over a 15-day retention interval suggesting no forgetting of the conditioning experience. However, a more subtle generalization test revealed that, as the retention interval increased, rats showed enhanced generalized fear to an altered context. Preexposure to the training context prior to conditioning,…

Abnormal sympathetic innervation of the heart in a patient with Emery-Dreifuss muscular dystrophy.

PubMed

Fujiita, Takashi; Shimizu, Masami; Kaku, Bunji; Kanaya, Hounin; Horita, Yuki; Uno, Yoshihide; Yamazaki, Tsukasa; Ohka, Takio; Sakata, Kenji; Mabuchi, Hiroshi

2005-07-01

A 33-year-old man was admitted for general malaise and vomiting. An electrocardiogram showed a complete atrioventricular block and an echocardiogram showed right atrial dilatation and normal wall motion of left ventricle (LV). Gene analysis showed nonsense mutation in the STA gene, which codes for emerin, and Emery-Dreifuss muscular dystrophy was diagnosed. An endomyocardial biopsy of right ventricle showed mild hypertrophy of myocytes. Myocardial scintigraphic studies with Tc-99m methoxyisobutylisonitrile (MIBI) and I-123-betamethyl-p-iodophenylpentadecanoic acid (BMIPP) scintigrams showed no abnormalities. In contrast, I-123 metaiodobenzylguanidine (MIBG) scintigrams showed a diffuse and severe decrease in accumulation of MIBG in the heart. Six months later, his LV wall motion on echocardiograms developed diffuse hypokinesis. These results suggest that the abnormality on I-123 MIBG myocardial scintigrams may predict LV dysfunction in Emery-Dreifuss muscular dystrophy.

Effects of a Passive Online Software Application on Heart Rate Variability and Autonomic Nervous System Balance.

PubMed

Rubik, Beverly

2017-01-01

This study investigated whether short-term exposure to a passive online software application of purported subtle energy technology would affect heart rate variability (HRV) and associated autonomic nervous system measures. This was a randomized, double-blinded, sham-controlled clinical trial (RCT). The study took place in a nonprofit laboratory in Emeryville, California. Twenty healthy, nonsmoking subjects (16 females), aged 40-75 years, participated. Quantum Code Technology ™ (QCT), a purported subtle energy technology, was delivered through a passive software application (Heart+ App) on a smartphone placed <1 m from subjects who were seated and reading a catalog. HRV was measured for 5 min in triplicate for each condition via finger plethysmography using a Food and Drug Administration medically approved HRV measurement device. Measurements were made at baseline and 35 min following exposure to the software applications. The following parameters were calculated and analyzed: heart rate, total power, standard deviation node-to-node, root mean square sequential difference, low frequency to high frequency ratio (LF/HF), low frequency (LF), and high frequency (HF). Paired samples t-tests showed that for the Heart+ App, mean LF/HF decreased (p = 9.5 × 10 -4 ), while mean LF decreased in a trend (p = 0.06), indicating reduced sympathetic dominance. Root mean square sequential difference increased for the Heart+ App, showing a possible trend (p = 0.09). Post-pre differences in LF/HF for sham compared with the Heart+ App were also significant (p < 0.008) by independent t-test, indicating clinical relevance. Significant beneficial changes in mean LF/HF, along with possible trends in mean LF and root mean square sequential difference, were observed in subjects following 35 min exposure to the Heart+ App that was working in the background on an active smartphone untouched by the subjects. This may be the first RCT to show that specific frequencies of a purported non-Hertzian type of subtle energy conveyed by software applications broadcast from personal electronic devices can be bioactive and beneficially impact autonomic nervous system balance.

Rapid multislice T1 mapping of mouse myocardium: Application to quantification of manganese uptake in α-Dystrobrevin knockout mice.

PubMed

Jiang, Kai; Li, Wen; Li, Wei; Jiao, Sen; Castel, Laurie; Van Wagoner, David R; Yu, Xin

2015-11-01

The aim of this study was to develop a rapid, multislice cardiac T1 mapping method in mice and to apply the method to quantify manganese (Mn(2+)) uptake in a mouse model with altered Ca(2+) channel activity. An electrocardiography-triggered multislice saturation-recovery Look-Locker method was developed and validated both in vitro and in vivo. A two-dose study was performed to investigate the kinetics of T1 shortening, Mn(2+) relaxivity in myocardium, and the impact of Mn(2+) on cardiac function. The sensitivity of Mn(2+)-enhanced MRI in detecting subtle changes in altered Ca(2+) channel activity was evaluated in a mouse model with α-dystrobrevin knockout. Validation studies showed strong agreement between the current method and an established method. High Mn(2+) dose led to significantly accelerated T1 shortening. Heart rate decreased during Mn(2+) infusion, while ejection ratio increased slightly at the end of imaging protocol. No statistical difference in cardiac function was detected between the two dose groups. Mice with α-dystrobrevin knockout showed enhanced Mn(2+) uptake in vivo. In vitro patch-clamp study showed increased Ca(2+) channel activity. The saturation recovery method provides rapid T1 mapping in mouse hearts, which allowed sensitive detection of subtle changes in Mn(2+) uptake in α-dystrobrevin knockout mice. © 2014 Wiley Periodicals, Inc.

Odd–even structural sensitivity on dynamics in network-forming ionic liquids

DOE PAGES

Yang, Ke; Cai, Zhikun; Tyagi, Madhusudan; ...

2016-04-13

Understanding structural sensitivity on properties of materials is an important step toward the rational design of materials. As a compelling case of sensitive structure-property relationship, an odd-even effect refers to the alternating trend of physical or chemical properties on odd/even number of repeating structural units. In crystalline or semi-crystalline materials, such odd-even variations of macroscopic properties emerge as manifestations of differences in the periodic packing patterns of molecules. Therefore, due to the lack of long-range order, such odd-even phenomenon is not expected in liquids. Herein, we report the discovery of a remarkable odd-even effect of the dynamical properties in themore » liquid phase, which challenges the traditional periodic packing explanations. In a class of network-forming ionic liquid (NIL), using incoherent quasi-elastic neutron scattering measurements, we measured the dynamical properties including the diffusion coefficient and the rotational relaxation time. These dynamical properties showed pronounced alternating trends with increased number of methylene (–CH 2– ) groups in the backbone. Meanwhile, the structure factor S(Q) showed no long-range periodic packing of molecules, while the pair distribution function g(r) revealed subtle differences in the local molecular morphology. As a result, the observed dynamical odd-even phenomenon in liquids showed that profound dynamical changes originate from subtle local structural differences.« less

Estimation of stress relaxation time for normal and abnormal breast phantoms using optical technique

NASA Astrophysics Data System (ADS)

Udayakumar, K.; Sujatha, N.

2015-03-01

Many of the early occurring micro-anomalies in breast may transform into a deadliest cancer tumor in future. Probability of curing early occurring abnormalities in breast is more if rightly identified. Even in mammogram, considered as a golden standard technique for breast imaging, it is hard to pick up early occurring changes in the breast tissue due to the difference in mechanical behavior of the normal and abnormal tissue when subjected to compression prior to x-ray or laser exposure. In this paper, an attempt has been made to estimate the stress relaxation time of normal and abnormal breast mimicking phantom using laser speckle image correlation. Phantoms mimicking normal breast is prepared and subjected to precise mechanical compression. The phantom is illuminated by a Helium Neon laser and by using a CCD camera, a sequence of strained phantom speckle images are captured and correlated by the image mean intensity value at specific time intervals. From the relation between mean intensity versus time, tissue stress relaxation time is quantified. Experiments were repeated for phantoms with increased stiffness mimicking abnormal tissue for similar ranges of applied loading. Results shows that phantom with more stiffness representing abnormal tissue shows uniform relaxation for varying load of the selected range, whereas phantom with less stiffness representing normal tissue shows irregular behavior for varying loadings in the given range.

The anatomy and development of normal and abnormal coronary arteries.

PubMed

Spicer, Diane E; Henderson, Deborah J; Chaudhry, Bill; Mohun, Timothy J; Anderson, Robert H

2015-12-01

At present, there is significant interest in the morphology of the coronary arteries, not least due to the increasingly well-recognised association between anomalous origin of the arteries and sudden cardiac death. Much has also been learnt over the last decade regarding the embryology of the arteries. In this review, therefore, we provide a brief introduction into the recent findings regarding their development. In particular, we emphasise that new evidence, derived using the developing murine heart, points to the arterial stems growing out from the adjacent sinuses of the aortic root, rather than the arteries growing in, as is currently assumed. As we show, the concept of outgrowth provides an excellent explanation for several of the abnormal arrangements encountered in the clinical setting. Before summarising these abnormal features, we draw attention to the need to describe the heart in an attitudinally appropriate manner, following the basic rule of human anatomy, rather than describing the cardiac components with the heart in the "Valentine" orientation. We then show how the major abnormalities involving the coronary arteries in humans can be summarised in terms of abnormal origin from the pulmonary circulation, abnormal aortic origin, or fistulous communications between the coronary arteries and the cardiac cavities. In the case of abnormal aortic origin, we highlight those malformations known to be associated with sudden cardiac death.

VASCULAR ABNORMALITIES IN DIABETIC RETINOPATHY ASSESSED WITH SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY WIDEFIELD IMAGING.

PubMed

Schaal, Karen B; Munk, Marion R; Wyssmueller, Iris; Berger, Lieselotte E; Zinkernagel, Martin S; Wolf, Sebastian

2017-11-10

To detect vascular abnormalities in diabetic retinopathy using swept-source optical coherence tomography angiography (SS-OCTA) widefield images, and to compare the findings with color fundus photographs (CFPs) using Early Treatment Diabetic Retinopathy Study severity grading. 3 mm × 3 mm and 12 mm × 12 mm scans were acquired to cover 70° to 80° of the posterior pole using a 100-kHz SS-OCTA instrument. Two masked graders assessed the presence of vascular abnormalities on SS-OCTA and the Early Treatment Diabetic Retinopathy Study level on CFP. The grading results were then compared. A total of 120 diabetic eyes (60 patients) were imaged with the SS-OCTA instrument. Cohort 1 (91 eyes; SS-OCTA grading only) showed microaneurysms in 91% (n = 83), intraretinal microvascular abnormalities in 79% (n = 72), and neovascularization in 21% (n = 19) of cases. Cohort 2 (52 eyes; CFP grading compared with SS-OCTA) showed microaneurysms on CFP in 90% (n = 47) and on SS-OCTA in 96% (n = 50) of cases. Agreement in intraretinal microvascular abnormality detection was fair (k = 0.2). Swept-source optical coherence tomography angiography detected 50% of intraretinal microvascular abnormality cases (n = 26), which were missed on CFP. Agreement in detecting neovascularization was moderate (k = 0.5). Agreement in detection of diabetic retinopathy features on CFP and SS-OCTA varies depending on the vascular changes examined. Swept-source optical coherence tomography angiography shows a higher detection rate of intraretinal microvascular abnormalities (P = 0.039), compared with Early Treatment Diabetic Retinopathy Study grading.

Clinical classification and neuro-vestibular evaluation in chronic dizziness.

PubMed

Oh, Sun-Young; Kim, Do-Hyung; Yang, Tae-Ho; Shin, Byoung-Soo; Jeong, Seul-Ki

2015-01-01

This study attempts to clarify the clinical characteristics of chronic dizziness and its relationships with specific vestibular, oculomotor, autonomic and psychiatric dysfunctions. 73 Patients with idiopathic chronic dizziness were recruited and classified based on history taking and clinical examination into the following four clinical subgroups; vestibular migraine (VM), dysautonomia, psychogenic, and unspecified groups. They were also evaluated using oculomotor, otolithic and autonomic function tests, and psychologic investigation. Patients in the VM group showed a high proportion of abnormality on smooth pursuit and otolithic function testing compared to the other groups. The dysautonomia group revealed significant abnormalities in sympathetic and cardiovagal autonomic function, while the psychogenic group had a high frequency of abnormality in sympathetic autonomic testing and in Beck's anxiety inventory scale. The unspecified group showed abnormalities on saccade, smooth pursuit and autonomic function testing. Clinical classification of patients with chronic dizziness was relevant and they showed a correlation with disease-specific abnormal results in oculomotor, otolithic, autonomic function and psychology testing. Appropriate diagnostic investigation based on precise clinical diagnosis of chronic dizziness reduces the need for extensive laboratory testing, neuroimaging, and other low-yield tests. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Detection of dominant flow and abnormal events in surveillance video

NASA Astrophysics Data System (ADS)

Kwak, Sooyeong; Byun, Hyeran

2011-02-01

We propose an algorithm for abnormal event detection in surveillance video. The proposed algorithm is based on a semi-unsupervised learning method, a kind of feature-based approach so that it does not detect the moving object individually. The proposed algorithm identifies dominant flow without individual object tracking using a latent Dirichlet allocation model in crowded environments. It can also automatically detect and localize an abnormally moving object in real-life video. The performance tests are taken with several real-life databases, and their results show that the proposed algorithm can efficiently detect abnormally moving objects in real time. The proposed algorithm can be applied to any situation in which abnormal directions or abnormal speeds are detected regardless of direction.

BcL-xL Conformational Changes upon Fragment Binding Revealed by NMR

PubMed Central

Aguirre, Clémentine; ten Brink, Tim; Walker, Olivier; Guillière, Florence; Davesne, Dany; Krimm, Isabelle

2013-01-01

Protein-protein interactions represent difficult but increasingly important targets for the design of therapeutic compounds able to interfere with biological processes. Recently, fragment-based strategies have been proposed as attractive approaches for the elaboration of protein-protein surface inhibitors from fragment-like molecules. One major challenge in targeting protein-protein interactions is related to the structural adaptation of the protein surface upon molecular recognition. Methods capable of identifying subtle conformational changes of proteins upon fragment binding are therefore required at the early steps of the drug design process. In this report we present a fast NMR method able to probe subtle conformational changes upon fragment binding. The approach relies on the comparison of experimental fragment-induced Chemical Shift Perturbation (CSP) of amine protons to CSP simulated for a set of docked fragment poses, considering the ring-current effect from fragment binding. We illustrate the method by the retrospective analysis of the complex between the anti-apoptotic Bcl-xL protein and the fragment 4′-fluoro-[1,1′-biphenyl]-4-carboxylic acid that was previously shown to bind one of the Bcl-xL hot spots. The CSP-based approach shows that the protein undergoes a subtle conformational rearrangement upon interaction, for residues located in helices 2, 3 and the very beginning of 5. Our observations are corroborated by residual dipolar coupling measurements performed on the free and fragment-bound forms of the Bcl-xL protein. These NMR-based results are in total agreement with previous molecular dynamic calculations that evidenced a high flexibility of Bcl-xL around the binding site. Here we show that CSP of protein amine protons are useful and reliable structural probes. Therefore, we propose to use CSP simulation to assess protein conformational changes upon ligand binding in the fragment-based drug design approach. PMID:23717610

Positron emission tomography with α-[11C]methyl-L-tryptophan in tuberous sclerosis complex-related epilepsy.

PubMed

Rubí, Sebastià; Costes, Nicolas; Heckemann, Rolf A; Bouvard, Sandrine; Hammers, Alexander; Martí Fuster, Berta; Ostrowsky, Karine; Montavont, Alexandra; Jung, Julien; Setoain, Xavier; Catenoix, Hélène; Hino, Keiko; Liger, François; Le Bars, Didier; Ryvlin, Philippe

2013-12-01

Tuberous sclerosis complex (TSC) is often associated with cerebral tubers and medically intractable epilepsy. We reevaluated whether increased uptake of α-[(11) C]methyl-l-tryptophan (AMT) in cerebral tubers is associated with tuber epileptogenicity. We included 12 patients (six male, 4-53 years old) with TSC and refractory seizures who were evaluated for epilepsy surgery in our center, including video-electroencephalographic (EEG) monitoring, fluid-attenuated inversion recovery magnetic resonance imaging (FLAIR MRI), and positron emission tomography (PET) with α-[(11) C]methyl-l-tryptophan (AMT-PET). Nine of these 12 patients also underwent intracerebral EEG recording. AMT uptake in each tuber was visually evaluated on PET coregistered with MRI. An AMT uptake index based on lesional/healthy cortex ratio was also calculated. Sensitivity and specificity values of AMT-PET in the detection of epileptogenic lesions were obtained, using the available electroclinical and neuroimaging evidence as the gold standard for epileptogenicity. A total of 126 tubers were identified. Two of 12 patients demonstrated a tuber with clearly increased AMT uptake, one of whom also showed a subtle increased AMT uptake in another contralateral tuber. Four other patients showed only subtle increased AMT uptake. The only two tubers with clearly increased AMT uptake proved to be epileptogenic based on intracerebral EEG data, whereas none of the tubers associated with subtle increased AMT uptake were involved at ictal onset. In a per-patient approach, this yielded a sensitivity of clearly increased AMT uptake in detecting tuber epileptogenicity of 17% (2/12 patients), whereas the per-lesion sensitivity and specificity were 12% (95% confidence interval [CI]: 3-34%) and 100% (95% CI: 97-100%), respectively. AMT-PET is a specific neuroimaging technique in the identification of epileptogenic tubers in TSC. Despite its low sensitivity, the clinical usefulness of AMT-PET still deserves to be considered according to the challenging complexity of epilepsy surgery in tuberous sclerosis. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Poverty, Ethnic Identity, and Health Care.

ERIC Educational Resources Information Center

Bullough, Bonnie; Bullough, Vern L.

This book tries to present the health care problems of the major ethnic minority groups in perspective. Although poverty is probably the most crucial variable in the genesis of these problems, there are still many subtle and not so subtle forms of discrimination operating in the health field. Unfortunately, discrimination in other aspects of…

A Rasch Analysis of the Substance Abuse Subtle Screening Inventory-3

ERIC Educational Resources Information Center

Hill, Tara M.; Laux, John M.; Stone, Gregory; Dupuy, Paula; Scott, Holly

2013-01-01

Rasch analysis of the Substance Abuse Subtle Screening Inventory-3 (SASSI-3; F. G. Miller & Lazowski, 1999) indicated that the SASSI-3 meets fundamental measurement properties; however, the authors of the current study recommend the elimination of nonfunctioning items and the improvement of response options for the face valid scales to…

The Substance Abuse Subtle Screening Inventory-3 and Stages of Change: A Screening Validity Study

ERIC Educational Resources Information Center

Laux, John M.; Piazza, Nick J.; Salyers, Kathleen; Roseman, Christopher P.

2012-01-01

The sensitivity of the Substance Abuse Subtle Screening Inventory-3 (SASSI-3) was examined among substance-dependent adults enrolled in a family drug court. The SASSI-3 had a high sensitivity rate with this population, even across varying levels of motivation to change. (Contains 2 tables.)

A Psychometric Study of the Substance Abuse Subtle Screening Inventory-3 Using Rasch Analysis

ERIC Educational Resources Information Center

Hill, Tara M.

2009-01-01

The Substance Abuse Subtle Screening Inventory-3 (SASSI-3; Miller & Lazowski, 1999) is a popular screening instrument used to assist professionals in the assessment of individuals who may be substance dependent. Many researchers have reported reliability and validity results on this instrument with mixed results, which at times have…

Feeding and Reflux: A Parent & Professional Perspective

ERIC Educational Resources Information Center

Roche, William J.; Martorana, Pamela; Vitello, Louise; Eicher, Peggy S.; LaCour, Tricia

2008-01-01

Gastroesophageal reflux (GER) as a cause of an infant or child's refusal to eat is becoming better recognized. However, the many more subtle influences that reflux can have on feeding are less often recognized. Although vomiting after meals is the classic presentation, infants and children may present with a variety of more subtle symptoms less…

An Examination of the Substance Abuse Subtle Screening Inventory-3 Correctional Scale in a College Student Population

ERIC Educational Resources Information Center

Burck, Andrew M.; Laux, John M.; Ritchie, Martin; Baker, David

2008-01-01

In this study, the authors examined the Substance Abuse Subtle Screening Inventory-3 Correctional scale's sensitivity and specificity at detecting college students' illegal behaviors. Sensitivity was strong, but specificity was weak. Implications for counseling and suggestions for future research are included. (Contains 3 tables.)

Integration Moves Backward in the 70s

ERIC Educational Resources Information Center

Coffin, Gregory C.

1973-01-01

Suggests that the failure of (1) school boards and superintendents to recognize the evil inherent in segragated schools -- both black and white -- and their lack of courage in dealing with the problem and (2) educators to recognize the subtle and not so subtle racial bias of their curriculum, curricular materials, personnel, and staffing practices…

Poisoned Waters: Sexual Harassment and the College Climate.

ERIC Educational Resources Information Center

Shepela, Sharon Toffey; Levesque, Laurie L.

1998-01-01

Studied sexual harassment, including mild forms of harassment, experienced by male and female college students (n=369). Men and women were harassed with similar frequency, and more subtle forms of harassment were common. The very frequency of these subtle behaviors may explain why they are less likely to be labeled as harassment. (SLD)

Black Women in Academe. Issues and Strategies.

ERIC Educational Resources Information Center

Moses, Yolanda T.

The climate for black women students, faculty members, and administrators in both predominantly white as well as historically black colleges and universities is explored, focusing on the subtle and not so subtle ways that race and gender stereotypes can combine to create double obstacles for black women. Black women students, faculty members, and…

42 CFR 37.53 - Notification of abnormal roentgenographic findings.

Code of Federal Regulations, 2010 CFR

2010-10-01

... suggesting, enlarged heart, tuberculosis, lung cancer, or any other significant abnormal findings other than... files and the most recent examination was interpreted to show enlarged heart, tuberculosis, cancer...

42 CFR 37.53 - Notification of abnormal roentgenographic findings.

Code of Federal Regulations, 2011 CFR

2011-10-01

... suggesting, enlarged heart, tuberculosis, lung cancer, or any other significant abnormal findings other than... files and the most recent examination was interpreted to show enlarged heart, tuberculosis, cancer...

Identifying aMCI with Functional Connectivity Network Characteristics based on Subtle AAL Atlas.

PubMed

Zhuo, Zhizheng; Mo, Xiao; Ma, Xiangyu; Han, Ying; Li, Haiyun

2018-05-02

To investigate the subtle functional connectivity alterations of aMCI based on AAL atlas with 1024 regions (AAL_1024 atlas). Functional MRI images of 32 aMCI patients (Male/Female:15/17, Ages:66.8±8.36y) and 35 normal controls (Male/Female:13/22, Ages: 62.4±8.14y) were obtained in this study. Firstly, functional connectivity networks were constructed by Pearson's Correlation based on the subtle AAL_1024 atlas. Then, local and global network parameters were calculated from the thresholding functional connectivity matrices. Finally, multiple-comparison analysis was performed on these parameters to find the functional network alterations of aMCI. And furtherly, a couple of classifiers were adopted to identify the aMCI by using the network parameters. More subtle local brain functional alterations were detected by using AAL_1024 atlas. And the predominate nodes including hippocampus, inferior temporal gyrus, inferior parietal gyrus were identified which was not detected by AAL_90 atlas. The identification of aMCI from normal controls were significantly improved with the highest accuracy (98.51%), sensitivity (100%) and specificity (97.14%) compared to those (88.06%, 84.38% and 91.43% for the highest accuracy, sensitivity and specificity respectively) obtained by using AAL_90 atlas. More subtle functional connectivity alterations of aMCI could be found based on AAL_1024 atlas than those based on AAL_90 atlas. Besides, the identification of aMCI could also be improved. Copyright © 2018. Published by Elsevier B.V.

Structure and stability of internodal myelin in mouse models of hereditary neuropathy.

PubMed

Avila, Robin L; Inouye, Hideyo; Baek, Rena C; Yin, Xinghua; Trapp, Bruce D; Feltri, M Laura; Wrabetz, Lawrence; Kirschner, Daniel A

2005-11-01

Peripheral neuropathies often result in abnormalities in the structure of internodal myelin, including changes in period and membrane packing, as observed by electron microscopy (EM). Mutations in the gene that encodes the major adhesive structural protein of internodal myelin in the peripheral nervous system of humans and mice--P0 glycoprotein--correlate with these defects. The mechanisms by which P0 mutations interfere with myelin packing and stability are not well understood and cannot be provided by EM studies that give static and qualitative information on fixed material. To gain insights into the pathogenesis of mutant P0, we used x-ray diffraction, which can detect more subtle and dynamic changes in native myelin, to investigate myelin structure in sciatic nerves from murine models of hereditary neuropathies. We used mice with disruption of one or both copies of the P0 gene (models of Charcot-Marie-Tooth-like neuropathy [CMT1B] or Dejerine-Sottas-like neuropathy) and mice with a CMT1B resulting from a transgene encoding P0 with an amino terminal myc-tag. To directly test the structural role of P0, we also examined a mouse that expresses P0 instead of proteolipid protein in central nervous system myelin. To link our findings on unfixed nerves with EM results, we analyzed x-ray patterns from unembedded, aldehyde-fixed nerves and from plastic-embedded nerves. From the x-ray patterns recorded from whole nerves, we assessed the amount of myelin and its quality (i.e. relative thickness and regularity). Among sciatic nerves having different levels of P0, we found that unfixed nerves and, to a lesser extent, fixed but unembedded nerves gave diffraction patterns of sufficient quality to distinguish periods, sometimes differing by a few Angstroms. Certain packing abnormalities were preserved qualitatively by aldehyde fixation, and the relative amount and structural integrity of myelin among nerves could be distinguished. Measurements from the same nerve over time showed that the amount of P0 affected myelin's stability against swelling, thus directly supporting the hypothesis that packing defects underlie instability in "live" or intact myelin. Our findings demonstrate that diffraction can provide a quantitative basis for understanding, at a molecular level, the membrane packing defects that occur in internodal myelin in demyelinating peripheral neuropathies.

First Case Report of Smith-Magenis Syndrome (SMS) Among the Arab Community in Nazareth: View and Overview.

PubMed

Nijim, Yousif; Adawi, Amin; Bisharat, Bishara; Bowirrat, Abdalla

2016-01-01

Smith-Magenis syndrome (SMS0) is a complex and rare genetic multisystem disorder characterized by a variable pattern of cognitive deficits accompanied by a1 distinctive behavioral phenotype. SMS is characterized by subtle facial dysmorphology, short stature, sleep disturbances, and neurobehavioral abnormalities. Little is known about the manifestation of his unique case among Arab population and its strategic treatment.This study comes to present a case of SMS in an Arab newborn male who was born in spontaneous delivery on June 29, 2015, with tachypnea, tracheomalacia, and mild hypotonia. The newborn was admitted on the Neonatal Intensive Care Unit (NICU), and various laboratory examinations and clinical examinations were performed.Throughout his hospitalization, feeding difficulties appeared and thus a peripheral venous catheter was inserted in the left leg.After 22 days of follow-up and hospitalizations, the patient status improved and he was discharged with recommendations to be in follow up in pediatric outpatient clinic.However, notwithstanding the different investigations, intermittent tachypnea continued at a rate of 72 to 77 breaths/min. Search for diagnosis begin intensively owing to persistence of tachypnia, mild hypotonia, feeding difficulties, sleep disturbances, and mild dysmorphic facial features. Suspicions of genetic abnormalities were considered and blood samples were sent for chromosome analysis and for fluorescent in situ hybridization (FISH) testing.The genetic results revealed the following: cytogenetic findings: 46, XY, del(17)(p11.2) and the FISH results: del(17)(p11.2p11.2) (D17S29). The chromosome diagnosis revealed an interstitial deletion of 17p11.2 and the diagnosis of the SMS was confirmed.Accurate clinical diagnosis, therapeutic assessments and a holistic management plans, including multidiscipline therapeutic strategies, periodic neuro-developmental assessments, and an early intervention programs, are recommended.However, cytogenetic analysis or FISH using an RAI1-specific probe is the most frequently used technique for DS. Sleep and behavioral disturbances treatment include a combination of the daytime dose of acebutolol with an evening oral dose of melatonin. Melatonin as chronobiotic, antioxidant, and analgesic agent showed to be effective in different primary sleep disorders and in those associated with neurobehavioral disorders. Based on the beneficial effect of melatonin, it will be useful to use serum levels of melatonin as a follow-up test.

Heel-toe running: A new look at the influence of foot strike pattern on impact force.

PubMed

Mercer, John A; Horsch, Sarah

2015-06-01

It is important to understand the factors that influence the impact force observed during running, since the impact force is likely to be related to overuse injuries. The purpose of this study was to compare the impact force during running when participants were instructed to use different foot strike patterns: obvious heel strike (Obvious-HS), subtle heel strike (Subtle-HS), midfoot strike (Mid-FS), and fore foot strike (Fore-FS) patterns. Participants ( n  = 10, 25 ± 5.7 years, 70.2 ± 12.1 kg, 174.6 ± 7.2 cm) completed four foot strike patterns while running over ground: Obvious-HS, Subtle-HS, Mid-FS, and Fore-FS. Speed was controlled between conditions (random order). Vertical ground reaction forces were recorded (1000 Hz) along with the impact force, peak force, and stance time for analysis. A repeated measures analysis of variance was used to compare each variable across foot strike instructions, with post hoc comparisons contrasting Obvious-HS to each of the other conditions. Impact force was influenced by foot strike instructions, with Obvious-HS being greater than Subtle-HS and Fore-FS ( p  < 0.05) but not different from Mid-FS ( p  > 0.05). The peak force was not influenced by foot strike instructions ( p  > 0.05); stance time was longer during Obvious-HS than during Mid-FS or Fore-FS ( p  < 0.05), but not different from Subtle-HS ( p  > 0.05). The unique observation of this study was that impact force was different when participants were instructed to run with either an Obvious-HS or a Subtle-HS at contact. Both these foot strike patterns would have been considered rear foot strike patterns, suggesting that something other than which specific part of the foot strikes the ground initially influenced impact force.

A temporal examination of co-activated emotion valence networks in schizophrenia and schizotypy

PubMed Central

Cohen, Alex S.; Callaway, Dallas A.; Mitchell, Kyle R.; Larsen, Jeff T.; Strauss, Gregory P.

2016-01-01

Emotional abnormalities are prominent across the schizophrenia spectrum. To better define these abnormalities, we examined state emotional functions across opposing ends of the spectrum, notably in chronic outpatients with schizophrenia (Study 1) and college students with psychometrically defined schizotypy (Study 2). In line with existing studies, we predicted that individuals with schizophrenia would show unusually co-activated positive and negative emotions while college students with schizotypy would show abnormally low positive and abnormally high negative emotions. Drawing from the affective science literature, we employed continuous emotion ratings in response to a dynamic and evocatively “bittersweet” stimulus. Participants included 27 individuals with schizophrenia, 39 individuals with psychometrically defined schizotypy and 26 community and 35 college control participants. Participants continuously rated their state happiness and sadness throughout a six-minute clip from a tragicomic film (i.e., Life is Beautiful). In contrast to expectations as well as the extant literature, there were no state emotional abnormalities noted from either schizophrenia-spectrum group. Of particular note, neither individuals with schizophrenia nor individuals with schizotypy were abnormal in their experience of state negative, positive or coactivated emotions. Conversely, abnormalities in trait emotion were observed in both groups relative to their respective control groups. These results help confirm that the schizophrenia-spectrum is not characterized by deficits in state emotional experience and suggest that sadness is not abnormally co-activated with pleasant emotions. These results are critical for clarifying the “chronometry” of emotional dysfunctions across the schizophrenia-spectrum. PMID:26711714

Effects of resocialization on post-weaning social isolation-induced abnormal aggression and social deficits in rats.

PubMed

Tulogdi, Aron; Tóth, Máté; Barsvári, Beáta; Biró, László; Mikics, Eva; Haller, József

2014-01-01

As previously shown, rats isolated from weaning develop abnormal social and aggressive behavior characterized by biting attacks targeting vulnerable body parts of opponents, reduced attack signaling, and increased defensive behavior despite increased attack counts. Here we studied whether this form of violent aggression could be reversed by resocialization in adulthood. During the first weak of resocialization, isolation-reared rats showed multiple social deficits including increased defensiveness and decreased huddling during sleep. Deficits were markedly attenuated in the second and third weeks. Despite improved social functioning in groups, isolated rats readily showed abnormal features of aggression in a resident-intruder test performed after the 3-week-long resocialization. Thus, post-weaning social isolation-induced deficits in prosocial behavior were eliminated by resocialization during adulthood, but abnormal aggression was resilient to this treatment. Findings are compared to those obtained in humans who suffered early social maltreatment, and who also show social deficits and dysfunctional aggression in adulthood. © 2013 Wiley Periodicals, Inc.

Solitary tuberculous brain lesions: 24 new cases and a review of the literature.

PubMed

Psimaras, D; Bonnet, C; Heinzmann, A; Cárdenas, G; Hernández José Luis, S; Tungaria, A; Behari, S; Lacrois, D; Mokhtari, K; Karantoni, E; Sokrab Tag, E; Idris Mohamed, N; Sönmez, G; Caumes, E; Roze, E

2014-01-01

A solitary tuberculous brain lesion (STBL) can be difficult to distinguish from a glioma, metastasis or other infectious disease, especially from a pyogenic brain abscess. We analyzed the clinical characteristics, diagnostic procedures and outcomes of 24 patients with STBL diagnosed in three centers from France, India and Mexico. We also reviewed 92 STBL cases previously reported in the literature. General symptoms were found in 54% of our patients, including enlarged lymph nodes in 20%. Cerebrospinal fluid was typically abnormal, with lymphocytic pleocytosis and a high protein level. The lung CT scan was abnormal in 56% of patients, showing lymphadenopathy or pachipleuritis. Brain MRI or CT was always abnormal, showing contrast-enhanced lesions. Typically, MRI abnormalities were hypointense on T1-weighted sequences, while T2-weighted sequences showed both a peripheral hypersignal and a central hyposignal. The diagnosis was documented microbiologically or supported histologically in 71% of cases. Clinical outcome was good in 83% of cases. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Complete trisomy 9 with unusual phenotypic associations: Dandy-Walker malformation, cleft lip and cleft palate, cardiovascular abnormalities.

PubMed

Tonni, Gabriele; Lituania, Mario; Chitayat, David; Bonasoni, Maria Paola; Keating, Sarah; Thompson, Megan; Shannon, Patrick

2014-12-01

Trisomy 9 is a rare chromosomal abnormality usually associated with first-trimester miscarriage; few fetuses survive until the second trimester. We report two new cases of complete trisomy 9 that both present unusual phenotypic associations, and we analyze the genetic pathway involved in this chromosomal abnormality. The first fetus investigated showed Dandy-Walker malformation, cleft lip, and cleft palate) at the second trimester scan. Cardiovascular abnormalities were characterized by a right-sided, U-shaped aortic arch associated with a ventricular septal defect (VSD). Symmetrical intrauterine growth restriction and multicystic dysplastic kidney disease were associated findings. The second fetus showed a dysmorphic face, bilateral cleft lip, hypoplastic corpus callosum, and a Dandy-Walker malformation. Postmortem examination revealed cardiovascular abnormalities such as persistent left superior vena cava draining into the coronary sinus, membranous ventricular septal defect, overriding aorta, pulmonary valve with two cusps and three sinuses, and the origin of the left subclavian artery distal to the junction of ductus arteriosus and aortic arch. Complete trisomy 9 may result in a wide spectrum of congenital abnormalities, and the presented case series contributes further details on the phenotype of this rare aneuploidy. Copyright © 2014. Published by Elsevier B.V.

ERG and OCT findings of a patient with a clinical diagnosis of occult macular dystrophy in a patient of Ashkenazi Jewish descent associated with a novel mutation in the gene encoding RP1L1.

PubMed

Saffra, Norman; Seidman, Carly Jane; Rakhamimov, Aleksandr; Tsang, Stephen H

2017-05-04

A 57-year-old man with a past medical history of diabetes presented for consultation with a several year history of slowly progressive vision loss in both eyes, which continued to deteriorate over 7 years of follow-up. Multimodal imaging was performed and was significant for the following: on spectral domain optical coherence tomography, a gap lesion was present in the ellipsoid layer, beneath the umbo, as well as subtle macular changes on auto fluorescence imaging. Multifocal electroretinography was performed and was abnormal, and a clinical diagnosis of occult macular dystrophy was made. The patient was subsequently evaluated with genetic testing that revealed a novel p.P73S:c 217C>T nonsense mutation within the retinitis pigmentosa 1-like-1 (RP1L1) gene. The clinical significance of the identified variation will require further investigation. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Conditional Creation and Rescue of Nipbl-Deficiency in Mice Reveals Multiple Determinants of Risk for Congenital Heart Defects

PubMed Central

Jacobs, Russell E.; Lopez-Burks, Martha E.; Choi, Hojae; Wikenheiser, Jamie; Hallgrimsson, Benedikt; Jamniczky, Heather A.; Fraser, Scott E.; Lander, Arthur D.; Calof, Anne L.

2016-01-01

Elucidating the causes of congenital heart defects is made difficult by the complex morphogenesis of the mammalian heart, which takes place early in development, involves contributions from multiple germ layers, and is controlled by many genes. Here, we use a conditional/invertible genetic strategy to identify the cell lineage(s) responsible for the development of heart defects in a Nipbl-deficient mouse model of Cornelia de Lange Syndrome, in which global yet subtle transcriptional dysregulation leads to development of atrial septal defects (ASDs) at high frequency. Using an approach that allows for recombinase-mediated creation or rescue of Nipbl deficiency in different lineages, we uncover complex interactions between the cardiac mesoderm, endoderm, and the rest of the embryo, whereby the risk conferred by genetic abnormality in any one lineage is modified, in a surprisingly non-additive way, by the status of others. We argue that these results are best understood in the context of a model in which the risk of heart defects is associated with the adequacy of early progenitor cell populations relative to the sizes of the structures they must eventually form. PMID:27606604

Exposure misclassification due to residential mobility during pregnancy.

PubMed

Hodgson, Susan; Lurz, Peter W W; Shirley, Mark D F; Bythell, Mary; Rankin, Judith

2015-06-01

Pregnant women are a highly mobile group, yet studies suggest exposure error due to migration in pregnancy is minimal. We aimed to investigate the impact of maternal residential mobility on exposure to environmental variables (urban fabric, roads and air pollution (PM10 and NO₂)) and socio-economic factors (deprivation) that varied spatially and temporally. We used data on residential histories for deliveries at ≥ 24 weeks gestation recorded by the Northern Congenital Abnormality Survey, 2000-2008 (n=5399) to compare: (a) exposure at conception assigned to maternal postcode at delivery versus maternal postcode at conception, and (b) exposure at conception assigned to maternal postcode at delivery versus mean exposure based on residences throughout pregnancy. In this population, 24.4% of women moved during pregnancy. Depending on the exposure variable assessed, 1-12% of women overall were assigned an exposure at delivery >1 SD different to that at conception, and 2-25% assigned an exposure at delivery >1 SD different to the mean exposure throughout pregnancy. To meaningfully explore the subtle associations between environmental exposures and health, consideration must be given to error introduced by residential mobility. Copyright © 2015 The Authors. Published by Elsevier GmbH.. All rights reserved.

Optical imaging of RNAi-mediated silencing of cancer

NASA Astrophysics Data System (ADS)

Ochiya, Takahiro; Honma, Kimi; Takeshita, Fumitaka; Nagahara, Shunji

2008-02-01

RNAi has rapidly become a powerful tool for drug target discovery and validation in an in vitro culture system and, consequently, interest is rapidly growing for extension of its application to in vivo systems, such as animal disease models and human therapeutics. Cancer is one obvious application for RNAi therapeutics, because abnormal gene expression is thought to contribute to the pathogenesis and maintenance of the malignant phenotype of cancer and thereby many oncogenes and cell-signaling molecules present enticing drug target possibilities. RNAi, potent and specific, could silence tumor-related genes and would appear to be a rational approach to inhibit tumor growth. In subsequent in vivo studies, the appropriate cancer model must be developed for an evaluation of siRNA effects on tumors. How to evaluate the effect of siRNA in an in vivo therapeutic model is also important. Accelerating the analyses of these models and improving their predictive value through whole animal imaging methods, which provide cancer inhibition in real time and are sensitive to subtle changes, are crucial for rapid advancement of these approaches. Bioluminescent imaging is one of these optically based imaging methods that enable rapid in vivo analyses of a variety of cellular and molecular events with extreme sensitivity.