Association of MTHFR polymorphisms and chromosomal abnormalities in leukemia.

PubMed

Sinthuwiwat, Thivaratana; Poowasanpetch, Phanasit; Wongngamrungroj, Angsana; Soonklang, Kamonwan; Promso, Somying; Auewarakul, Chirayu; Tocharoentanaphol, Chintana

2012-01-01

Genetic variation in MTHFR gene might explain the interindividual differences in the reduction of DNA repaired and the increase of chromosome breakage and damage. Nowadays, chromosomal rearrangement is recognized as a major cause of lymphoid malignancies. In addition, the association of MTHFR polymorphisms with aneuploidy was found in several studies, making the MTHFR gene as a good candidate for leukemia etiology. Therefore, in this study, we investigated the common sequence variation, 677C>T and 1298A>C in the MTHFR gene of 350 fixed cell specimens archived after chromosome analysis. The distribution of the MTHFR polymorphisms frequency was compared in leukemic patients with structural chromosome abnormality and chromosome aneuploidy, as well as in those with no evidence of chromosome abnormalities. We observed a significant decrease in the distribution of T allele in 677C>T polymorphisms among patients with chromosomal abnormalities including both structural aberration and aneuploidy. The same significance result also found in patients with structural aberration when compare with the normal karyotype patients. Suggesting that polymorphism in the MTHFR gene was involved in chromosome abnormalities of leukemia. However, further investigation on the correlation with the specific types of chromosomal aberrations is needed.

[Chromosome examination of missed abortion patients].

PubMed

Hu, Haomei; Yang, Hua; Yin, Zhenhui; Zhao, Lu

2015-09-15

To investigate the relationship between the missed abortion and chromosome abnormality and guide the healthy birth. From June 2014 to April 2015 in Tianjin central hospital of gynecology and obstetrics, we examined venous blood from 90 missed abortion couples for chromosome karyotype by lymphocyte culture method and we also examined their chromosome karyotype of abortion villus samples by high-throughput sequencing technologies. Out of the 90 couples' blood chromosome examinations, 7 were abnormal, and the abnormal rate was 3.89%, including 3 cases reciprocal translocation, 2 cases robertsonian translocation and 2 cases inversion. Abortion villus samples from the same population were also checked, of which 85 cases succeeded, with the success rate of 94.4%. Among them, villi chromosome abnormalities were found in 50 cases, including 39 cases with abnormal chromosome numbers, 11 cases with abnormal chromosome structure, and the total abnormal rate was 58.8%. In addition, the villi chromosome abnormality rate of patients with recurrent missed abortion (≥2 times) and first missed abortion were 61.7% and 55.2%, respectively, and the difference was not significant (P>0.05). The villi chromosome abnormality rate of pregnant women with age≥35 years old was 71.1%, while the pregnant women with aged <35 years old was 45% (P<0.05). Chromosome abnormality is an important cause of missed abortion; villi chromosome abnormality rate has nothing to do with the number of missed abortion; pregnant woman with age≥35 years old is risk factor of the villi chromosome abnormality.

Sensory aspects of movement disorders

PubMed Central

Patel, Neepa; Jankovic, Joseph; Hallett, Mark

2016-01-01

Movement disorders, which include disorders such as Parkinson’s disease, dystonia, Tourette’s syndrome, restless legs syndrome, and akathisia, have traditionally been considered to be disorders of impaired motor control resulting predominantly from dysfunction of the basal ganglia. This notion has been revised largely because of increasing recognition of associated behavioural, psychiatric, autonomic, and other non-motor symptoms. The sensory aspects of movement disorders include intrinsic sensory abnormalities and the effects of external sensory input on the underlying motor abnormality. The basal ganglia, cerebellum, thalamus, and their connections, coupled with altered sensory input, seem to play a key part in abnormal sensorimotor integration. However, more investigation into the phenomenology and physiological basis of sensory abnormalities, and about the role of the basal ganglia, cerebellum, and related structures in somatosensory processing, and its effect on motor control, is needed. PMID:24331796

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.

Detecting rare, abnormally large grains by x-ray diffraction

DOE PAGES

Boyce, Brad L.; Furnish, Timothy Allen; Padilla, H. A.; ...

2015-07-16

Bimodal grain structures are common in many alloys, arising from a number of different causes including incomplete recrystallization and abnormal grain growth. These bimodal grain structures have important technological implications, such as the well-known Goss texture which is now a cornerstone for electrical steels. Yet our ability to detect bimodal grain distributions is largely confined to brute force cross-sectional metallography. The present study presents a new method for rapid detection of unusually large grains embedded in a sea of much finer grains. Traditional X-ray diffraction-based grain size measurement techniques such as Scherrer, Williamson–Hall, or Warren–Averbach rely on peak breadth andmore » shape to extract information regarding the average crystallite size. However, these line broadening techniques are not well suited to identify a very small fraction of abnormally large grains. The present method utilizes statistically anomalous intensity spikes in the Bragg peak to identify regions where abnormally large grains are contributing to diffraction. This needle-in-a-haystack technique is demonstrated on a nanocrystalline Ni–Fe alloy which has undergone fatigue-induced abnormal grain growth. In this demonstration, the technique readily identifies a few large grains that occupy <0.00001 % of the interrogation volume. Finally, while the technique is demonstrated in the current study on nanocrystalline metal, it would likely apply to any bimodal polycrystal including ultrafine grained and fine microcrystalline materials with sufficiently distinct bimodal grain statistics.« less

Clinical and mutational spectrum in Korean patients with Rubinstein-Taybi syndrome: the spectrum of brain MRI abnormalities.

PubMed

Lee, Jin Sook; Byun, Christine K; Kim, Hunmin; Lim, Byung Chan; Hwang, Hee; Choi, Ji Eun; Hwang, Yong Seung; Seong, Moon-Woo; Park, Sung Sup; Kim, Ki Joong; Chae, Jong-Hee

2015-04-01

Rubinstein-Taybi syndrome (RSTS) is one of the neurodevelopmental disorders caused by mutations of epigenetic genes. The CREBBP gene is the most common causative gene, encoding the CREB-binding protein with histone acetyltransferase (HAT) activity, an epigenetic modulator. To date, there have been few reports on the structural abnormalities of the brain in RSTS patients. In addition, there are no reports on the analysis of CREBBP mutations in Korean RSTS patients. We performed mutational analyses on 16 unrelated patients with RSTS, with diagnosis based on the typical clinical features. Their medical records and brain MRI images were reviewed retrospectively. Ten of 16 patients (62.5%) had mutations in the CREBBP gene. The mutations included five frameshift mutations (31.2%), two nonsense mutations (12.5%), and three multiexon deletions (18.8%). There were no remarkable significant differences in the clinical features between those with and without a CREBBP mutation, although brain MRI abnormalities were more frequently observed in those with a CREBBP mutation. Seven of 10 patients in whom brain imaging was performed had structural abnormalities, including Chiari malformation type 1, thinning of the corpus callosum, and delayed myelination. There were no differences in delayed development or cognitive impairment between those with and without abnormal brain images, while epilepsy was involved in two patients who had abnormalities on brain MRI images. We investigated the spectrum of CREBBP mutations in Korean patients with RSTS for the first time. Eight novel mutations extended the genetic spectrum of CREBBP mutations in RSTS patients. This is also the first study showing the prevalence and spectrum of abnormalities on brain MRI in RSTS patients. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Schizophrenia and the corpus callosum: developmental, structural and functional relationships.

PubMed

David, A S

1994-10-20

Several empirical and theoretical connections exist between schizophrenia and the corpus callosum: (1) disconnection symptoms resemble certain psychotic phenomena; (2) abnormal interhemispheric transmission could explain typically schizophrenic phenomena; (3) cases of psychosis have been found in association with complete and partial agenesis of the callosum; (4) experimental neuropsychology with schizophrenic patients has revealed abnormal patterns of interhemispheric transfer; (5) studies using magnetic resonance imaging have shown abnormal callosal dimensions in schizophrenic patients. The evidence in support of these links is discussed critically. Novel neuropsychological approaches in the study of information transfer in the visual modality between the cerebral hemispheres, consistent with callosal hyperconnectivity in schizophrenic patients but not matched psychiatric controls are highlighted. Some suggestions for further work including integrating functional and structural measures are offered.

Epilepsy in the setting of full trisomy 18: A multicenter study on 18 affected children with and without structural brain abnormalities.

PubMed

Matricardi, Sara; Spalice, Alberto; Salpietro, Vincenzo; Di Rosa, Gabriella; Balistreri, Maria Cristina; Grosso, Salvatore; Parisi, Pasquale; Elia, Maurizio; Striano, Pasquale; Accorsi, Patrizia; Cusmai, Raffaella; Specchio, Nicola; Coppola, Giangennaro; Savasta, Salvatore; Carotenuto, Marco; Tozzi, Elisabetta; Ferrara, Pietro; Ruggieri, Martino; Verrotti, Alberto

2016-09-01

This paper reports on the clinical aspects, electroencephalographic (EEG) features, and neuroimaging findings in children with full trisomy 18 and associated epilepsy, and compares the evolution and outcome of their neurological phenotype. We retrospectively studied 18 patients (10 males and 8 females; aged 14 months to 9 years) with full trisomy 18 and epilepsy. All patients underwent comprehensive assessment including neuroimaging studies of the brain. We divided patients into two groups according to neuroimaging findings: (Group 1) 10 patients harboring structural brain malformations, and (Group 2) 8 patients with normal brain images. Group 1 had a significantly earlier age at seizure onset (2 months) compared to Group 2 (21 months). The seizure semiology was more severe in Group 1, who presented multiple seizure types, need for polytherapy (80% of patients), multifocal EEG abnormalities and poorer outcome (drug resistant epilepsy in 90% of patients) than Group 2 who presented a single seizure type, generalized or focal, and non-specific EEG pattern; these patients were successfully treated with monotherapy with good outcome. Imaging revealed a wide and complex spectrum of structural brain abnormalities including anomalies of the commissures, cerebellar malformations, cortical abnormalities, and various degrees of cortical atrophy. Epilepsy in full trisomy 18 may develop during the first months of life and can be associated with structural brain malformations. Patients with brain malformations can show multiple seizure types and can frequently be resistant to therapy with antiepileptic drugs. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Structural Brain Abnormalities of Attention-Deficit/Hyperactivity Disorder With Oppositional Defiant Disorder.

PubMed

Noordermeer, Siri D S; Luman, Marjolein; Greven, Corina U; Veroude, Kim; Faraone, Stephen V; Hartman, Catharina A; Hoekstra, Pieter J; Franke, Barbara; Buitelaar, Jan K; Heslenfeld, Dirk J; Oosterlaan, Jaap

2017-11-01

Attention-deficit/hyperactivity disorder (ADHD) is associated with structural abnormalities in total gray matter, basal ganglia, and cerebellum. Findings of structural abnormalities in frontal and temporal lobes, amygdala, and insula are less consistent. Remarkably, the impact of comorbid oppositional defiant disorder (ODD) (comorbidity rates up to 60%) on these neuroanatomical differences is scarcely studied, while ODD (in combination with conduct disorder) has been associated with structural abnormalities of the frontal lobe, amygdala, and insula. The aim of this study was to investigate the effect of comorbid ODD on cerebral volume and cortical thickness in ADHD. Three groups, 16 ± 3.5 years of age (mean ± SD; range 7-29 years), were studied on volumetric and cortical thickness characteristics using structural magnetic resonance imaging (surface-based morphometry): ADHD+ODD (n = 67), ADHD-only (n = 243), and control subjects (n = 233). Analyses included the moderators age, gender, IQ, and scan site. ADHD+ODD and ADHD-only showed volumetric reductions in total gray matter and (mainly) frontal brain areas. Stepwise volumetric reductions (ADHD+ODD < ADHD-only < control subjects) were found for mainly frontal regions, and ADHD+ODD was uniquely associated with reductions in several structures (e.g., the precuneus). In general, findings remained significant after accounting for ADHD symptom severity. There were no group differences in cortical thickness. Exploratory voxelwise analyses showed no group differences. ADHD+ODD and ADHD-only were associated with volumetric reductions in brain areas crucial for attention, (working) memory, and decision-making. Volumetric reductions of frontal lobes were largest in the ADHD+ODD group, possibly underlying observed larger impairments in neurocognitive functions. Previously reported striatal abnormalities in ADHD may be caused by comorbid conduct disorder rather than ODD. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Antenatal diagnosis of complete facial duplication--a case report of a rare craniofacial defect.

PubMed

Rai, V S; Gaffney, G; Manning, N; Pirrone, P G; Chamberlain, P F

1998-06-01

We report a case of the prenatal sonographic detection of facial duplication, the diprosopus abnormality, in a twin pregnancy. The characteristic sonographic features of the condition include duplication of eyes, mouth, nose and both mid- and anterior intracranial structures. A heart-shaped abnormality of the cranial vault should prompt more detailed examination for other supportive features of this rare condition.

[Cytogenetics, cytogenomics and cancer].

PubMed

Bernheim, Alain

2002-02-01

Chromosomal study in malignancy has demonstrated the pivotal role of somatic chromosomal rearrangements in oncogenesis and tumoral progression. Structural or quantitative these abnormalities can now be studied in great details with the various Fish techniques, including CGH on chromosomes or in a near future on micro arrays. The multistep pattern of most solid tumors is characterized and their genomic abnormalities more and more used for the diagnosis and the prognosis.

Comparison of brain volume abnormalities between ADHD and conduct disorder in adolescence

PubMed Central

Stevens, Michael C.; Haney-Caron, Emily

2012-01-01

Background Previous studies of brain structure abnormalities in conduct disorder and attention-deficit/hyperactivity disorder (ADHD) samples have been limited owing to cross-comorbidity, preventing clear understanding of which structural brain abnormalities might be specific to or shared by each disorder. To our knowledge, this study was the first direct comparison of grey and white matter volumes in diagnostically “pure” (i.e., no comorbidities) conduct disorder and ADHD samples. Methods Groups of adolescents with noncormobid conduct disorder and with noncomorbid, combined-subtype ADHD were compared with age- and sex-matched controls using DARTEL voxel-based analysis of T1-weighted brain structure images. Analysis of variance with post hoc analyses compared whole brain grey and white matter volumes among the groups. Results We included 24 adolescents in each study group. There was an overall 13% reduction in grey matter volume in adolescents with conduct disorder, reflecting numerous frontal, temporal, parietal and subcortical deficits. The same grey matter regions typically were not abnormal in those with ADHD. Deficits in frontal lobe regions previously identified in studies of patients with ADHD either were not detected, or group differences from controls were not as strong as those between the conduct disorder and control groups. White matter volume measurements did not differentiate conduct disorder and ADHD. Limitations Our modest sample sizes prevented meaningful examination of individual features of ADHD or conduct disorder, such as aggression, callousness, or hyperactive versus inattentive symptom subtypes. Conclusion The evidence supports theories of frontotemporal abnormalities in adolescents with conduct disorder, but raises questions about the prominence of frontal lobe and striatal structural abnormalities in those with noncomorbid, combined-subtype ADHD. The latter point is clinically important, given the widely held belief that ADHD is associated with numerous frontal lobe structural deficits, a conclusion that is not strongly supported following direct comparison of diagnostically pure groups. The results are important for future etiological studies, particularly those seeking to identify how early expression of specific brain structure abnormalities could potentiate the risk for antisocial behaviour. PMID:22663946

Structural brain changes versus self-report: machine-learning classification of chronic fatigue syndrome patients.

PubMed

Sevel, Landrew S; Boissoneault, Jeff; Letzen, Janelle E; Robinson, Michael E; Staud, Roland

2018-05-30

Chronic fatigue syndrome (CFS) is a disorder associated with fatigue, pain, and structural/functional abnormalities seen during magnetic resonance brain imaging (MRI). Therefore, we evaluated the performance of structural MRI (sMRI) abnormalities in the classification of CFS patients versus healthy controls and compared it to machine learning (ML) classification based upon self-report (SR). Participants included 18 CFS patients and 15 healthy controls (HC). All subjects underwent T1-weighted sMRI and provided visual analogue-scale ratings of fatigue, pain intensity, anxiety, depression, anger, and sleep quality. sMRI data were segmented using FreeSurfer and 61 regions based on functional and structural abnormalities previously reported in patients with CFS. Classification was performed in RapidMiner using a linear support vector machine and bootstrap optimism correction. We compared ML classifiers based on (1) 61 a priori sMRI regional estimates and (2) SR ratings. The sMRI model achieved 79.58% classification accuracy. The SR (accuracy = 95.95%) outperformed both sMRI models. Estimates from multiple brain areas related to cognition, emotion, and memory contributed strongly to group classification. This is the first ML-based group classification of CFS. Our findings suggest that sMRI abnormalities are useful for discriminating CFS patients from HC, but SR ratings remain most effective in classification tasks.

Pulmonary and cardiac pathology in sudden unexpected death in epilepsy (SUDEP).

PubMed

Nascimento, Fábio A; Tseng, Zian H; Palmiere, Cristian; Maleszewski, Joseph J; Shiomi, Takayuki; McCrillis, Aileen; Devinsky, Orrin

2017-08-01

To review studies on structural pulmonary and cardiac changes in SUDEP cases as well as studies showing pulmonary or cardiac structural changes in living epilepsy patients. We conducted electronic literature searches using the PubMed database for articles published in English, regardless of publication year, that included data on cardiac and/or pulmonary structural abnormalities in SUDEP cases or in living epilepsy patients during the postictal period. Fourteen postmortem studies reported pulmonary findings in SUDEP cases. Two focused mainly on assessing lung weights in SUDEP cases versus controls; no group difference was found. The other 12 reported descriptive autopsy findings. Among all SUDEP cases with available descriptive postmortem pulmonary examination, 72% had pulmonary changes, most often pulmonary edema/congestion, and, less frequently, intraalveolar hemorrhage. Eleven studies reported on cardiac pathology in SUDEP. Cardiac abnormalities were found in approximately one-fourth of cases. The most common findings were myocyte hypertrophy and myocardial fibrosis of various degrees. Among living epilepsy patients, postictal pulmonary pathology was the most commonly reported pulmonary abnormality and the most common postictal cardiac abnormality was transient left ventricular dysfunction - Takotsubo or neurogenic stunned myocardium. Cardiac and pulmonary pathological abnormalities are frequent among SUDEP cases, most commonly pulmonary edema/congestion and focal interstitial myocardial fibrosis. Most findings are not quantified, with subjective elements and undefined interobserver reliability, and lack of controls such as matched epilepsy patients who died from other causes. Further, studies have not systematically evaluated potential confounding factors, including postmortem interval to autopsy, paramedic resuscitation and IV fluids administration, underlying heart/lung disease, and risk factors for cardiac or pulmonary disease. Prospective studies with controls are needed to define the heart and lung changes in SUDEP and understand their potential relationship to mechanisms of death in SUDEP. Copyright © 2017 Elsevier Inc. All rights reserved.

Pregnancy interruption after second trimester diagnosis of fetal structural anomalies: the New Jersey Fetal Abnormalities Registry.

PubMed

Rauch, Eden R; Smulian, John C; DePrince, Kristin; Ananth, Cande V; Marcella, Stephen W

2005-10-01

The purpose of this study was to identify factors that predict a decision to interrupt a pregnancy in which there are fetal anomalies in the second trimester. The New Jersey Fetal Abnormalities Registry prospectively recruits and collects information on pregnancies (> or = 15 weeks of gestation) from New Jersey residents in whom a fetal structural anomaly has been suspected by maternal-fetal medicine specialists. Enrolled pregnancies that have major fetal structural abnormalities identified from 15 to 23 weeks of gestation were included. Outcomes were classified as either elective interruption or a natural pregnancy course, which might include a spontaneous fetal death or live birth. Predictors of elective interruption of pregnancy were examined with univariable and multivariable logistic regression analyses. Of the 97 cases, 33% of the women (n = 32) interrupted the pregnancy. Significant variables in the regression model that were associated with a decision to interrupt a pregnancy were earlier identification of fetal anomalies (19.0 +/- 2 weeks of gestation vs 20.5 +/- 2 weeks of gestation; P = .003), the presence of multiple anomalies (78% [25/32] vs 52% [33/63]; P = .01], and a presumption of lethality (56% [18/32] vs 14% [9/65]; P = .0001). These variables corresponded to an odds ratio for pregnancy interruption of 4.2 (95% CI, 1.0, 17.0) for multiple anomalies, 0.8 (95% CI, 0.7, 1.0) for each week of advancing gestational age, and 36.1 (95% CI, 2.9, 450.7) for presumed lethal abnormalities. Early diagnosis, the identification of multiple abnormalities, and an assessment of likely lethality of fetal anomalies are important factors for the optimization of parental autonomy in deciding pregnancy management.

Integrating normal and abnormal personality structure: a proposal for DSM-V.

PubMed

Widiger, Thomas A

2011-06-01

The personality disorders section of the American Psychiatric Association's fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) is currently being developed. The purpose of the current paper is to encourage the authors of DSM-V to integrate normal and abnormal personality structure within a common, integrative model, and to suggest that the optimal choice for such an integration would be the five-factor model (FFM) of general personality structure. A proposal for the classification of personality disorder from the perspective of the FFM is provided. Discussed as well are implications and issues associated with an FFM of personality disorder, including validity, coverage, feasibility, clinical utility, and treatment implications.

Evidence that the notochord may be pivotal in the development of sacral and anorectal malformations.

PubMed

Qi, Bao Quan; Beasley, Spencer W; Frizelle, Francis A

2003-09-01

The notochord is known to organize normal development of central axial structures, such as the spinal cord, vertebral column, and anorectum, but its role in abnormal development of these organs has not been well documented. The current study has used Ethylenethiourea to induce anorectal malformations in fetal rats, allowing investigation of abnormalities of the notochord and their relationship to the axial structural abnormalities that occur. Timed-mated pregnant rats were fed Ethylenethiourea by gavage on gestational day 10. Their embryos were harvested on gestational days 13 to 16 and sectioned in either the transverse or sagittal plane. Sections were stained with H and E and examined serially. Anorectal malformations were identified in 29 of 34 embryos and neural tube defects in 24, ranging from an accessory neural tube to lumbo-sacral rachischisis. There was no tail or only a rudimentary tail in the majority of embryos. Abnormalities of the notochord in the lumbo-sacral area included ventro-dorsal branching, ventral deviation, and ectopic notochordal tissue. Most abnormal notochord branches and ectopic notochordal tissue were abnormally close to or in contact with the wall of the cloaca or neural tube. Given the known role of the notochord in controlling normal development, this study would suggest that abnormal notochord development may be pivotal in producing neural tube defects and anorectal malformations, possibly by altering sonic hedgehog signalling.

Meta-analytic investigations of structural grey matter, executive domain-related functional activations, and white matter diffusivity in obsessive compulsive disorder: an integrative review.

PubMed

Eng, Goi Khia; Sim, Kang; Chen, Shen-Hsing Annabel

2015-05-01

Obsessive-compulsive disorder (OCD) is a debilitating disorder. However, existing neuroimaging findings involving executive function and structural abnormalities in OCD have been mixed. Here we conducted meta-analyses to investigate differences in OCD samples and controls in: Study 1 - grey matter structure; Study 2 - executive function task-related activations during (i) response inhibition, (ii) interference, and (iii) switching tasks; and Study 3 - white matter diffusivity. Results showed grey matter differences in the frontal, striatal, thalamus, parietal and cerebellar regions; task domain-specific neural differences in similar regions; and abnormal diffusivity in major white matter regions in OCD samples compared to controls. Our results reported concurrence of abnormal white matter diffusivity with corresponding abnormalities in grey matter and task-related functional activations. Our findings suggested the involvement of other brain regions not included in the cortico-striato-thalamo-cortical network, such as the cerebellum and parietal cortex, and questioned the involvement of the orbitofrontal region in OCD pathophysiology. Future research is needed to clarify the roles of these brain regions in the disorder. Copyright © 2015 Elsevier Ltd. All rights reserved.

Psychosocial correlates, outcome, and stability of abnormal adolescent eating behavior in community samples of young people.

PubMed

Steinhausen, Hans-Christoph; Gavez, Silvia; Winkler Metzke, Christa

2005-03-01

The current study investigated psychosocial correlates of abnormal adolescent eating behavior at three times during adolescence and young adulthood and its association with psychiatric diagnosis in young adulthood in a community sample. Sixty-four (10.5%) high-risk subjects (mean age 15 years) with abnormal eating behavior were identified at Time 1, another 252 (16.9%) were identified at Time 2 (mean age 16.2 years), and 164 (16.9%) were identified at Time 3 (mean age 19.7 years) and compared with three control groups matched for age and gender. Dependent measures included emotional and behavioral problems, life events, coping capacities, self-related cognition, social network, and family functions. Outcome was measured additionally by structured psychiatric interviews, and stability of abnormal eating behavior was studied in a longitudinal sample of 330 subjects. Few subjects showed more than one of five criteria of abnormal eating behavior. High-risk subjects shared a very similar pattern at all three times. They were characterized by higher scores for emotional and behavioral problems, more life events including more negative impact, less active coping, lower self-esteem, and less family cohesion. Among 10 major psychiatric disorders, only clinical eating disorders at Time 3 shared a significant association with abnormal eating disorder at the same time whereas high-risk status at Times 1 and 2 did not predict any psychiatric disorder at Time 3. Stability of abnormal eating behavior across time was very low. Stability of abnormal eating behavior across time was very low. Abnormal eating behavior in adolescence and young adulthood is clearly associated with various indicators of psychosocial maladaption. In adolescence, it does not significantly predict any psychiatric disorder including eating disorder in young adulthood and it is predominantly a transient feature. (c) 2005 by Wiley Periodicals, Inc.

[Clinical manifestation and cytogenetic analysis of 607 patients with Turner syndrome].

PubMed

Zheng, Jiemei; Liu, Zhiying; Xia, Pei; Lai, Yi; Wei, Yangjun; Liu, Yanyan; Chen, Jiurong; Qin, Li; Xie, Liangyu; Wang, He

2017-02-10

To explore the correlation between cytogenetic findings and clinical manifestations of Turner syndrome. 607 cases of cytogenetically diagnosed Turner syndrome, including those with a major manifestation of Turner syndrome, were analyzed with conventional G-banding. Correlation between the karyotypes and clinical features were analyzed. Among the 607 cases, there were 154 cases with monosomy X (25.37%). Mosaicism monosomy X was found in 240 patients (39.54%), which included 194 (80.83%) with a low proportion of 45,X (3 ≤ the number of 45, X ≤5, while the normal cells ≥ 30). Structural X chromosome abnormalities were found in 173 patients (28.50%). A supernumerary marker chromosome was found in 40 cases (6.59%). Most patients with typical manifestations of Turner syndrome were under 11 years of age and whose karyotypes were mainly 45,X. The karyotype of patients between 11 and 18 years old was mainly 45,X, 46,X,i(X)(q10) and mos45,X/46,X,i(X)(q10), which all had primary amenorrhea in addition to the typical clinical manifestations. The karyotype of patients over 18 years of age were mainly mosaicism with a low proportion of 45,X, whom all had primary infertility. 53 patients had a history of pregnancy, which included 48 with non-structural abnormalities of X chromosome and 5 with abnormal structure of X chromosome. Generally, the higher proportion of cells with an abnormal karyotype, the more severe were the clinical symptoms and the earlier clinical recognition. Karyotyping analysis can provide guidance for the early diagnosis of Turner syndrome, especially those with a low proportion of 45,X.

Peritoneal manifestations of fascioliasis on CT images: a new observation.

PubMed

Song, Kyoung Doo; Lim, Jae Hoon; Kim, Mi Jeong; Jang, Yun Jin; Kim, Jae Woon; Cho, Seung Hyun; Kwon, Jung Hyeok

2013-08-01

To describe peritoneal manifestations of fascioliasis on CT. We reviewed CT images in 31 patients with fascioliasis confirmed by enzyme-linked immunosorbent assay (ELISA) (n = 24) or surgery (n = 7). Image analyses were performed to identify hepatic, biliary, and peritoneal abnormalities. Hepatic abnormalities were seen in 28 (90.3 %) of the 31 patients. The most common finding was caves sign, which was present in 25 (80.1 %) patients. Three patients (9.7 %) presented with biliary abnormalities exhibiting dilatation and enhancing wall thickening of the bile duct, wall thickening of the gallbladder, and elongated structures in the bile duct or gallbladder. Peritoneal abnormalities were seen in 14 (45.2 %) of the 31 patients. The most common peritoneal abnormality was mesenteric or omental infiltration, which was seen in 9 (29.0 %) patients. Other peritoneal findings included lymph node enlargement (n = 7), ascites (n = 7), thickening of ligamentum teres (n = 2), and peritoneal mass (n = 2). Peritoneal manifestations of fascioliasis are relatively common, and CT findings include mesenteric or omental infiltration, lymph node enlargement, ascites, thickening of the ligamentum teres, and peritoneal masses.

The mushroom ribosome-inactivating protein lyophyllin exerts deleterious effects on mouse embryonic development in vitro.

PubMed

Chan, W Y; Ng, T B; Lam, Joyce S Y; Wong, Jack H; Chu, K T; Ngai, P H K; Lam, S K; Wang, H X

2010-01-01

Earlier investigations disclose that some plant ribosome-inactivating proteins (RIPs) adversely affect mouse embryonic development. In the present study, a mushroom RIP, namely lyophyllin from Lyophyllum shimeji, was isolated, partially sequenced, and its translation inhibitory activity determined. Its teratogenicity was studied by using a technique entailing microinjection and postimplantation whole-embryo culture. It was found that embryonic abnormalities during the period of organogenesis from E8.5 to E9.5 were induced by lyophyllin at a concentration as low as 50 microg/ml, and when the lyophyllin concentration was raised, the number of abnormal embryos increased, the final somite number decreased, and the abnormalities increased in severity. The affected embryonic structures included the cranial neural tube, forelimb buds, branchial arches, and body axis, while optic and otic placodes were more resistant. Lyophyllin at a concentration higher than 500 microg/ml also induced forebrain blisters within the cranial mesenchyme. When the abnormal embryos were examined histologically, an increase of cell death was found to be associated with abnormal structures, indicating that cell death may be one of the underlying causes of teratogenicity of the mushroom RIP. This constitutes the first report on the teratogenicity of a mushroom RIP.

Structural brain abnormalities in patients with inflammatory illness acquired following exposure to water-damaged buildings: a volumetric MRI study using NeuroQuant®.

PubMed

Shoemaker, Ritchie C; House, Dennis; Ryan, James C

2014-01-01

Executive cognitive and neurologic abnormalities are commonly seen in patients with a chronic inflammatory response syndrome (CIRS) acquired following exposure to the interior environment of water-damaged buildings (WDB), but a clear delineation of the physiologic or structural basis for these abnormalities has not been defined. Symptoms of affected patients routinely include headache, difficulty with recent memory, concentration, word finding, numbness, tingling, metallic taste and vertigo. Additionally, persistent proteomic abnormalities in inflammatory parameters that can alter permeability of the blood-brain barrier, such as C4a, TGFB1, MMP9 and VEGF, are notably present in cases of CIRS-WDB compared to controls, suggesting a consequent inflammatory injury to the central nervous system. Findings of gliotic areas in MRI scans in over 45% of CIRS-WDB cases compared to 5% of controls, as well as elevated lactate and depressed ratios of glutamate to glutamine, are regularly seen in MR spectroscopy of cases. This study used the volumetric software program NeuroQuant® (NQ) to determine specific brain structure volumes in consecutive patients (N=17) seen in a medical clinic specializing in inflammatory illness. Each of these patients presented for evaluation of an illness thought to be associated with exposure to WDB, and received an MRI that was evaluated by NQ. When compared to those of a medical control group (N=18), statistically significant differences in brain structure proportions were seen for patients in both hemispheres of two of the eleven brain regions analyzed; atrophy of the caudate nucleus and enlargement of the pallidum. In addition, the left amygdala and right forebrain were also enlarged. These volumetric abnormalities, in conjunction with concurrent abnormalities in inflammatory markers, suggest a model for structural brain injury in "mold illness" based on increased permeability of the blood-brain barrier due to chronic, systemic inflammation. Copyright © 2014 Elsevier Inc. All rights reserved.

LIPID ABNORMALITIES AND LIPID-BASED REPAIR STRATEGIES IN ATOPIC DERMATITIS

PubMed Central

Elias, Peter M.

2013-01-01

Prior studies have revealed the key roles played by Th1/Th2 cell dysregulation, IgE production, mast cell hyperactivity, and dendritic cell signaling in the evolution of the chronic, pruritic, inflammatory dermatosis that characterizes atopic dermatitis (AD). We review here increasing evidence that the inflammation in AD results primarily from inherited abnormalities in epidermal structural and enzymatic proteins that impact permeability barrier function. We also will show that the barrier defect can be attributed to a paracellular abnormality due to a variety of abnormalities in lipid composition, transport and extracellular organization. Accordingly, we also review the therapeutic implications of this emerging pathogenic paradigm, including several current and potentially novel, lipid-based approaches to corrective therapy. PMID:24128970

Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A

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

Brunner, H.G.; Nelen, M.; Ropers, H.H.

1993-10-22

Genetic and metabolic studies have been done on a large kindred in which several males are affected by a syndrome of borderline mental retardation and abnormal behavior. The types of behavior that occurred include impulsive aggression, arson, attempted rape, and exhibitionism. Analysis of 24-hour urine samples indicated markedly disturbed monoamine metabolism. This syndrome was associated with a complete and selective deficiency of enzymatic activity of monoamine oxidase A (MAOA). In each of five affected males, a point mutation was identified in the eighth exon of the MAOA structural gene, which changes a glutamine to a termination codon. Thus, isolated completemore » MAOA deficiency in this family is associated with a recognizable behavioral phenotype that includes disturbed regulation of impulsive aggression.« less

Functional and clinical neuroanatomy of morality.

PubMed

Fumagalli, Manuela; Priori, Alberto

2012-07-01

Morality is among the most sophisticated features of human judgement, behaviour and, ultimately, mind. An individual who behaves immorally may violate ethical rules and civil rights, and may threaten others' individual liberty, sometimes becoming violent and aggressive. In recent years, neuroscience has shown a growing interest in human morality, and has advanced our understanding of the cognitive and emotional processes involved in moral decisions, their anatomical substrates and the neurology of abnormal moral behaviour. In this article, we review research findings that have provided a key insight into the functional and clinical neuroanatomy of the brain areas involved in normal and abnormal moral behaviour. The 'moral brain' consists of a large functional network including both cortical and subcortical anatomical structures. Because morality is a complex process, some of these brain structures share their neural circuits with those controlling other behavioural processes, such as emotions and theory of mind. Among the anatomical structures implicated in morality are the frontal, temporal and cingulate cortices. The prefrontal cortex regulates activity in subcortical emotional centres, planning and supervising moral decisions, and when its functionality is altered may lead to impulsive aggression. The temporal lobe is involved in theory of mind and its dysfunction is often implicated in violent psychopathy. The cingulate cortex mediates the conflict between the emotional and the rational components of moral reasoning. Other important structures contributing to moral behaviour include the subcortical nuclei such as the amygdala, hippocampus and basal ganglia. Brain areas participating in moral processing can be influenced also by genetic, endocrine and environmental factors. Hormones can modulate moral behaviour through their effects on the brain. Finally, genetic polymorphisms can predispose to aggressivity and violence, arguing for a genetic-based predisposition to morality. Because abnormal moral behaviour can arise from both functional and structural brain abnormalities that should be diagnosed and treated, the neurology of moral behaviour has potential implications for clinical practice and raises ethical concerns. Last, since research has developed several neuromodulation techniques to improve brain dysfunction (deep brain stimulation, transcranial magnetic stimulation and transcranial direct current stimulation), knowing more about the 'moral brain' might help to develop novel therapeutic strategies for neurologically based abnormal moral behaviour.

Gestational Age is Dimensionally Associated with Structural Brain Network Abnormalities Across Development.

PubMed

Nassar, Rula; Kaczkurkin, Antonia N; Xia, Cedric Huchuan; Sotiras, Aristeidis; Pehlivanova, Marieta; Moore, Tyler M; Garcia de La Garza, Angel; Roalf, David R; Rosen, Adon F G; Lorch, Scott A; Ruparel, Kosha; Shinohara, Russell T; Davatzikos, Christos; Gur, Ruben C; Gur, Raquel E; Satterthwaite, Theodore D

2018-04-21

Prematurity is associated with diverse developmental abnormalities, yet few studies relate cognitive and neurostructural deficits to a dimensional measure of prematurity. Leveraging a large sample of children, adolescents, and young adults (age 8-22 years) studied as part of the Philadelphia Neurodevelopmental Cohort, we examined how variation in gestational age impacted cognition and brain structure later in development. Participants included 72 preterm youth born before 37 weeks' gestation and 206 youth who were born at term (37 weeks or later). Using a previously-validated factor analysis, cognitive performance was assessed in three domains: (1) executive function and complex reasoning, (2) social cognition, and (3) episodic memory. All participants completed T1-weighted neuroimaging at 3 T to measure brain volume. Structural covariance networks were delineated using non-negative matrix factorization, an advanced multivariate analysis technique. Lower gestational age was associated with both deficits in executive function and reduced volume within 11 of 26 structural covariance networks, which included orbitofrontal, temporal, and parietal cortices as well as subcortical regions including the hippocampus. Notably, the relationship between lower gestational age and executive dysfunction was accounted for in part by structural network deficits. Together, these findings emphasize the durable impact of prematurity on cognition and brain structure, which persists across development.

Detecting Regional Myocardial Abnormalities in Patients With Wolff-Parkinson-White Syndrome With the Use of ECG-Gated Cardiac MDCT.

PubMed

Lee, Hye-Jeong; Uhm, Jae-Sun; Joung, Boyoung; Hong, Yoo Jin; Hur, Jin; Choi, Byoung Wook; Kim, Young Jin

2016-04-01

Myocardial dyskinesia caused by the accessory pathway and related reversible heart failure have been well documented in echocardiographic studies of pediatric patients with Wolff-Parkinson-White (WPW) syndrome. However, the long-term effects of dyskinesia on the myocardium of adult patients have not been studied in depth. The goal of the present study was to evaluate regional myocardial abnormalities on cardiac CT examinations of adult patients with WPW syndrome. Of 74 patients with WPW syndrome who underwent cardiac CT from January 2006 through December 2013, 58 patients (mean [± SD] age, 52.2 ± 12.7 years), 36 (62.1%) of whom were men, were included in the study after the presence of combined cardiac disease was excluded. Two observers blindly evaluated myocardial thickness and attenuation on cardiac CT scans. On the basis of CT findings, patients were classified as having either normal or abnormal findings. We compared the two groups for other clinical findings, including observations from ECG, echocardiography, and electrophysiologic study. Of the 58 patients studied, 16 patients (27.6%) were found to have myocardial abnormalities (i.e., abnormal wall thinning with or without low attenuation). All abnormal findings corresponded with the location of the accessory pathway. Patients with abnormal findings had statistically significantly decreased left ventricular function, compared with patients with normal findings (p < 0.001). The frequency of regional wall motion abnormality was statistically significantly higher in patients with abnormal findings (p = 0.043). However, echocardiography documented structurally normal hearts in all patients. A relatively high frequency (27.6%) of regional myocardial abnormalities was observed on the cardiac CT examinations of adult patients with WPW syndrome. These abnormal findings might reflect the long-term effects of dyskinesia, suggesting irreversible myocardial injury that ultimately causes left ventricular dysfunction.

Magnetic resonance imaging in the evaluation of sports injuries of the foot and ankle: a pictorial essay.

PubMed

Riley, Geoffrey M

2007-01-01

Magnetic resonance imaging is playing an increasingly important role in evaluation of the injured athlete's foot and ankle. Magnetic resonance imaging allows accurate detection of bony abnormalities, such as stress fractures, and soft-tissue abnormalities, including ligament tears, tendon tears, and tendinopathy. The interpreter of magnetic resonance images should systematically review the images, noting normal structures and accounting for changes in soft-tissue and bony signal.

Brain Structure Abnormalities in Adolescent Girls with Conduct Disorder

ERIC Educational Resources Information Center

Fairchild, Graeme; Hagan, Cindy C.; Walsh, Nicholas D.; Passamonti, Luca; Calder, Andrew J.; Goodyer, Ian M.

2013-01-01

Background: Conduct disorder (CD) in female adolescents is associated with a range of negative outcomes, including teenage pregnancy and antisocial personality disorder. Although recent studies have documented changes in brain structure and function in male adolescents with CD, there have been no neuroimaging studies of female adolescents with CD.…

Central nervous system abnormalities in Fanconi anaemia: patterns and frequency on magnetic resonance imaging

PubMed Central

Alston, Robert; Wright, Neville B; Chandler, Kate; Bonney, Denise; Wynn, Robert F; Will, Andrew M; Punekar, Maqsood; Loughran, Sean; Kilday, John-Paul; Schindler, Detlev; Patel, Leena; Meyer, Stefan

2015-01-01

Objective: Fanconi anaemia (FA) is an inherited disease associated with congenital and developmental abnormalities resulting from the disruption of a multigenic DNA damage response pathway. This study aimed to define the MRI appearances of the brain in patients with FA in correlation with their genetic and clinical features. Methods: A review of the brain MRI in 20 patients with FA was performed. Pituitary size and frequencies of the radiological findings of individuals with FA and age-matched controls were determined. Results: Abnormalities were identified in 18 (90%) patients with FA, the commonest being a small pituitary (68%, p < 0.01 females and p < 0.001 males). In five cases (25%, p = 0.02), the pituitary morphology was also abnormal. Posterior fossa abnormalities were seen in six cases (30%, p = 0.01) including Chiari I malformation (n = 3), Dandy–Walker variant (n = 2) and cerebellar atrophy (n = 2). Six patients (30%, p = 0.01) had morphological structural variation of the corpus callosum (CC). Conclusion: The incidence of central nervous system (CNS) abnormalities in FA is higher than previously reported, with a midline predominance that points to impact in the early stages of CNS development. MRI brain imaging is important for endocrine assessment and pre-transplant evaluation and can make an important contribution to clinical decision-making. Advances in knowledge: The incidence of brain structural abnormalities in FA is higher than previously reported, with abnormalities of the posterior fossa, CC and pituitary being common. There is an association with gender and reduction in pituitary size which does not strongly correlate with biochemically evident endocrine abnormality. PMID:26369989

Lobar holoprosencephaly in a Miniature Schnauzer with hypodipsic hypernatremia.

PubMed

Sullivan, Stacey A; Harmon, Barry G; Purinton, P Thomas; Greene, Craig E; Glerum, Leigh E

2003-12-15

A 9-month-old male Miniature Schnauzer was examined because of a lifelong history of behavioral abnormalities, including hypodipsia. Diagnostic evaluation revealed marked hypernatremia and a single forebrain ventricle. The behavioral abnormalities did not resolve with correction of the hypernatremia, and the dog was euthanatized. At necropsy, midline forebrain structures were absent or reduced in size, and normally paired forebrain structures were incompletely separated. Findings were diagnostic for holoprosencephaly, a potentially genetic disorder and the likely cause of the hypodipsia. Similar evaluation of affected Miniature Schnauzer dogs may reveal whether holoprosencephaly routinely underlies the thirst deficiency that may be seen in dogs of this breed.

[Anomalous systemic arterial supply to normal basal segments of the left lung (Pryce type I)].

PubMed

Ryu, Chusei; Sawada, Takahiro; Machino, Ryusuke

2013-03-01

Patient 1 was a 54-year-old female diagnosed with anomalous systemic arterial supply to normal basal segments of the left lung discovered as an abnormality on chest X-ray radiography. Patient 2 was a 47-year-old male in whom the disease was diagnosed by close examination of bloody sputum. Division of the abnormal artery and left lower lobectomy were performed in patient 1. Arterial congestion and serpentine distribution were noted in the basal segments of the lung, which was the region perfused by the abnormal artery, on histopathological examination. Arteriosclerotic changes were noted in the vascular wall, but no abnormal vascular wall or alveolar structure was noted in S6, which was not included in theperfused region. Based on the above findings, division of the abnormal artery and left basal segmentectomy were performed in patient 2. Bloody sputum disappeared, and activity of daily living( ADL) were not impaired after surgery.

Imaginal Disc Abnormalities in Lethal Mutants of Drosophila

PubMed Central

Shearn, Allen; Rice, Thomas; Garen, Alan; Gehring, Walter

1971-01-01

Late lethal mutants of Drosophila melanogaster, dying after the larval stage of development, were isolated. The homozygous mutant larvae were examined for abnormal imaginal disc morphology, and the discs were injected into normal larval hosts to test their capacities to differentiate into adult structures. In about half of the mutants analyzed, disc abnormalities were found. Included among the abnormalities were missing discs, small discs incapable of differentiating, morphologically normal discs with limited capacities for differentiation, and discs with homeotic transformations. In some mutants all discs were affected, and in others only certain discs. The most extreme abnormal phenotype is a class of “discless” mutants. The viability of these mutant larvae indicates that the discs are essential only for the development of an adult and not of a larva. The late lethals are therefore a major source of mutants for studying the genetic control of disc formation. Images PMID:5002822

Strabismus and the Oculomotor System: Insights from Macaque Models

PubMed Central

Das, Vallabh E.

2017-01-01

Disrupting binocular vision in infancy leads to strabismus and oftentimes to a variety of associated visual sensory deficits and oculomotor abnormalities. Investigation of this disorder has been aided by the development of various animal models, each of which has advantages and disadvantages. In comparison to studies of binocular visual responses in cortical structures, investigations of neural oculomotor structures that mediate the misalignment and abnormalities of eye movements have been more recent, and these studies have shown that different brain areas are intimately involved in driving several aspects of the strabismic condition, including horizontal misalignment, dissociated deviations, A and V patterns of strabismus, disconjugate eye movements, nystagmus, and fixation switch. The responses of cells in visual and oculomotor areas that potentially drive the sensory deficits and also eye alignment and eye movement abnormalities follow a general theme of disrupted calibration, lower sensitivity, and poorer specificity compared with the normally developed visual oculomotor system. PMID:28532347

Increased nuchal traslucency in normal karyotype fetuses

PubMed Central

De Domenico, Roberta; Faraci, Marianna; Hyseni, Entela; Di Prima, Fosca A. F.; Valenti, Oriana; Monte, Santo; Giorgio, Elsa; Renda, Eliana

2011-01-01

Nuchal traslucency (NT) measurement between 11 and 14 weeks’ gestation is a reliable marker for chromosomal abnormalities, including trisomy 21. However, even if conventional karyotyping is normal, increased NT is a predictive value of adverse pregnancy outcome, because it is associated with several fetal malformations, congenital heart defects, genetic syndromes, intrauterine death and miscarriages; the majority of these structural anomalies are undetectable before birth. The risk is proportional to the nuchal translucency thickness, in fact it statistically increases after measurement reaching 3.5 mm or more. However, when these chromosomally normal fetuses with an enlarged NT survive, even if a detailed ultrasound examination and echocardiography fail to reveal any abnormalities, their uneventful outcome and postnatal developmental delay will be not statistically increased when compared to the general population. These parents should be confidently reassured that the residual chance of structural anomalies and abnormal neurodevelopment may not be higher than in the general population. PMID:22439071

Congenital malformations among newborns admitted in the neonatal unit of a tertiary hospital in Enugu, South-East Nigeria - a retrospective study

PubMed Central

2012-01-01

Background Congenital abnormalities are not uncommon among newborns and contribute to neonatal and infant morbidity and mortality. The prevalence and pattern of presentation vary from place to place. Many a time the exact etiology is unknown but genetic and environmental factors tend to be implicated. Methods The objective of this study was to determine the prevalence of congenital malformations among newborns admitted in a tertiary hospital in Enugu, the nature of these abnormalities and the outcome/prognosis. For purposes of this study, congenital abnormalities are defined as obvious abnormality of structure or form which is present at birth or noticed within a few days after birth. A cross-sectional retrospective study in which a review of the records of all babies admitted in the Newborn Special Care Unit (NBSCU) of the University of Nigeria Teaching Hospital (UNTH), Ituku/Ozalla, Enugu over a four year period (January 2007-April 2011) was undertaken. All babies admitted in the unit with the diagnosis of congenital abnormality were included in the study. Information extracted from the records included characteristics of the baby, maternal characteristics, nature/type of abnormalities and outcome. Data obtained was analyzed using SPSS 13. Rates and proportions were calculated with 95% confidence interval. The proportions were compared using students T-test. Level of significance was set at P < 0.05 Results Seventeen (17) out of a total of six hundred and seven newborn babies admitted in the newborn unit of UNTH over the study period (Jan 2007-March 2011) were found to have congenital abnormalities of various types, giving a prevalence of 2.8%. Common abnormalities seen in these babies were mainly surgical birth defects and included cleft lip/cleft palate, neural tube defects (occurring either singly or in combination with other abnormalities), limb abnormalities (often in combination with neural tube defects of various types), omphalocoele, umbilical herniae, ano-rectal malformations and dysmorphism associated with multiple congenital abnormalities. Conclusions The results of this study show that 2.8% of babies admitted to a Newborn Special Care Unit in a teaching hospital in Enugu had congenital abnormalities and that the commonest forms seen were mainly surgical birth defects and includes cleft lip/cleft palate and neural tube defects. PMID:22472067

The effect of adriamycin exposure on the notochord of mouse embryos.

PubMed

Hajduk, Piotr; May, Alison; Puri, Prem; Murphy, Paula

2012-04-01

The notochord has important structural and signaling properties during vertebrate development with key roles in patterning surrounding tissues, including the foregut. The adriamycin mouse model is an established model of foregut anomalies where exposure of embryos in utero to the drug adriamycin leads to malformations including oesophageal atresia and tracheoesophageal fistula. In addition to foregut abnormalities, treatment also causes branching, displacement, and hypertrophy of the notochord. Here, we explore the hypothesis that the notochord may be a primary target of disruption leading to abnormal patterning of the foregut by examining notochord position and structure in early embryos following adriamycin exposure. Treated (n = 46) and control (n = 30) embryos were examined during the crucial period when the notochord normally delaminates away from the foregut endoderm (6-28 somite pairs). Transverse sections were derived from the anterior foregut and analyzed by confocal microscopy following immunodetection of extracellular matrix markers E-cadherin and Laminin. In adriamycin-treated embryos across all stages, the notochord was abnormally displaced ventrally with prolonged attachment to the foregut endoderm. While E-cadherin was normally detected in the foregut endoderm with no expression in the notochord of control embryos, treated embryos up to 24 somites showed ectopic notochordal expression indicating a change in characteristics of the tissue; specifically an increase in intracellular adhesiveness, which may be instrumental in structural changes, affecting mechanical and signaling properties. This is consistent with disruption of the notochord leading to altered signaling to the foregut causing abnormal patterning and congenital foregut malformations. © 2012 Wiley Periodicals, Inc.

In Amnio MRI of Mouse Embryos

PubMed Central

Roberts, Thomas A.; Norris, Francesca C.; Carnaghan, Helen; Savery, Dawn; Wells, Jack A.; Siow, Bernard; Scambler, Peter J.; Pierro, Agostino; De Coppi, Paolo; Eaton, Simon; Lythgoe, Mark F.

2014-01-01

Mouse embryo imaging is conventionally carried out on ex vivo embryos excised from the amniotic sac, omitting vital structures and abnormalities external to the body. Here, we present an in amnio MR imaging methodology in which the mouse embryo is retained in the amniotic sac and demonstrate how important embryonic structures can be visualised in 3D with high spatial resolution (100 µm/px). To illustrate the utility of in amnio imaging, we subsequently apply the technique to examine abnormal mouse embryos with abdominal wall defects. Mouse embryos at E17.5 were imaged and compared, including three normal phenotype embryos, an abnormal embryo with a clear exomphalos defect, and one with a suspected gastroschisis phenotype. Embryos were excised from the mother ensuring the amnion remained intact and stereo microscopy was performed. Embryos were next embedded in agarose for 3D, high resolution MRI on a 9.4T scanner. Identification of the abnormal embryo phenotypes was not possible using stereo microscopy or conventional ex vivo MRI. Using in amnio MRI, we determined that the abnormal embryos had an exomphalos phenotype with varying severities. In amnio MRI is ideally suited to investigate the complex relationship between embryo and amnion, together with screening for other abnormalities located outside of the mouse embryo, providing a valuable complement to histology and existing imaging methods available to the phenotyping community. PMID:25330230

The epileptology of Koolen-de Vries syndrome: Electro-clinico-radiologic findings in 31 patients.

PubMed

Myers, Kenneth A; Mandelstam, Simone A; Ramantani, Georgia; Rushing, Elisabeth J; de Vries, Bert B; Koolen, David A; Scheffer, Ingrid E

2017-06-01

This study was designed to describe the spectrum of epilepsy phenotypes in Koolen-de Vries syndrome (KdVS), a genetic syndrome involving dysmorphic features, intellectual disability, hypotonia, and congenital malformations, that occurs secondary to 17q21.31 microdeletions and heterozygous mutations in KANSL1. We were invited to attend a large gathering of individuals with KdVS and their families. While there, we recruited individuals with KdVS and seizures, and performed thorough phenotyping. Additional subjects were included who approached us after the family support group brought attention to our research via social media. Inclusion criteria were genetic testing results demonstrating 17q21.31 deletion or KANSL1 mutation, and at least one seizure. Thirty-one individuals were studied, aged 2-35 years. Median age at seizure onset was 3.5 years, and 9 of 22 had refractory seizures 2 years after onset. Focal impaired awareness seizures were the most frequent seizure type occurring in 20 of 31, usually with prominent autonomic features. Twenty-one patients had prolonged seizures and, at times, refractory status epilepticus. Electroencephalography (EEG) showed focal/multifocal epileptiform discharges in 20 of 26. MRI studies of 13 patients were reviewed, and all had structural anomalies. Corpus callosum dysgenesis, abnormal hippocampi, and dilated ventricles were the most common, although periventricular nodular heterotopia, focal cortical dysplasia, abnormal sulcation, and brainstem and cerebellum abnormalities were also observed. One patient underwent epilepsy surgery for a lesion that proved to be an angiocentric glioma. The typical epilepsy phenotype of KdVS involves childhood-onset focal seizures that are prolonged and have prominent autonomic features. Multifocal epileptiform discharges are the typical EEG pattern. Structural brain abnormalities may be universal, including signs of abnormal neuroblast migration and abnormal axonal guidance. Epilepsy surgery should be undertaken with care given the widespread neuroanatomic abnormalities; however, tumors are a rare, yet important, occurrence. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Abnormalities in larvae from the once-largest Pacific herring population in Washington State result primarily from factors independent of spawning location

USGS Publications Warehouse

Hershberger, P.K.; Elder, N.E.; Wittouck, J.; Stick, K.; Kocan, R.M.

2005-01-01

Among larvae from populations of Pacific herring Clupea pallasii in Washington State those from Cherry Point have consistently demonstrated abnormalities indicative of distress, including low weights and lengths at hatch, increased prevalences of skeletal abnormalities, and shorter survival times in food deprivation studies. The biomass of adult, prespawn Pacific herring at Cherry Point declined from 13,606 metric tons in 1973 to a record low 733 metric tons in 2000. However, correlation of larval abnormalities with adult recruitment was weak, indicating that the larval abnormalities did not directly cause the decline. Larval abnormalities originated primarily from factors independent of conditions at the spawning location because they were not reproduced by incubation of foreign zygotes along the Cherry Point shoreline but were reproduced after the development of indigenous zygotes in controlled laboratory conditions. Although the precise cause of the abnormalities was not determined, recent zoographic trends in elevated natural mortality among adult Pacific herring and resulting reduced age structures may be involved. ?? Copyright by the American Fisheries Society 2005.

Abnormal Structure–Function Relationship in Spasmodic Dysphonia

PubMed Central

Ludlow, Christy L.

2012-01-01

Spasmodic dysphonia (SD) is a primary focal dystonia characterized by involuntary spasms in the laryngeal muscles during speech production. Although recent studies have found abnormal brain function and white matter organization in SD, the extent of gray matter alterations, their structure–function relationships, and correlations with symptoms remain unknown. We compared gray matter volume (GMV) and cortical thickness (CT) in 40 SD patients and 40 controls using voxel-based morphometry and cortical distance estimates. These measures were examined for relationships with blood oxygen level–dependent signal change during symptomatic syllable production in 15 of the same patients. SD patients had increased GMV, CT, and brain activation in key structures of the speech control system, including the laryngeal sensorimotor cortex, inferior frontal gyrus (IFG), superior/middle temporal and supramarginal gyri, and in a structure commonly abnormal in other primary dystonias, the cerebellum. Among these regions, GMV, CT and activation of the IFG and cerebellum showed positive relationships with SD severity, while CT of the IFG correlated with SD duration. The left anterior insula was the only region with decreased CT, which also correlated with SD symptom severity. These findings provide evidence for coupling between structural and functional abnormalities at different levels within the speech production system in SD. PMID:21666131

Variations in the ultrastructure of human nasal cilia including abnormalities found in retinitis pigmentosa.

PubMed Central

Fox, B; Bull, T B; Arden, G B

1980-01-01

The electron microscopic structure of cilia from the inferior turbinate of the nose was studied in 12 adults, four with chronic sinusitis, one with allergic rhinitis, two with bronchiectasis, three with deviated nasal septum, and two normals. The changes are compared with those found in nasal cilia in 14 patients with retinitis pigmentosa. There were compound cilia in the seven cases with chronic sinusitis, allergic rhinitis, and bronchiectasis but, apart from this, the structure of the cilia was similar in all 12 cases. There were variations in the microtubular pattern in about 4% of cilia, dynein arms were not seen in 4%, and in the rest an average of 5-6 dynein arms were seen in each cilium. The orientation of the cilia was 0 to 90 degrees. In the retinitis pigmentosa patients there was a highly significant increase in cilial abnormalities. The establishment on a quantitative basis of the variations in normal structure of nasal cilila facilitated the recognition of an association between cilial abnormalities and retinitis pigmentosa and should help in the identification of associations that may exist between cilial abnormalities and other diseases. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 7 Fig. 8 PMID:7400333

Morphometric brain abnormalities in boys with conduct disorder.

PubMed

Huebner, Thomas; Vloet, Timo D; Marx, Ivo; Konrad, Kerstin; Fink, Gereon R; Herpertz, Sabine C; Herpertz-Dahlmann, Beate

2008-05-01

Children with the early-onset type of conduct disorder (CD) are at high risk for developing an antisocial personality disorder. Although there have been several neuroimaging studies on morphometric differences in adults with antisocial personality disorder, little is known about structural brain aberrations in boys with CD. Magnetic resonance imaging and voxel-based morphometry were used to assess abnormalities in gray matter volumes in 23 boys ages 12 to 17 years with CD (17 comorbid for attention-deficit/hyperactivity disorder) in comparison with age- and IQ-matched controls. Compared with healthy controls, mean gray matter volume was 6% smaller in the clinical group. Compared with controls, reduced gray matter volumes were found in the left orbitofrontal region and bilaterally in the temporal lobes, including the amygdala and hippocampus on the left side in the CD group. Regression analyses in the clinical group indicated an inverse association of hyperactive/impulsive symptoms and widespread gray matter abnormalities in the frontoparietal and temporal cortices. By contrast, CD symptoms correlated primarily with gray matter reductions in limbic brain structures. The data suggest that boys with CD and comorbid attention-deficit/hyperactivity disorder show brain abnormalities in frontolimbic areas that resemble structural brain deficits, which are typically observed in adults with antisocial behavior.

Evaluation of thoracic radiographs as a screening test for dogs and cats admitted to a tertiary-care veterinary hospital for noncardiopulmonary disease.

PubMed

Keyserling, Christine L; Buriko, Yekaterina; Lyons, Bridget M; Drobatz, Kenneth J; Fischetti, Anthony J

2017-09-01

Thoracic radiographs are used as a screening tool for dogs and cats with a variety of disorders that have no clinical signs associated with thoracic structures. However, this practice has never been supported by an evidence-based study. The objective of this retrospective observational study was to determine if certain canine and feline populations have a higher proportion of radiographic abnormalities, and whether any of these abnormalities are associated with patient hospitalization and outcome. Patients were excluded if current or previous examinations revealed evidence of primary respiratory or cardiac disease, malignant neoplasia, or an abnormal breathing pattern consistent with pulmonary pathology. Any notable thoracic change in the radiology report was considered important and evaluated in this study. One hundred and sixty-six of these included patients were dogs and 65 were cats. Of the 166 dog radiographs evaluated, 120 (72.3%) had normal thoracic radiographs, while 46 (27.7%) had radiographic abnormalities. Of the sixty-five cats included, 36 (55.4%) had normal radiographs, while 29 (44.6%) had abnormal radiographs. Canine patients with abnormal radiographs had a significantly higher lactate level (P-value 0.0348) and feline patients with abnormal radiographs had a significantly lower packed cell volume (P-value 0.012). A large proportion of patients that had screening thoracic radiographs (32.5%) had documented abnormalities, but a relatively low percentage (6.5%) of our total population had their clinical plan changed as a consequence of detection of these abnormalities. Findings indicated that abnormal screening thoracic radiographs are more likely in dogs with an elevated lactate and cats with anemia, or a low normal hematocrit. © 2017 American College of Veterinary Radiology.

Pharmacological inhibition of soluble epoxide hydrolase ameliorates diet-induced metabolic syndrome in rats.

PubMed

Iyer, Abishek; Kauter, Kathleen; Alam, Md Ashraful; Hwang, Sung Hee; Morisseau, Christophe; Hammock, Bruce D; Brown, Lindsay

2012-01-01

The signs of metabolic syndrome following chronic excessive macronutrient intake include body weight gain, excess visceral adipose deposition, hyperglycaemia, glucose and insulin intolerances, hypertension, dyslipidaemia, endothelial damage, cardiovascular hypertrophy, inflammation, ventricular contractile dysfunction, fibrosis, and fatty liver disease. Recent studies show increased activity of soluble epoxide hydrolase (sEH) during obesity and metabolic dysfunction. We have tested whether sEH inhibition has therapeutic potential in a rat model of diet-induced metabolic syndrome. In these high-carbohydrate, high-fat-fed rats, chronic oral treatment with trans-4-[4-(3-adamantan-1-ylureido)-cyclohexyloxy]-benzoic acid (t-AUCB), a potent sEH inhibitor, alleviated the signs of metabolic syndrome in vivo including glucose, insulin, and lipid abnormalities, changes in pancreatic structure, increased systolic blood pressure, cardiovascular structural and functional abnormalities, and structural and functional changes in the liver. The present study describes the pharmacological responses to this selective sEH inhibitor in rats with the signs of diet-induced metabolic syndrome.

Detection of Structural Abnormalities Using Neural Nets

NASA Technical Reports Server (NTRS)

Zak, M.; Maccalla, A.; Daggumati, V.; Gulati, S.; Toomarian, N.

1996-01-01

This paper describes a feed-forward neural net approach for detection of abnormal system behavior based upon sensor data analyses. A new dynamical invariant representing structural parameters of the system is introduced in such a way that any structural abnormalities in the system behavior are detected from the corresponding changes to the invariant.

Cone Photoreceptor Abnormalities Correlate with Vision Loss in Patients with Stargardt Disease

PubMed Central

Chen, Yingming; Ratnam, Kavitha; Sundquist, Sanna M.; Lujan, Brandon; Ayyagari, Radha; Gudiseva, V. Harini; Roorda, Austin

2011-01-01

Purpose. To study the relationship between macular cone structure, fundus autofluorescence (AF), and visual function in patients with Stargardt disease (STGD). Methods. High-resolution images of the macula were obtained with adaptive optics scanning laser ophthalmoscopy (AOSLO) and spectral domain optical coherence tomography in 12 patients with STGD and 27 age-matched healthy subjects. Measures of retinal structure and AF were correlated with visual function, including best-corrected visual acuity, color vision, kinetic and static perimetry, fundus-guided microperimetry, and full-field electroretinography. Mutation analysis of the ABCA4 gene was completed in all patients. Results. Patients were 15 to 55 years old, and visual acuity ranged from 20/25–20/320. Central scotomas were present in all patients, although the fovea was spared in three patients. The earliest cone spacing abnormalities were observed in regions of homogeneous AF, normal visual function, and normal outer retinal structure. Outer retinal structure and AF were most normal near the optic disc. Longitudinal studies showed progressive increases in AF followed by reduced AF associated with losses of visual sensitivity, outer retinal layers, and cones. At least one disease-causing mutation in the ABCA4 gene was identified in 11 of 12 patients studied; 1 of 12 patients showed no disease-causing ABCA4 mutations. Conclusions. AOSLO imaging demonstrated abnormal cone spacing in regions of abnormal fundus AF and reduced visual function. These findings provide support for a model of disease progression in which lipofuscin accumulation results in homogeneously increased AF with cone spacing abnormalities, followed by heterogeneously increased AF with cone loss, then reduced AF with cone and RPE cell death. (ClinicalTrials.gov number, NCT00254605.) PMID:21296825

Association of left ventricular structural and functional abnormalities with aortic and brachial blood pressure variability in hypertensive patients: the SAFAR study.

PubMed

Chi, C; Yu, S-K; Auckle, R; Argyris, A A; Nasothimiou, E; Tountas, C; Aissopou, E; Blacher, J; Safar, M E; Sfikakis, P P; Zhang, Y; Protogerou, A D

2017-10-01

Both brachial blood pressure (BP) level and its variability (BPV) significantly associate with left ventricular (LV) structure and function. Recent studies indicate that aortic BP is superior to brachial BP in the association with LV abnormalities. However, it remains unknown whether aortic BPV better associate with LV structural and functional abnormalities. We therefore aimed to investigate and compare aortic versus brachial BPV, in terms of the identification of LV abnormalities. Two hundred and three participants who underwent echocardiography were included in this study. Twenty-four-hour aortic and brachial ambulatory BP was measured simultaneously by a validated BP monitor (Mobil-O-Graph, Stolberg, Germany) and BPV was calculated with validated formulae. LV mass and LV diastolic dysfunction (LVDD) were evaluated by echocardiography. The prevalence of LV hypertrophy (LVH) and LVDD increased significantly with BPV indices (P⩽0.04) in trend tests. After adjustment to potential confounders, only aortic average real variability (ARV), but not brachial ARV or weighted s.d. (wSD, neither aortic nor brachial) significantly associated with LV mass index (P=0.02). Similar results were observed in logistic regression. After adjustment, only aortic ARV significantly associated with LVH (odds ratio (OR) and 95% confidence interval (CI): 2.28 (1.08, 4.82)). As for LVDD, neither the brachial nor the aortic 24-hour wSD, but the aortic and brachial ARV, associated with LVDD significantly, with OR=2.28 (95% CI: (1.03, 5.02)) and OR=2.36 (95% CI: (1.10, 5.05)), respectively. In summary, aortic BPV, especially aortic ARV, seems to be superior to brachial BPV in the association of LV structural and functional abnormalities.

Abnormal rich club organization and impaired correlation between structural and functional connectivity in migraine sufferers.

PubMed

Li, Kang; Liu, Lijun; Yin, Qin; Dun, Wanghuan; Xu, Xiaolin; Liu, Jixin; Zhang, Ming

2017-04-01

Because of the unique position of the topologically central role of densely interconnected brain hubs, our study aimed to investigate whether these regions and their related connections would be particularly vulnerable to migraine. In our study, we explored the rich club structure and its role in global functional dynamics in 30 patients with migraine without aura and 30 healthy controls. DTI and resting fMRI were used to construct structural connectivity (SC) and functional connectivity (FC) networks. An independent replication data set of 26 patients and 26 controls was included to replicate and validate significant findings. As compared with the controls, the structural networks of patients exhibited altered rich club organization with higher level of feeder connection density, abnormal small-world organization with increased global efficiency and decreased strength of SC-FC coupling. As these abnormal topological properties and headache attack duration exhibited a significant association with increased density of feeder connections, our results indicated that migraine may be characterized by a selective alteration of the structural connectivity of the rich club regions, tending to have higher 'bridgeness' with non-rich club regions, which may increase the integration among pain-related brain circuits with more excitability but less inhibition for the modulation of migraine.

Delineating the Structure of Normal and Abnormal Personality: An Integrative Hierarchical Approach

PubMed Central

Markon, Kristian E.; Krueger, Robert F.; Watson, David

2008-01-01

Increasing evidence indicates that normal and abnormal personality can be treated within a single structural framework. However, identification of a single integrated structure of normal and abnormal personality has remained elusive. Here, a constructive replication approach was used to delineate an integrative hierarchical account of the structure of normal and abnormal personality. This hierarchical structure, which integrates many Big Trait models proposed in the literature, replicated across a meta-analysis as well as an empirical study, and across samples of participants as well as measures. The proposed structure resembles previously suggested accounts of personality hierarchy and provides insight into the nature of personality hierarchy more generally. Potential directions for future research on personality and psychopathology are discussed. PMID:15631580

Delineating the structure of normal and abnormal personality: an integrative hierarchical approach.

PubMed

Markon, Kristian E; Krueger, Robert F; Watson, David

2005-01-01

Increasing evidence indicates that normal and abnormal personality can be treated within a single structural framework. However, identification of a single integrated structure of normal and abnormal personality has remained elusive. Here, a constructive replication approach was used to delineate an integrative hierarchical account of the structure of normal and abnormal personality. This hierarchical structure, which integrates many Big Trait models proposed in the literature, replicated across a meta-analysis as well as an empirical study, and across samples of participants as well as measures. The proposed structure resembles previously suggested accounts of personality hierarchy and provides insight into the nature of personality hierarchy more generally. Potential directions for future research on personality and psychopathology are discussed.

Preoperative Status and Risk of Complications in Patients with Hip Fracture

PubMed Central

McLaughlin, Mary Ann; Orosz, Gretchen M; Magaziner, Jay; Hannan, Edward L; McGinn, Thomas; Morrison, R Sean; Hochman, Tsivia; Koval, Kenneth; Gilbert, Marvin; Siu, Albert L

2006-01-01

BACKGROUND Limited information is available on preoperative status and risks for complications for older patients having surgery for hip fracture. Our objective was to identify potentially modifiable clinical findings that should be considered in decisions about the timing of surgery. METHODS We conducted a prospective cohort study with data obtained from medical records and through structured interviews with patients. A total of 571 adults with hip fracture who were admitted to 4 metropolitan hospitals were included. RESULTS Multiple logistic regression was used to identify risk factors (including 11 categories of physical and laboratory findings, classified as mild and severe abnormalities) for in-hospital complications. The presence of more than 1 (odds ratiol [OR] 9.7, 95% confidence interval [CI] 2.8 to 33.0) major abnormality before surgery or the presence of major abnormalities on admission that were not corrected prior to surgery (OR 2.8, 95% CI 1.2 to 6.4) was independently associated with the development of postoperative complications. We also found that minor abnormalities, while warranting correction, did not increase risk (OR 0.70, 95% CI 0.28 to 1.73). CONCLUSIONS In this study of older adults undergoing urgent surgery, potentially reversible abnormalities in laboratory and physical examination occurred frequently and significantly increased the risk of postoperative complications. Major clinical abnormalities should be corrected prior to surgery, but patients with minor abnormalities may proceed to surgery with attention to these medical problems perioperatively. PMID:16390507

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

PubMed Central

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

2007-01-01

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

Management of Abnormal Uterine Bleeding with Emphasis on Alternatives to Hysterectomy.

PubMed

Billow, Megan R; El-Nashar, Sherif A

2016-09-01

Abnormal uterine bleeding (AUB) is a common problem that negatively impacts a woman's health-related quality of life and activity. Initial medical treatment includes hormonal and nonhormonal medications. If bleeding persists and no structural abnormalities are present, a repeat trial of medical therapy, a levonorgestrel intrauterine system, or an endometrial ablation can be used dependent on future fertility wishes. The levonorgestrel intrauterine system and endometrial ablation are effective, less invasive, and safe alternatives to a hysterectomy in women with AUB. A hysterectomy is the definitive treatment of AUB irrespective of the suspected cause when alternative treatments fail. Future studies should focus on detection of predictors for treatment outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

Functional anorectal disorders.

PubMed

Bharucha, Adil E; Wald, Arnold; Enck, Paul; Rao, Satish

2006-04-01

This report defines criteria for diagnosing functional anorectal disorders (ie, fecal incontinence, anorectal pain, and disorders of defecation). Functional fecal incontinence is defined as the uncontrolled passage of fecal material recurring for > or =3 months in an individual with a developmental age of > or =4 years that is associated with: (1) abnormal functioning of normally innervated and structurally intact muscles, and/or (2) no or minor abnormalities of sphincter structure and/or innervation insufficient to explain fecal incontinence, and/or (3) normal or disordered bowel habits (ie, fecal retention or diarrhea), and/or (4) psychological causes. However, conditions wherein structural and/or neurogenic abnormalities explain the symptom, or are part of a generalized process (eg, diabetic neuropathy) are not included within functional fecal incontinence. Functional fecal incontinence is a common, but underrecognized symptom, which is equally prevalent in men and women, and can often cause considerable distress. The clinical features are useful for guiding diagnostic testing and therapy. Functional anorectal pain syndromes include proctalgia fugax (fleeting pain) and chronic proctalgia; chronic proctalgia may be subdivided into levator ani syndrome and unspecified anorectal pain, which are defined by arbitrary clinical criteria. Functional defecation disorders are characterized by 2 or more symptoms of constipation, with > or =2 of the following features during defecation: impaired evacuation, inappropriate contraction of the pelvic floor muscles, and inadequate propulsive forces. Functional disorders of defecation may be amenable to pelvic floor retraining by biofeedback therapy (such as dyssynergic defecation).

Brain anomalies in velo-cardio-facial syndrome

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

Mitnick, R.J.; Bello, J.A.; Shprintzen, R.J.

Magnetic resonance imaging of the brain in 11 consecutively referred patients with velo-cardio-facial syndrome (VCF) showed anomalies in nine cases including small vermis, cysts adjacent to the frontal horns, and small posterior fossa. Focal signal hyperintensities in the white matter on long TR images were also noted. The nine patients showed a variety of behavioral abnormalities including mild development delay, learning disabilities, and characteristic personality traits typical of this common multiple anomaly syndrome which has been related to a microdeletion at 22q11. Analysis of the behavorial findings showed no specific pattern related to the brain anomalies, and the patients withmore » VCF who did not have detectable brain lesions also had behavioral abnormalities consistent with VCF. The significance of the lesions is not yet known, but the high prevalence of anomalies in this sample suggests that structural brain abnormalities are probably common in VCF. 25 refs.« less

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.

Structural abnormality of the corticospinal tract in major depressive disorder

PubMed Central

2014-01-01

Background Scientists are beginning to document abnormalities in white matter connectivity in major depressive disorder (MDD). Recent developments in diffusion-weighted image analyses, including tractography clustering methods, may yield improved characterization of these white matter abnormalities in MDD. In this study, we acquired diffusion-weighted imaging data from MDD participants and matched healthy controls. We analyzed these data using two tractography clustering methods: automated fiber quantification (AFQ) and the maximum density path (MDP) procedure. We used AFQ to compare fractional anisotropy (FA; an index of water diffusion) in these two groups across major white matter tracts. Subsequently, we used the MDP procedure to compare FA differences in fiber paths related to the abnormalities in major fiber tracts that were identified using AFQ. Results FA was higher in the bilateral corticospinal tracts (CSTs) in MDD (p’s < 0.002). Secondary analyses using the MDP procedure detected primarily increases in FA in the CST-related fiber paths of the bilateral posterior limbs of the internal capsule, right superior corona radiata, and the left external capsule. Conclusions This is the first study to implicate the CST and several related fiber pathways in MDD. These findings suggest important new hypotheses regarding the role of CST abnormalities in MDD, including in relation to explicating CST-related abnormalities to depressive symptoms and RDoC domains and constructs. PMID:25295159

Ultrastructural findings in noncompaction prevail with neuromuscular disorders.

PubMed

Finsterer, Josef; Stöllberger, Claudia

2013-01-01

Little is known about the ultrastructural abnormalities of left ventricular hypertrabeculation/noncompaction (LVHT). This literature review aimed to summarize and discuss ultrastructural abnormalities described in LVHT so far. The literature search was conducted via MEDLINE using the search terms 'non-compaction', 'noncompaction', 'left ventricular hypertrabeculation', 'spongy myocardium' in combination with the terms 'ultra-structural', or 'electron microscopy'. Altogether, 11 studies reporting ultrastructural investigations of LVHT were retrieved. In these 11 studies, data on 13 patients with LVHT were presented. Ultrastructural abnormalities found in these study patients were generally nonspecific and included an increase in the number of mitochondria (n = 3), abnormally shaped mitochondria (n = 2), distorted cristae (n = 3), sarcomeric derangement (n = 3), immature cardiomyocytes (n = 1), lipid-like inclusions (n = 1), enlarged interstitial spaces (n = 1), increased interstitial collagen (n = 1), or increased glycogen (n = 1). The morphological abnormalities were most prominent in patients with a neuromuscular disorder like Barth syndrome or mitochondrial myopathy. Only in few patients with LVHT, ultrastructural investigations have been performed so far. Ultrastructural abnormalities in LVHT are nonspecific and most prominent in patients with a neuromuscular disorder. There is a strong need to carry out thorough ultrastructural investigations of LVHT to contribute to the understanding of this still unexplained myocardial abnormality.

Chromosomal abnormalities, meiotic behavior and fertility in domestic animals.

PubMed

Villagómez, D A F; Pinton, A

2008-01-01

Since the advent of the surface microspreading technique for synaptonemal complex analysis, increasing interest in describing the synapsis patterns of chromosome abnormalities associated with fertility of domestic animals has been noticed during the past three decades. In spite of the number of scientific reports describing the occurrence of structural chromosome abnormalities, their meiotic behavior and gametic products, little is known in domestic animal species about the functional effects of such chromosome aberrations in the germ cell line of carriers. However, some interesting facts gained from recent and previous studies on the meiotic behavior of chromosome abnormalities of domestic animals permit us to discuss, in the frame of recent knowledge emerging from mouse and human investigations, the possible mechanism implicated in the well known association between meiotic disruption and chromosome pairing failure. New cytogenetic techniques, based on molecular and immunofluorescent analyses, are allowing a better description of meiotic processes, including gamete production. The present communication reviews the knowledge of the meiotic consequences of chromosome abnormalities in domestic animals. Copyright 2008 S. Karger AG, Basel.

A rare single cytogenetic finding of isochromosome 14q in a female with refractory anemia with ring sideroblasts (RARS)

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

Haag, M.M.; Sutcliffe, M.J.; Nelson, R.P.

1994-09-01

Clonal cytogenetic abnormalities occur in 79% of patients with myelodysplastic syndrome (MDS) and can be used to diagnose malignancy. Some of these clonal chromosomal changes have been useful in evaluation of the pathobiological similarity between MDS and acute nonlymphocytic leukemia (ANLL) and can be used to monitor the disease progression. A 44-year-old woman, presenting with normochromic, normocytic anemia was clinically asymptomatic and physical examination revealed no lymphadenopathy or hepatosplenomegaly. Stains for iron demonstrated adequate stores but with numerours ring sideroblasts which constituted approximately 15% of the total erythoblastic population. No increased reticulum or fibrosis was noted. These findings supported amore » diagnosis of MDS, classification refractory anemia with ring sideroblasts (RARS). Bone marrow cytogentic analysis showed an isochromosome 14q as the sole chromosome abnormality and this was confirmed by molecular cytogenetics using a whole chromosome Coatasome probe for No. 14. A population of 46,XX cells (20%) was also observed. Numerous interphase cells had three isolated fluorescent signals for No. 14. Structural and numerical abnormalities of chromosome No. 14 are reported in many hematological disorders, but few structural abnormalities have been reported for RARS and no extra copies, including i(14q), have been reported for MD or RARS. However, examples of extra copies of No. 14, including the isochromosome form, have been reported for ANLL. Since 15% of RARS patients progress to ANLL, there may be prognostic significance to this chromosome abnormality for his patient. The patient is awaiting a suitable donor for bone marrow transplantation. The presence of isochromosome No. 14 in the malignant cells offers an opportunity to monitor disease progression pre-transplantation and minimal residual disease post-transplantation.« less

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.

Magnetic resonance imaging findings in pediatric bilateral vocal fold dysfunction.

PubMed

Steiner, Joel I; Fink, A Michelle; Berkowitz, Robert G

2013-07-01

We studied the findings of brain magnetic resonance imaging (MRI) in infants with idiopathic congenital bilateral vocal fold dysfunction (CBVFD). We performed a retrospective investigation of a case series. We identified 26 children (14 male, 12 female) over 11 years. Three children were excluded. Thirteen patients required airway interventions, including continuous positive airway pressure (4 patients), endotracheal intubation (1), and tracheostomy (8). The findings on brain MRI were abnormal in 8 patients (35%). Tracheostomy was required in 3 patients (38%) with abnormal MRI findings, as compared with 5 of 15 patients (33%) with normal MRI findings. The MRI abnormalities involved evidence of white matter injury (2), abnormal white matter signal (1), subdural blood (3), cerebral swelling (1), and perisylvian polymicrogyria (1). The cranial ultrasound findings were abnormal in 4 of 11 patients. The MRI findings were abnormal in 2 of 7 children in whom the cranial ultrasound findings were normal, and in 2 of the 4 patients in whom the cranial ultrasound findings were abnormal. The MRI abnormalities were nonspecific; however, they may indicate unrecognized perinatal intracranial injury as being related to CBVFD. In addition, MRI may reveal an underlying structural brain anomaly. Cranial ultrasound has poor sensitivity and specificity. Hence, MRI should be considered as part of the routine assessment of neonates with CBVFD.

[Non-structural abnormalities of CNS function resulting in coincidence of endocrinopathies, epilepsy and psychoneurologic disorders in children and adolescents].

PubMed

Starzyk, Jerzy; Pituch-Noworolska, Anna; Pietrzyk, Jacek A; Urbanik, Andrzej; Kroczka, Sławomir; Drozdz, Ryszard; Wójcik, Małgorzata

2010-01-01

In the population of children and adolescents, epilepsy affects approximately 1% of cases, nonepileptic seizures are seen in approximately 3%, and endocrine disorders are several times more common. For this reason, coincidence of endocrine disorders and epilepsy and psychoneurologic disorders is frequent. Much less common are structural abnormalities (tumors, developmental abnormalities), and especially non-structural CNS abnormalities, resulting in coincidence of both disorders. There are no reports available in the literature that would address the problem. 1) Assessment of the frequency of coincidental epilepsy and endocrine disorders in patients without structural CSN abnormalities treated as outpatients and inpatients of Department of Endocrinology University Children's Hospital of Krakow. 2) Presentation of diagnostic and therapeutic difficulties in these patients, and 3) An attempt at defining the common etiology of both disorders. On the basis of ICD code patients with coincidance of endocrine disorders, epilepsy and psychoneurologic disorders were selected from several thousands of children treated between 2000 and 2009 in Pediatric Endocrinology Department. The neurologic disorders were diagnosed and treated in Chair and Department of Children's and Adolescents Neurology or in another pediatric neurology center. Various forms of epilepsy (symptomatic or idiopathic) and other psychoneurological disorders (disorders of behavior and emotions, obsession-compulsion syndromes, stereotypias, aggression, autoaggression, or hypothalamic obesity) coincident with one or more endocrine disorders, such as growth disorders, disorders of pubertal development, obesity, thyroid diseases, adrenal diseases, hyperprolactinemia, hypoparathyroidism and ion metabolism disorders were diagnosed in 49 patients. The group included: i) children after cranial irradiation and chemotherapy due to medulloblastoma (3 patients), oligodenroglioma (1 patient), ependymoma (1 patient), optic chiasm glioma (2 patients), suprasellar germinal tumor (1 patient), ii) children with Hashimoto encephalopathy (2 patients), iii) children with Prader-Willi syndrome (20 patients), with Klinefelter syndrome (10 patients), with Albright syndrome (9 patients). Of the 49 patients, a group of 6 children representative for individual disorders was selected. In those patients, the etiology of both endocrine disorders, epilepsy and neuropsychiatric disorders was suspected to be common, and the diagnosis was usually delayed. 1. Cranial irradiation and chemotherapy, encephalopathy associated with Hashimoto disease and some of the syndromes with the chromosomal and genetic background are the causes of non-structural CNS abnormalities and coincidence of endocrinopathies, epilepsy and psychoneurologic disorders. 2. MR/CT CNS imaging should be performed in any case of central neurological disorders, disorders of behavior, epilepsy or seizures, but also in patients with delayed psycho-motor development, delayed or accelerated growth and pubertal development. All of the above-mentioned manifestations may be symptoms of structural CNS abnormalities and their early treatment determines the child's future. 3. Excluding structural CNS abnormalities allows for forming suspicions associated with diseases resulting in non-structural disorders of the CNS function, predisposing to coincidence of endocrine and neurological disorders. 4. In the diagnosis of Hashimoto's encephalopathy, a decisive factor is exclusion of structural, infectious, traumatic and metabolic causes, intoxications, epilepsy and presence of neuropsychiatric symptoms in patients with high level of against TPO antibodies. In cases of steroids resistance, a good therapeutic effect may be achieved by plasmapheresis, Rituximab therapy and progestagene inhibition of the menstrual cycle.

CT-Definable Subtypes of Chronic Obstructive Pulmonary Disease: A Statement of the Fleischner Society

PubMed Central

Austin, John H. M.; Hogg, James C.; Grenier, Philippe A.; Kauczor, Hans-Ulrich; Bankier, Alexander A.; Barr, R. Graham; Colby, Thomas V.; Galvin, Jeffrey R.; Gevenois, Pierre Alain; Coxson, Harvey O.; Hoffman, Eric A.; Newell, John D.; Pistolesi, Massimo; Silverman, Edwin K.; Crapo, James D.

2015-01-01

The purpose of this statement is to describe and define the phenotypic abnormalities that can be identified on visual and quantitative evaluation of computed tomographic (CT) images in subjects with chronic obstructive pulmonary disease (COPD), with the goal of contributing to a personalized approach to the treatment of patients with COPD. Quantitative CT is useful for identifying and sequentially evaluating the extent of emphysematous lung destruction, changes in airway walls, and expiratory air trapping. However, visual assessment of CT scans remains important to describe patterns of altered lung structure in COPD. The classification system proposed and illustrated in this article provides a structured approach to visual and quantitative assessment of COPD. Emphysema is classified as centrilobular (subclassified as trace, mild, moderate, confluent, and advanced destructive emphysema), panlobular, and paraseptal (subclassified as mild or substantial). Additional important visual features include airway wall thickening, inflammatory small airways disease, tracheal abnormalities, interstitial lung abnormalities, pulmonary arterial enlargement, and bronchiectasis. © RSNA, 2015 PMID:25961632

Cytogenetic landscape of paired neurospheres and traditional monolayer cultures in pediatric malignant brain tumors.

PubMed

Zhao, Xiumei; Zhao, Yi-Jue; Lin, Qi; Yu, Litian; Liu, Zhigang; Lindsay, Holly; Kogiso, Mari; Rao, Pulivarthi; Li, Xiao-Nan; Lu, Xinyan

2015-07-01

New therapeutic targets are needed to eliminate cancer stem cells (CSCs). We hypothesize that direct comparison of paired CSCs and nonstem tumor cells (NSTCs) will facilitate identification of primary "driver" chromosomal aberrations that can serve as diagnostic markers and/or therapeutic targets. We applied spectral karyotyping and G-banding to matched pairs of neurospheres (CSC-enriched cultures) and fetal bovine serum-based monolayer cultures (enriched with NSTCs) from 16 patient-derived orthotopic xenograft mouse models, including 9 medulloblastomas (MBs) and 7 high-grade gliomas (HGGs), followed by direct comparison of their numerical and structural abnormalities. Chromosomal aberrations were detected in neurospheres of all 16 models, and 82.0% numerical and 82.4% structural abnormalities were maintained in their matching monolayer cultures. Among the shared abnormalities, recurrent clonal changes were identified including gain of chromosomes 18 and 7 and loss of chromosome 10/10q (5/16 models), isochromosome 17q in 2 MBs, and a new breakpoint of 13q14 in 3 HGGs. Chromothripsis-like evidence was also observed in 3 HGG pairs. Additionally, we noted 20 numerical and 15 structural aberrations that were lost from the neurospheres and found 26 numerical and 23 structural aberrations that were only present in the NSTCs. Compared with MBs, the neurosphere karyotypes of HGG were more complex, with fewer chromosomal aberrations preserved in their matching NSTCs. Self-renewing CSCs in MBs and pediatric HGGs harbor recurrent numerical and structural aberrations that were maintained in the matching monolayer cultures. These primary chromosomal changes may represent new markers for anti-CSC therapies. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Association between structural and functional brain alterations in drug-free patients with schizophrenia: a multimodal meta-analysis

PubMed

Gao, Xin; Zhang, Wenjing; Yao, Li; Xiao, Yuan; Liu, Lu; Liu, Jieke; Li, Siyi; Tao, Bo; Shah, Chandan; Gong, Qiyong; Sweeney, John; Lui, Su

2017-12-05

Neuroimaging studies have shown both structural and functional abnormalities in patients with schizophrenia. Recently, studies have begun to explore the association between structural and functional grey matter abnormalities. By conducting a meta­-analysis on morphometric and functional imaging studies of grey matter alterations in drug-free patients, the present study aims to examine the degree of overlap between brain regions with anatomic and functional changes in patients with schizophrenia. We performed a systematic search of PubMed, Embase, Web of Science and the Cochrane Library to identify relevant publications. A multimodal analysis was then conducted using Seed-based d Mapping software. Exploratory analyses included jackknife, subgroup and meta-regression analyses. We included 15 structural MRI studies comprising 486 drug-free patients and 485 healthy controls, and 16 functional MRI studies comprising 403 drug-free patients and 428 controls in our meta-analysis. Drug-free patients were examined to reduce pharmacological effects on the imaging data. Multimodal analysis showed considerable overlap between anatomic and functional changes, mainly in frontotemporal regions, bilateral medial posterior cingulate/paracingulate gyrus, bilateral insula, basal ganglia and left cerebellum. There were also brain regions showing only anatomic changes in the right superior frontal gyrus, left supramarginal gyrus, right lingual gyrus and functional alternations involving the right angular ­gyrus. The methodological aspects, patient characteristics and clinical variables of the included studies were heterogeneous, and we cannot exclude medication effects. The present study showed overlapping anatomic and functional brain abnormalities mainly in the default mode (DMN) and auditory networks (AN) in drug-free patients with schizophrenia. However, the pattern of changes differed in these networks. Decreased grey matter was associated with decreased activation within the DMN, whereas it was associated with increased activation within the AN. These discrete patterns suggest different pathophysiological changes impacting structural and functional associations within different neural networks in patients with schizophrenia. 2017 Joule Inc., or its licensors

Association between structural and functional brain alterations in drug-free patients with schizophrenia: a multimodal meta-analysis.

PubMed

Gao, Xin; Zhang, Wenjing; Yao, Li; Xiao, Yuan; Liu, Lu; Liu, Jieke; Li, Siyi; Tao, Bo; Shah, Chandan; Gong, Qiyong; Sweeney, John A; Lui, Su

2018-03-01

Neuroimaging studies have shown both structural and functional abnormalities in patients with schizophrenia. Recently, studies have begun to explore the association between structural and functional grey matter abnormalities. By conducting a meta-analysis on morphometric and functional imaging studies of grey matter alterations in drug-free patients, the present study aims to examine the degree of overlap between brain regions with anatomic and functional changes in patients with schizophrenia. We performed a systematic search of PubMed, Embase, Web of Science and the Cochrane Library to identify relevant publications. A multimodal analysis was then conducted using Seed-based d Mapping software. Exploratory analyses included jackknife, subgroup and meta-regression analyses. We included 15 structural MRI studies comprising 486 drug-free patients and 485 healthy controls, and 16 functional MRI studies comprising 403 drug-free patients and 428 controls in our meta-analysis. Drug-free patients were examined to reduce pharmacological effects on the imaging data. Multimodal analysis showed considerable overlap between anatomic and functional changes, mainly in frontotemporal regions, bilateral medial posterior cingulate/paracingulate gyrus, bilateral insula, basal ganglia and left cerebellum. There were also brain regions showing only anatomic changes in the right superior frontal gyrus, left supramarginal gyrus, right lingual gyrus and functional alternations involving the right angular gyrus. The methodological aspects, patient characteristics and clinical variables of the included studies were heterogeneous, and we cannot exclude medication effects. The present study showed overlapping anatomic and functional brain abnormalities mainly in the default mode (DMN) and auditory networks (AN) in drug-free patients with schizophrenia. However, the pattern of changes differed in these networks. Decreased grey matter was associated with decreased activation within the DMN, whereas it was associated with increased activation within the AN. These discrete patterns suggest different pathophysiological changes impacting structural and functional associations within different neural networks in patients with schizophrenia.

Association between structural and functional brain alterations in drug-free patients with schizophrenia: a multimodal meta-analysis.

PubMed

Gao, Xin; Zhang, Wenjing; Yao, Li; Xiao, Yuan; Liu, Lu; Liu, Jieke; Li, Siyi; Tao, Bo; Shah, Chandan; Gong, Qiyong; Sweeney, John A; Lui, Su

2017-12-15

Neuroimaging studies have shown both structural and functional abnormalities in patients with schizophrenia. Recently, studies have begun to explore the association between structural and functional grey matter abnormalities. By conducting a meta-analysis on morphometric and functional imaging studies of grey matter alterations in drug-free patients, the present study aims to examine the degree of overlap between brain regions with anatomic and functional changes in patients with schizophrenia. We performed a systematic search of PubMed, Embase, Web of Science and the Cochrane Library to identify relevant publications. A multimodal analysis was then conducted using Seed-based d Mapping software. Exploratory analyses included jackknife, subgroup and meta-regression analyses. We included 15 structural MRI studies comprising 486 drug-free patients and 485 healthy controls, and 16 functional MRI studies comprising 403 drug-free patients and 428 controls in our meta-analysis. Drug-free patients were examined to reduce pharmacological effects on the imaging data. Multimodal analysis showed considerable overlap between anatomic and functional changes, mainly in frontotemporal regions, bilateral medial posterior cingulate/paracingulate gyrus, bilateral insula, basal ganglia and left cerebellum. There were also brain regions showing only anatomic changes in the right superior frontal gyrus, left supramarginal gyrus, right lingual gyrus and functional alternations involving the right angular gyrus. The methodological aspects, patient characteristics and clinical variables of the included studies were heterogeneous, and we cannot exclude medication effects. The present study showed overlapping anatomic and functional brain abnormalities mainly in the default mode (DMN) and auditory networks (AN) in drug-free patients with schizophrenia. However, the pattern of changes differed in these networks. Decreased grey matter was associated with decreased activation within the DMN, whereas it was associated with increased activation within the AN. These discrete patterns suggest different pathophysiological changes impacting structural and functional associations within different neural networks in patients with schizophrenia.

Muscular Dystrophy with Ribitol-Phosphate Deficiency: A Novel Post-Translational Mechanism in Dystroglycanopathy

PubMed Central

Kanagawa, Motoi; Toda, Tatsushi

2017-01-01

Muscular dystrophy is a group of genetic disorders characterized by progressive muscle weakness. In the early 2000s, a new classification of muscular dystrophy, dystroglycanopathy, was established. Dystroglycanopathy often associates with abnormalities in the central nervous system. Currently, at least eighteen genes have been identified that are responsible for dystroglycanopathy, and despite its genetic heterogeneity, its common biochemical feature is abnormal glycosylation of alpha-dystroglycan. Abnormal glycosylation of alpha-dystroglycan reduces its binding activities to ligand proteins, including laminins. In just the last few years, remarkable progress has been made in determining the sugar chain structures and gene functions associated with dystroglycanopathy. The normal sugar chain contains tandem structures of ribitol-phosphate, a pentose alcohol that was previously unknown in humans. The dystroglycanopathy genes fukutin, fukutin-related protein (FKRP), and isoprenoid synthase domain-containing protein (ISPD) encode essential enzymes for the synthesis of this structure: fukutin and FKRP transfer ribitol-phosphate onto sugar chains of alpha-dystroglycan, and ISPD synthesizes CDP-ribitol, a donor substrate for fukutin and FKRP. These findings resolved long-standing questions and established a disease subgroup that is ribitol-phosphate deficient, which describes a large population of dystroglycanopathy patients. Here, we review the history of dystroglycanopathy, the properties of the sugar chain structure of alpha-dystroglycan, dystroglycanopathy gene functions, and therapeutic strategies. PMID:29081423

Specific Shoulder Pathoanatomy in Semiprofessional Water Polo Players

PubMed Central

Klein, Maria; Tarantino, Ignazio; Warschkow, René; Berger, Claus Joachim; Zdravkovic, Vilijam; Jost, Bernhard; Badulescu, Michael

2014-01-01

Background: Shoulders of throwing and swimming athletes are highly stressed joints that often show structural abnormalities on magnetic resonance imaging (MRI). However, while water polo players exhibit a combination of throwing and swimming movements, a specific pattern of pathological findings has not been described. Purpose: To assess specific MRI abnormalities in shoulders of elite water polo players and to compare these findings with a healthy control group. Study Design: Cross-sectional study; Level of evidence, 3. Methods: After performing a power analysis, volunteers were recruited for this study. Both shoulders of 28 semiprofessional water polo players and 15 healthy volunteers were assessed clinically (based on the Constant score) and had bilateral shoulder MRIs. The shoulders were clustered into 3 groups: 28 throwing and 28 nonthrowing shoulders of water polo athletes and 30 shoulders of healthy control subjects. Results: Twenty-eight male water polo players with an average age of 24 years and 15 healthy subjects (30 shoulders) with an average age of 31 years were examined. Compared with controls, significantly more MRI abnormalities in the water polo players' throwing shoulders could be found in the subscapularis, infraspinatus, and posterior labrum (P = .001, P = .024, and P = .041, respectively). Other structures showed no statistical differences between the 3 groups, including the supraspinatus tendon, which had abnormalities in 36% of throwing versus 32% of nonthrowing shoulders and 33% of control shoulders. All throwing shoulders showed abnormal findings in the MRI, but only 8 (29%) were symptomatic. Conclusion: The shoulders of semiprofessional water polo players demonstrated abnormalities in subscapularis and infraspinatus tendons that were not typical abnormalities for swimmers or throwing athletes. Clinical Relevance: The throwing shoulders of water polo players have specific MRI changes. Clinical symptoms do not correlate with the MRI findings. PMID:26535326

New MR imaging assessment tool to define brain abnormalities in very preterm infants at term.

PubMed

Kidokoro, H; Neil, J J; Inder, T E

2013-01-01

WM injury is the dominant form of injury in preterm infants. However, other cerebral structures, including the deep gray matter and the cerebellum, can also be affected by injury and/or impaired growth. Current MR imaging injury assessment scales are subjective and are challenging to apply. Thus, we developed a new assessment tool and applied it to MR imaging studies obtained from very preterm infants at term age. MR imaging scans from 97 very preterm infants (< 30 weeks' gestation) and 22 healthy term-born infants were evaluated retrospectively. The severity of brain injury (defined by signal abnormalities) and impaired brain growth (defined with biometrics) was scored in the WM, cortical gray matter, deep gray matter, and cerebellum. Perinatal variables for clinical risks were collected. In very preterm infants, brain injury was observed in the WM (n=23), deep GM (n=5), and cerebellum (n=23). Combining measures of injury and impaired growth showed moderate to severe abnormalities most commonly in the WM (n=38) and cerebellum (n=32) but still notable in the cortical gray matter (n=16) and deep gray matter (n=11). WM signal abnormalities were associated with a reduced deep gray matter area but not with cerebellar abnormality. Intraventricular and/or parenchymal hemorrhage was associated with cerebellar signal abnormality and volume reduction. Multiple clinical risk factors, including prolonged intubation, prolonged parenteral nutrition, postnatal corticosteroid use, and postnatal sepsis, were associated with increased global abnormality on MR imaging. Very preterm infants demonstrate a high prevalence of injury and growth impairment in both the WM and gray matter. This MR imaging scoring system provides a more comprehensive and objective classification of the nature and extent of abnormalities than existing measures.

Structural performance of light-frame roof assemblies. I, Truss assemblies designed for high variability and wood failure

Treesearch

R.W. Wolfe; Monica McCarthy

1989-01-01

The first report of a three-part series that covers results of a full-scale roof assemblies research program. The focus of this report is the structural performance of truss assemblies comprising trusses with abnormally high stiffness variability and critical joint strength. Results discussed include properties of truss members and connections. individual truss...

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

Neonatal physiological correlates of near-term brain development on MRI and DTI in very-low-birth-weight preterm infants.

PubMed

Rose, Jessica; Vassar, Rachel; Cahill-Rowley, Katelyn; Stecher Guzman, Ximena; Hintz, Susan R; Stevenson, David K; Barnea-Goraly, Naama

2014-01-01

Structural brain abnormalities identified at near-term age have been recognized as potential predictors of neurodevelopment in children born preterm. The aim of this study was to examine the relationship between neonatal physiological risk factors and early brain structure in very-low-birth-weight (VLBW) preterm infants using structural MRI and diffusion tensor imaging (DTI) at near-term age. Structural brain MRI, diffusion-weighted scans, and neonatal physiological risk factors were analyzed in a cross-sectional sample of 102 VLBW preterm infants (BW ≤ 1500 g, gestational age (GA) ≤ 32 weeks), who were admitted to the Lucile Packard Children's Hospital, Stanford NICU and recruited to participate prior to routine near-term brain MRI conducted at 36.6 ± 1.8 weeks postmenstrual age (PMA) from 2010 to 2011; 66/102 also underwent a diffusion-weighted scan. Brain abnormalities were assessed qualitatively on structural MRI, and white matter (WM) microstructure was analyzed quantitatively on DTI in six subcortical regions defined by DiffeoMap neonatal brain atlas. Specific regions of interest included the genu and splenium of the corpus callosum, anterior and posterior limbs of the internal capsule, the thalamus, and the globus pallidus. Regional fractional anisotropy (FA) and mean diffusivity (MD) were calculated using DTI data and examined in relation to neonatal physiological risk factors including gestational age (GA), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), and sepsis, as well as serum levels of C-reactive protein (CRP), glucose, albumin, and total bilirubin. Brain abnormalities were observed on structural MRI in 38/102 infants including 35% of females and 40% of males. Infants with brain abnormalities observed on MRI had higher incidence of BPD (42% vs. 25%) and sepsis (21% vs. 6%) and higher mean and peak serum CRP levels, respectively, (0.64 vs. 0.34 mg/dL, p = .008; 1.57 vs. 0.67 mg/dL, p= .006) compared to those without. The number of signal abnormalities observed on structural MRI correlated to mean and peak CRP (rho = .316, p = .002; rho = .318, p= .002). The number of signal abnormalities observed on MRI correlated with thalamus MD (left: r= .382, p= .002; right: r= .400, p= .001), controlling for PMA-at-scan. Thalamus WM microstructure demonstrated the strongest associations with neonatal risk factors. Higher thalamus MD on the left and right, respectively, was associated with lower GA (r = -.322, p = .009; r= -.381, p= .002), lower mean albumin (r = -.276, p= .029; r= -.385, p= .002), and lower mean bilirubin (r = -.293, p= .020; r= -.337 p= .007). Results suggest that at near-term age, thalamus WM microstructure may be particularly vulnerable to certain neonatal risk factors. Interactions between albumin, bilirubin, phototherapy, and brain development warrant further investigation. Identification of physiological risk factors associated with selective vulnerability of certain brain regions at near-term age may clarify the etiology of neurodevelopmental impairment and inform neuroprotective treatment for VLBW preterm infants.

The Schizophrenic Brain: Rewriting the Chapter.

ERIC Educational Resources Information Center

Greenberg, Joel

1979-01-01

Evidence of last two decades indicates schizophrenic disorders related to imbalance of brain chemicals. Recent discovery made of association between chronic schizophrenia and variety of structural abnormalities. Included are frontal lobe reversal and accipital lobe reversal. Computer tomography scans and data presented. (SA)

Achilles tendon: US examination

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

Fornage, B.D.

Real-time ultrasonography (US) using linear-array probes and a stand-off pad as a ''waterpath'' was performed to evaluate the Achilles tendon in 67 patients (including 24 athletes) believed to have acute or chronic traumatic or inflammatory pathologic conditions. Tendons in 23 patients appeared normal on US scans. The 44 abnormal tendons comprised five complete and four partial ruptures, seven instances of postoperative change, and 28 cases of tendonitis. US depiction of the inner structure of the tendon resulted in the diagnosis of focal abnormalities, including partial ruptures, nodules, and calcifications. Tendonitis was characterized by enlargement and decreased echogenicity of the tendon.more » The normal US appearance of the Achilles tendon is described.« less

Current Opinions and Areas of Consensus on the Role of the Cerebellum in Dystonia

PubMed Central

Batla, Amit; Bhatia, Kailash; Dauer, William T; Dresel, Christian; Niethammer, Martin; Eidelberg, David; Raike, Robert S.; Smith, Yoland; Jinnah, H. A.; Hess, Ellen J.; Meunier, Sabine; Hallett, Mark; Fremont, Rachel; Khodakhah, Kamran; LeDoux, Mark S.; Popa, Traian; Gallea, Cécile; Lehericy, Stéphane; Bostan, Andreea C.; Strick, Peter L.

2016-01-01

A role for the cerebellum in causing ataxia, a disorder characterized by uncoordinated movement, is widely accepted. Recent work has suggested that alterations in activity, connectivity, and structure of the cerebellum are also associated with dystonia, a neurological disorder characterized by abnormal and sustained muscle contractions often leading to abnormal maintained postures. In this manuscript, the authors discuss their views on how the cerebellum may play a role in dystonia. The following topics are discussed: The relationships between neuronal/network dysfunctions and motor abnormalities in rodent models of dystonia.Data about brain structure, cerebellar metabolism, cerebellar connections, and noninvasive cerebellar stimulation that support (or not) a role for the cerebellum in human dystonia.Connections between the cerebellum and motor cortical and sub-cortical structures that could support a role for the cerebellum in dystonia. Overall points of consensus include: Neuronal dysfunction originating in the cerebellum can drive dystonic movements in rodent model systems.Imaging and neurophysiological studies in humans suggest that the cerebellum plays a role in the pathophysiology of dystonia, but do not provide conclusive evidence that the cerebellum is the primary or sole neuroanatomical site of origin. PMID:27734238

Current Opinions and Areas of Consensus on the Role of the Cerebellum in Dystonia.

PubMed

Shakkottai, Vikram G; Batla, Amit; Bhatia, Kailash; Dauer, William T; Dresel, Christian; Niethammer, Martin; Eidelberg, David; Raike, Robert S; Smith, Yoland; Jinnah, H A; Hess, Ellen J; Meunier, Sabine; Hallett, Mark; Fremont, Rachel; Khodakhah, Kamran; LeDoux, Mark S; Popa, Traian; Gallea, Cécile; Lehericy, Stéphane; Bostan, Andreea C; Strick, Peter L

2017-04-01

A role for the cerebellum in causing ataxia, a disorder characterized by uncoordinated movement, is widely accepted. Recent work has suggested that alterations in activity, connectivity, and structure of the cerebellum are also associated with dystonia, a neurological disorder characterized by abnormal and sustained muscle contractions often leading to abnormal maintained postures. In this manuscript, the authors discuss their views on how the cerebellum may play a role in dystonia. The following topics are discussed: The relationships between neuronal/network dysfunctions and motor abnormalities in rodent models of dystonia. Data about brain structure, cerebellar metabolism, cerebellar connections, and noninvasive cerebellar stimulation that support (or not) a role for the cerebellum in human dystonia. Connections between the cerebellum and motor cortical and sub-cortical structures that could support a role for the cerebellum in dystonia. Overall points of consensus include: Neuronal dysfunction originating in the cerebellum can drive dystonic movements in rodent model systems. Imaging and neurophysiological studies in humans suggest that the cerebellum plays a role in the pathophysiology of dystonia, but do not provide conclusive evidence that the cerebellum is the primary or sole neuroanatomical site of origin.

Structural and behavioral correlates of abnormal encoding of money value in the sensorimotor striatum in cocaine addiction

PubMed Central

Konova, Anna B.; Moeller, Scott J.; Tomasi, Dardo; Parvaz, Muhammad A.; Alia-Klein, Nelly; Volkow, Nora D.; Goldstein, Rita Z.

2012-01-01

Abnormalities in frontostriatal systems are thought to be central to the pathophysiology of addiction, and may underlie maladaptive processing of the highly generalizable reinforcer, money. Although abnormal frontostriatal structure and function have been observed in individuals addicted to cocaine, it is less clear how individual variability in brain structure is associated with brain function to influence behavior. Our objective was to examine frontostriatal structure and neural processing of money value in chronic cocaine users and closely matched healthy controls. A reward task that manipulated different levels of money was used to isolate neural activity associated with money value. Gray matter volume measures were used to assess frontostriatal structure. Our results indicated that cocaine users had an abnormal money value signal in the sensorimotor striatum (right putamen/globus pallidus) which was negatively associated with accuracy adjustments to money and was more pronounced in individuals with more severe use. In parallel, group differences were also observed in both function and gray matter volume of the ventromedial prefrontal cortex; in the cocaine users, the former was directly associated with response to money in the striatum. These results provide strong evidence for abnormalities in the neural mechanisms of valuation in addiction and link these functional abnormalities with deficits in brain structure. In addition, as value signals represent acquired associations, their abnormal processing in the sensorimotor striatum, a region centrally implicated in habit formation, could signal disadvantageous associative learning in cocaine addiction. PMID:22775285

Impaired embryonic development in glucose-6-phosphate dehydrogenase-deficient Caenorhabditis elegans due to abnormal redox homeostasis induced activation of calcium-independent phospholipase and alteration of glycerophospholipid metabolism.

PubMed

Chen, Tzu-Ling; Yang, Hung-Chi; Hung, Cheng-Yu; Ou, Meng-Hsin; Pan, Yi-Yun; Cheng, Mei-Ling; Stern, Arnold; Lo, Szecheng J; Chiu, Daniel Tsun-Yee

2017-01-12

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a commonly pervasive inherited disease in many parts of the world. The complete lack of G6PD activity in a mouse model causes embryonic lethality. The G6PD-deficient Caenorhabditis elegans model also shows embryonic death as indicated by a severe hatching defect. Although increased oxidative stress has been implicated in both cases as the underlying cause, the exact mechanism has not been clearly delineated. In this study with C. elegans, membrane-associated defects, including enhanced permeability, defective polarity and cytokinesis, were found in G6PD-deficient embryos. The membrane-associated abnormalities were accompanied by impaired eggshell structure as evidenced by a transmission electron microscopic study. Such loss of membrane structural integrity was associated with abnormal lipid composition as lipidomic analysis revealed that lysoglycerophospholipids were significantly increased in G6PD-deficient embryos. Abnormal glycerophospholipid metabolism leading to defective embryonic development could be attributed to the increased activity of calcium-independent phospholipase A 2 (iPLA) in G6PD-deficient embryos. This notion is further supported by the fact that the suppression of multiple iPLAs by genetic manipulation partially rescued the embryonic defects in G6PD-deficient embryos. In addition, G6PD deficiency induced disruption of redox balance as manifested by diminished NADPH and elevated lipid peroxidation in embryos. Taken together, disrupted lipid metabolism due to abnormal redox homeostasis is a major factor contributing to abnormal embryonic development in G6PD-deficient C. elegans.

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.

Novel chromatin texture features for the classification of pap smears

NASA Astrophysics Data System (ADS)

Bejnordi, Babak E.; Moshavegh, Ramin; Sujathan, K.; Malm, Patrik; Bengtsson, Ewert; Mehnert, Andrew

2013-03-01

This paper presents a set of novel structural texture features for quantifying nuclear chromatin patterns in cells on a conventional Pap smear. The features are derived from an initial segmentation of the chromatin into bloblike texture primitives. The results of a comprehensive feature selection experiment, including the set of proposed structural texture features and a range of different cytology features drawn from the literature, show that two of the four top ranking features are structural texture features. They also show that a combination of structural and conventional features yields a classification performance of 0.954±0.019 (AUC±SE) for the discrimination of normal (NILM) and abnormal (LSIL and HSIL) slides. The results of a second classification experiment, using only normal-appearing cells from both normal and abnormal slides, demonstrates that a single structural texture feature measuring chromatin margination yields a classification performance of 0.815±0.019. Overall the results demonstrate the efficacy of the proposed structural approach and that it is possible to detect malignancy associated changes (MACs) in Papanicoloau stain.

Natural History of the Central Structural Abnormalities in Choroideremia: A Prospective Cross-Sectional Study.

PubMed

Aleman, Tomas S; Han, Grace; Serrano, Leona W; Fuerst, Nicole M; Charlson, Emily S; Pearson, Denise J; Chung, Daniel C; Traband, Anastasia; Pan, Wei; Ying, Gui-Shuang; Bennett, Jean; Maguire, Albert M; Morgan, Jessica I W

2017-03-01

To describe in detail the central retinal structure of a large group of patients with choroideremia (CHM). A prospective, cross-sectional, descriptive study. Patients (n = 97, age 6-71 years) with CHM and subjects with normal vision (n = 44; ages 10-50 years) were included. Subjects were examined with spectral-domain optical coherence tomography (SD OCT) and near-infrared reflectance imaging. Visual acuity (VA) was measured during their encounter or obtained from recent ophthalmic examinations. Visual thresholds were measured in a subset of patients (n = 24) with automated static perimetry within the central regions (±15°) examined with SD OCT. Visual acuity and visual thresholds; total nuclear layer, inner nuclear layer (INL), and outer nuclear layer (ONL) thicknesses; and horizontal extent of the ONL and the photoreceptor outer segment (POS) interdigitation zone (IZ). Earliest abnormalities in regions with normally appearing retinal pigment epithelium (RPE) were the loss of the POS and ellipsoid zone associated with rod dysfunction. Transition zones (TZs) from relatively preserved retina to severe ONL thinning and inner retinal thickening moved centripetally with age. Most patients (88%) retained VAs better than 20/40 until their fifth decade of life. The VA decline coincided with migration of the TZ near the foveal center. There were outer retinal tubulations in degenerated, nonatrophic retina in the majority (69%) of patients. In general, RPE abnormalities paralleled photoreceptor degeneration, although there were regions with detectable but abnormally thin ONL co-localizing with severe RPE depigmentation and choroidal thinning. Abnormalities of the POS and rod dysfunction are the earliest central abnormalities observed in CHM. Foveal function is relatively preserved until the fifth decade of life. Migration of the TZs to the foveal center with foveal thinning and structural disorganization heralded central VA loss. The relationships established may help outline the eligibility criteria and outcome measures for clinical trials for CHM. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Neonatal brain structure on MRI and diffusion tensor imaging, sex, and neurodevelopment in very-low-birthweight preterm children.

PubMed

Rose, Jessica; Butler, Erin E; Lamont, Lauren E; Barnes, Patrick D; Atlas, Scott W; Stevenson, David K

2009-07-01

The neurological basis of an increased incidence of cerebral palsy (CP) in preterm males is unknown. This study examined neonatal brain structure on magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) at term-equivalent age, sex, and neurodevelopment at 1 year 6 months on the basis of the Amiel-Tison neurological examination, Gross Motor Function Classification System, and Bayley Scales of Infant Development in 78 very-low-birthweight preterm children (41 males, 37 females; mean gestational age 27.6 wks, SD 2.5; mean birthweight 1021 g, SD 339). Brain abnormalities on MRI and DTI were not different between males and females except in the splenium of the corpus callosum, where males had lower DTI fractional anisotropy (p=0.025) and a higher apparent diffusion coefficient (p=0.013), indicating delayed splenium development. In the 26 infants who were at higher risk on the basis of DTI, males had more abnormalities on MRI (p=0.034) and had lower fractional anisotropy and a higher apparent diffusion coefficient in the splenium (p=0.049; p=0.025) and right posterior limb of the internal capsule (PLIC; p=0.003; p=0.033). Abnormal neurodevelopment was more common in males (n=9) than in females (n=2; p=0.036). Children with abnormal neurodevelopment had more abnormalities on MRI (p=0.014) and reduced splenium and right PLIC fractional anisotropy (p=0.001; p=0.035). In children with abnormal neurodevelopment, right PLIC fractional anisotropy was lower than left (p=0.035), whereas in those with normal neurodevelopment right PLIC fractional anisotropy was higher than left (p=0.001). Right PLIC fractional anisotropy correlated to neurodevelopment (rho=0.371, p=0.002). Logistic regression predicted neurodevelopment with 94% accuracy; only right PLIC fractional anisotropy was a significant logistic coefficient. Results indicate that the higher incidence of abnormal neurodevelopment in preterm males relates to greater incidence and severity of brain abnormalities, including reduced PLIC and splenium development.

Fetal alcohol exposure leads to abnormal olfactory bulb development and impaired odor discrimination in adult mice.

PubMed

Akers, Katherine G; Kushner, Steven A; Leslie, Ana T; Clarke, Laura; van der Kooy, Derek; Lerch, Jason P; Frankland, Paul W

2011-07-07

Children whose mothers consumed alcohol during pregnancy exhibit widespread brain abnormalities and a complex array of behavioral disturbances. Here, we used a mouse model of fetal alcohol exposure to investigate relationships between brain abnormalities and specific behavioral alterations during adulthood. Mice drank a 10% ethanol solution throughout pregnancy. When fetal alcohol-exposed offspring reached adulthood, we used high resolution MRI to conduct a brain-wide screen for structural changes and found that the largest reduction in volume occurred in the olfactory bulbs. Next, we tested adult mice in an associative olfactory task and found that fetal alcohol exposure impaired discrimination between similar odors but left odor memory intact. Finally, we investigated olfactory bulb neurogenesis as a potential mechanism by performing an in vitro neurosphere assay, in vivo labeling of new cells using BrdU, and in vivo labeling of new cells using a transgenic reporter system. We found that fetal alcohol exposure decreased the number of neural precursor cells in the subependymal zone and the number of new cells in the olfactory bulbs during the first few postnatal weeks. Using a combination of techniques, including structural brain imaging, in vitro and in vivo cell detection methods, and behavioral testing, we found that fetal alcohol exposure results in smaller olfactory bulbs and impairments in odor discrimination that persist into adulthood. Furthermore, we found that these abnormalities in olfactory bulb structure and function may arise from deficits in the generation of new olfactory bulb neurons during early postnatal development.

Easier to swallow: pictorial review of structural findings of the pharynx at barium pharyngography.

PubMed

Tao, Ting Y; Menias, Christine O; Herman, Thomas E; McAlister, William H; Balfe, Dennis M

2013-01-01

Barium pharyngography remains an important diagnostic tool in the evaluation of patients with dysphagia. Pharyngography can not only help detect functional abnormalities but also help identify a wide spectrum of structural abnormalities in children and adults. These structural abnormalities may reflect malignant or nonmalignant oropharyngeal, hypopharyngeal, or laryngeal processes that deform or alter normal coated mucosal surfaces. Therefore, an understanding of the normal appearance of the pharynx at contrast material-enhanced imaging is necessary for accurate detection and interpretation of abnormal findings. Congenital malformations are more typically identified in the younger population; inflammatory and infiltrative diseases, trauma, foreign bodies, and laryngeal cysts can be seen in all age groups; and Zenker and Killian-Jamieson diverticula tend to occur in the older population. Squamous cell carcinoma is by far the most common malignant process, with contrast-enhanced imaging findings that depend on tumor location and morphology. Treatments of head and neck cancers include total laryngectomy and radiation therapy, both of which alter normal anatomy. Patients are usually evaluated immediately after laryngectomy to detect complications such as fistulas; later, pharyngography is useful for identifying and characterizing strictures. Deviation from the expected posttreatment appearance, such as irregular narrowing or mucosal nodularity, should prompt direct visualization to evaluate for recurrence. Contrast-enhanced imaging of the pharynx is commonly used in patients who present with dysphagia, and radiologists should be familiar with the barium pharyngographic appearance of the normal pharyngeal anatomy and of some of the processes that alter normal anatomy. © RSNA, 2013.

Striatal abnormalities in trichotillomania: a multi-site MRI analysis.

PubMed

Isobe, Masanori; Redden, Sarah A; Keuthen, Nancy J; Stein, Dan J; Lochner, Christine; Grant, Jon E; Chamberlain, Samuel R

2018-01-01

Trichotillomania (hair-pulling disorder) is characterized by the repetitive pulling out of one's own hair, and is classified as an Obsessive-Compulsive Related Disorder. Abnormalities of the ventral and dorsal striatum have been implicated in disease models of trichotillomania, based on translational research, but direct evidence is lacking. The aim of this study was to elucidate subcortical morphometric abnormalities, including localized curvature changes, in trichotillomania. De-identified MRI scans were pooled by contacting authors of previous peer-reviewed studies that examined brain structure in adult patients with trichotillomania, following an extensive literature search. Group differences on subcortical volumes of interest were explored (t-tests) and localized differences in subcortical structure morphology were quantified using permutation testing. The pooled sample comprised N=68 individuals with trichotillomania and N=41 healthy controls. Groups were well-matched in terms of age, gender, and educational levels. Significant volumetric reductions were found in trichotillomania patients versus controls in right amygdala and left putamen. Localized shape deformities were found in bilateral nucleus accumbens, bilateral amygdala, right caudate and right putamen. Structural abnormalities of subcortical regions involved in affect regulation, inhibitory control, and habit generation, play a key role in the pathophysiology of trichotillomania. Trichotillomania may constitute a useful model through which to better understand other compulsive symptoms. These findings may account for why certain medications appear effective for trichotillomania, namely those modulating subcortical dopamine and glutamatergic function. Future work should study the state versus trait nature of these changes, and the impact of treatment.

Abnormal XPD-induced nuclear receptor transactivation in DNA repair disorders: trichothiodystrophy and xeroderma pigmentosum.

PubMed

Zhou, Xiaolong; Khan, Sikandar G; Tamura, Deborah; Ueda, Takahiro; Boyle, Jennifer; Compe, Emmanuel; Egly, Jean-Marc; DiGiovanna, John J; Kraemer, Kenneth H

2013-08-01

XPD (ERCC2) is a DNA helicase involved in nucleotide excision repair and in transcription as a structural bridge tying the transcription factor IIH (TFIIH) core with the cdk-activating kinase complex, which phosphorylates nuclear receptors. Mutations in XPD are associated with several different phenotypes, including trichothiodystrophy (TTD), with sulfur-deficient brittle hair, bone defects, and developmental abnormalities without skin cancer, xeroderma pigmentosum (XP), with pigmentary abnormalities and increased skin cancer, or XP/TTD with combined features, including skin cancer. We describe the varied clinical features and mutations in nine patients examined at the National Institutes of Health who were compound heterozygotes for XPD mutations but had different clinical phenotypes: four TTD, three XP, and two combined XP/TTD. We studied TFIIH-dependent transactivation by nuclear receptor for vitamin D (VDR) and thyroid in cells from these patients. The vitamin D stimulation ratio of CYP24 and osteopontin was associated with specific pairs of mutations (reduced in 5, elevated in 1) but not correlated with distinct clinical phenotypes. Thyroid receptor stimulation ratio for KLF9 was not significantly different from normal. XPD mutations frequently were associated with abnormal VDR stimulation in compound heterozygote patients with TTD, XP, or XP/TTD.

The accuracy of ultrasound in the diagnosis of congenital abnormalities.

PubMed

Munim, Shama; Nadeem, Salva; Khuwaja, Nadya Ali

2006-01-01

To determine the accuracy of ultrasound in the diagnosis of congenital abnormalities at the Aga Khan University Hospital, Karachi. The data of congenital abnormalities was obtained from the obstetrical database and medical records of all cases complicated by congenital abnormalities, delivering from January 2001 to December 2003 and was reviewed. Antenatal ultrasounds had been performed by operators with different level of experience. In addition this data was retrieved from the termination and Congenital anomaly register. A structured data collection form was used to collect information of different variables of interest. Congenital abnormalities, complicated 2.8% (n=170), of all deliveries, including all cases of termination of pregnancy, stillbirth and live births. Out of the total, 11.6% occurred in women above the age of 35 years. Consanguinity was found in 18.2% cases. Prenatal diagnosis was made in just under half of the cases (48.8%). Central nervous system and renal abnormalities were commonly diagnosed. However, facial defects, heart defects or skeletal defects were more commonly missed. Antenatal ultrasound successfully diagnosed foetal abnormalities in 48.8% of cases, and more than 90% Central Nervous system defects and renal abnormalities. In contrast about a quarter of Cardiac defects and none of the facial defects were detected. Based on these findings we recommend that the Sonologist should incorporate four chamber view of the heart and also look at the face carefully.

Medication Overuse Headache: Pathophysiological Insights from Structural and Functional Brain MRI Research.

PubMed

Schwedt, Todd J; Chong, Catherine D

2017-07-01

Research imaging of brain structure and function has helped to elucidate the pathophysiology of medication overuse headache (MOH). This is a narrative review of imaging research studies that have investigated brain structural and functional alterations associated with MOH. Studies included in this review have investigated abnormal structure and function of pain processing regions in people with MOH, functional patterns that might predispose individuals to development of MOH, similarity of brain functional patterns in patients with MOH to those found in people with addiction, brain structure that could predict headache improvement following discontinuation of the overused medication, and changes in brain structure and function after discontinuation of medication overuse. MOH is associated with atypical structure and function of brain regions responsible for pain processing as well as brain regions that are commonly implicated in addiction. Several studies have shown "normalization" of structure and function in pain processing regions following discontinuation of the overused medication and resolution of MOH. However, some of the abnormalities in regions also implicated in addiction tend to persist following discontinuation of the overused medication, suggesting that they are a brain trait that predisposes certain individuals to medication overuse and MOH. © 2017 American Headache Society.

Neonatal White Matter Abnormalities an Important Predictor of Neurocognitive Outcome for Very Preterm Children

PubMed Central

Woodward, Lianne J.; Clark, Caron A. C.; Bora, Samudragupta; Inder, Terrie E.

2012-01-01

Background Cerebral white matter abnormalities on term MRI are a strong predictor of motor disability in children born very preterm. However, their contribution to cognitive impairment is less certain. Objective Examine relationships between the presence and severity of cerebral white matter abnormalities on neonatal MRI and a range of neurocognitive outcomes assessed at ages 4 and 6 years. Design/Methods The study sample consisted of a regionally representative cohort of 104 very preterm (≤32 weeks gestation) infants born from 1998–2000 and a comparison group of 107 full-term infants. At term equivalent, all preterm infants underwent a structural MRI scan that was analyzed qualitatively for the presence and severity of cerebral white matter abnormalities, including cysts, signal abnormalities, loss of white matter volume, ventriculomegaly, and corpus callosal thinning/myelination. At corrected ages 4 and 6 years, all children underwent a comprehensive neurodevelopmental assessment that included measures of general intellectual ability, language development, and executive functioning. Results At 4 and 6 years, very preterm children without cerebral white matter abnormalities showed no apparent neurocognitive impairments relative to their full-term peers on any of the domain specific measures of intelligence, language, and executive functioning. In contrast, children born very preterm with mild and moderate-to-severe white matter abnormalities were characterized by performance impairments across all measures and time points, with more severe cerebral abnormalities being associated with increased risks of cognitive impairment. These associations persisted after adjustment for gender, neonatal medical risk factors, and family social risk. Conclusions Findings highlight the importance of cerebral white matter connectivity for later intact cognitive functioning amongst children born very preterm. Preterm born children without cerebral white matter abnormalities on their term MRI appear to be spared many of the cognitive impairments commonly associated with preterm birth. Further follow-up will be important to assess whether this finding persists into the school years. PMID:23284800

Structural and behavioral correlates of abnormal encoding of money value in the sensorimotor striatum in cocaine addiction.

PubMed

Konova, Anna B; Moeller, Scott J; Tomasi, Dardo; Parvaz, Muhammad A; Alia-Klein, Nelly; Volkow, Nora D; Goldstein, Rita Z

2012-10-01

Abnormalities in frontostriatal systems are thought to be central to the pathophysiology of addiction, and may underlie the maladaptive processing of the highly generalizable reinforcer, money. Although abnormal frontostriatal structure and function have been observed in individuals addicted to cocaine, it is less clear how individual variability in brain structure is associated with brain function to influence behavior. Our objective was to examine frontostriatal structure and neural processing of money value in chronic cocaine users and closely matched healthy controls. A reward task that manipulated different levels of money was used to isolate neural activity associated with money value. Gray matter volume measures were used to assess frontostriatal structure. Our results indicated that cocaine users had an abnormal money value signal in the sensorimotor striatum (right putamen/globus pallidus) that was negatively associated with accuracy adjustments to money and was more pronounced in individuals with more severe use. In parallel, group differences were also observed in both the function and gray matter volume of the ventromedial prefrontal cortex; in the cocaine users, the former was directly associated with response to money in the striatum. These results provide strong evidence for abnormalities in the neural mechanisms of valuation in addiction and link these functional abnormalities with deficits in brain structure. In addition, as value signals represent acquired associations, their abnormal processing in the sensorimotor striatum, a region centrally implicated in habit formation, could signal disadvantageous associative learning in cocaine addiction. © 2012 Published 2012. This article is a US Government work and is in the public domain in the USA.

Volumetric structural brain abnormalities in men with schizophrenia or antisocial personality disorder.

PubMed

Barkataki, Ian; Kumari, Veena; Das, Mrigendra; Taylor, Pamela; Sharma, Tonmoy

2006-05-15

Brain abnormalities are found in association with antisocial personality disorder and schizophrenia, the two mental disorders most implicated in violent behaviour. Structural magnetic resonance imaging was used to investigate the whole brain, cerebellum, temporal lobe, lateral ventricles, caudate nucleus, putamen, thalamus, hippocampus, amygdala and the prefrontal, pre-motor, sensorimotor, occipito-parietal regions in 13 men with antisocial personality disorder, 13 men with schizophrenia and a history of violence, 15 men with schizophrenia without violent history and 15 healthy non-violent men. Compared to controls, the antisocial personality disorder group displayed reductions in whole brain volume and temporal lobe as well as increases in putamen volume. Both schizophrenia groups regardless of violence history exhibited increased lateral ventricle volume, while the schizophrenia group with violent history showed further abnormalities including reduced whole brain and hippocampal volumes and increased putamen size. The findings suggest that individuals with antisocial personality disorder as well as those with schizophrenia and a history of violence have common neural abnormalities, but also show neuro-anatomical differences. The processes by which they came to apparently common ground may, however, differ. The finding of temporal lobe reductions prevalent among those with antisocial personality disorder and hippocampal reduction in the violent men with schizophrenia contributes support for the importance of this region in mediating violent behaviour.

The FIGO systems for nomenclature and classification of causes of abnormal uterine bleeding in the reproductive years: who needs them?

PubMed

Munro, Malcolm G; Critchley, Hilary O D; Fraser, Ian S

2012-10-01

In November 2010, the International Federation of Gynecology and Obstetrics formally accepted a new classification system for causes of abnormal uterine bleeding in the reproductive years. The system, based on the acronym PALM-COEIN (polyps, adenomyosis, leiomyoma, malignancy and hyperplasia-coagulopathy, ovulatory disorders, endometrial causes, iatrogenic, not classified) was developed in response to concerns about the design and interpretation of basic science and clinical investigation that relates to the problem of abnormal uterine bleeding. A system of nomenclature for the description of normal uterine bleeding and the various symptoms that comprise abnormal bleeding has also been included. This article describes the rationale, the structured methods that involved stakeholders worldwide, and the suggested use of the International Federation of Gynecology and Obstetrics system for research, education, and clinical care. Investigators in the field are encouraged to use the system in the design of their abnormal uterine bleeding-related research because it is an approach that should improve our understanding and management of this often perplexing clinical condition. Copyright © 2012. Published by Mosby, Inc.

Preliminary evidence for obesity and elevations in fasting insulin mediating associations between cortisol awakening response and hippocampal volumes and frontal atrophy.

PubMed

Ursache, Alexandra; Wedin, William; Tirsi, Aziz; Convit, Antonio

2012-08-01

Recent studies have demonstrated alterations in the cortisol awakening response (CAR) and brain abnormalities in adults with obesity and type 2 diabetes mellitus (T2DM). While adolescents with T2DM exhibit similar brain abnormalities, less is known about whether brain impairments and hypothalamic-pituitary-adrenal (HPA) axis abnormalities are already present in adolescents with pre-diabetic conditions such as insulin resistance (IR). This study included 33 adolescents with IR and 20 without IR. Adolescents with IR had a blunted CAR, smaller hippocampal volumes, and greater frontal lobe atrophy compared to controls. Mediation analyses indicated pathways whereby a smaller CAR was associated with higher BMI which was in turn associated with fasting insulin levels, which in turn was related to smaller hippocampal volume and greater frontal lobe atrophy. While we had hypothesized that HPA dysregulation may result from brain abnormalities, our findings suggest that HPA dysregulation may also impact brain structures through associations with metabolic abnormalities. Copyright © 2012 Elsevier Ltd. All rights reserved.

Intravitreal bevacizumab versus laser treatment in type 1 retinopathy of prematurity: report on fluorescein angiographic findings.

PubMed

Lepore, Domenico; Quinn, Graham E; Molle, Fernando; Baldascino, Antonio; Orazi, Lorenzo; Sammartino, Maria; Purcaro, Velia; Giannantonio, Carmen; Papacci, Patrizia; Romagnoli, Costantino

2014-11-01

To compare the structural outcome at 9 months of eyes treated with intravitreal injection of bevacizumab with fellow eyes treated with conventional laser photoablation in zone I type 1 retinopathy of prematurity (ROP). Single randomized controlled trial. All inborn babies with type 1 zone I ROP at a single institution were included in the study. One eye was randomized to receive an intravitreal injection of 0.5 mg bevacizumab; the fellow eye received conventional laser photoablation. Digital fundus photographs and fluorescein angiography (FA) using the RetCam (Clarity Medical Systems Inc., Pleasanton, CA) were performed before treatment and 9 months after treatment. Presence of retinal and choroidal abnormalities on FA at 9 months. Thirteen infants were enrolled; 1 died 3 months after birth. One laser-treated eye progressed to stage 5 retinal detachment. The remaining 23 eyes had favorable structural results at the 9-month follow-up and provided FA results. At 9 months of age, all eyes treated with a bevacizumab injection were noted to have abnormalities at the periphery (large avascular area, abnormal branching, shunt) or the posterior pole (hyperfluorescent lesion, absence of foveal avascular zone). These posterior and peripheral lesions were not observed in the majority of the lasered eyes. This study documents significant vascular and macular abnormalities of eyes in the bevacizumab group. Long-lasting implications of these abnormalities for visual function of the child need to be studied. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Environmental Complexity and Central Nervous System Development and Function

ERIC Educational Resources Information Center

Lewis, Mark H.

2004-01-01

Environmental restriction or deprivation early in development can induce social, cognitive, affective, and motor abnormalities similar to those associated with autism. Conversely, rearing animals in larger, more complex environments results in enhanced brain structure and function, including increased brain weight, dendritic branching,…

The Aging Lung: Clinical and Imaging Findings and the Fringe of Physiological State.

PubMed

Schröder, T H; Storbeck, B; Rabe, K F; Weber, C

2015-06-01

Since aspects of demographic transition have become an essential part of socioeconomic, medical and health-care research in the last decades, it is vital for the radiologist to discriminate between normal ageing related effects and abnormal imaging findings in the elderly. This article reviews functional and structural aspects of the ageing lung and focuses on typical ageing related radiological patterns. • The physiological aging process of the thoracic organs shows typical structural and functional aspects.• Mild interstitial fibrosis and focal parenchymal abnormalities like septal thickening can be diagnosed frequently - whereas a clinical correlate is often lacking.• With increasing patient age, the influence by various intrinsic and extrinsic factors (including comorbidities of the patient, and drug inhalation toxicants) also increases.• A growing spectrum of imaging techniques (including functional cardiopulmonary MRI, MRI spectroscopy, hybrid-techniques) is confronted by rare empiric data in the very old people (aging 80 years and older). © Georg Thieme Verlag KG Stuttgart · New York.

Frontotemporal white matter changes in amyotrophic lateral sclerosis.

PubMed

Abrahams, Sharon; Goldstein, Laura H; Suckling, John; Ng, Virginia; Simmons, Andy; Chitnis, Xavier; Atkins, Louise; Williams, Steve C R; Leigh, P N

2005-03-01

Cognitive dysfunction can occur in some patients with amyotrophic lateral sclerosis (ALS) who are not suffering from dementia. The most striking and consistent cognitive deficit has been found using tests of verbal fluency. ALS patients with verbal fluency deficits have shown functional imaging abnormalities predominantly in frontotemporal regions using positron emission tomography (PET). This study used automated volumetric voxel-based analysis of grey and white matter densities of structural magnetic resonance imaging (MRI) scans to explore the underlying pattern of structural cerebral change in nondemented ALS patients with verbal fluency deficits. Two groups of ALS patients, defined by the presence or absence of cognitive impairment on the basis of the Written Verbal Fluency Test (ALSi, cognitively impaired, n=11; ALSu, cognitively unimpaired n=12) were compared with healthy age matched controls (n=12). A comparison of the ALSi group with controls revealed significantly (p<0.002) reduced white matter volume in extensive motor and non-motor regions, including regions corresponding to frontotemporal association fibres. These patients demonstrated a corresponding cognitive profile of executive and memory dysfunction. Less extensive white matter reductions were revealed in the comparison of the ALSu and control groups in regions corresponding to frontal association fibres. White matter volumes were also found to correlate with performance on memory tests. There were no significant reductions in grey matter volume in the comparison of either patient group with controls. The structural white matter abnormalities in frontal and temporal regions revealed here may underlie the cognitive and functional imaging abnormalities previously reported in non-demented ALS patients. The results also suggest that extra-motor structural abnormalities may be present in ALS patients with no evidence of cognitive change. The findings support the hypothesis of a continuum of extra-motor cerebral and cognitive change in this disorder.

Abnormalities of thalamic activation and cognition in schizophrenia.

PubMed

Andrews, Jessica; Wang, Lei; Csernansky, John G; Gado, Mokhtar H; Barch, Deanna M

2006-03-01

Functional and structural magnetic resonance imaging (MRI) was used to investigate relationships among structure, functional activation, and cognitive deficits related to the thalamus in individuals with schizophrenia and healthy comparison subjects. Thirty-six schizophrenia subjects and 28 healthy comparison subjects matched by age, gender, race, and parental socioeconomic status underwent structural and functional MRI while performing a series of memory tasks, including an N-back task (working memory), intentional memorization of a series of pictures or words (episodic encoding), and a yes/no recognition task. Functional activation magnitudes in seven regions of interest within the thalamic complex, as defined by anatomical and functional criteria, were computed for each group. Participants with schizophrenia exhibited decreased activation within the whole thalamus, the anterior nuclei, and the medial dorsal nucleus. These nuclei overlap with subregions of the thalamic surface that the authors previously reported to exhibit morphological abnormalities in schizophrenia. However, there were no significant correlations between specific dimensions of thalamic shape variation (i.e., eigenvectors) and the activation patterns within thalamic regions of interest. Better performance on the working memory task among individuals with schizophrenia was significantly associated with increased activation in the anterior nuclei, the centromedian nucleus, the pulvinar, and the ventrolateral nuclei. These results suggest that there are limited relationships between morphological and functional abnormalities of the thalamus in schizophrenia subjects and highlight the importance of investigating relationships between brain structure and function.

Congenital microcephaly: A diagnostic challenge during Zika epidemics.

PubMed

Alvarado-Socarras, Jorge L; Idrovo, Álvaro J; Contreras-García, Gustavo A; Rodriguez-Morales, Alfonso J; Audcent, Tobey A; Mogollon-Mendoza, Adriana C; Paniz-Mondolfi, Alberto

2018-02-19

The multiple, wide and diverse etiologies of congenital microcephaly are complex and multifactorial. Recent advances in genetic testing have improved understanding of novel genetic causes of congenital microcephaly. The recent Zika virus (ZIKV) epidemic in Latin America has highlighted the need for a better understanding of the underlying pathological mechanisms of microcephaly including both infectious and non-infectious causes. The diagnostic approach to microcephaly needs to include potential infectious and genetic etiologies, as well as environmental in-utero exposures such as alcohol, toxins, and medications. Emerging genetic alterations linked to microcephaly include abnormal mitotic microtubule spindle structure and abnormal function of centrosomes. We discuss the diagnostic challenge of congenital microcephaly in the context of understanding the links with ZIKV emergence as a new etiological factor involved in this birth defect. Copyright © 2018 Elsevier Ltd. All rights reserved.

Genes relacionados con microftalmia y anoftalmia hereditarias.

PubMed

Matías-Pérez, Diana; García-Montalvo, Iván Antonio; Zenteno, Juan Carlos

2017-01-01

Congenital eye malformations are the second most common cause of childhood blindness and are originated by disruption of the normal process of eye development during embryonic stage. Their etiology is variable, although monogenic causes are of great importance as they have a high risk of familial recurrence. Included among the most severe congenital eye abnormalities are microphthalmia, defined by an abnormally small eye, and anophthalmia, characterized by congenital absence of ocular structures. The currrent knowledge of the genes involved in human microphthalmia and anophthalmia in humans is revised in this work. Copyright: © 2017 SecretarÍa de Salud.

[EXOSKELETON ABNORMALITIES IN TAIGA TICK FEMALES FROM POPULATIONS OF THE ASIATIC PART OF RUSSIA].

PubMed

Nikitin, A Ya; Morozov, I M

2016-01-01

Studies of the phenotypic structure of Ixodes persulcatus (Schulze, 1930) populations in relation to their exoskeleton abnormalities are important in both theoretical and practical respects. The data on the species' population structure in Asiatic part of Russia are fragmentary. The goal of the study was to describe taiga tick population structure based on the pattern of females' exoskeleton abnormalities revealed in Asiatic part of Russia. A total of 3872 I. persulcatus females from 16 geographically remote sites of Far Eastern, Siberian, and Ural Federal Districts (FEFD, SFD, and UFD accordingly) were studied. It was demonstrated that all the populations possessed specimens with exoskeleton abnormalities. The «shagreen skin» abnormality was dominant in all these areas. At the same time, the percentage of abnormalities among the specimens collected to the north of 55°N is considerably higher (63.4 ± 3.39 %) than that of samples from the SFD southward territories (33.1 ± 3.43 %). The frequency of abnormalities in its turn is lower (24.4 ± 1.93 %) in the females from the territories with moderate monsoon and moderate continental climate (FEFD) than that in specimens from SFD and UFD areas with sharp continental climate. Thus, such polymorphism of the females' exoskeleton structure may reflect the natural phenogeographical variability of the character rather than the result of the anthropogenic impact. 403

Categorization of fetal external findings in developmental toxicology studies by the Terminology Committee of the Japanese Teratology Society.

PubMed

Izumi, Yuko; Ooshima, Yojiro; Chihara, Kazuhiro; Fujiwara, Michio; Katsumata, Yoshihiro; Shiota, Kohei

2018-05-01

Categorization of fetal external findings in common laboratory animals, intended to make the agreement at Berlin Workshop in 2014 more practical, was proposed by the Terminology Committee of the Japanese Teratology Society at the Workshop in the 55th Japanese Teratology Society Annual Meeting in 2015. In the Workshop, 73 external findings, which had been categorized as "Gray zone" anomalies but not as "Malformation" or "Variation" in the 2014 Berlin Workshop, were discussed and classified as Malformation, "Non-structural abnormality," Variation, and "Not applicable." The proposal was based on the results of a survey conducted in 2014, where 20 facilities (including pharmaceutical, chemical, and pesticide companies and contract laboratories) and 2 selected expert teratologists in Japan were asked for their opinions on the categorization of these findings. Based on the discussion, Japanese Teratology Society members have agreed that 42 out of the 73 findings can be classified as Malformations (38), Non-structural abnormalities (3), Malformations/Non-structural abnormalities (1), and Variations (0), while the remaining 31 findings were recommended to be categorized as Not applicable for fetuses. The details of the classification are shown on the website of the Japanese Teratology Society (http://www.umin.ac.jp/cadb/External.pdf). © 2018 Japanese Teratology Society.

Fetal alcohol exposure leads to abnormal olfactory bulb development and impaired odor discrimination in adult mice

PubMed Central

2011-01-01

Background Children whose mothers consumed alcohol during pregnancy exhibit widespread brain abnormalities and a complex array of behavioral disturbances. Here, we used a mouse model of fetal alcohol exposure to investigate relationships between brain abnormalities and specific behavioral alterations during adulthood. Results Mice drank a 10% ethanol solution throughout pregnancy. When fetal alcohol-exposed offspring reached adulthood, we used high resolution MRI to conduct a brain-wide screen for structural changes and found that the largest reduction in volume occurred in the olfactory bulbs. Next, we tested adult mice in an associative olfactory task and found that fetal alcohol exposure impaired discrimination between similar odors but left odor memory intact. Finally, we investigated olfactory bulb neurogenesis as a potential mechanism by performing an in vitro neurosphere assay, in vivo labeling of new cells using BrdU, and in vivo labeling of new cells using a transgenic reporter system. We found that fetal alcohol exposure decreased the number of neural precursor cells in the subependymal zone and the number of new cells in the olfactory bulbs during the first few postnatal weeks. Conclusions Using a combination of techniques, including structural brain imaging, in vitro and in vivo cell detection methods, and behavioral testing, we found that fetal alcohol exposure results in smaller olfactory bulbs and impairments in odor discrimination that persist into adulthood. Furthermore, we found that these abnormalities in olfactory bulb structure and function may arise from deficits in the generation of new olfactory bulb neurons during early postnatal development. PMID:21736737

Detection of chromosomal abnormalities, congenital abnormalities and transfusion syndrome in twins.

PubMed

Sperling, L; Kiil, C; Larsen, L U; Brocks, V; Wojdemann, K R; Qvist, I; Schwartz, M; Jørgensen, C; Espersen, G; Skajaa, K; Bang, J; Tabor, A

2007-05-01

To evaluate the outcome of screening for structural malformations in twins and the outcome of screening for twin-twin transfusion syndrome (TTTS) among monochorionic twins through a number of ultrasound scans from 12 weeks' gestation. Enrolled into this prospective multicenter observational study were women with twin pregnancies diagnosed before 14 + 6 gestational weeks. The monochorionic pregnancies were scanned every second week until 23 weeks in order to rule out early TTTS. All pregnancies had an anomaly scan in week 19 and fetal echocardiography in week 21 that was performed by specialists in fetal echocardiography. Zygosity was determined by DNA analysis in all twin pairs with the same sex. Among the 495 pregnancies the prenatal detection rate for severe structural abnormalities including chromosomal aneuploidies was 83% by the combination of a first-trimester nuchal translucency scan and the anomaly scan in week 19. The incidence of severe structural abnormalities was 2.6% and two-thirds of these anomalies were cardiac. There was no significant difference between the incidence in monozygotic and dizygotic twins, nor between twins conceived naturally or those conceived by assisted reproduction. The incidence of TTTS was 23% from 12 weeks until delivery, and all those monochorionic twin pregnancies that miscarried had signs of TTTS. Twin pregnancies have an increased risk of congenital malformations and one out of four monochorionic pregnancies develops TTTS. Ultrasound screening to assess chorionicity and follow-up of monochorionic pregnancies to detect signs of TTTS, as well as malformation screening, are therefore essential in the antenatal care of twin pregnancies. Copyright (c) 2007 ISUOG.

Alterations in Brain Structure and Functional Connectivity in Alcohol Dependent Patients and Possible Association with Impulsivity.

PubMed

Wang, Junkai; Fan, Yunli; Dong, Yue; Ma, Mengying; Ma, Yi; Dong, Yuru; Niu, Yajuan; Jiang, Yin; Wang, Hong; Wang, Zhiyan; Wu, Liuzhen; Sun, Hongqiang; Cui, Cailian

2016-01-01

Previous studies have documented that heightened impulsivity likely contributes to the development and maintenance of alcohol use disorders. However, there is still a lack of studies that comprehensively detected the brain changes associated with abnormal impulsivity in alcohol addicts. This study was designed to investigate the alterations in brain structure and functional connectivity associated with abnormal impulsivity in alcohol dependent patients. Brain structural and functional magnetic resonance imaging data as well as impulsive behavior data were collected from 20 alcohol dependent patients and 20 age- and sex-matched healthy controls respectively. Voxel-based morphometry was used to investigate the differences of grey matter volume, and tract-based spatial statistics was used to detect abnormal white matter regions between alcohol dependent patients and healthy controls. The alterations in resting-state functional connectivity in alcohol dependent patients were examined using selected brain areas with gray matter deficits as seed regions. Compared with healthy controls, alcohol dependent patients had significantly reduced gray matter volume in the mesocorticolimbic system including the dorsal posterior cingulate cortex, the dorsal anterior cingulate cortex, the medial prefrontal cortex, the orbitofrontal cortex and the putamen, decreased fractional anisotropy in the regions connecting the damaged grey matter areas driven by higher radial diffusivity value in the same areas and decreased resting-state functional connectivity within the reward network. Moreover, the gray matter volume of the left medial prefrontal cortex exhibited negative correlations with various impulse indices. These findings suggest that chronic alcohol dependence could cause a complex neural changes linked to abnormal impulsivity.

Abnormal brain magnetic resonance imaging in two patients with Smith-Magenis syndrome.

PubMed

Maya, Idit; Vinkler, Chana; Konen, Osnat; Kornreich, Liora; Steinberg, Tamar; Yeshaya, Josepha; Latarowski, Victoria; Shohat, Mordechai; Lev, Dorit; Baris, Hagit N

2014-08-01

Smith-Magenis syndrome (SMS) is a clinically recognizable contiguous gene syndrome ascribed to an interstitial deletion in chromosome 17p11.2. Seventy percent of SMS patients have a common deletion interval spanning 3.5 megabases (Mb). Clinical features of SMS include characteristic mild dysmorphic features, ocular anomalies, short stature, brachydactyly, and hypotonia. SMS patients have a unique neurobehavioral phenotype that includes intellectual disability, self-injurious behavior and severe sleep disturbance. Little has been reported in the medical literature about anatomical brain anomalies in patients with SMS. Here we describe two patients with SMS caused by the common deletion in 17p11.2 diagnosed using chromosomal microarray (CMA). Both patients had a typical clinical presentation and abnormal brain magnetic resonance imaging (MRI) findings. One patient had subependymal periventricular gray matter heterotopia, and the second had a thin corpus callosum, a thin brain stem and hypoplasia of the cerebellar vermis. This report discusses the possible abnormal MRI images in SMS and reviews the literature on brain malformations in SMS. Finally, although structural brain malformations in SMS patients are not a common feature, we suggest baseline routine brain imaging in patients with SMS in particular, and in patients with chromosomal microdeletion/microduplication syndromes in general. Structural brain malformations in these patients may affect the decision-making process regarding their management. © 2014 Wiley Periodicals, Inc.

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.

Insults to the Developing Brain and Impact on Neurodevelopmental Outcome

ERIC Educational Resources Information Center

Adams-Chapman, Ira

2009-01-01

Premature infants have a disproportionately increased risk for brain injury based on several mechanisms including intraventricular hemorrhage, ischemia and the vulnerability of developing neuronal progenitor cells. Injury to the developing brain often results in neurologic abnormalities that can be correlated with a structural lesion; however more…

Outcome of chromosomally abnormal pregnancies in Lebanon: obstetricians' roles during and after prenatal diagnosis.

PubMed

Eldahdah, Lama T; Ormond, Kelly E; Nassar, Anwar H; Khalil, Tayma; Zahed, Laila F

2007-06-01

To better understand obstetrician experiences in Lebanon when disclosing abnormal amniocentesis results. Structured interviews with 38 obstetricians identified as caregivers from the American University of Beirut Medical Center Cytogenetics Laboratory database of patients with abnormal amniocentesis results between 1999 and 2005. Obstetricians were primarily male, Christian, and with an average of 14 years of experience. They reported doing most pre-amniocentesis counseling, including discussion of risk for common autosomal aneuplodies (95%), and procedure-related risk (95%). Obstetricians reported that 80% of patients at risk for aneuploidy underwent amniocentesis. The study population reported on 143 abnormal test results (124 autosomal abnormalities). When disclosing results, obstetricians reportedly discussed primarily physical and cognitive features of the diagnosis. They varied in levels of directiveness and comfort in providing information. Our records showed that 59% of pregnancies with sex chromosome abnormalities were terminated compared to 90% of those with autosomal aneuploidies; various reasons were proposed by obstetricians. This study is among the few to assess prenatal diagnosis practices in the Middle East, with a focus on the role of the obstetrician. Given the influence of culture and social norms on prenatal decision-making, it remains important to understand the various impacts on clinical practice in many nations. (c) 2007 John Wiley & Sons, Ltd.

Structural airway abnormalities contribute to dysphagia in children with esophageal atresia and tracheoesophageal fistula.

PubMed

Baxter, Katherine J; Baxter, Lauren M; Landry, April M; Wulkan, Mark L; Bhatia, Amina M

2018-01-31

Long-term dysphagia occurs in up to 50% of repaired esophageal atresia and tracheoesophageal fistula (EA/TEF) patients. The underlying factors are unclear and may include stricture, esophageal dysmotility, or associated anomalies. Our purpose was to determine whether structural airway abnormalities (SAA) are associated with dysphagia in EA/TEF. We conducted a retrospective chart review of children who underwent EA/TEF repair in our hospital system from 2007 to 2016. Children with identified SAA (oropharyngeal abnormalities, laryngeal clefts, laryngomalacia, vocal cord paralysis, and tracheomalacia) were compared to those without airway abnormalities. Dysphagia outcomes were determined by the need for tube feeding and the modified pediatric Functional Oral Intake Scale (FOIS) at 1 year. SAA was diagnosed in 55/145 (37.9%) patients with EA/TEF. Oropharyngeal aspiration was more common in children with SAA (58.3% vs. 36.4%, p=0.028). Children with SAA were more likely to require tube feeding both at discharge (79.6% vs. 48.3%, p<0.001) and at 1 year (52.7% vs. 13.6%, p<0.001) and had lower mean FOIS (4.18 vs. 6.21, p<0.001). In the logistic regression model adjusting for gestational age, long gap EA, and esophageal stricture, the presence of SAA remained a significant risk factor for dysphagia (OR 4.17 (95% CI 1.58-11.03)). SAA are common in children with EA/TEF and are associated with dysphagia, even after accounting for gestational age, esophageal gap and stricture. This study highlights the need for a multidisciplinary approach, including early laryngoscopy and bronchoscopy, in the evaluation of the EA/TEF child with dysphagia. Level II retrospective prognostic study. Copyright © 2018. Published by Elsevier Inc.

Genetic and Diagnostic Biomarker Development in ASD Toddlers Using Resting State Functional MRI

DTIC Science & Technology

2017-11-01

and activation-based fMRI from the Courchesne lab report the presence of structural and functional abnormality in these structures by ages 1 to 2...young ages. With this invaluable resource, we will identify early developmental patterns of intrinsic functional network abnormalities in ASD infants...all infants and toddlers, analyses also investigate whether there may be subtypes of abnormal intrinsic connectivity patterns based on early clinical

Anomalous basal ganglia connectivity and obsessive–compulsive behaviour in patients with Prader Willi syndrome

PubMed Central

Pujol, Jesus; Blanco-Hinojo, Laura; Esteba-Castillo, Susanna; Caixàs, Assumpta; Harrison, Ben J.; Bueno, Marta; Deus, Joan; Rigla, Mercedes; Macià, Dídac; Llorente-Onaindia, Jone; Novell-Alsina, Ramón

2016-01-01

Background Prader Willi syndrome is a genetic disorder with a behavioural expression characterized by the presence of obsessive–compulsive phenomena ranging from elaborate obsessive eating behaviour to repetitive skin picking. Obsessive–compulsive disorder (OCD) has been recently associated with abnormal functional coupling between the frontal cortex and basal ganglia. We have tested the potential association of functional connectivity anomalies in basal ganglia circuits with obsessive–compulsive behaviour in patients with Prader Willi syndrome. Methods We analyzed resting-state functional MRI in adult patients and healthy controls. Whole-brain functional connectivity maps were generated for the dorsal and ventral aspects of the caudate nucleus and putamen. A selected obsessive–compulsive behaviour assessment included typical OCD compulsions, self picking and obsessive eating behaviour. Results We included 24 adults with Prader Willi syndrome and 29 controls in our study. Patients with Prader Willi syndrome showed abnormal functional connectivity between the prefrontal cortex and basal ganglia and within subcortical structures that correlated with the presence and severity of obsessive–compulsive behaviours. In addition, abnormally heightened functional connectivity was identified in the primary sensorimotor cortex–putamen loop, which was strongly associated with self picking. Finally, obsessive eating behaviour correlated with abnormal functional connectivity both within the basal ganglia loops and between the striatum and the hypothalamus and the amygdala. Limitations Limitations of the study include the difficulty in evaluating the nature of content of obsessions in patients with Prader Willi Syndrome and the risk of excessive head motion artifact on brain imaging. Conclusion Patients with Prader Willi syndrome showed broad functional connectivity anomalies combining prefrontal loop alterations characteristic of OCD with 1) enhanced coupling in the primary sensorimotor loop that correlated with the most impulsive aspects of the behaviour and 2) reduced coupling of the ventral striatum with limbic structures for basic internal homeostasis that correlated with the obsession to eat. PMID:26645739

Abnormal XPD-induced nuclear receptor transactivation in DNA repair disorders: trichothiodystrophy and xeroderma pigmentosum

PubMed Central

Zhou, Xiaolong; Khan, Sikandar G; Tamura, Deborah; Ueda, Takahiro; Boyle, Jennifer; Compe, Emmanuel; Egly, Jean-Marc; DiGiovanna, John J; Kraemer, Kenneth H

2013-01-01

XPD (ERCC2) is a DNA helicase involved in nucleotide excision repair and in transcription as a structural bridge tying the transcription factor IIH (TFIIH) core with the cdk-activating kinase complex, which phosphorylates nuclear receptors. Mutations in XPD are associated with several different phenotypes, including trichothiodystrophy (TTD), with sulfur-deficient brittle hair, bone defects, and developmental abnormalities without skin cancer, xeroderma pigmentosum (XP), with pigmentary abnormalities and increased skin cancer, or XP/TTD with combined features, including skin cancer. We describe the varied clinical features and mutations in nine patients examined at the National Institutes of Health who were compound heterozygotes for XPD mutations but had different clinical phenotypes: four TTD, three XP, and two combined XP/TTD. We studied TFIIH-dependent transactivation by nuclear receptor for vitamin D (VDR) and thyroid in cells from these patients. The vitamin D stimulation ratio of CYP24 and osteopontin was associated with specific pairs of mutations (reduced in 5, elevated in 1) but not correlated with distinct clinical phenotypes. Thyroid receptor stimulation ratio for KLF9 was not significantly different from normal. XPD mutations frequently were associated with abnormal VDR stimulation in compound heterozygote patients with TTD, XP, or XP/TTD. PMID:23232694

Dissociated functional connectivity profiles for motor and attention deficits in acute right-hemisphere stroke

PubMed Central

Ramsey, Lenny; Rengachary, Jennifer; Zinn, Kristi; Siegel, Joshua S.; Metcalf, Nicholas V.; Strube, Michael J.; Snyder, Abraham Z.; Corbetta, Maurizio; Shulman, Gordon L.

2016-01-01

Strokes often cause multiple behavioural deficits that are correlated at the population level. Here, we show that motor and attention deficits are selectively associated with abnormal patterns of resting state functional connectivity in the dorsal attention and motor networks. We measured attention and motor deficits in 44 right hemisphere-damaged patients with a first-time stroke at 1–2 weeks post-onset. The motor battery included tests that evaluated deficits in both upper and lower extremities. The attention battery assessed both spatial and non-spatial attention deficits. Summary measures for motor and attention deficits were identified through principal component analyses on the raw behavioural scores. Functional connectivity in structurally normal cortex was estimated based on the temporal correlation of blood oxygenation level-dependent signals measured at rest with functional magnetic resonance imaging. Any correlation between motor and attention deficits and between functional connectivity in the dorsal attention network and motor networks that might spuriously affect the relationship between each deficit and functional connectivity was statistically removed. We report a double dissociation between abnormal functional connectivity patterns and attention and motor deficits, respectively. Attention deficits were significantly more correlated with abnormal interhemispheric functional connectivity within the dorsal attention network than motor networks, while motor deficits were significantly more correlated with abnormal interhemispheric functional connectivity patterns within the motor networks than dorsal attention network. These findings indicate that functional connectivity patterns in structurally normal cortex following a stroke link abnormal physiology in brain networks to the corresponding behavioural deficits. PMID:27225794

En face OCT in Stargardt disease.

PubMed

Sodi, Andrea; Mucciolo, Dario Pasquale; Cipollini, Francesca; Murro, Vittoria; Caporossi, Orsola; Virgili, Gianni; Rizzo, Stanislao

2016-09-01

To evaluate the structural features of the macular region by enface OCT imaging in patients with clinical diagnosis of Stargardt disease, confirmed by the detection of ABCA4 mutations. Thirty-two STGD patients were included in the study for a total of 64 eyes. All patients received a comprehensive ophthalmological examination, color fundus photography, fundus auto-fluorescence imaging and OCT. Five OCT scans were considered: ILM and RPE scans (both automatically obtained from the instrument), above-RPE slab, photoreceptor slab and sub-RPE slab (these last three manually obtained). ILM scans showed evident radial folds on the retinal surface in 8/64 eyes (12.5 %). In 6 of the 7 patients, these vitreo-retinal interface abnormalities were unilateral. The photoreceptor slab showed some macular alterations ranging from dis-homogeneous, hypo-reflective abnormalities (7/64 eyes, 11 %) to a homogeneous, well-defined, roundish, hypo-reflective area (17/64 eyes, 27 %) in all the eyes. The sub-RPE slab showed a centrally evident, hyper-reflective abnormality in 58/64 eyes (90.6 %). Superimposing the sub-RPE slab over the images corresponding to the photoreceptor slab, the area of the photoreceptor atrophy sharply exceeded that of the RPE atrophy (44/46 eyes, 96 %). Enface OCT proved to be a clinically useful tool for the management of STGD patients, illustrating in vivo the structural abnormalities of the different retinal layers.

Somatic Pairing of Chromosome 19 in Renal Oncocytoma Is Associated with Deregulated ELGN2-Mediated Oxygen-Sensing Response

PubMed Central

Petillo, David; Westphal, Michael; Koelzer, Katherine; Metcalf, Julie L.; Zhang, Zhongfa; Matsuda, Daisuke; Dykema, Karl J.; Houseman, Heather L.; Kort, Eric J.; Furge, Laura L.; Kahnoski, Richard J.; Richard, Stéphane; Vieillefond, Annick; Swiatek, Pamela J.; Teh, Bin Tean; Ohh, Michael; Furge, Kyle A.

2008-01-01

Chromosomal abnormalities, such as structural and numerical abnormalities, are a common occurrence in cancer. The close association of homologous chromosomes during interphase, a phenomenon termed somatic chromosome pairing, has been observed in cancerous cells, but the functional consequences of somatic pairing have not been established. Gene expression profiling studies revealed that somatic pairing of chromosome 19 is a recurrent chromosomal abnormality in renal oncocytoma, a neoplasia of the adult kidney. Somatic pairing was associated with significant disruption of gene expression within the paired regions and resulted in the deregulation of the prolyl-hydroxylase ELGN2, a key protein that regulates the oxygen-dependent degradation of hypoxia-inducible factor (HIF). Overexpression of ELGN2 in renal oncocytoma increased ubiquitin-mediated destruction of HIF and concomitantly suppressed the expression of several HIF-target genes, including the pro-death BNIP3L gene. The transcriptional changes that are associated with somatic pairing of chromosome 19 mimic the transcriptional changes that occur following DNA amplification. Therefore, in addition to numerical and structural chromosomal abnormalities, alterations in chromosomal spatial dynamics should be considered as genomic events that are associated with tumorigenesis. The identification of EGLN2 as a significantly deregulated gene that maps within the paired chromosome region directly implicates defects in the oxygen-sensing network to the biology of renal oncocytoma. PMID:18773095

Glutamatergic abnormalities of the thalamus in schizophrenia: a systematic review.

PubMed

Watis, L; Chen, S H; Chua, H C; Chong, S A; Sim, K

2008-01-01

The thalamus, a key information processing centre in facilitating sensory discrimination and cognitive processes, has been implicated in schizophrenia due to the increasing evidence showing structural and functional thalamic abnormalities. Glutamatergic abnormalities, in particular, have been examined since glutamate is one of the main neurotransmitters found in the thalamus. We aimed to review the existing literature (1978 till 2007) on post-mortem and in vivo studies of the various components of glutamatergic neurotransmission as well as studies of the glutamate receptor genes within the thalamus in schizophrenia. The literature search was done using multiple databases including Scopus, Web of Science, EBSCO host, Pubmed and ScienceDirect. Keywords used were "glutamate", "thalamus", "schizophrenia", "abnormalities", and "glutamatergic". Further searches were made using the bibliographies in the main journals and related papers were obtained. The extant data suggest that abnormalities of the glutamate receptors as well as other molecules involved in glutamatergic neurotransmission (including glutamate transporters and associated proteins, N-methyl D-aspartate (NMDA) receptor-associated intracellular signaling proteins, and glutamatergic enzymes) are found within the thalamus in schizophrenia. There is a pressing need for more rapid replication of findings from post mortem and genetic studies as well as the promotion of multi-component or multi-modality assessments of glutamatergic anomalies within the thalamus in order to allow a better appreciation of disruptions in these molecular networks in schizophrenia. These and future findings may represent potential novel targets for antipsychotic drugs to ameliorate the symptoms of schizophrenia.

Sperm chromatin structure assay results after swim-up are related only to embryo quality but not to fertilization and pregnancy rates following IVF.

PubMed

Niu, Zhi-Hong; Shi, Hui-Juan; Zhang, Hui-Qin; Zhang, Ai-Jun; Sun, Yi-Juan; Feng, Yun

2011-11-01

The aim of this study was to investigate whether the sperm chromatin structure assay (SCSA) results after swim-up are related to fertilization rates, embryo quality and pregnancy rates following in vitro fertilization (IVF). A total of 223 couples undergoing IVF in our hospital from October 2008 to September 2009 were included in this study. Data on the IVF process and sperm chromatin structure assay results were collected. Fertilization rate, embryo quality and IVF success rates of different DNA fragmentation index (DFI) subgroups and high DNA stainability (HDS) subgroups were compared. There were no significant differences in fertilization rate, clinical pregnancy or delivery rates between the DFI and HDS subgroups. However, the group with abnormal DFI had a lower good embryo rate. So, we concluded that the SCSA variables, either DFI or HDS after swim-up preparation, were not valuable in predicting fertilization failure or pregnancy rate, but an abnormal DFI meant a lower good embryo rate following IVF.

Chromosomal abnormalities in human sperm

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

Martin, R.H.

1985-01-01

The ability to analyze human sperm chromosome complements after penetration of zona pellucida-free hamster eggs provides the first opportunity to study the frequency and type of chromosomal abnormalities in human gametes. Two large-scale studies have provided information on normal men. We have studied 1,426 sperm complements from 45 normal men and found an abnormality rate of 8.9%. Brandriff et al. (5) found 8.1% abnormal complements in 909 sperm from 4 men. The distribution of numerical and structural abnormalities was markedly dissimilar in the 2 studies. The frequency of aneuploidy was 5% in our sample and only 1.6% in Brandriff's, perhapsmore » reflecting individual variability among donors. The frequency of 24,YY sperm was low: 0/1,426 and 1/909. This suggests that the estimates of nondisjunction based on fluorescent Y body data (1% to 5%) are not accurate. We have also studied men at increased risk of sperm chromosomal abnormalities. The frequency of chromosomally unbalanced sperm in 6 men heterozygous for structural abnormalities varied dramatically: 77% for t11;22, 32% for t6;14, 19% for t5;18, 13% for t14;21, and 0% for inv 3 and 7. We have also studied 13 cancer patients before and after radiotherapy and demonstrated a significant dose-dependent increase of sperm chromosome abnormalities (numerical and structural) 36 months after radiation treatment.« less

Hidden chromosome 8 abnormalities detected by FISH in adult primary myelodysplastic syndromes.

PubMed

Panani, Anna D; Pappa, Vasiliki

2005-01-01

Acquired clonal chromosomal abnormalities are found in about 30-50% of primary myelodysplastic syndromes (MDS). These abnormalities are predominantly characterized by total/partial chromosomal losses or gains and rarely by balanced structural aberrations. Trisomy 8 represents the most common chromosomal gain. In the present study, the numerical aberration of chromosome 8 was evaluated by the fluorescence in situ hybridization (FISH) technique in MDS, and the results compared with those of conventional cytogenetics. Thirty adult patients with primary MDS, 17 with a normal karyotype and 13 with several chromosomal abnormalities except chromosome 8, were included in this study. On comparing the results of FISH and conventional cytogenetics, a superiority of FISH over the karyotype was detected in 3 cases. In one of them, further cytogenetic analysis confirmed the FISH results. Nevertheless, the FISH technique has limitations, detecting only abnormalities specific for the target FISH probe used In clinical practice, conventional cytogenetics continues to be the basic technique for MDS patient evaluation. However, a large number of metaphases, even those of poor quality, must be analyzed in each case. The FISH technique could be considered to be complementary to achieve a more accurate analysis.

Ear abnormalities in patients with oculo-auriculo-vertebral spectrum (Goldenhar syndrome).

PubMed

Rosa, Rafael Fabiano Machado; Silva, Alessandra Pawelec da; Goetze, Thayse Bienert; Bier, Bianca de Almeida; Almeida, Sheila Tamanini de; Paskulin, Giorgio Adriano; Zen, Paulo Ricardo Gazzola

2011-01-01

Oculo-auriculo-vertebral spectrum (OAVS) is a rare condition characterized by the involvement of the first branchial arches. To investigate the ear abnormalities of a sample of patients with OAVS. The sample consisted of 12 patients with OAVS seen at the Clinical Genetics Unit, UFCSPA/CHSCPA. The study included only patients who underwent mastoid computed tomography and with normal karyotype. We performed a review of its clinical features, giving emphasis to the ear findings. Nine patients were male, the ages ranged from 1 day to 17 years. Ear abnormalities were observed in all patients and involved the external (n = 12), middle (n = 10) and inner ear (n = 3). Microtia was the most frequent finding (n = 12). The most common abnormalities of the middle ear were: opacification (n = 2), displacement (n = 2) and malformation of the ossicular chain. Agenesis of the internal auditory canal (n = 2) was the most frequent alteration of the inner ear. Ear abnormalities are variable in patients with OAVS and often there is no correlation between findings in the external, middle and inner ear. The evaluation of these structures is important in the management of individuals with OAVS.

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

A novel murine allele of Intraflagellar Transport Protein 172 causes a syndrome including VACTERL-like features with hydrocephalus.

PubMed

Friedland-Little, Joshua M; Hoffmann, Andrew D; Ocbina, Polloneal Jymmiel R; Peterson, Mike A; Bosman, Joshua D; Chen, Yan; Cheng, Steven Y; Anderson, Kathryn V; Moskowitz, Ivan P

2011-10-01

The primary cilium is emerging as a crucial regulator of signaling pathways central to vertebrate development and human disease. We identified atrioventricular canal 1 (avc1), a mouse mutation that caused VACTERL association with hydrocephalus, or VACTERL-H. We showed that avc1 is a hypomorphic mutation of intraflagellar transport protein 172 (Ift172), required for ciliogenesis and Hedgehog (Hh) signaling. Phenotypically, avc1 caused VACTERL-H but not abnormalities in left-right (L-R) axis formation. Avc1 resulted in structural cilia defects, including truncated cilia in vivo and in vitro. We observed a dose-dependent requirement for Ift172 in ciliogenesis using an allelic series generated with Ift172(avc1) and Ift172(wim), an Ift172 null allele: cilia were present on 42% of avc1 mouse embryonic fibroblast (MEF) and 28% of avc1/wim MEFs, in contrast to >90% of wild-type MEFs. Furthermore, quantitative cilium length analysis identified two specific cilium populations in mutant MEFS: a normal population with normal IFT and a truncated population, 50% of normal length, with disrupted IFT. Cells from wild-type embryos had predominantly full-length cilia, avc1 embryos, with Hh signaling abnormalities but not L-R abnormalities, had cilia equally divided between full-length and truncated, and avc1/wim embryos, with both Hh signaling and L-R abnormalities, were primarily truncated. Truncated Ift172 mutant cilia showed defects of the distal ciliary axoneme, including disrupted IFT88 localization and Hh-dependent Gli2 localization. We propose a model in which mutation of Ift172 results in a specific class of abnormal cilia, causing disrupted Hh signaling while maintaining L-R axis determination, and resulting in the VACTERL-H phenotype.

A Practice-Oriented Bifurcation Analysis for Pulse Energy Converters. Part 2: An Operating Regime

NASA Astrophysics Data System (ADS)

Kolokolov, Yury; Monovskaya, Anna

The paper continues the discussion on bifurcation analysis for applications in practice-oriented solutions for pulse energy conversion systems (PEC-systems). Since a PEC-system represents a nonlinear object with a variable structure, then the description of its dynamics evolution involves bifurcation analysis conceptions. This means the necessity to resolve the conflict-of-units between the notions used to describe natural evolution (i.e. evolution of the operating process towards nonoperating processes and vice versa) and the notions used to describe a desirable artificial regime (i.e. an operating regime). We consider cause-effect relations in the following sequence: nonlinear dynamics-output signal-operating characteristics, where these characteristics include stability and performance. Then regularities of nonlinear dynamics should be translated into regularities of the output signal dynamics, and, after, into an evolutional picture of each operating characteristic. In order to make the translation without losses, we first take into account heterogeneous properties within the structures of the operating process in the parametrical (P-) and phase (X-) spaces, and analyze regularities of the operating stability and performance on the common basis by use of the modified bifurcation diagrams built in joint PX-space. Then, the correspondence between causes (degradation of the operating process stability) and effects (changes of the operating characteristics) is decomposed into three groups of abnormalities: conditionally unavoidable abnormalities (CU-abnormalities); conditionally probable abnormalities (CP-abnormalities); conditionally regular abnormalities (CR-abnormalities). Within each of these groups the evolutional homogeneity is retained. After, the resultant evolution of each operating characteristic is naturally aggregated through the superposition of cause-effect relations in accordance with each of the abnormalities. We demonstrate that the practice-oriented bifurcation analysis has fundamentally specific purposes and tools, like for the computer-based bifurcation analysis and the experimental bifurcation analysis. That is why, from our viewpoint, it seems to be a rather novel direction in the general context of bifurcation analysis conceptions. We believe that the discussion could be interesting to pioneer research intended for the design of promising systems of pulse energy conversion.

[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.

Fetal Alcohol Spectrum Disorders: An Overview from the Glia Perspective.

PubMed

Wilhelm, Clare J; Guizzetti, Marina

2015-01-01

Alcohol consumption during pregnancy can produce a variety of central nervous system (CNS) abnormalities in the offspring resulting in a broad spectrum of cognitive and behavioral impairments that constitute the most severe and long-lasting effects observed in fetal alcohol spectrum disorders (FASD). Alcohol-induced abnormalities in glial cells have been suspected of contributing to the adverse effects of alcohol on the developing brain for several years, although much research still needs to be done to causally link the effects of alcohol on specific brain structures and behavior to alterations in glial cell development and function. Damage to radial glia due to prenatal alcohol exposure may underlie observations of abnormal neuronal and glial migration in humans with Fetal Alcohol Syndrome (FAS), as well as primate and rodent models of FAS. A reduction in cell number and altered development has been reported for several glial cell types in animal models of FAS. In utero alcohol exposure can cause microencephaly when alcohol exposure occurs during the brain growth spurt a period characterized by rapid astrocyte proliferation and maturation; since astrocytes are the most abundant cells in the brain, microenchephaly may be caused by reduced astrocyte proliferation or survival, as observed in in vitro and in vivo studies. Delayed oligodendrocyte development and increased oligodendrocyte precursor apoptosis has also been reported in experimental models of FASD, which may be linked to altered myelination/white matter integrity found in FASD children. Children with FAS exhibit hypoplasia of the corpus callosum and anterior commissure, two areas requiring guidance from glial cells and proper maturation of oligodendrocytes. Finally, developmental alcohol exposure disrupts microglial function and induces microglial apoptosis; given the role of microglia in synaptic pruning during brain development, the effects of alcohol on microglia may be involved in the abnormal brain plasticity reported in FASD. The consequences of prenatal alcohol exposure on glial cells, including radial glia and other transient glial structures present in the developing brain, astrocytes, oligodendrocytes and their precursors, and microglia contributes to abnormal neuronal development, reduced neuron survival and disrupted brain architecture and connectivity. This review highlights the CNS structural abnormalities caused by in utero alcohol exposure and outlines which abnormalities are likely mediated by alcohol effects on glial cell development and function.

Association Between Subcortical Volumes and Verbal Memory in Unmedicated Depressed Patients and Healthy Controls

PubMed Central

Turner, Arlener D.; Furey, Maura; Drevets, Wayne C.; Zarate, Carlos; Nugent, Allison

2012-01-01

Research has shown poor performance on verbal memory tasks in patients with major depressive disorder relative to healthy controls, as well as structural abnormalities in the subcortical structures that form the limbic-cortical-striatal-pallidal-thalamic circuitry. Few studies, however, have attempted to link the impairments in learning and memory in depression with these structural abnormalities, and of those which have done so, most have included patients medicated with psychotropic agents likely to influence cognitive performance. This study thus examines the relationship between subcortical structural abnormalities and verbal memory using the California Verbal Learning Test (CVLT) in unmedicated depressed patients. A T1 weighted Magnetic Resonance Imaging scan and the CVLT were obtained on 45 subjects with major depressive disorder and 44 healthy controls. Using the FMRIB’s Integrated Registration and Segmentation Tool (FIRST) volumes of selected subcortical structures were segmented and correlated with CVLT performance. Depressed participants showed significantly smaller right thalamus and right hippocampus volumes than healthy controls. Depressed participants also showed impaired performance on global verbal learning ability, and appeared to depend upon an inferior memory strategy (serial clustering). Measures of serial clustering were correlated significantly with right hippocampal volumes in depressed participants. Our findings indicate that depressed participants and healthy controls differ in the memory strategies they employ, and that while depressed participants had a smaller hippocampal volume, there was a positive correlation between volume and use of an inferior memory strategy. This suggests that larger hippocampal volume is related to better memory recall in depression, but specifically with regard to utilizing an inferior memory strategy. PMID:22714007

Abnormal functional connectivity during visuospatial processing is associated with disrupted organisation of white matter in autism

PubMed Central

McGrath, Jane; Johnson, Katherine; O'Hanlon, Erik; Garavan, Hugh; Leemans, Alexander; Gallagher, Louise

2013-01-01

Disruption of structural and functional neural connectivity has been widely reported in Autism Spectrum Disorder (ASD) but there is a striking lack of research attempting to integrate analysis of functional and structural connectivity in the same study population, an approach that may provide key insights into the specific neurobiological underpinnings of altered functional connectivity in autism. The aims of this study were (1) to determine whether functional connectivity abnormalities were associated with structural abnormalities of white matter (WM) in ASD and (2) to examine the relationships between aberrant neural connectivity and behavior in ASD. Twenty-two individuals with ASD and 22 age, IQ-matched controls completed a high-angular-resolution diffusion MRI scan. Structural connectivity was analysed using constrained spherical deconvolution (CSD) based tractography. Regions for tractography were generated from the results of a previous study, in which 10 pairs of brain regions showed abnormal functional connectivity during visuospatial processing in ASD. WM tracts directly connected 5 of the 10 region pairs that showed abnormal functional connectivity; linking a region in the left occipital lobe (left BA19) and five paired regions: left caudate head, left caudate body, left uncus, left thalamus, and left cuneus. Measures of WM microstructural organization were extracted from these tracts. Fractional anisotropy (FA) reductions in the ASD group relative to controls were significant for WM connecting left BA19 to left caudate head and left BA19 to left thalamus. Using a multimodal imaging approach, this study has revealed aberrant WM microstructure in tracts that directly connect brain regions that are abnormally functionally connected in ASD. These results provide novel evidence to suggest that structural brain pathology may contribute (1) to abnormal functional connectivity and (2) to atypical visuospatial processing in ASD. PMID:24133425

Basal Ganglia Shape Abnormalities in the Unaffected Siblings of Schizophrenia Patients

PubMed Central

Mamah, Daniel; Harms, Michael P.; Wang, Lei; Barch, Deanna; Thompson, Paul; Kim, Jaeyun; Miller, Michael I.; Csernansky, John G.

2008-01-01

Objective Abnormalities of basal ganglia structure in schizophrenia have been attributed to the effects of antipsychotic drugs. Our aim was to test the hypothesis that abnormalities of basal ganglia structure are intrinsic features of schizophrenia, by assessing basal ganglia volume and shape in the unaffected siblings of schizophrenia subjects. Method The study involved 25 pairs of schizophrenia subjects and their unaffected siblings and 40 pairs of healthy controls and their siblings. Large deformation, high-dimensional brain mapping was used to obtain surface representations of the caudate, putamen, and globus pallidus. Surfaces were derived from transformations of anatomical templates and shapes were analyzed using reduced-dimensional measures of surface variability (i.e. principal components and canonical analysis). Canonical functions were derived using schizophrenia and control groups, and were then used to compare shapes in the sibling groups. To visualize shape differences, maps of the estimated surface displacement between groups were created. Results In the caudate, putamen and globus pallidus, the degree of shape abnormality observed in the siblings of the schizophrenia subjects was intermediate between the schizophrenia subjects and the controls. In the schizophrenia subjects, significant correlations were observed between measures of caudate, putamen and globus pallidus structure and the selected measures of lifetime psychopathology. Conclusions Attenuated abnormalities of basal ganglia structure are present in the unaffected siblings of schizophrenia subjects. This finding implies that basal ganglia structural abnormalities observed in subjects with schizophrenia are at least in part an intrinsic feature of the illness. PMID:18295189

Amenorrhoea and reversible infertility due to obstructive hydrocephalus: literature review and case report.

PubMed

Hamilton, Kimberly; Iskandar, Bermans

2018-02-12

Endocrine abnormalities are well-recognized consequences of intracranial pathology such as pituitary tumours. Less commonly, hydrocephalus may lead to dysfunction of the endocrine system, presenting as amenorrhoea or precocious puberty. We present a case report and literature review of hydrocephalus causing endocrine abnormalities including reversible infertility. A 34 year-old female presented with amenorrhoea and infertility. MRI showed a third ventricular mass and hydrocephalus. The amenorrhoea resolved within weeks of endoscopic third ventriculostomy and tumour biopsy; pregnancy ensued within 6 months. Thirty-two cases of hydrocephalus-related amenorrhoea were reported between 1915 and 2007. All patients who underwent modern hydrocephalus treatment experienced partial or complete resolution of endocrine dysfunction. Successful pregnancy was reported in three patients, as in our case presentation. While mechanisms of dysfunction have not been completely elucidated, studies point toward loss of GnRH pulsatility due to compression of the medio-basal hypothalamic structures. Hydrocephalus can cause endocrine dysfunction, including amenorrhoea, which may reverse with CSF diversion. Therefore, cranial imaging is an important component in the evaluation of such endocrine abnormalities.

Predicting the intrauterine fetal death of fetuses with cystic hygroma in early pregnancy.

PubMed

Shimura, Mai; Ishikawa, Hiroshi; Nagase, Hiromi; Mochizuki, Akihiko; Sekiguchi, Futoshi; Koshimizu, Naho; Itai, Toshiyuki; Odagami, Mizuha

2018-01-11

We investigated whether it was possible to predict the prognosis of fetuses with cystic hygroma in early pregnancy based on the degree of neck thickening. We retrospectively analyzed 57 singleton pregnancies with fetuses with cystic hygroma who were examined before the 22nd week of pregnancy. The fetuses were categorized according to the outcome, structural abnormalities at birth, and chromosomal abnormalities. Here, we proposed a new sonographic predictor with which we assessed neck thickening by dividing the width of the neck thickening by the biparietal diameter, which is expressed as the cystic hygroma width/biparietal diameter ratio. The median cystic hygroma width/biparietal diameter ratio in the intrauterine fetal death group (0.51) was significantly higher than that in the live birth group (0.27). No significant difference in the median cystic hygroma width/biparietal diameter ratio was found between the structural abnormalities group at birth and the no structural abnormalities group, and no significant difference in the median cystic hygroma width/biparietal diameter ratio was found between the chromosomal abnormality group and the no chromosomal abnormality group. We used receiver operating characteristic analysis to evaluate the cystic hygroma width/biparietal diameter ratio to predict intrauterine fetal death. When the cystic hygroma width/biparietal diameter ratio cut-off value was 0.5, intrauterine fetal death could be predicted with a sensitivity of 52.9% and a specificity of 100%. It is possible to predict intrauterine fetal death in fetuses with cystic hygroma in early pregnancy if cystic hygroma width/biparietal diameter ratio is measured. However, even if cystic hygroma width/biparietal diameter ratio is measured, predicting the presence or absence of a structural abnormality at birth or a chromosomal abnormality is difficult. © 2018 Japanese Teratology Society.

Hair shafts in trichoscopy: clues for diagnosis of hair and scalp diseases.

PubMed

Rudnicka, Lidia; Rakowska, Adriana; Kerzeja, Marta; Olszewska, Małgorzata

2013-10-01

Trichoscopy (hair and scalp dermoscopy) analyzes the structure and size of growing hair shafts, providing diagnostic clues for inherited and acquired causes of hair loss. Types of hair shaft abnormalities observed include exclamation mark hairs (alopecia areata, trichotillomania, chemotherapy-induced alopecia), Pohl-Pinkus constrictions (alopecia areata, chemotherapy-induced alopecia, blood loss, malnutrition), comma hairs (tinea capitis), corkscrew hairs (tinea capitis), coiled hairs (trichotillomania), flame hairs (trichotillomania), and tulip hairs (in trichotillomania, alopecia areata). Trichoscopy allows differential diagnosis of most genetic hair shaft disorders. This article proposes a classification of hair shaft abnormalities observed by trichoscopy. Copyright © 2013. Published by Elsevier Inc.

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.

Coping with Low Back Pain.

ERIC Educational Resources Information Center

Kindig, L. E.; Mrvos, S. R.

Guidelines are offered for the prevention and relief of lower back pain. The structure of the spine is described, and the functions and composition of spinal disks are explained. A list is included of common causes of abnormalities of the spinal column, and injuries which may cause the fracture of the vertebrae are described. Factors causing low…

An Examination of Brain Abnormalities and Mobility in Individuals with Mild Cognitive Impairment and Alzheimer's Disease

PubMed Central

Fischer, Barbara L.; Bacher, Rhonda; Bendlin, Barbara B.; Birdsill, Alex C.; Ly, Martina; Hoscheidt, Siobhan M.; Chappell, Richard J.; Mahoney, Jane E.; Gleason, Carey E.

2017-01-01

Background: Mobility changes are concerning for elderly patients with cognitive decline. Given frail older individuals' vulnerability to injury, it is critical to identify contributors to limited mobility. Objective: To examine whether structural brain abnormalities, including reduced gray matter volume and white matter hyperintensities, would be associated with limited mobility among individuals with cognitive impairment, and to determine whether cognitive impairment would mediate this relationship. Methods: Thirty-four elderly individuals with mild cognitive impairment (MCI) and Alzheimer's disease underwent neuropsychological evaluation, mobility assessment, and structural brain neuroimaging. Linear regression was conducted with predictors including gray matter volume in six regions of interest (ROI) and white matter hyperintensity (WMH) burden, with mobility measures as outcomes. Results: Lower gray matter volume in caudate nucleus was associated with slower speed on a functional mobility task. Higher cerebellar volume was also associated with slower functional mobility. White matter hyperintensity burden was not significantly associated with mobility. Conclusion: Our findings provide evidence for associations between subcortical gray matter volume and speed on a functional mobility task among cognitively impaired individuals. PMID:28424612

Murine craniofacial development requires Hdac3-mediated repression of Msx gene expression

PubMed Central

Singh, Nikhil; Gupta, Mudit; Trivedi, Chinmay M.; Singh, Manvendra K.; Li, Li; Epstein, Jonathan A.

2013-01-01

Craniofacial development is characterized by reciprocal interactions between neural crest cells and neighboring cell populations of ectodermal, endodermal and mesodermal origin. Various genetic pathways play critical roles in coordinating the development of cranial structures by modulating the growth, survival and differentiation of neural crest cells. However, the regulation of these pathways, particularly at the epigenomic level, remains poorly understood. Using murine genetics, we show that neural crest cells exhibit a requirement for the class I histone deacetylase Hdac3 during craniofacial development. Mice in which Hdac3 has been conditionally deleted in neural crest demonstrate fully penetrant craniofacial abnormalities, including microcephaly, cleft secondary palate and dental hypoplasia. Consistent with these abnormalities, we observe dysregulation of cell cycle genes and increased apoptosis in neural crest structures in mutant embryos. Known regulators of cell cycle progression and apoptosis in neural crest, including Msx1, Msx2 and Bmp4, are upregulated in Hdac3-deficient cranial mesenchyme. These results suggest that Hdac3 serves as a critical regulator of craniofacial morphogenesis, in part by repressing core apoptotic pathways in cranial neural crest cells. PMID:23506836

Brain structure characteristics in intellectually superior schizophrenia.

PubMed

Vaskinn, Anja; Hartberg, Cecilie B; Sundet, Kjetil; Westlye, Lars T; Andreassen, Ole A; Melle, Ingrid; Agartz, Ingrid

2015-04-30

The current study aims to fill a gap in the knowledge base by investigating the structural brain characteristics of individuals with schizophrenia and superior intellectual abilities. Subcortical volumes, cortical thickness and cortical surface area were examined in intellectually normal and intellectually superior participants with schizophrenia and their IQ-matched healthy controls, as well as in intellectually low schizophrenia participants. We replicated significant diagnostic group effects on hippocampal and ventricular size after correction for multiple comparisons. There were no statistically significant effects of intellectual level or of the interaction between diagnostic group and intellectual level. Effect sizes indicated that differences between schizophrenia and healthy control participants were of similar magnitude at both intellectual levels for all three types of morphological data. A secondary analysis within the schizophrenia group, including participants with low intellectual abilities, yielded numerical, but no statistically significant differences on any structural brain measure. The present findings indicate that the brain structure abnormalities in schizophrenia are present at all intellectual levels, and individuals with schizophrenia and superior intellectual abilities have brain structure abnormalities of the same magnitude as individuals with schizophrenia and normal intellectual abilities. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[Research advances on cortical functional and structural deficits of amblyopia].

PubMed

Wu, Y; Liu, L Q

2017-05-11

Previous studies have observed functional deficits in primary visual cortex. With the development of functional magnetic resonance imaging and electrophysiological technique, the research of the striate, extra-striate cortex and higher-order cortical deficit underlying amblyopia reaches a new stage. The neural mechanisms of amblyopia show that anomalous responses exist throughout the visual processing hierarchy, including the functional and structural abnormalities. This review aims to summarize the current knowledge about structural and functional deficits of brain regions associated with amblyopia. (Chin J Ophthalmol, 2017, 53: 392 - 395) .

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

PubMed

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

2015-05-01

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

Abnormal brain activation during working memory in children with prenatal exposure to drugs of abuse: the effects of methamphetamine, alcohol, and polydrug exposure.

PubMed

Roussotte, Florence F; Bramen, Jennifer E; Nunez, S Christopher; Quandt, Lorna C; Smith, Lynne; O'Connor, Mary J; Bookheimer, Susan Y; Sowell, Elizabeth R

2011-02-14

Structural and metabolic abnormalities in fronto-striatal structures have been reported in children with prenatal methamphetamine (MA) exposure. The current study was designed to quantify functional alterations to the fronto-striatal circuit in children with prenatal MA exposure using functional magnetic resonance imaging (fMRI). Because many women who use MA during pregnancy also use alcohol, a known teratogen, we examined 50 children (age range 7-15), 19 with prenatal MA exposure, 15 of whom had concomitant prenatal alcohol exposure (the MAA group), 13 with heavy prenatal alcohol but no MA exposure (ALC group), and 18 unexposed controls (CON group). We hypothesized that MA exposed children would demonstrate abnormal brain activation during a visuospatial working memory (WM) "N-Back" task. As predicted, the MAA group showed less activation than the CON group in many brain areas, including the striatum and frontal lobe in the left hemisphere. The ALC group showed less activation than the MAA group in several regions, including the right striatum. We found an inverse correlation between performance and activity in the striatum in both the CON and MAA groups. However, this relationship was significant in the caudate of the CON group but not the MAA group, and in the putamen of the MAA group but not the CON group. These findings suggest that structural damage in the fronto-striatal circuit after prenatal MA exposure leads to decreased recruitment of this circuit during a WM challenge, and raise the possibility that a rewiring of cortico-striatal networks may occur in children with prenatal MA exposure. Copyright © 2010 Elsevier Inc. All rights reserved.

Amygdala Volumetry in Patients with Temporal Lobe Epilepsy and Normal Magnetic Resonance Imaging

PubMed Central

Singh, Paramdeep; Kaur, Rupinderjeet; Saggar, Kavita; Singh, Gagandeep; Aggarwal, Simmi

2016-01-01

Summary Background It has been suggested that the pathophysiology of temporal lobe epilepsy may relate to abnormalities in various brain structures, including the amygdala. Patients with mesial temporal lobe epilepsy (MTLE) without MRI abnormalities (MTLE-NMRI) represent a challenge for diagnosis of the underlying abnormality and for presurgical evaluation. To date, however, only few studies have used quantitative structural Magnetic Resonance Imaging-based techniques to examine amygdalar pathology in these patients. Material/Methods Based on clinical examination, 24-hour video EEG recordings and MRI findings, 50 patients with EEG lateralized TLE and normal structural Magnetic Resonance Imaging results were included in this study. Volumetric magnetic resonance imaging (MRI) studies of the amygdalas and hippocampi were conducted in 50 non-epileptic controls (age 7–79 years) and 50 patients with MTLE with normal MRI on a 1.5-Tesla scanner. Visual assessment and amygdalar volumetry were performed on oblique coronal T2W and T1W MP-RAGE images respectively. The T2 relaxation times were measured using the 16-echo Carr-Purcell-Meiboom-Gill sequence (TE, 22–352). Volumetric data were normalized for variation in head size between individuals. Results were assessed by SSPS statistic program. Results Individual manual volumetric analysis confirmed statistically significant amygdala enlargement (AE) in eight (16%) patients. Overall, among all patients with AE and a defined epileptic focus, 7 had predominant increased volume ipsilateral to the epileptic focus. The T2 relaxometry demonstrated no hyperintense signal of the amygdala in any patient with significant AE. Conclusions This paper presented AE in a few patients with TLE and normal MRI. These findings support the hypothesis that there might be a subgroup of patients with MTLE-NMRI in which the enlarged amygdala could be related to the epileptogenic process. PMID:27231493

Detection of early subclinical lung disease in children with cystic fibrosis by lung ventilation imaging with hyperpolarised gas MRI.

PubMed

Marshall, Helen; Horsley, Alex; Taylor, Chris J; Smith, Laurie; Hughes, David; Horn, Felix C; Swift, Andrew J; Parra-Robles, Juan; Hughes, Paul J; Norquay, Graham; Stewart, Neil J; Collier, Guilhem J; Teare, Dawn; Cunningham, Steve; Aldag, Ina; Wild, Jim M

2017-08-01

Hyperpolarised 3 He ventilation-MRI, anatomical lung MRI, lung clearance index (LCI), low-dose CT and spirometry were performed on 19 children (6-16 years) with clinically stable mild cystic fibrosis (CF) (FEV 1 >-1.96), and 10 controls. All controls had normal spirometry, MRI and LCI. Ventilation-MRI was the most sensitive method of detecting abnormalities, present in 89% of patients with CF, compared with CT abnormalities in 68%, LCI 47% and conventional MRI 22%. Ventilation defects were present in the absence of CT abnormalities and in patients with normal physiology, including LCI. Ventilation-MRI is thus feasible in young children, highly sensitive and provides additional information about lung structure-function relationships. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The Spectrum of Mitochondrial Ultrastructural Defects in Mitochondrial Myopathy

PubMed Central

Vincent, Amy E.; Ng, Yi Shiau; White, Kathryn; Davey, Tracey; Mannella, Carmen; Falkous, Gavin; Feeney, Catherine; Schaefer, Andrew M.; McFarland, Robert; Gorman, Grainne S.; Taylor, Robert W.; Turnbull, Doug M.; Picard, Martin

2016-01-01

Mitochondrial functions are intrinsically linked to their morphology and membrane ultrastructure. Characterizing abnormal mitochondrial structural features may thus provide insight into the underlying pathogenesis of inherited and acquired mitochondrial diseases. Following a systematic literature review on ultrastructural defects in mitochondrial myopathy, we investigated skeletal muscle biopsies from seven subjects with genetically defined mtDNA mutations. Mitochondrial ultrastructure and morphology were characterized using two complimentary approaches: transmission electron microscopy (TEM) and serial block face scanning EM (SBF-SEM) with 3D reconstruction. Six ultrastructural abnormalities were identified including i) paracrystalline inclusions, ii) linearization of cristae and abnormal angular features, iii) concentric layering of cristae membranes, iv) matrix compartmentalization, v) nanotunelling, and vi) donut-shaped mitochondria. In light of recent molecular advances in mitochondrial biology, these findings reveal novel aspects of mitochondrial ultrastructure and morphology in human tissues with implications for understanding the mechanisms linking mitochondrial dysfunction to disease. PMID:27506553

[Bone structure in rheumatoid arthritis].

PubMed

Ono, Kumiko; Ohashi, Satoru; Tanaka, Sakae; Matsumoto, Takuya

2013-07-01

In rheumatoid arthritis (RA) , the osteoclast pathway is activated by abnormal immune conditions accompanied by chronic inflammation, resulting in periarticular osteoporosis and local bone destruction around joints. In addition, multiple factors, including reduced physical activity and pharmacotherapies such as steroids, lead to systemic osteoporosis. These conditions cause decreasing bone mineral density and deterioration of bone quality, and expose patients to increased risk of fracture. Understanding the bone structures of RA and evaluating fracture risk are central to the treatment of RA.

Chloroquine-induced cardiomyopathy: a reversible cause of heart failure.

PubMed

Yogasundaram, Haran; Hung, Whitney; Paterson, Ian D; Sergi, Consolato; Oudit, Gavin Y

2018-06-01

Chloroquine (CQ) and hydroxychloroquine (HCQ) are anti-rheumatic medications frequently used in the treatment of connective tissue disorders. We present the case of a 45-year-old woman with CQ-induced cardiomyopathy leading to severe heart failure. Electrocardiographic abnormalities included bifascicular block, while structural disease consisted of severe biventricular and biatrial hypertrophy. Appropriate diagnosis via endomyocardial biopsy led to cessation of CQ and subsequent dramatic improvement in symptoms and structural heart disease. Cardiac toxicity is an under-recognized adverse effect of CQ/HCQ leading to cardiomyopathy with concentric hypertrophy and conduction abnormalities, with the potential for significant morbidity and mortality. Predisposing factors for CQ/HCQ-induced cardiomyopathy have been proposed. CQ/HCQ cardiomyopathy is a phenocopy of Fabry disease, and α-galactosidase A polymorphism may account for some heterogeneity of disease presentation. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Microscopy and Microanalysis of Blood in a Snake Head Fish, Channa gachua Exposed to Environmental Pollution.

PubMed

Pala, Eva M; Dey, Sudip

2016-02-01

Conventional and highly sophisticated analytical methods (Cyria et al., 1989; Massar et al., 2012a) were used to analyze micro-structural and micro-analytical aspects of the blood of snake head fish, Channa gachua, exposed to municipal wastes and city garbage. Red (RBC) and white blood cell (WBC) counts and hemhemoglobin content were found to be higher in pollution affected fish as compared with control. Scanning electron microscopy revealed the occurrence of abnormal erythrocytes such as crenated cells, echinocytes, lobopodial projections, membrane internalization, spherocytes, ruptured cells, contracted cells, depression, and uneven elongation of erythrocyte membranes in fish inhabiting the polluted sites. Energy-dispersive X-ray spectroscopy (EDS) revealed the presence of silicon and lead in the RBCs of pollution affected fish. Significance of the study includes the highly sophisticated analytical approach, which revealed the aforementioned micro-structural abnormalities.

Structural abnormalities and altered regional brain activity in multiple sclerosis with simple spinal cord involvement.

PubMed

Yin, Ping; Liu, Yi; Xiong, Hua; Han, Yongliang; Sah, Shambhu Kumar; Zeng, Chun; Wang, Jingjie; Li, Yongmei

2018-02-01

To assess the changes of the structural and functional abnormalities in multiple sclerosis with simple spinal cord involvement (MS-SSCI) by using resting-state functional MRI (RS-fMRI), voxel based morphology (VBM) and diffusion tensor tractography. The amplitude of low-frequency fluctuation (ALFF) of 22 patients with MS-SSCI and 22 healthy controls (HCs) matched for age, gender and education were compared by using RS-fMRI. We also compared the volume, fractional anisotropy (FA) and apparent diffusion coefficient of the brain regions in baseline brain activity by using VBM and diffusion tensor imaging. The relationships between the expanded disability states scale (EDSS) scores, changed parameters of structure and function were further explored. (1) Compared with HCs, the ALFF of the bilateral hippocampus and right middle temporal gyrus in MS-SSCI decreased significantly. However, patients exhibited increased ALFF in the left middle frontal gyrus, left posterior cingulate gyrus and right middle occipital gyrus ( two-sample t-test, after AlphaSim correction, p < 0.01, voxel size > 40). The volume of right middle frontal gyrus reduced significantly (p < 0.01). The FA and ADC of right hippocampus, the FA of left hippocampus and right middle temporal gyrus were significantly different. (2) A significant correlation between EDSS scores and ALFF was noted only in the left posterior cingulate gyrus. Our results detected structural and functional abnormalities in MS-SSCI and functional parameters were associated with clinical abnormalities. Multimodal imaging plays an important role in detecting structural and functional abnormalities in MS-SSCI. Advances in knowledge: This is the first time to apply RS-fMRI, VBM and diffusion tensor tractography to study the structural and functional abnormalities in MS-SSCI, and to explore its correlation with EDSS score.

Corpus callosum volumes in the 5 years following the first-episode of schizophrenia: Effects of antipsychotics, chronicity and maturation.

PubMed

de Moura, Mariana T M; Zanetti, Marcus V; Duran, Fabio L S; Schaufelberger, Maristela S; Menezes, Paulo R; Scazufca, Marcia; Busatto, Geraldo F; Serpa, Mauricio H

2018-01-01

White matter (WM) structural changes, particularly affecting the corpus callosum (CC), seem to be critically implicated in psychosis. Whether such abnormalities are progressive or static is still a matter of debate in schizophrenia research. Aberrant maturation processes might also influence the longitudinal trajectory of age-related CC changes in schizophrenia patients. We investigated whether patients with first-episode schizophrenia-related psychoses (FESZ) would present longitudinal CC and whole WM volume changes over the 5 years after disease onset. Thirty-two FESZ patients and 34 controls recruited using a population-based design completed a 5-year assessment protocol, including structural MRI scanning at baseline and follow-up. The linear effects of disease duration, clinical outcome and antipsychotic (AP) use over time on WM and CC volumes were studied using both voxelwise and volume-based morphometry analyses. We also examined maturation/aging abnormalities through cross-sectional analyses of age-related trajectories of total WM and CC volume changes. No interaction between diagnosis and time was observed, and clinical outcome did not influence CC volumes in patients. On the other hand, FESZ patients continuously exposed to AP medication showed volume increase over time in posterior CC. Curve-estimation analyses revealed a different aging pattern in FESZ patients versus controls: while patients displayed a linear decline of total WM and anterior CC volumes with age, a non-linear trajectory of total WM and relative preservation of CC volumes were observed in controls. Continuous AP exposure can influence CC morphology during the first years after schizophrenia onset. Schizophrenia is associated with an abnormal pattern of total WM and anterior CC aging during non-elderly adulthood, and this adds complexity to the discussion on the static or progressive nature of structural abnormalities in psychosis.

Medical Advocacy and Supportive Environments for African-Americans Following Abnormal Mammograms.

PubMed

Molina, Yamile; Hempstead, Bridgette H; Thompson-Dodd, Jacci; Weatherby, Shauna Rae; Dunbar, Claire; Hohl, Sarah D; Malen, Rachel C; Ceballos, Rachel M

2015-09-01

African-American women experience disproportionately adverse outcomes relative to non-Latina White women after an abnormal mammogram result. Research has suggested medical advocacy and staff support may improve outcomes among this population. The purpose of the study was to understand reasons African-American women believe medical advocacy to be important and examine if and how staff can encourage and be supportive of medical advocacy. A convenience-based sample of 30-74-year-old women who self-identified as African-American/Black/of African descent and who had received an abnormal mammogram result was recruited from community-based organizations, mobile mammography services, and the local department of health. This qualitative study included semi-structured interviews. Patients perceived medical advocacy to be particularly important for African-Americans, given mistrust and discrimination present in medical settings and their own familiarity with their bodies and symptoms. Respondents emphasized that staff can encourage medical advocacy through offering information in general in a clear, informative, and empathic style. Cultural competency interventions that train staff how to foster medical advocacy may be a strategy to improve racial disparities following an abnormal mammogram.

Assessing the Benefit-Risk Profile for Pediatric Implantable Auditory Prostheses.

PubMed

Fisher, Laurel M; Martinez, Amy S; Richmond, Frances J; Krieger, Mark D; Wilkinson, Eric P; Eisenberg, Laurie S

2017-01-01

Children with congenital cochleovestibular abnormalities associated with profound hearing loss have few treatment options if cochlear implantation does not yield benefit. An alternative is the auditory brainstem implant (ABI). Regulatory authority device approvals currently include a structured benefit-risk assessment. Such an assessment, for regulatory purposes or to guide clinical decision making, has not been published, to our knowledge, for the ABI and may lead to the design of a research program that incorporates regulatory authority, family, and professional input. Much structured benefit-risk research has been conducted in the context of drug trials; here we apply this approach to device studies. A qualitative framework organized benefit (speech recognition, parent self-report measures) and risk (surgery- and device-related) information to guide the selection of candidates thought to have potential benefit from ABI. Children with cochleovestibular anatomical abnormalities are challenging for appropriate assessment of candidacy for a cochlear implant or an ABI. While the research is still preliminary, children with an ABI appear to slowly obtain benefit over time. A team of professionals, including audiological, occupational, and educational therapy, affords maximum opportunity for benefit. Pediatric patients who have abnormal anatomy and are candidates for an implantable auditory prosthetic require an individualized, multisystems review. The qualitative benefit-risk assessment used here to characterize the condition, the medical need, potential benefits, risks, and risk management strategies has revealed the complex factors involved. After implantation, continued team support for the family during extensive postimplant therapy is needed to develop maximum auditory skill benefit.

Telomere dysfunction and chromosome structure modulate the contribution of individual chromosomes in abnormal nuclear morphologies.

PubMed

Pampalona, J; Soler, D; Genescà, A; Tusell, L

2010-01-05

The cytokinesis-block micronucleus assay has emerged as a biomarker of chromosome damage relevant to cancer. Although it was initially developed to measure micronuclei, it is also useful for measuring nucleoplasmic bridges and nuclear buds. Abnormal nuclear morphologies are frequently observed in malignant tissues and short-term tumour cell cultures. Changes in chromosome structure and number resulting from chromosome instability are important factors in oncogenesis. Telomeres have become key players in the initiation of chromosome instability related to carcinogenesis by means of breakage-fusion-bridge cycles. To better understand the connection between telomere dysfunction and the appearance of abnormal nuclear morphologies, we have characterised the presence of micronuclei, nucleoplasmic bridges and nuclear buds in human mammary primary epithelial cells. These cells can proliferate beyond the Hayflick limit by spontaneously losing expression of the p16(INK4a) protein. Progressive telomere shortening leads to the loss of the capping function, and the appearance of end-to-end chromosome fusions that can enter into breakage-fusion-bridge cycles generating massive chromosomal instability. In human mammary epithelial cells, different types of abnormal nuclear morphologies were observed, however only nucleoplasmatic bridges and buds increased significantly with population doublings. Fluorescent in situ hybridisation using centromeric and painting specific probes for chromosomes with eroded telomeres has revealed that these chromosomes are preferentially included in the different types of abnormal nuclear morphologies observed, thus reflecting their common origin. Accordingly, real-time imaging of cell divisions enabled us to determine that anaphase bridge resolution was mainly through chromatin breakage and the formation of symmetric buds in daughter nuclei. Few micronuclei emerged in this cell system thus validating the scoring of nucleoplasmic bridges and nuclear buds for measuring chromosome instability in telomere-dysfunction cell environments.

Evaluation of ex-vivo 9.4T MRI in post-surgical specimens from temporal lobe epilepsy patients.

PubMed

Kwan, Benjamin Y M; Salehi, Fateme; Kope, Ryan; Lee, Donald H; Sharma, Manas; Hammond, Robert; Burneo, Jorge G; Steven, David; Peters, Terry; Khan, Ali R

2017-10-01

This study evaluates hippocampal pathology through usage of ultra-high field 9.4T ex-vivo imaging of resected surgical specimens in patients who have undergone temporal lobe epilepsy surgery. This is a retrospective interpretation of prospectively acquired data. MRI scanning of resected surgical specimens from patients who have undergone temporal lobe epilepsy surgery was performed on a 9.4T small bore Varian MR magnet. Structural images employed a balanced steady-state free precession sequence (TrueFISP). Six patients (3 females; 3 males) were included in this study with an average age at surgery of 40.7 years (range 20Y_"60) (one was used as a control reference). Two neuroradiologists qualitatively reviewed the ex-vivo MRIs of resected specimens while blinded to the histopathology reports for the ability to identify abnormal features in hippocampal subfield structures. The hippocampal subfields were reliably identified on the 9.4T ex-vivo scans in the hippocampal head region and hippocampal body region by both neuroradiologists in all 6 patients. There was high concordance to pathology for abnormalities detected in the CA1, CA2, CA3 and CA4 subfields. Detection of abnormalities in the dentate gyrus was also high with detection in 4 of 5 cases. The Cohen's kappa between the two neuroradiologists was calculated at 0.734 SE=0.102. Ex-vivo 9.4T specimen imaging can detect abnormalities in CA1, CA2, CA3, CA4 and DG in both the hippocampal head and body. There was good concordance between qualitative findings and histopathological abnormalities for CA1, CA2, CA3, CA4 and DG. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Structural cerebral abnormalities and neurodevelopmental status in single ventricle congenital heart disease before Fontan procedure.

PubMed

Knirsch, Walter; Mayer, Kristina Nadine; Scheer, Ianina; Tuura, Ruth; Schranz, Dietmar; Hahn, Andreas; Wetterling, Kristina; Beck, Ingrid; Latal, Beatrice; Reich, Bettina

2017-04-01

Neonates with single ventricle congenital heart disease are at risk for structural cerebral abnormalities. Little is known about the further evolution of cerebral abnormalities until Fontan procedure. Between August 2012 and July 2015, we conducted a prospective cross-sectional two centre study using cerebral magnetic resonance imaging (MRI) and neuro-developmental outcome assessed by the Bayley-III. Forty-seven children (31 male) were evaluated at a mean age of 25.9 ± 3.4 months with hypoplastic left heart syndrome (25) or other single ventricle (22). Cerebral MRI was abnormal in 17 patients (36.2%) including liquor space enlargements (10), small grey (9) and minimal white (5) matter injuries. Eight of 17 individuals had combined lesions. Median (range) cognitive composite score (CCS) (100, 65-120) and motor composite score (MCS) (97, 55-124) were comparable to the reference data, while language composite score (LCS) (97, 68-124) was significantly lower ( P  = 0.040). Liquor space enlargement was associated with poorer performance on all Bayley-III subscores (CCS: P  = 0.02; LCS: P  = 0.002; MCS: P  = 0.013). The number of re-operations [odds ratio (OR) 2.2, 95% confidence interval (CI) 1.1-4.3] ( P  = 0.03) and re-interventions (OR 2.1, 95% CI 1.1-3.8) ( P  = 0.03) was associated with a higher rate of overall MRI abnormalities. Cerebral MRI abnormalities occur in more than one third of children with single ventricle, while the neuro-developmental status is less severely affected before Fontan procedure. Liquor space enlargement is the predominant MRI finding associated with poorer neuro-developmental status, warranting further studies to determine aetiology and further evolution until school-age. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Anatomical study of minor alterations in neonate vocal folds.

PubMed

Silva, Adriano Rezende; Machado, Almiro José; Crespo, Agrício Nubiato

2014-01-01

Minor structural alterations of the vocal fold cover are frequent causes of voice abnormalities. They may be difficult to diagnose, and are expressed in different manners. Cases of intracordal cysts, sulcus vocalis, mucosal bridge, and laryngeal micro-diaphragm form the group of minor structural alterations of the vocal fold cover investigated in the present study. The etiopathogenesis and epidemiology of these alterations are poorly known. To evaluate the existence and anatomical characterization of minor structural alterations in the vocal folds of newborns. 56 larynxes excised from neonates of both genders were studied. They were examined fresh, or defrosted after conservation via freezing, under a microscope at magnifications of 25× and 40×. The vocal folds were inspected and palpated by two examiners, with the aim of finding minor structural alterations similar to those described classically, and other undetermined minor structural alterations. Larynges presenting abnormalities were submitted to histological examination. Six cases of abnormalities were found in different larynges: one (1.79%) compatible with a sulcus vocalis and five (8.93%) compatible with a laryngeal micro-diaphragm. No cases of cysts or mucosal bridges were found. The observed abnormalities had characteristics similar to those described in other age groups. Abnormalities similar to sulcus vocalis or micro-diaphragm may be present at birth. Copyright © 2014 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

A Comparative Analysis of the Murine Thymic Microenvironment in Normal, Autoimmune, and Immunodeficiency States

PubMed Central

Takeoka, Yuichi; Chen, Shao-Yuan; Boyd, Richard L.; Tsuneyama, Koichi; Taguchi, Nobuhisa; Morita, Shinji; Yago, Hisashi; Suehiro, Seishi; Ansari, Aftab A.; Shultz, Leonard D.

1997-01-01

It is widely accepted that the thymic microenvironment regulates normal thymopoiesis through a highly coordinated and complex series of cellular and cytokine interactions. A direct corollary of this is that abnormalities within the microenvironment could be of etiologic significance in T-cell-based diseases. Our laboratory has developed a large panel of monoclonal antibodies (mAbs) that react specifically with epithelial or nonepithelial markers in the thymus. We have taken advantage of these reagents to characterize the thymic microenvironment of several genetic strains of mice, including BALB/cJ, C57BL/6J, NZB/BlnJ, SM/J, NOD/Ltz, NOD/Ltz-scid/sz, C57BL/6J-Hcph me/Hcph me, and ALY/NscJcl-aly/aly mice, and littermate control animals. We report herein that control mice, including strains of several backgrounds, have a very consistent phenotypic profile with this panel of monoclonal antibodies, including reactivity with thymic epithelial cells in the cortex, the medulla and the corticomedullary junction, and the extracellular matrix. In contrast, the disease-prone strains studied have unique, abnormal staining of thymic cortex and medulla at both the structural and cellular levels. These phenotypic data suggest that abnormalities in interactions between developing thymocytes and stromal cells characterize disease-prone mice. PMID:9587708

Effect of cobalt doping on the structural, magnetic and abnormal thermal expansion properties of NaZn13-type La(Fe1-xCox)11.4Al1.6 compounds.

PubMed

Zhao, Yuqiang; Huang, Rongjin; Li, Shaopeng; Wang, Wei; Jiang, Xingxing; Lin, Zheshuai; Li, Jiangtao; Li, Laifeng

2016-07-27

Cubic NaZn13-type La(Fe1-xCox)11.4Al1.6 compounds were synthesized and extensively explored through crystal structure and magnetization analyses. By optimizing the chemical composition, the isotropic abnormal properties of excellent zero and giant negative thermal expansion in a pure form were both found at different temperature ranges through room temperature. Moreover, the temperature regions with the remarkable abnormal thermal expansion (ATE) properties have been broadened which are controlled by the dM/dT. The present study demonstrates that the ATE behavior mainly depends on special structural and magnetic properties. These diverse properties suggest the high potential of La(Fe1-xCox)11.4Al1.6 for the development of abnormal expansion materials.

[Memory peculiarities in patients with schizophrenia and their first-degree relatives].

PubMed

Savina, T D; Orlova, V A; Shcherbakova, N P; Korsakova, N K; Malova, Iu A; Efanova, N N; Ganisheva, T K; Nikolaev, R A

2008-01-01

Eighty-four families with schizophrenia: 84 patients (probands) and 73 their first-degree unaffected relatives as well as 37 normals and their relatives have been studied using pathopsychological (pictogram) and Luria's neuropsychological tests. The most prominent abnormalities both in patients and relatives were global characteristics of auditory-speech memory predominantly related to left subcortical and left temporal regions. Abnormalities of immediate recall of short logic story (SLS) were connected with dysfunction of the same brain regions. Less prominent delayed recall abnormalities of SLS were revealed only in patients and connected with left subcortical, left subcortical-frontal and left subcortical-temporal zones. This abnormality was absent in relatives and age-matched controls. The span of mediated retention was decreased in patients and, to a less degree, in relatives. A quantitative psychological analysis has demonstrated the disintegration ("schizys") between semantic conception and image memory structure in patients and, to a less degree, in relatives. Data obtained show primary memory abnormalities in families with schizophrenia related to the impairment of decoding information process in the subcortical structures, the left-side dysfunction of brain structures being predominantly typical.

Validation of a condition-specific measure for women having an abnormal screening mammography.

PubMed

Brodersen, John; Thorsen, Hanne; Kreiner, Svend

2007-01-01

The aim of this study is to assess the validity of a new condition-specific instrument measuring psychosocial consequences of abnormal screening mammography (PCQ-DK33). The draft version of the PCQ-DK33 was completed on two occasions by 184 women who had received an abnormal screening mammography and on one occasion by 240 women who had received a normal screening result. Item Response Theories and Classical Test Theories were used to analyze data. Construct validity, concurrent validity, known group validity, objectivity and reliability were established by item analysis examining the fit between item responses and Rasch models. Six dimensions covering anxiety, behavioral impact, sense of dejection, impact on sleep, breast examination, and sexuality were identified. One item belonging to the dejection dimension had uniform differential item functioning. Two items not fitting the Rasch models were retained because of high face validity. A sick leave item added useful information when measuring side effects and socioeconomic consequences of breast cancer screening. Five "poor items" were identified and should be deleted from the final instrument. Preliminary evidence for a valid and reliable condition-specific measure for women having an abnormal screening mammography was established. The measure includes 27 "good" items measuring different attributes of the same overall latent structure-the psychosocial consequences of abnormal screening mammography.

Inter-hemispheric functional connectivity disruption in children with prenatal alcohol exposure

PubMed Central

Wozniak, Jeffrey R.; Mueller, Bryon A.; Muetzel, Ryan L.; Bell, Christopher J.; Hoecker, Heather L.; Nelson, Miranda L.; Chang, Pi-Nian; Lim, Kelvin O.

2010-01-01

Background MRI studies, including recent diffusion tensor imaging (DTI) studies, have shown corpus callosum abnormalities in children prenatally exposed to alcohol, especially in the posterior regions. These abnormalities appear across the range of Fetal Alcohol Spectrum Disorders (FASD). Several studies have demonstrated cognitive correlates of callosal abnormalities in FASD including deficits in visual-motor skill, verbal learning, and executive functioning. The goal of this study was to determine if inter-hemispheric structural connectivity abnormalities in FASD are associated with disrupted inter-hemispheric functional connectivity and disrupted cognition. Methods Twenty-one children with FASD and 23 matched controls underwent a six minute resting-state functional MRI scan as well as anatomical imaging and DTI. Using a semiautomated method, we parsed the corpus callosum and delineated seven inter-hemispheric white matter tracts with DTI tractography. Cortical regions of interest (ROIs) at the distal ends of these tracts were identified. Right-left correlations in resting fMRI signal were computed for these sets of ROIs and group comparisons were done. Correlations with facial dysmorphology, cognition, and DTI measures were computed. Results A significant group difference in inter-hemispheric functional connectivity was seen in a posterior set of ROIs, the para-central region. Children with FASD had functional connectivity that was 12% lower than controls in this region. Sub-group analyses were not possible due to small sample size, but the data suggest that there were effects across the FASD spectrum. No significant association with facial dysmorphology was found. Para-central functional connectivity was significantly correlated with DTI mean diffusivity, a measure of microstructural integrity, in posterior callosal tracts in controls but not in FASD. Significant correlations were seen between these structural and functional measures and Wechsler perceptual reasoning ability. Conclusions Inter-hemispheric functional connectivity disturbances were observed in children with FASD relative to controls. The disruption was measured in medial parietal regions (para-central) that are connected by posterior callosal fiber projections. We have previously shown microstructural abnormalities in these same posterior callosal regions and the current study suggests a possible relationship between the two. These measures have clinical relevance as they are associated with cognitive functioning. PMID:21303384

Do anesthetics harm the developing human brain? An integrative analysis of animal and human studies.

PubMed

Lin, Erica P; Lee, Jeong-Rim; Lee, Christopher S; Deng, Meng; Loepke, Andreas W

Anesthetics that permit surgical procedures and stressful interventions have been found to cause structural brain abnormalities and functional impairment in immature animals, generating extensive concerns among clinicians, parents, and government regulators regarding the safe use of these drugs in young children. Critically important questions remain, such as the exact age at which the developing brain is most vulnerable to the effects of anesthetic exposure, whether a particular age exists beyond which anesthetics are devoid of long-term effects on the brain, and whether any specific exposure duration exists that does not lead to deleterious effects. Accordingly, the present analysis attempts to put the growing body of animal studies, which we identified to include >440 laboratory studies to date, into a translational context, by integrating the preclinical data on brain structure and function with clinical results attained from human neurocognitive studies, which currently exceed 30 studies. Our analysis demonstrated no clear exposure duration threshold below which no structural injury or subsequent cognitive abnormalities occurred. Animal data did not clearly identify a specific age beyond which anesthetic exposure did not cause any structural or functional abnormalities. Several potential mitigating strategies were found, however, no general anesthetic was identified that consistently lacked neurodegenerative properties and could be recommended over other anesthetics. It therefore is imperative, to expand efforts to devise safer anesthetic techniques and mitigating strategies, even before long-term alterations in brain development are unequivocally confirmed to occur in millions of young children undergoing anesthesia every year. Copyright © 2016 Elsevier Inc. All rights reserved.

Small gray matter volume in orbitofrontal cortex in Prader-Willi syndrome: a voxel-based MRI study.

PubMed

Ogura, Kaeko; Fujii, Toshikatsu; Abe, Nobuhito; Hosokai, Yoshiyuki; Shinohara, Mayumi; Takahashi, Shoki; Mori, Etsuro

2011-07-01

Prader-Willi syndrome (PWS) is a genetically determined neurodevelopmental disorder presenting with behavioral symptoms including hyperphagia, disinhibition, and compulsive behavior. The behavioral problems in individuals with PWS are strikingly similar to those in patients with frontal pathologies, particularly those affecting the orbitofrontal cortex (OFC). However, neuroanatomical abnormalities in the frontal lobe have not been established in PWS. The aim of this study was to look, using volumetric analysis, for morphological changes in the frontal lobe, especially the OFC, of the brains of individuals with PWS. Twelve adults with PWS and 13 age- and gender-matched control subjects participated in structural magnetic resonance imaging (MRI) scans. The whole-brain images were segmented and normalized to a standard stereotactic space. Regional gray matter volumes were compared between the PWS group and the control group using voxel-based morphometry. The PWS subjects showed small gray-matter volume in several regions, including the OFC, caudate nucleus, inferior temporal gyrus, precentral gyrus, supplementary motor area, postcentral gyrus, and cerebellum. The small gray-matter volume in the OFC remained significant in a separate analysis that included total gray matter volume as a covariate. These preliminary findings suggest that the neurobehavioral symptoms in individuals with PWS are related to structural brain abnormalities in these areas. Copyright © 2010 Wiley-Liss, Inc.

Age-dependent long-term structural and functional effects of early life seizures: evidence for a hippocampal critical period influencing plasticity in adulthood

PubMed Central

Meyerand, M.E.; Sutula, T.

2015-01-01

Neural activity promotes circuit formation in developing systems and during critical periods permanently modifies circuit organization and functional properties. These observations suggest that excessive neural activity, as occurs during seizures, might influence developing neural circuitry with long-term outcomes that depend on age at the time of seizures. We systematically examined long-term structural and functional consequences of seizures induced in rats by kainic acid, pentylenetetrazol, and hyperthermia across postnatal ages from birth through postnatal day 90 in adulthood (P90). Magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and electrophysiological methods at ≥P95 following seizures induced from P1 to P90 demonstrated consistent patterns of gross atrophy, microstructural abnormalities in the corpus callosum and hippocampus, and functional alterations in hippocampal circuitry at ≥P95 that were independent of the method of seizure induction and varied systematically as a function of age at the time of seizures. Three distinct epochs were observed in which seizures resulted in distinct long-term structural and functional outcomes at ≥P95. Seizures prior to P20 resulted in DTI abnormalities in corpus callosum and hippocampus in the absence of gross cerebral atrophy, and increased paired pulse inhibition (PPI) in the dentate gyrus at ≥P95. Seizures after P30 induced a different pattern of DTI abnormalities in the fimbria and hippocampus accompanied by gross cerebral atrophy with increases in lateral ventricular volume, as well as increased PPI in the dentate gyrus at ≥P95. In contrast, seizures between P20-P30 did not result in cerebral atrophy or significant imaging abnormalities in the hippocampus or white matter, but irreversibly decreased PPI in the dentate gyrus compared to normal adult controls. These age-specific long-term structural and functional outcomes identify P20-P30 as a potential critical period in hippocampal development defined by distinctive long-term structural and functional properties in adult hippocampal circuitry, including loss of capacity for seizure-induced plasticity in adulthood that could influence epileptogenesis and other hippocampal – dependent behaviors and functional properties. PMID:25555928

Brain alterations in paedophilia: a critical review.

PubMed

Mohnke, Sebastian; Müller, Sabine; Amelung, Till; Krüger, Tillmann H C; Ponseti, Jorge; Schiffer, Boris; Walter, Martin; Beier, Klaus M; Walter, Henrik

2014-11-01

Psychosocial and biological factors have been implicated in paedophilia, such as alterations in brain structure and function. The purpose of this paper is to review the expanding body of literature on this topic including brain abnormality case reports, as well as structural and functional neuroimaging studies. Case studies of men who have committed sexual offences against children implicate frontal and temporal abnormalities that may be associated with impaired impulse inhibition. Structural neuroimaging investigations show volume reductions in paedophilic men. Although the findings have been heterogeneous, smaller amygdala volume has been replicated repeatedly. Functional neuroimaging investigations demonstrate an overlap between paedophiles and teleiophiles during sexual arousal processing. While it is controversial among studies regarding group differences, reliable discrimination between paedophilic and teleiophilic men may be achieved using functional activation patterns. Nevertheless, the heterogeneous findings published so far suggest further research is necessary to disentangle the neurobiological mechanisms of paedophilic preference. A number of methodological confounds have been identified, which may account for the inconsistent results that could prove to be beneficial for future investigations. Copyright © 2014 Elsevier Ltd. All rights reserved.

DTI study of Children with Congenital Hydrocephalus: 1 Year Post-Surgical Outcomes

PubMed Central

Mangano, Francesco T.; Altaye, Mekibib; McKinstry, Robert C.; Shimony, Joshua S.; Powell, Stephanie K.; Phillips, Jannel M.; Barnard, Holly; Limbrick, David D.; Holland, Scott K.; Jones, Blaise V.; Dodd, Jonathon; Simpson, Sarah; Deanna, Mercer; Rajagopal, Akila; Bidwell, Sarah; Yuan, Weihong

2016-01-01

Object To investigate white matter structural abnormalities using diffusion tensor imaging (DTI) in children with hydrocephalus before CSF diversionary surgery (including ventriculoperitoneal shunting and endoscopic third ventriculoscopy) and the course of recovery post-surgery in association with neuropsychological and behavioral outcome. Methods This was a prospective study that included 54 children with congenital hydrocephalus (21F/33M; age range: 0.03–194.5 months) who underwent surgery and 64 normal controls (30F/34M, age range: 0.30–197.75 months). DTI and neurodevelopmental outcome data were collected once in the control group and at pre-surgery, 3-month, and 12-month post-surgery in the patients. DTI measures, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) values were extracted from the genu of corpus callosum (gCC) and the posterior limb of internal capsule (PLIC). Group analysis was performed first cross-sectionally to quantify DTI abnormalities at three time points by comparing the controls and the patients group at the three time points separately. Longitudinal comparisons were conducted pairwise between different time points in patients whose data were acquired at multiple time points. Neurodevelopmental data were collected and analyzed using the Adaptive Behavior Assessment System, Second Edition (ABAS-II) and the Bayley Scales of Infant Development, Third Edition (Bayley-III). Correlation analyses were performed between DTI and behavioral outcomes. Results Significant DTI abnormalities were found in both the gCC (lower FA and higher MD, AD, and RD) and the PLIC (higher FA, lower AD and RD) at pre-surgery. The DTI measures in the gCC remained mostly abnormal at 3-month and 12-month post-surgery. The DTI abnormalities in the PLIC were significant in FA and AD at 3-month post-surgery but did nor persist when tested at 12-month post-surgery. Significant longitudinal DTI changes in the patients were found in the gCC between 3-month and 12-month post-surgery. In the PLIC, trend level longitudinal changes were found between pre-surgery and 3-month post-surgery as well as between 3-month and 12-month post-surgery. Significant correlation between DTI and developmental outcome were found at all three time points. Notably, significant correlation was found between DTI in the PLIC at 3-month post-surgery and developmental outcome at 12-month pots-surgery. Conclusion Our data showed significant WM abnormality based on DTI in both the gCC and the PLIC in children with congenital hydrocephalus before surgery and the abnormalities persisted in both the gCC and the PLIC at 3-month post-surgery. The DTI values remained significantly abnormal in the gCC at 12-month post-surgery. Longitudinal analysis showed signs of recovery in both WM structures between different time points. Combined with the significant correlation found between DTI and neuropsychological outcome, our study suggests that DTI can serve as a sensitive imaging biomarker for underlying neuroanatomical changes and post-surgical developmental outcome and even as a predictor for future outcomes. PMID:27203134

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

PubMed Central

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

2012-01-01

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

Non-achalasic motor disorders of the oesophagus.

PubMed

Sifrim, Daniel; Fornari, Fernando

2007-01-01

Motor abnormalities of the oesophagus are characterised by a chronic impairment of the neuromuscular structures that co-ordinate oesophageal function. The best-defined entity is achalasia, which is discussed in a separate chapter. Other motor disorders with clinical relevance include diffuse oesophageal spasm, oesophageal dysmotility associated with scleroderma, and ineffective oesophageal motility. These non-achalasic motor disorders have variable prevalence but they could be associated with invalidating symptoms such as dysphagia, chest pain and gastro-oesophageal reflux disease. New oesophageal diagnostic techniques, including high-resolution manometry, high-frequency intraluminal ultrasound and intraluminal impedance, allow (1) better definition of peristalsis and sphincter function, (2) assessment of changes in oesophageal wall thickness, and (3) evaluation of pressure gradients within the oesophagus and across the sphincters that can produce normal or abnormal patterns of bolus transport. This chapter discusses recent advances in physiology, pathophysiology, diagnosis and treatment of non-achalasic oesophageal motor disorders.

Effects of Age and Symptomatology on Cortical Thickness in Autism Spectrum Disorders

ERIC Educational Resources Information Center

Doyle-Thomas, Krissy A. R.; Duerden, Emma G.; Taylor, Margot J.; Lerch, Jason P.; Soorya, Latha V.; Wang, A. Ting; Fan, Jin; Hollander, Eric; Anagnostou, Evdokia

2013-01-01

Several brain regions show structural and functional abnormalities in individuals with autism spectrum disorders (ASD), but the developmental trajectory of abnormalities in these structures and how they may relate to social and communicative impairments are still unclear. We assessed the effects of age on cortical thickness in individuals with…

Widespread Volumetric Reductions in Schizophrenia and Schizoaffective Patients Displaying Compromised Cognitive Abilities.

PubMed

Van Rheenen, Tamsyn E; Cropley, Vanessa; Zalesky, Andrew; Bousman, Chad; Wells, Ruth; Bruggemann, Jason; Sundram, Suresh; Weinberg, Danielle; Lenroot, Roshel K; Pereira, Avril; Shannon Weickert, Cynthia; Weickert, Thomas W; Pantelis, Christos

2018-04-06

Progress toward understanding brain mechanisms in psychosis is hampered by failures to account for within-group heterogeneity that exists across neuropsychological domains. We recently identified distinct cognitive subgroups that might assist in identifying more biologically meaningful subtypes of psychosis. In the present study, we examined whether underlying structural brain abnormalities differentiate these cognitively derived subgroups. 1.5T T1 weighted structural scans were acquired for 168 healthy controls and 220 patients with schizophrenia/schizoaffective disorder. Based on previous work, 47 patients were categorized as being cognitively compromised (impaired premorbid and current IQ), 100 as cognitively deteriorated (normal premorbid IQ, impaired current IQ), and 73 as putatively cognitively preserved (premorbid and current IQ within 1 SD of controls). Global, subcortical and cortical volume, thickness, and surface area measures were compared among groups. Whole cortex, subcortical, and regional volume and thickness reductions were evident in all subgroups compared to controls, with the largest effect sizes in the compromised group. This subgroup also showed abnormalities in regions not seen in the other patient groups, including smaller left superior and middle frontal areas, left anterior and inferior temporal areas and right lateral medial and inferior frontal, occipital lobe and superior temporal areas. This pattern of more prominent brain structural abnormalities in the group with the most marked cognitive impairments-both currently and putatively prior to illness onset, is consistent with the concept of schizophrenia as a progressive neurodevelopmental disorder. In this group, neurodevelopmental and neurodegenerative factors may be important for cognitive function.

Abnormal myocardial fluid retention as an early manifestation of ischemic injury.

PubMed Central

Willerson, J. T.; Scales, F.; Mukherjee, A.; Platt, M.; Templeton, G. H.; Fink, G. S.; Buja, L. M.

1977-01-01

Fifty-seven isolated, blood perfused, continuously weighed canine hearts have been utilized to study the development of abnormal myocardial fluid retention during early myocardial ischemic injury. Inflatable balloon catheters were positioned around the left anterior descending coronary arteries (LAD) of 54 hearts or the proximal left circumflex coronary arteries of three hearts for study of the following intervals of coronary occlusion: a) 10 minutes followed by 20 minutes of reflow, b) 40 minutes followed by either no reflow or by 20 minutes of reflow, and c) 60 minutes without reflow. After 60 minutes of fixed coronary occlusion, histologic and ultrastructural examination revealed mild swelling of many ischemic cardiac muscle cells in the absence of interstitial edema, cardiac weight gain, and obvious structural defects in cell membrane integrity. After 40 minutes of coronary occlusion and 20 minutes of reflow, significant cardiac weight gain occurred in association with characteristic alterations in the ischemic region, including widespread interstitial edema and focal vascular congestion and hemorrhage and swelling of cardiac muscle cells. Focal structural defects in cell membrane integrity were also noted. The development of abnormal myocardial fluid retention after 40 minutes of LAD occlusion occurred in association with a significant reduction in sodium-potassium-ATPase activity in the ischemic area, but with no significant alteration in either creatine phosphokinase or citrate synthase activity in the same region. Despite the abnormal myocardial fluid retention in these hearts, it was possible pharmacologically to vasodilate coronary vessels with adenosine and nitroglycerin infusion to maintain a consistently high coronary flow following release of the coronary occlusion after 40 minutes and to even exceed initial hyperemic flow values following release of the occlusion when adenosine and nitroglycerin infusion was delayed until 15 minutes after reflow. Thus, the data indicate that impaired cell volume regulation and interstitial fluid accumulation and focal structural defects in cell membrane integrity are early manifestations of ischemic injury followed by reflow, but fail to establish a major role for the abnormal fluid retention in altering coronary blood flow prior to the development of extensive myocardial necrosis. In contrast, fixed coronary occlusion for 60 minutes results in mild intracellular swelling but no significant interstitial edema and no obvious structural defects in cell membrane integrity. Images Figure 1 Figure 5 Figure 6 Figure 2 Figure 3 Figure 4 PMID:139829

Assessment of nuclear abnormalities in exfoliated cells from the oral epithelium of mobile phone users.

PubMed

Souza, Leonardo da Cunha Menezes; Cerqueira, Eneida de Moraes Marcílio; Meireles, José Roberto Cardoso

2014-06-01

Transmission and reception of mobile telephony signals take place through electromagnetic wave radiation, or electromagnetic radiofrequency fields, between the mobile terminal and the radio base station. Based on reports in the literature on adverse effects from exposure to this type of radiation, the objective of this study was to evaluate the genotoxic and cytotoxic potential of such exposure, by means of the micronucleus test on exfoliated cells from the oral epithelium. The sample included 45 individuals distributed in 3 groups according to the amount of time in hours per week (t) spent using mobile phones: group I, t > 5 h; group II, t > 1 h and ≤ 5 h; and group III, t ≤ 1 h. Cells from the oral mucosa were analyzed to assess the numbers of micronuclei, broken egg structures and degenerative nuclear abnormalities indicative of apoptosis (condensed chromatin, karyorrhexis and pyknosis) or necrosis (karyolysis in addition to these changes). The occurrences of micronuclei and degenerative nuclear abnormalities did not differ between the groups, but the number of broken egg (structures that may be associated with gene amplification) was significantly greater in the individuals in group I (p < 0.05).

Macrostructural abnormalities in Korsakoff syndrome compared with uncomplicated alcoholism.

PubMed

Pitel, A-L; Chételat, G; Le Berre, A P; Desgranges, B; Eustache, F; Beaunieux, H

2012-04-24

To distinguish, in patients with Korsakoff syndrome (KS), the structural brain abnormalities shared with alcoholic patients without KS (AL), from those specific to KS. MRI data were collected in 11 alcoholic patients with KS, 34 alcoholic patients without KS, and 25 healthy control subjects (CS). Gray and white matter volumes were compared in the 3 groups using a voxel-based approach. A conjunction analysis indicated a large pattern of shared gray and white matter volume deficits in AL and KS. There were graded effects of volume deficits (KS < AL < CS) in the medial portion of the thalami, hypothalamus (mammillary bodies), left insula, and genu of the corpus callosum. Abnormalities in the left thalamic radiation were observed only in KS. Our results indicate considerable similarities in the pattern of gray and white matter damage in AL and KS. This finding confirms the widespread neurotoxic effect of chronic alcohol consumption. Only a few cerebral regions, including the medial thalami, mammillary bodies, and corpus callosum, were more severely damaged in KS than in AL. The continuum of macrostructural damage from AL to KS is therefore restricted to key brain structures. Longitudinal investigations are required to determine whether alcoholic patients with medial thalamic volumes that are comparable to those of patients with KS are at increased risk of developing KS.

Multiphoton gonioscopy to image the trabecular meshwork of porcine eyes

NASA Astrophysics Data System (ADS)

Masihzadeh, Omid; Ammar, David A.; Kahook, Malik Y.; Gibson, Emily A.; Lei, Tim C.

2013-03-01

The aqueous outflow system (AOS), including the trabecular meshwork (TM), the collector channels (CC) and the Schlemm's canal (SC), regulates intraocular pressure (IOP) through the drainage of the aqueous humor (AH). Abnormal IOP elevation leads to increased pressure stress to retinal ganglion cells, resulting in cell loss that can ultimately lead to complete loss of eyesight. Therefore, development of imaging tools to detect abnormal structural and functional changes of the AOS is important in early diagnosis and prevention of glaucoma. Multiphoton microscopy (MPM), including twophoton autofluorescence (TPAF) and second harmonic generation (SHG), is a label-free microscopic technique that allows molecular specific imaging of biological tissues like the TM. Since the TM and other AOS structures are located behind the highly scattering scleral tissue, transscleral imaging of the TM does not provide enough optical resolution. In this work, a gonioscopic lens is used to allow direct optical access of the TM through the cornea for MPM imaging. Compared to transscleral imaging, the acquired MPM images show improved resolution as individual collagen fiber bundles of the TM can be observed. MPM gonioscopy may have the potential to be developed as a future clinical imaging tool for glaucoma diagnostics.

Murine craniofacial development requires Hdac3-mediated repression of Msx gene expression.

PubMed

Singh, Nikhil; Gupta, Mudit; Trivedi, Chinmay M; Singh, Manvendra K; Li, Li; Epstein, Jonathan A

2013-05-15

Craniofacial development is characterized by reciprocal interactions between neural crest cells and neighboring cell populations of ectodermal, endodermal and mesodermal origin. Various genetic pathways play critical roles in coordinating the development of cranial structures by modulating the growth, survival and differentiation of neural crest cells. However, the regulation of these pathways, particularly at the epigenomic level, remains poorly understood. Using murine genetics, we show that neural crest cells exhibit a requirement for the class I histone deacetylase Hdac3 during craniofacial development. Mice in which Hdac3 has been conditionally deleted in neural crest demonstrate fully penetrant craniofacial abnormalities, including microcephaly, cleft secondary palate and dental hypoplasia. Consistent with these abnormalities, we observe dysregulation of cell cycle genes and increased apoptosis in neural crest structures in mutant embryos. Known regulators of cell cycle progression and apoptosis in neural crest, including Msx1, Msx2 and Bmp4, are upregulated in Hdac3-deficient cranial mesenchyme. These results suggest that Hdac3 serves as a critical regulator of craniofacial morphogenesis, in part by repressing core apoptotic pathways in cranial neural crest cells. Copyright © 2013 Elsevier Inc. All rights reserved.

MRI Post-processing in Pre-surgical Evaluation

PubMed Central

Wang, Z. Irene; Alexopoulos, Andreas V.

2016-01-01

Purpose of Review Advanced MRI post-processing techniques are increasingly used to complement visual analysis and elucidate structural epileptogenic lesions. This review summarizes recent developments in MRI post-processing in the context of epilepsy pre-surgical evaluation, with the focus on patients with unremarkable MRI by visual analysis (i.e., “nonlesional” MRI). Recent Findings Various methods of MRI post-processing have been reported to show additional clinical values in the following areas: (1) lesion detection on an individual level; (2) lesion confirmation for reducing the risk of over reading the MRI; (3) detection of sulcal/gyral morphologic changes that are particularly difficult for visual analysis; and (4) delineation of cortical abnormalities extending beyond the visible lesion. Future directions to improve performance of MRI post-processing include using higher magnetic field strength for better signal and contrast to noise ratio, adopting a multi-contrast frame work, and integration with other noninvasive modalities. Summary MRI post-processing can provide essential value to increase the yield of structural MRI and should be included as part of the presurgical evaluation of nonlesional epilepsies. MRI post-processing allows for more accurate identification/delineation of cortical abnormalities, which should then be more confidently targeted and mapped. PMID:26900745

Differentiation between inflammatory and neoplastic orbital conditions based on computed tomographic signs.

PubMed

Lederer, Kristina; Ludewig, Eberhard; Hechinger, Harald; Parry, Andrew T; Lamb, Christopher R; Kneissl, Sibylle

2015-07-01

To identify computed tomographic (CT) signs that could be used to differentiate inflammatory from neoplastic orbital conditions in small animals. Fifty-two animals (25 cats, 21 dogs, 4 rabbits, and 2 rodents). Case-control study in which CT images of animals with histopathologic diagnosis of inflammatory (n = 11), neoplastic orbital conditions (n = 31), or normal control animals (n = 10) were reviewed independently by five observers without the knowledge of the history or diagnosis. Observers recorded their observations regarding specific anatomical structures within the orbit using an itemized form containing the following characteristics: definitely normal; probably normal; equivocal; probably abnormal; and definitely abnormal. Results were statistically analyzed using Fleiss' kappa and logistic regression analyses. The overall level of agreement between observers about the presence or absence of abnormal CT signs in animals with orbital disease was poor to moderate, but was highest for observations concerning orbital bones (κ = 0.62) and involvement of the posterior segment (κ = 0.52). Significant associations between abnormalities and diagnosis were found for four structures: Abnormalities affecting orbital bones (odds ratio [OR], 1.7) and anterior ocular structures (OR, 1.5) were predictive of neoplasia, while abnormalities affecting extraconal fat (OR, 1.7) and skin (OR, 1.4) were predictive of inflammatory conditions. Orbital CT is an imaging test with high specificity. Fat stranding, a CT sign not previously emphasized in veterinary medicine, was significantly associated with inflammatory conditions. Low observer agreement probably reflects the limited resolution of CT for small orbital structures. © 2014 American College of Veterinary Ophthalmologists.

Alterations in brain temperatures as a possible cause of migraine headache.

PubMed

Horváth, Csilla

2014-05-01

Migraine is a debilitating disease with a recurring generally unilateral headache and concomitant symptoms of nausea, vomiting and photo- and/or phonophobia that affects some 11-18% of the population. Most of the mechanisms previously put forward to explain the attacks have been questioned or give an explanation only some of the symptoms. Moreover, the best drugs for treatment are still the 20-year-old triptans, which have serious limitations as regards both efficacy and tolerability. As the dura and some cranial vessels are the only intracranial structures capable of pain sensations, a vascular theory of migraine emerged, but has been debated. Recent theories identified the hyperexcitability of structures involved in pain transmission, such as the trigeminal system or the cortex, or an abnormal modulatory function of the brainstem. However, there is ongoing scientific debate concerning these theories, neither of which is fully capable of explaining the occurrence of a migraine attack. The present article puts forward a hypothesis of the possibility of abnormal temperature regulation in certain regions or the overall brain in migraineurs, the attack being a defense mechanism to prevent neuronal damage. Few examinations have been made of temperature regulation in the human brain. It lacks the carotid rete, a vascular heat exchanger that serves in many animals to provide constant brain temperature. The human brain contains a high density of neurons with a considerable energy demand that is converted to heat. The human brain has a higher temperature than other parts of the body and needs continuous cooling. Recent studies revealed unexpectedly great variations in temperature of various structures of the brain and considerable changes in response to functional activation. There is various evidence in support of the hypothesis that accumulated heat in some structure or the overall brain may be behind the symptoms observed, such as a platelet abnormality, a decreased serotonin content, and dural "inflammation" including vasodilation and brainstem activation. The hypothesis postulates that a migraine attack serves to restore the brain temperature. Abnormally low temperatures in the brain can also result in headache. Surprisingly, no systematic examination of brain temperature changes in migraineurs has been published. Certain case reports support the present hypothesis. Various noninvasive technologies (e.g. MR) capable of monitoring brain temperature are available. If a systematic examination of local brain temperature revealed abnormalities in structures presumed to be involved in migraine, that would increase our understanding of the disease and trigger the development of improved treatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

Temporal lobe epilepsy: analysis of patients with dual pathology.

PubMed

Salanova, V; Markand, O; Worth, R

2004-02-01

To determine the frequency and types of dual pathology in patients with temporal lobe epilepsy (TLE) and to analyze the clinical manifestations and surgical outcome. A total of 240 patients with TLE underwent temporal resections following a comprehensive pre-surgical evaluation. Thirty-seven (15.4%) of these had hippocampal sclerosis (HS) or temporal lobe gliosis in association with another lesion (dual pathology). Eighteen of 37 patients with dual pathology had heterotopia of the temporal lobe, nine had cortical dysplasia, four had cavernous angiomas or arteriovenous malformations, one had a dysembryoplastic neuroepithelial tumor, one had a contusion and four patients had cerebral infarctions in childhood. 68.5% had abnormal head magnetic resonance imagings, 91.3% had abnormal positron emission tomography scans, and 96% had abnormal ictal SPECT. The intracarotid amobarbital procedure (IAP) showed impaired memory of the epileptogenic side in 72% of the patients. Twenty patients had left and 17 had right-sided en bloc temporal resections, including the lesion and mesial temporal structures. Twenty-six (70.2%) became seizure-free, eight (21.6%) had rare seizures, two (5.4%) had worthwhile seizure reduction and one (2.7%) had no improvement (range of follow-up 1-16 years, mean = 7.4 years). 15.4% had dual pathology. The dual pathology was almost exclusively seen in patients whose lesions were congenital, or occurred early in life, suggesting that the hippocampus is more vulnerable and more readily develops HS in early childhood. Resections, including the lateral and mesial temporal structures led to a favorable outcome with no mortality and little morbidity.

Morphological and Glucose Metabolism Abnormalities in Alcoholic Korsakoff's Syndrome: Group Comparisons and Individual Analyses

PubMed Central

Pitel, Anne-Lise; Aupée, Anne-Marie; Chételat, Gaël; Mézenge, Florence; Beaunieux, Hélène; de la Sayette, Vincent; Viader, Fausto; Baron, Jean-Claude; Eustache, Francis; Desgranges, Béatrice

2009-01-01

Background Gray matter volume studies have been limited to few brain regions of interest, and white matter and glucose metabolism have received limited research attention in Korsakoff's syndrome (KS). Because of the lack of brain biomarkers, KS was found to be underdiagnosed in postmortem studies. Methodology/Principal Findings Nine consecutively selected patients with KS and 22 matched controls underwent both structural magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography examinations. Using a whole-brain analysis, the between-group comparisons of gray matter and white matter density and relative glucose uptake between patients with KS and controls showed the involvement of both the frontocerebellar and the Papez circuits, including morphological abnormalities in their nodes and connection tracts and probably resulting hypometabolism. The direct comparison of the regional distribution and degree of gray matter hypodensity and hypometabolism within the KS group indicated very consistent gray matter distribution of both abnormalities, with a single area of significant difference in the middle cingulate cortex showing greater hypometabolism than hypodensity. Finally, the analysis of the variability in the individual patterns of brain abnormalities within our sample of KS patients revealed that the middle cingulate cortex was the only brain region showing significant GM hypodensity and hypometabolism in each of our 9 KS patients. Conclusions/Significance These results indicate widespread brain abnormalities in KS including both gray and white matter damage mainly involving two brain networks, namely, the fronto-cerebellar circuit and the Papez circuit. Furthermore, our findings suggest that the middle cingulate cortex may play a key role in the pathophysiology of KS and could be considered as a potential in vivo brain biomarker. PMID:19936229

Hearing Loss in a Mouse Model of 22q11.2 Deletion Syndrome

PubMed Central

Fuchs, Jennifer C.; Zinnamon, Fhatarah A.; Taylor, Ruth R.; Ivins, Sarah; Scambler, Peter J.; Forge, Andrew; Tucker, Abigail S.; Linden, Jennifer F.

2013-01-01

22q11.2 Deletion Syndrome (22q11DS) arises from an interstitial chromosomal microdeletion encompassing at least 30 genes. This disorder is one of the most significant known cytogenetic risk factors for schizophrenia, and can also cause heart abnormalities, cognitive deficits, hearing difficulties, and a variety of other medical problems. The Df1/+ hemizygous knockout mouse, a model for human 22q11DS, recapitulates many of the deficits observed in the human syndrome including heart defects, impaired memory, and abnormal auditory sensorimotor gating. Here we show that Df1/+ mice, like human 22q11DS patients, have substantial rates of hearing loss arising from chronic middle ear infection. Auditory brainstem response (ABR) measurements revealed significant elevation of click-response thresholds in 48% of Df1/+ mice, often in only one ear. Anatomical and histological analysis of the middle ear demonstrated no gross structural abnormalities, but frequent signs of otitis media (OM, chronic inflammation of the middle ear), including excessive effusion and thickened mucosa. In mice for which both in vivo ABR thresholds and post mortem middle-ear histology were obtained, the severity of signs of OM correlated directly with the level of hearing impairment. These results suggest that abnormal auditory sensorimotor gating previously reported in mouse models of 22q11DS could arise from abnormalities in auditory processing. Furthermore, the findings indicate that Df1/+ mice are an excellent model for increased risk of OM in human 22q11DS patients. Given the frequently monaural nature of OM in Df1/+ mice, these animals could also be a powerful tool for investigating the interplay between genetic and environmental causes of OM. PMID:24244619

Hearing loss in a mouse model of 22q11.2 Deletion Syndrome.

PubMed

Fuchs, Jennifer C; Zinnamon, Fhatarah A; Taylor, Ruth R; Ivins, Sarah; Scambler, Peter J; Forge, Andrew; Tucker, Abigail S; Linden, Jennifer F

2013-01-01

22q11.2 Deletion Syndrome (22q11DS) arises from an interstitial chromosomal microdeletion encompassing at least 30 genes. This disorder is one of the most significant known cytogenetic risk factors for schizophrenia, and can also cause heart abnormalities, cognitive deficits, hearing difficulties, and a variety of other medical problems. The Df1/+ hemizygous knockout mouse, a model for human 22q11DS, recapitulates many of the deficits observed in the human syndrome including heart defects, impaired memory, and abnormal auditory sensorimotor gating. Here we show that Df1/+ mice, like human 22q11DS patients, have substantial rates of hearing loss arising from chronic middle ear infection. Auditory brainstem response (ABR) measurements revealed significant elevation of click-response thresholds in 48% of Df1/+ mice, often in only one ear. Anatomical and histological analysis of the middle ear demonstrated no gross structural abnormalities, but frequent signs of otitis media (OM, chronic inflammation of the middle ear), including excessive effusion and thickened mucosa. In mice for which both in vivo ABR thresholds and post mortem middle-ear histology were obtained, the severity of signs of OM correlated directly with the level of hearing impairment. These results suggest that abnormal auditory sensorimotor gating previously reported in mouse models of 22q11DS could arise from abnormalities in auditory processing. Furthermore, the findings indicate that Df1/+ mice are an excellent model for increased risk of OM in human 22q11DS patients. Given the frequently monaural nature of OM in Df1/+ mice, these animals could also be a powerful tool for investigating the interplay between genetic and environmental causes of OM.

Ultrastructural characterization of the tau-immunoreactive tubules in the oligodendroglial perikarya and their inner loop processes in progressive supranuclear palsy.

PubMed

Arima, K; Nakamura, M; Sunohara, N; Ogawa, M; Anno, M; Izumiyama, Y; Hirai, S; Ikeda, K

1997-06-01

Coiled bodies and interfascicular threads are conspicuous white matter abnormalities of brains of patients with progressive supranuclear palsy (PSP). Both structures are argyrophilic and immunoreactive for the microtubule-binding protein tau. This report concerns the ultrastructural localization of interfascicular threads and their relationship to coiled bodies in five PSP patients. We showed for the first time that abnormal tubules with a 13- to 15-nm diameter and fuzzy outer contours were the common structures of coiled bodies in the oligodendroglial perikarya and of interfascicular threads. Moreover, the tubules were immunolabeled by anti-tau antibodies. The abnormal tau-positive tubules of interfascicular threads were located in the inner loop of the myelin sheath. Our study further indicated that the thread-like structures in the white matter comprised, at least in part, oligodendroglial processes, and that they were also present in gray matter. We consider that the formation of coiled bodies in the perikarya and of interfascicular threads represents a common cytoskeletal abnormality of the oligodendroglia of PSP patients. Moreover, even though the white matter alterations of PSP resemble those of corticobasal degeneration, there are certain ultrastructural differences in the abnormal oligodendroglial tubules of the two diseases.

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.

Cytogenetic study of a patient with infant acute lymphoblastic leukemia using GTG-banding and chromosome painting.

PubMed

Alter, D; Mark, H F

2000-10-01

Numerical and structural chromosomal abnormalities occur in up to 90% of cases of childhood acute lymphoblastic leukemia (ALL). Two-thirds of these abnormalities are recurrent. The most common abnormalities are pseudodiploidy and t(1;19), occurring 40 and 5-6% of the time. Hyperdiploidy has the best prognosis, with an 80-90% 5-year survival. The 4;11 translocation has the worst prognosis, with a 10-35% 5-year survival. We report a patient with infant acute lymphoblastic leukemia and nonrecurrent rearrangements of chromosomes 10 and 11. Structural rearrangements between chromosomes 10 and 11 have been observed in 0.5% of all cases of childhood ALL with cytogenetic abnormalities. The identification of the apparently unique structural abnormalities was achieved using fluorescent in situ hybridization (FISH) with chromosome 10- and chromosome 11-specific painting probes as an adjunct to conventional cytogenetics. As is often the case, suboptimal preparations often preclude unequivocal identification of complex rearrangements by conventional banding techniques. The cytogenetic diagnosis of our patient was established as 46,XY, der(10)-t(10;11)(p15;q14)t(10;11)(q25;p11), der(11)t(10;11)(p15;q14)t(10;11)-(q25;p11). The benefits of FISH serve to increase the resolution of detection for chromosomal abnormalities and the understanding of the pathogenic mechanisms of childhood ALL. Copyright 2000 Academic Press.

Glial activation colocalizes with structural abnormalities in amyotrophic lateral sclerosis.

PubMed

Alshikho, Mohamad J; Zürcher, Nicole R; Loggia, Marco L; Cernasov, Paul; Chonde, Daniel B; Izquierdo Garcia, David; Yasek, Julia E; Akeju, Oluwaseun; Catana, Ciprian; Rosen, Bruce R; Cudkowicz, Merit E; Hooker, Jacob M; Atassi, Nazem

2016-12-13

In this cross-sectional study, we aimed to evaluate brain structural abnormalities in relation to glial activation in the same cohort of participants. Ten individuals with amyotrophic lateral sclerosis (ALS) and 10 matched healthy controls underwent brain imaging using integrated MR/PET and the radioligand [ 11 C]-PBR28. Diagnosis history and clinical assessments including Upper Motor Neuron Burden Scale (UMNB) were obtained from patients with ALS. Diffusion tensor imaging (DTI) analyses including tract-based spatial statistics and tractography were applied. DTI metrics including fractional anisotropy (FA) and diffusivities (mean, axial, and radial) were measured in regions of interest. Cortical thickness was assessed using surface-based analysis. The locations of structural changes, measured by DTI and the areas of cortical thinning, were compared to regional glial activation measured by relative [ 11 C]-PBR28 uptake. In this cohort of individuals with ALS, reduced FA and cortical thinning colocalized with regions demonstrating higher radioligand binding. [ 11 C]-PBR28 binding in the left motor cortex was correlated with FA (r = -0.68, p < 0.05) and cortical thickness (r = -0.75, p < 0.05). UMNB was correlated with glial activation (r = +0.75, p < 0.05), FA (r = -0.77, p < 0.05), and cortical thickness (r = -0.75, p < 0.05) in the motor cortex. Increased uptake of the glial marker [ 11 C]-PBR28 colocalizes with changes in FA and cortical thinning. This suggests a link between disease mechanisms (gliosis and inflammation) and structural changes (cortical thinning and white and gray matter changes). In this multimodal neuroimaging work, we provide an in vivo model to investigate the pathogenesis of ALS. © 2016 American Academy of Neurology.

Glial activation colocalizes with structural abnormalities in amyotrophic lateral sclerosis

PubMed Central

Alshikho, Mohamad J.; Zürcher, Nicole R.; Loggia, Marco L.; Cernasov, Paul; Chonde, Daniel B.; Izquierdo Garcia, David; Yasek, Julia E.; Akeju, Oluwaseun; Catana, Ciprian; Rosen, Bruce R.; Cudkowicz, Merit E.

2016-01-01

Objective: In this cross-sectional study, we aimed to evaluate brain structural abnormalities in relation to glial activation in the same cohort of participants. Methods: Ten individuals with amyotrophic lateral sclerosis (ALS) and 10 matched healthy controls underwent brain imaging using integrated MR/PET and the radioligand [11C]-PBR28. Diagnosis history and clinical assessments including Upper Motor Neuron Burden Scale (UMNB) were obtained from patients with ALS. Diffusion tensor imaging (DTI) analyses including tract-based spatial statistics and tractography were applied. DTI metrics including fractional anisotropy (FA) and diffusivities (mean, axial, and radial) were measured in regions of interest. Cortical thickness was assessed using surface-based analysis. The locations of structural changes, measured by DTI and the areas of cortical thinning, were compared to regional glial activation measured by relative [11C]-PBR28 uptake. Results: In this cohort of individuals with ALS, reduced FA and cortical thinning colocalized with regions demonstrating higher radioligand binding. [11C]-PBR28 binding in the left motor cortex was correlated with FA (r = −0.68, p < 0.05) and cortical thickness (r = −0.75, p < 0.05). UMNB was correlated with glial activation (r = +0.75, p < 0.05), FA (r = −0.77, p < 0.05), and cortical thickness (r = −0.75, p < 0.05) in the motor cortex. Conclusions: Increased uptake of the glial marker [11C]-PBR28 colocalizes with changes in FA and cortical thinning. This suggests a link between disease mechanisms (gliosis and inflammation) and structural changes (cortical thinning and white and gray matter changes). In this multimodal neuroimaging work, we provide an in vivo model to investigate the pathogenesis of ALS. PMID:27837005

Chronic Methamphetamine Abuse and Corticostriatal Deficits Revealed by Neuroimaging

PubMed Central

London, Edythe D.; Kohno, Milky; Morales, Angelica; Ballard, Michael E.

2014-01-01

Despite aggressive efforts to contain it, methamphetamine use disorder continues to be major public health problem; and with generic behavioral therapies still the mainstay of treatment for methamphetamine abuse, rates of attrition and relapse remain high. This review summarizes the findings of structural, molecular, and functional neuroimaging studies of methamphetamine abusers, focusing on cortical and striatal abnormalities and their potential contributions to cognitive and behavioral phenotypes that can serve to promote compulsive drug use. These studies indicate that individuals with a history of chronic methamphetamine abuse often display several signs of corticostriatal dysfunction, including abnormal gray- and white-matter integrity, monoamine neurotransmitter system deficiencies, neuroinflammation, poor neuronal integrity, and aberrant patterns of brain connectivity and function, both when engaged in cognitive tasks and at rest. More importantly, many of these neural abnormalities were found to be linked with certain addiction-related phenotypes that may influence treatment response (e.g., poor self-control, cognitive inflexibility, maladaptive decision-making), raising the possibility that they may represent novel therapeutic targets. PMID:25451127

Cross-Sectional and Longitudinal Abnormalities in Brain Structure in Children with Severe Mood Dysregulation or Bipolar Disorder

ERIC Educational Resources Information Center

Adleman, Nancy E.; Fromm, Stephen J.; Razdan, Varun; Kayser, Reilly; Dickstein, Daniel P.; Brotman, Melissa A.; Pine, Daniel S.; Leibenluft, Ellen

2012-01-01

Background: There is debate as to whether chronic irritability (operationalized as severe mood dysregulation, SMD) is a developmental form of bipolar disorder (BD). Although structural brain abnormalities in BD have been demonstrated, no study compares neuroanatomy among SMD, BD, and healthy volunteers (HV) either cross-sectionally or over time.…

Neural signatures of cognitive and emotional biases in depression

PubMed Central

Fossati, Philippe

2008-01-01

Functional brain imaging studies suggest that depression is a system-level disorder affecting discrete but functionally linked cortical and limbic structures, with abnormalities in the anterior cingulate, lateral, ami medial prefrontal cortex, amygdala, ami hippocampus. Within this circuitry, abnormal corticolimbic interactions underlie cognitive deficits ami emotional impairment in depression. Depression involves biases toward processing negative emotional information and abnormal self-focus in response to emotional stimuli. These biases in depression could reflect excessive analytical self-focus in depression, as well as impaired cognitive control of emotional response to negative stimuli. By combining structural and functional investigations, brain imaging studies mav help to generate novel antidepressant treatments that regulate structural and factional plasticity within the neural network regulating mood and affective behavior.

Red cell membrane skeleton: structure-function relationships.

PubMed

Palek, J; Liu, S C

1980-01-01

This papaer reviews our present understanding of ultrastructure, organization, and functional characteristics of the erythrocyte membrane cytoskeleton. This two-dimensional fibrillar network of submembrane proteins can be visualized after extraction of lipids and integral membrane proteins by Triton X-100. Current data suggest that the major structural components of the cytoskeleton are heterodimers of double-stranded spectrin that form tetramers by head-to-head associations. The tetramers may be connected into a fibrillar meshwork by oligomers of actin. The control of membrane integrity by this network is illustrated by examples of two hemolyotic anemias characterized by marked membrane instability and vesiculation: 1) hereditary spherocytic anemia of the house mouse associated with spectrin deficiency and 2) hereditary pyropoikilocytosis, a hemolytic anemia in man characterized by thermal instability of the membrane and the presence of abnormal spectrin, which exhibits an increased propensity to thermal denaturation. Stabilization of the cytoskeletal network by covalent cross-links between the nearest cytoskeletal and integral membrane proteins results in a decrease of membrane deformability and a fixation of erythrocytes in their abnormal shape. Such cross-linkings include: 1) transamidative cross-links produced by introduction of Ca2+ (>0.5 mM) into fresh erythrocytes, and 2) intermolecular disulfide couplings, which are formed after extensive oxidation of fresh erythrocytes or after mild oxidation of ATP-depleted, but not fresh, erythrocytes. The significance of these cross-links in stabilization of shape of abnormal erythrocytes such as schistocytes remains to be determined. We conclude that spectrin and actin form a fibrillar submembrane network that plays an important role in control of membrane integrity, erythrocyte deformability, and stabilization of cells in abnormal shapes.

The Brain Basis for Misophonia.

PubMed

Kumar, Sukhbinder; Tansley-Hancock, Olana; Sedley, William; Winston, Joel S; Callaghan, Martina F; Allen, Micah; Cope, Thomas E; Gander, Phillip E; Bamiou, Doris-Eva; Griffiths, Timothy D

2017-02-20

Misophonia is an affective sound-processing disorder characterized by the experience of strong negative emotions (anger and anxiety) in response to everyday sounds, such as those generated by other people eating, drinking, chewing, and breathing [1-8]. The commonplace nature of these sounds (often referred to as "trigger sounds") makes misophonia a devastating disorder for sufferers and their families, and yet nothing is known about the underlying mechanism. Using functional and structural MRI coupled with physiological measurements, we demonstrate that misophonic subjects show specific trigger-sound-related responses in brain and body. Specifically, fMRI showed that in misophonic subjects, trigger sounds elicit greatly exaggerated blood-oxygen-level-dependent (BOLD) responses in the anterior insular cortex (AIC), a core hub of the "salience network" that is critical for perception of interoceptive signals and emotion processing. Trigger sounds in misophonics were associated with abnormal functional connectivity between AIC and a network of regions responsible for the processing and regulation of emotions, including ventromedial prefrontal cortex (vmPFC), posteromedial cortex (PMC), hippocampus, and amygdala. Trigger sounds elicited heightened heart rate (HR) and galvanic skin response (GSR) in misophonic subjects, which were mediated by AIC activity. Questionnaire analysis showed that misophonic subjects perceived their bodies differently: they scored higher on interoceptive sensibility than controls, consistent with abnormal functioning of AIC. Finally, brain structural measurements implied greater myelination within vmPFC in misophonic individuals. Overall, our results show that misophonia is a disorder in which abnormal salience is attributed to particular sounds based on the abnormal activation and functional connectivity of AIC. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Biophysical properties of normal and diseased renal glomeruli.

PubMed

Wyss, Hans M; Henderson, Joel M; Byfield, Fitzroy J; Bruggeman, Leslie A; Ding, Yaxian; Huang, Chunfa; Suh, Jung Hee; Franke, Thomas; Mele, Elisa; Pollak, Martin R; Miner, Jeffrey H; Janmey, Paul A; Weitz, David A; Miller, R Tyler

2011-03-01

The mechanical properties of tissues and cells including renal glomeruli are important determinants of their differentiated state, function, and responses to injury but are not well characterized or understood. Understanding glomerular mechanics is important for understanding renal diseases attributable to abnormal expression or assembly of structural proteins and abnormal hemodynamics. We use atomic force microscopy (AFM) and a new technique, capillary micromechanics, to measure the elastic properties of rat glomeruli. The Young's modulus of glomeruli was 2,500 Pa, and it was reduced to 1,100 Pa by cytochalasin and latunculin, and to 1,400 Pa by blebbistatin. Cytochalasin or latrunculin reduced the F/G actin ratios of glomeruli but did not disrupt their architecture. To assess glomerular biomechanics in disease, we measured the Young's moduli of glomeruli from two mouse models of primary glomerular disease, Col4a3(-/-) mice (Alport model) and Tg26(HIV/nl) mice (HIV-associated nephropathy model), at stages where glomerular injury was minimal by histopathology. Col4a3(-/-) mice express abnormal glomerular basement membrane proteins, and Tg26(HIV/nl) mouse podocytes have multiple abnormalities in morphology, adhesion, and cytoskeletal structure. In both models, the Young's modulus of the glomeruli was reduced by 30%. We find that glomeruli have specific and quantifiable biomechanical properties that are dependent on the state of the actin cytoskeleton and nonmuscle myosins. These properties may be altered early in disease and represent an important early component of disease. This increased deformability of glomeruli could directly contribute to disease by permitting increased distension with hemodynamic force or represent a mechanically inhospitable environment for glomerular cells.

Altered sperm chromatin structure in mice exposed to sodium fluoride through drinking water.

PubMed

Sun, Zilong; Niu, Ruiyan; Wang, Bin; Wang, Jundong

2014-06-01

This study investigated the effects of sodium fluoride (NaF) on sperm abnormality, sperm chromatin structure, protamine 1 and protamine 2 (P1 and P2) mRNA expression, and histones expression in sperm in male mice. NaF was orally administrated to male mice at 30, 70, and 150 mg/l for 49 days (more than one spermatogenic cycle). Sperm head and tail abnormalities were significantly enhanced at middle and high doses. Similarly, sperm chromatin structure was also adversely affected by NaF exposure, indicating DNA integrity damage. Furthermore, middle and high NaF significantly reduced the mRNA expressions of P1 and P2, and P1/P2 ratio, whereas the sperm histones level was increased, suggesting the abnormal histone-protamine replacement. Therefore, we concluded that the mechanism by which F induced mice sperm abnormality and DNA integrity damage may involved in the alterations in P1, P2, and histones expression in sperm of mice. Copyright © 2012 Wiley Periodicals, Inc.

Patients with primary biliary cholangitis and fatigue present with depressive symptoms and selected cognitive deficits, but with normal attention performance and brain structure.

PubMed

Zenouzi, Roman; von der Gablentz, Janina; Heldmann, Marcus; Göttlich, Martin; Weiler-Normann, Christina; Sebode, Marcial; Ehlken, Hanno; Hartl, Johannes; Fellbrich, Anja; Siemonsen, Susanne; Schramm, Christoph; Münte, Thomas F; Lohse, Ansgar W

2018-01-01

In primary biliary cholangitis (PBC) fatigue is a major clinical challenge of unknown etiology. By demonstrating that fatigue in PBC is associated with an impaired cognitive performance, previous studies have pointed out the possibility of brain abnormalities underlying fatigue in PBC. Whether structural brain changes are present in PBC patients with fatigue, however, is unclear. To evaluate the role of structural brain abnormalities in PBC patients severely affected from fatigue we, therefore, performed a case-control cerebral magnetic resonance imaging (cMRI) study and correlated changes of white and grey brain matter with the cognitive and attention performance. 20 female patients with PBC and 20 female age-matched controls were examined in this study. The assessment of fatigue, psychological symptoms, cognitive and attention performance included clinical questionnaires, established cognition tests and a computerized test battery of attention performance. T1-weighted cMRI and diffusion tensor imaging (DTI) scans were acquired with a 3 Tesla scanner. Structural brain alterations were investigated with voxel-based morphometry (VBM) and DTI analyses. Results were correlated to the cognitive and attention performance. Compared to healthy controls, PBC patients had significantly higher levels of fatigue and associated psychological symptoms. Except for an impairment of verbal fluency, no cognitive or attention deficits were found in the PBC cohort. The VBM and DTI analyses revealed neither major structural brain abnormalities in the PBC cohort nor correlations with the cognitive and attention performance. Despite the high burden of fatigue and selected cognitive deficits, the attention performance of PBC patients appears to be comparable to healthy people. As structural brain alterations do not seem to be present in PBC patients with fatigue, fatigue in PBC must be regarded as purely functional. Future studies should evaluate, whether functional brain changes underlie fatigue in PBC.

New Insights on the Morphology of Adult Mouse Penis1

PubMed Central

Rodriguez, Esequiel; Weiss, Dana A.; Yang, Jennifer H.; Menshenina, Julia; Ferretti, Max; Cunha, Tristan J.; Barcellos, Dale; Chan, Lok Yun; Risbridger, Gail; Cunha, Gerald R.; Baskin, Laurence S.

2011-01-01

ABSTRACT The adult mouse penis represents the end point of masculine sex differentiation of the embryonic genital tubercle and contains bone, cartilage, the urethra, erectile bodies, several types of epithelium, and many individual cell types arrayed into specific anatomical structures. Using contemporary high-resolution imaging techniques, we sought to provide new insights to the current description of adult mouse penile morphology to enable understanding of penile abnormalities, including hypospadias. Examination of serial transverse and longitudinal sections, scanning electron microscopy, and three-dimensional (3D) reconstruction provided a new appreciation of the individual structures in the adult mouse penis and their 3D interrelationships. In so doing, we discovered novel paired erectile bodies, the male urogenital mating protuberance (MUMP), and more accurately described the urethral meatus. These morphological observations were quantified by morphometric analysis and now provide accurate morphological end points of sex differentiation of mouse penis that will be the foundation of future studies to identify normal and abnormal penile development. PMID:21918128

Selective Impairment of Spatial Cognition Caused by Autoantibodies to the N-Methyl-d-Aspartate Receptor

PubMed Central

Chang, Eric H.; Volpe, Bruce T.; Mackay, Meggan; Aranow, Cynthia; Watson, Philip; Kowal, Czeslawa; Storbeck, Justin; Mattis, Paul; Berlin, RoseAnn; Chen, Huiyi; Mader, Simone; Huerta, Tomás S.; Huerta, Patricio T.; Diamond, Betty

2015-01-01

Patients with systemic lupus erythematosus (SLE) experience cognitive abnormalities in multiple domains including processing speed, executive function, and memory. Here we show that SLE patients carrying antibodies that bind DNA and the GluN2A and GluN2B subunits of the N-methyl-d-aspartate receptor (NMDAR), termed DNRAbs, displayed a selective impairment in spatial recall. Neural recordings in a mouse model of SLE, in which circulating DNRAbs penetrate the hippocampus, revealed that CA1 place cells exhibited a significant expansion in place field size. Structural analysis showed that hippocampal pyramidal cells had substantial reductions in their dendritic processes and spines. Strikingly, these abnormalities became evident at a time when DNRAbs were no longer detectable in the hippocampus. These results suggest that antibody-mediated neurocognitive impairments may be highly specific, and that spatial cognition may be particularly vulnerable to DNRAb-mediated structural and functional injury to hippocampal cells that evolves after the triggering insult is no longer present. PMID:26286205

Bilateral ocular abnormalities in a wild stranded harp seal (Phoca groenlandica) suggestive of anterior segment dysgenesis and persistent hyperplastic primary vitreous.

PubMed

Erlacher-Reid, Claire; Colitz, Carmen M H; Abrams, Ken; Smith, Ainsley; Tuttle, Allison D

2011-06-01

A male yearling harp seal (Phoca groenlandica) stranded and was brought to Mystic Aquarium & Institute for Exploration's Seal Rescue and Rehabilitation Center. The seal presented with a bilateral pendular vertical nystagmus, negative menace response, and a positive palpebral response. Ophthalmological examination by slit lamp biomicroscopy revealed perilimbal corneal edema, excessive iridal surface structures, pupils that appeared to be shaped improperly (dyscoria), and suspected cataracts. Attempts to dilate the pupils with both dark-lighted conditions and repeated dosages of 10% phenylephrine and 1% atropine ophthalmic solution in each eye (OU) were unsuccessful. Ocular ultrasonography findings suggested bilateral cataracts with flattened anterior-posterior (A-P) diameter and possible persistent hyperplastic primary vitreous. It is possible that these structural congenital abnormalities could produce further ocular complications for this seal including uveitis, secondary glaucoma, retinal detachment, and/or vitreal hemorrhage in the future. This case demonstrates the importance of a thorough ophthalmological examination in stranded wild animals, especially if their symptoms appear neurological.

A Structural Perspective on the Modulation of Protein-Protein Interactions with Small Molecules.

PubMed

Demirel, Habibe Cansu; Dogan, Tunca; Tuncbag, Nurcan

2018-05-31

Protein-protein interactions (PPIs) are the key components in many cellular processes including signaling pathways, enzymatic reactions and epigenetic regulation. Abnormal interactions of some proteins may be pathogenic and cause various disorders including cancer and neurodegenerative diseases. Although inhibiting PPIs with small molecules is a challenging task, it gained an increasing interest because of its strong potential for drug discovery and design. The knowledge of the interface as well as the structural and chemical characteristics of the PPIs and their roles in the cellular pathways are necessary for a rational design of small molecules to modulate PPIs. In this study, we review the recent progress in the field and detail the physicochemical properties of PPIs including binding hot spots with a focus on structural methods. Then, we review recent approaches for structural prediction of PPIs. Finally, we revisit the concept of targeting PPIs in a systems biology perspective and we refer to the non-structural approaches, usually employed when the structural information is not present. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Trends in gestational age at time of surgical abortion for fetal aneuploidy and structural abnormalities.

PubMed

Davis, Anne R; Horvath, Sarah K; Castaño, Paula M

2017-03-01

Screening for fetal aneuploidy has evolved over the past 2 decades. Whether these advances impact gestational age at abortion has received little study. We sought to describe trends in the gestational age at the time of abortion by fetal diagnosis over an 11-year study period. We hypothesized that gestational age at time of abortion would decrease for fetal aneuploidy but remain unchanged for structural abnormalities. We conducted a retrospective case series of all women undergoing surgical abortion for fetal aneuploidy or structural abnormalities up to 24 weeks' gestation from 2004 through 2014 in a hospital operating room setting at a single, urban medical center. We excluded labor induction abortions (<1% of abortions at our medical center) and suction aspirations performed in the office practice. We performed suction aspiration up to 14 weeks and dilation and evacuation after that gestational age. We describe the median gestational age at abortion by fetal indication and year. For women undergoing abortion for fetal aneuploidy (n = 392), the median gestational age at time of abortion decreased from 19.0 weeks (interquartile range 18.0-21.0) in 2004 to 14.0 weeks (interquartile range 13.0-17.0) in 2014 (Kruskal-Wallis P < .0001). For women undergoing abortion for fetal structural abnormalities (n = 586), the median gestational age was ≥20 weeks for each year during the study interval (P = .1). As gestational age decreased in the fetal aneuploidy group, fewer women underwent dilation and evacuation and more became eligible for suction aspiration (<14 weeks). In 2004, >90% of women underwent dilation and evacuation for either indication. By 2014, 31% of women with fetal aneuploidy were eligible for suction aspiration compared to 11% of those with structural anomalies. Gestational age at the time of abortion for fetal aneuploidy decreased substantially from 2004 through 2014; earlier abortion is safer for women. In contrast, women seeking abortion for fetal structural abnormalities did not experience a change in timing. Legislation restricting gestational age at the time of abortion could disproportionately affect women with fetal structural abnormalities. Copyright © 2016 Elsevier Inc. All rights reserved.

The impact of ADHD persistence, recent cannabis use, and age of regular cannabis use onset on subcortical volume and cortical thickness in young adults.

PubMed

Lisdahl, Krista M; Tamm, Leanne; Epstein, Jeffery N; Jernigan, Terry; Molina, Brooke S G; Hinshaw, Stephen P; Swanson, James M; Newman, Erik; Kelly, Clare; Bjork, James M

2016-04-01

Both Attention Deficit Hyperactivity Disorder (ADHD) and chronic cannabis (CAN) use have been associated with brain structural abnormalities, although little is known about the effects of both in young adults. Participants included: those with a childhood diagnosis of ADHD who were CAN users (ADHD_CAN; n=37) and non-users (NU) (ADHD_NU; n=44) and a local normative comparison group (LNCG) who did (LNCG_CAN; n=18) and did not (LNCG_NU; n=21) use CAN regularly. Multiple regressions and MANCOVAs were used to examine the independent and interactive effects of a childhood ADHD diagnosis and CAN group status and age of onset (CUO) on subcortical volumes and cortical thickness. After controlling for age, gender, total brain volume, nicotine use, and past-year binge drinking, childhood ADHD diagnosis did not predict brain structure; however, persistence of ADHD was associated with smaller left precentral/postcentral cortical thickness. Compared to all non-users, CAN users had decreased cortical thickness in right hemisphere superior frontal sulcus, anterior cingulate, and isthmus of cingulate gyrus regions and left hemisphere superior frontal sulcus and precentral gyrus regions. Early cannabis use age of onset (CUO) in those with ADHD predicted greater right hemisphere superior frontal and postcentral cortical thickness. Young adults with persistent ADHD demonstrated brain structure abnormalities in regions underlying motor control, working memory and inhibitory control. Further, CAN use was linked with abnormal brain structure in regions with high concentrations of cannabinoid receptors. Additional large-scale longitudinal studies are needed to clarify how substance use impacts neurodevelopment in youth with and without ADHD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Impact of ADHD Persistence, Recent Cannabis Use, and Age of Regular Cannabis Use Onset on Subcortical Volume and Cortical Thickness in Young Adults

PubMed Central

Lisdahl, Krista M.; Tamm, Leanne; Epstein, Jeffery N.; Jernigan, Terry; Molina, Brooke S.G.; Hinshaw, Stephen P.; Swanson, James M.; Newman, Erik; Kelly, Clare; Bjork, James M.

2017-01-01

Background Both Attention Deficit Hyperactivity Disorder (ADHD) and chronic cannabis (CAN) use have been associated with brain structural abnormalities, although little is known about the effects of both in young adults. Methods Participants included: those with a childhood diagnosis of ADHD who were CAN users (ADHD_CAN; n=37) and non-users (NU) (ADHD_NU; n=44) and a local normative comparison group (LNCG) who did (LNCG_CAN; n=18) and did not (LNCG_NU; n=21) use CAN regularly. Multiple regressions and MANCOVAs were used to examine the independent and interactive effects of a childhood ADHD diagnosis and CAN group status and age of onset (CUO) on subcortical volumes and cortical thickness. Results After controlling for age, gender, total brain volume, nicotine use, and past-year binge drinking, childhood ADHD diagnosis did not predict brain structure; however, persistence of ADHD was associated with smaller left precentral/postcentral cortical thickness. Compared to all non-users, CAN users had decreased cortical thickness in right hemisphere superior frontal sulcus, anterior cingulate, and isthmus of cingulate gyrus regions and left hemisphere superior frontal sulcus and precentral gyrus regions. Early cannabis use age of onset (CUO) in those with ADHD predicted greater right hemisphere superior frontal and postcentral cortical thickness. Discussion Young adults with persistent ADHD demonstrated brain structure abnormalities in regions underlying motor control, working memory and inhibitory control. Further, CAN use was linked with abnormal brain structure in regions with high concentrations of cannabinoid receptors. Additional large-scale longitudinal studies are needed to clarify how substance use impacts neurodevelopment in youth with and without ADHD. PMID:26897585

Abnormal aortic arch morphology in Turner syndrome patients is a risk factor for hypertension.

PubMed

De Groote, Katya; Devos, Daniël; Van Herck, Koen; Demulier, Laurent; Buysse, Wesley; De Schepper, Jean; De Wolf, Daniël

2015-09-01

Hypertension in Turner syndrome (TS) is a multifactorial, highly prevalent and significant problem that warrants timely diagnosis and rigorous treatment. The objective of this study was to investigate the association between abnormal aortic arch morphology and hypertension in adult TS patients. This was a single centre retrospective study in 74 adult TS patients (age 29.41 ± 8.91 years) who underwent a routine cardiac MRI. Patients were assigned to the hypertensive group (N = 31) if blood pressure exceeded 140/90 mmHg and/or if they were treated with antihypertensive medication. Aortic arch morphology was evaluated on MRI images and initially assigned as normal (N = 54) or abnormal (N = 20), based on the curve of the transverse arch and the distance between the left common carotid-left subclavian artery. We additionally used a new more objective method to describe aortic arch abnormality in TS by determination of the relative position of the highest point of the transverse arch (AoHP). Logistic regression analysis showed that hypertension is significantly and independently associated with age, BMI and abnormal arch morphology, with a larger effect size for the new AoHP method than for the classical method. TS patients with hypertension and abnormal arch morphology more often had dilatation of the ascending aorta. There is a significant association between abnormal arch morphology and hypertension in TS patients, independent of age and BMI, and not related to other structural heart disease. We suggest that aortic arch morphology should be included in the risk stratification for hypertension in TS and propose a new quantitative method to express aortic arch morphology.

PHACE syndrome: new views on diagnostic criteria.

PubMed

Poetke, M; Frommeld, T; Berlien, H P

2002-12-01

The association of large facial hemangiomas with posterior fossa malformations and vascular anomalies has been termed the PHACE syndrome. It is characterized by the association of posterior fossa malformations, hemangiomas, arterial anomalies, coarctation of the aorta and other cardiac defects, and eye abnormalities. Since most articles focus on isolated case reports, an extended retrospective literature review of all reports of large hemangiomas with associated abnormalities of the central nervous system and other malformations was performed to examine the clinical features, and other not as yet reported associated anomalies. Reports were found on 59 patients with PHACE syndrome, to which we added ten cases of our own. The Dandy-Walker syndrome is the most common CNS abnormality reported in association with PHACE syndrome and was seen in 48 (81 %) patients. Arterial malformations were found in 13 (22 %) cases; only 11 patients (19 %) had structural arterial abnormalities without associated Dandy-Walker complex. As published, about one third of patients (31 %) had further ophthalmologic abnormalities, and cardiac anomalies, including coarctation of the aorta. Subglottic hemangiomas were seen in 4 (7 %) patients and ventral developmental defects also in 3 cases. In seven of 59 patients (12 %) with PHACE syndrome, intracranial hemangiomas were present. This study demonstrates that among other CNS abnormalities, special attention should be given to intracranial hemangiomas which seems to be a peculiar phenotype of PHACE syndrome. We therefore suggest that a sixth criterion should be added to the five minimal inclusion criteria for PHACE syndrome. The inclusion criteria would then be: arterial abnormalities or/and intracranial hemangiomas. On the basis of our experience with our patients and with those previously reported, we stress the importance of using contrast-enhanced imaging to detect intracranial lesions.

DTI-measured white matter abnormalities in adolescents with Conduct Disorder

PubMed Central

Haney-Caron, Emily; Caprihan, Arvind; Stevens, Michael C.

2013-01-01

Emerging research suggests that antisocial behavior in youth is linked to abnormal brain white matter microstructure, but the extent of such anatomical connectivity abnormalities remain largely untested because previous Conduct Disorder (CD) studies typically have selectively focused on specific frontotemporal tracts. This study aimed to replicate and extend previous frontotemporal diffusion tensor imaging (DTI) findings to determine whether noncomorbid CD adolescents have white matter microstructural abnormalities in major white matter tracts across the whole brain. Seventeen CD-diagnosed adolescents recruited from the community were compared to a group of 24 non-CD youth which did not differ in average age (12–18) or gender proportion. Tract-based spatial statistics (TBSS) fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) measurements were compared between groups using FSL nonparametric two-sample t test, clusterwise whole-brain corrected, p<.05. CD FA and AD deficits were widespread, but unrelated to gender, verbal ability, or CD age of onset. CD adolescents had significantly lower FA and AD values in frontal lobe and temporal lobe regions, including frontal lobe anterior/superior corona radiata, and inferior longitudinal and fronto-occpital fasciculi passing through the temporal lobe. The magnitude of several CD FA deficits was associated with number of CD symptoms. Because AD, but not RD, differed between study groups, abnormalities of axonal microstructure in CD rather than myelination are suggested. This study provides evidence that adolescent antisocial disorder is linked to abnormal white matter microstructure in more than just the uncinate fasciulcus as identified in previous DTI studies, or frontotemporal brain structures as suggested by functional neuroimaging studies. Instead, neurobiological risk specific to antisociality in adolescence is linked to microstructural abnormality in numerous long-range white matter connections among many diverse different brain regions. PMID:24139595

Use of magnetic resonance imaging in short stature: data from National Cooperative Growth Study (NCGS) Substudy 8.

PubMed

Kemp, Stephen F; Alter, Craig A; Dana, Ken; Baptista, Joyce; Blethen, Sandra L

2002-05-01

The primary use of magnetic resonance imaging (MRI) in the evaluation of children with short stature (SS) is to discover lesions in the central nervous system (CNS), particularly tumors that may require intervention. MRI has a secondary role in identifying structural abnormalities responsible for growth hormone deficiency (GHD). We examined data from the National Cooperative Growth Study (NCGS) Substudy 8 to determine how American physicians are using MRI in evaluating children with SS. Of the 21,738 short children enrolled in NCGS, 5% underwent MRI during their follow-up. Children who had GH stimulation testing were more likely to have had an MRI than those in whom no GH stimulation test was performed (19% vs 2%, p <0.0001). Moreover, children diagnosed with severe GHD (maximum GH <5 ng/ml) were more likely to have an abnormal finding on MRI. Of these patients, 27% demonstrated an abnormality as compared to 12% and 12.5% in patients with partial GHD and normal GH stimulation test results (>10 ng/ml), respectively. Abnormalities unrelated to the hypothalamus or pituitary represented 30% of these findings, while disorders in pituitary anatomy, including pituitary hypoplasia, pituitary stalk interruption, and ectopic posterior pituitary, represented an additional 30% of abnormal MRI examinations. CNS tumors comprised 23% of abnormal findings in these patients. We conclude that MRI provides significant value in the evaluation of children with SS, by identifying CNS tumors associated with growth failure as well as anatomical abnormalities of the pituitary. These findings are useful in confirming the diagnosis of GHD in children and identifying potential candidates for continued GH replacement in adulthood.

Prevalence and consequences of chromosomal abnormalities in Canadian commercial swine herds.

PubMed

Quach, Anh T; Revay, Tamas; Villagomez, Daniel A F; Macedo, Mariana P; Sullivan, Alison; Maignel, Laurence; Wyss, Stefanie; Sullivan, Brian; King, W Allan

2016-09-12

Structural chromosome abnormalities are well known as factors that reduce fertility rate in domestic pigs. According to large-scale national cytogenetic screening programs that are implemented in France, it is estimated that new chromosome abnormalities occur at a rate of 0.5 % in fertility-unproven boars. This work aimed at estimating the prevalence and consequences of chromosome abnormalities in commercial swine operations in Canada. We found pig carriers at a frequency of 1.64 % (12 out of 732 boars). Carrier pigs consistently showed lower fertility values. The total number of piglets born for litters from carrier boars was between 4 and 46 % lower than the herd average. Similarly, carrier boars produced litters with a total number of piglets born alive that was between 6 and 28 % lower than the herd average. A total of 12 new structural chromosome abnormalities were identified. Reproductive performance is significantly reduced in sires with chromosome abnormalities. The incidence of such abnormal sires appears relatively high in populations without routine cytogenetic screening such as observed for Canada in this study. Systematic cytogenetic screening of potential breeding boars would minimise the risk of carriers of chromosome aberrations entering artificial insemination centres. This would avoid the large negative effects on productivity for the commercial sow herds and reduce the risk of transmitting abnormalities to future generations in nucleus farms.

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

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

Walton, B.T.; Ho, C.H.; Ma, C.Y.

Morphological abnormalities including extra compound eyes, extra heads, and distally duplicated legs were generated in cricket embryos by treating eggs with single doses of either benz(g)isoquinoline-5,10-dione or benzo(h)quinoline-5,6-dione. Slight structural modifications of the molecules resulted in a loss of teratogenic activity, although embryotoxicity occurred. These potent insect teratogens can be used for analysis of developmental events during embryogenesis. 13 references, 4 figures, 1 table.

A Model for Predicting Cognitive and Emotional Health from Structural and Functional Neurocircuitry Following Traumatic Brain Injury

DTIC Science & Technology

2017-10-01

Neuroimaging 2006 Reviewer, Journal of Abnormal Psychology 2006 Reviewer, Psychopharmacology 2006 Reviewer, Developmental Science 2006 Reviewer...This study will address this problem by collecting measures of white matter integrity and concomitant neuropsychological status at five time points...hypothesize that structural white matter tract disintegrity will underlie abnormalities in functional connectivity, neurocognitive performance and

Development and experimental validation of computational methods to simulate abnormal thermal and structural environments

NASA Astrophysics Data System (ADS)

Moya, J. L.; Skocypec, R. D.; Thomas, R. K.

1993-09-01

Over the past 40 years, Sandia National Laboratories (SNL) has been actively engaged in research to improve the ability to accurately predict the response of engineered systems to abnormal thermal and structural environments. These engineered systems contain very hazardous materials. Assessing the degree of safety/risk afforded the public and environment by these engineered systems, therefore, is of upmost importance. The ability to accurately predict the response of these systems to accidents (to abnormal environments) is required to assess the degree of safety. Before the effect of the abnormal environment on these systems can be determined, it is necessary to ascertain the nature of the environment. Ascertaining the nature of the environment, in turn, requires the ability to physically characterize and numerically simulate the abnormal environment. Historically, SNL has demonstrated the level of safety provided by these engineered systems by either of two approaches: a purely regulatory approach, or by a probabilistic risk assessment (PRA). This paper will address the latter of the two approaches.

Is the coexistence of sustained ST-segment elevation and abnormal Q waves a risk factor for electrical storm in implanted cardioverter defibrillator patients with structural heart diseases?

PubMed

Furushima, Hiroshi; Chinushi, Masaomi; Iijima, Kenichi; Hasegawa, Kanae; Sato, Akinori; Izumi, Daisuke; Watanabe, Hiroshi; Aizawa, Yoshifusa

2012-05-01

The aim of this study was to determine whether or not the coexistence of sustained ST-segment elevation and abnormal Q waves (STe-Q) could be a risk factor for electrical storm (ES) in implanted cardioverter defibrillator (ICD) patients with structural heart diseases. In all, 156 consecutive patients received ICD therapy for secondary prevention of sudden cardiac death and/or sustained ventricular tachyarrhythmias were included. Electrical storm was defined as ≥3 separate episodes of ventricular tachycardia (VT) and/or ventricular fibrillation (VF) terminated by ICD therapies within 24 h. During a mean follow-up of 1825 ± 1188 days, 42 (26.9%) patients experienced ES, of whom 12 had coronary artery disease, 15 had idiopathic dilated cardiomyopathy, 6 had hypertrophic cardiomyopathy, 4 had arrhythmogenic right ventricular cardiomyopathy, 4 had cardiac sarcoidosis, and 1 had valvular heart disease. Sustained ST-segment elevation and abnormal Q waves in ≥2 leads on the 12-lead electrocardiography was observed in 33 (21%) patients. On the Kaplan-Meier analysis, patients with STe-Q had a markedly higher risk of ES than those without STe-Q (P< 0.0001). The multivariate Cox proportional hazards regression model indicated that STe-Q and left ventricular ejection fraction (LVEF) (<30%) were independent risk factors associated with the recurrence of VT/VF (STe-Q: HR 1.962, 95% CI 1.24-3.12, P= 0.004; LVEF: HR 1.860, 95% CI 1.20-2.89, P= 0.006), and STe-Q was an independent risk factor associated with ES (HR 4.955, 95% CI 2.69-9.13, P< 0.0001). Sustained ST-segment elevation and abnormal Q waves could be a risk factor of not only recurrent VT/VF but also ES in patients with structural heart diseases.

Predictors of electrocardiographic abnormalities in type 1 Diabetes: the Wisconsin Epidemiologic Study of Diabetic Retinopathy.

PubMed

O'Neal, Wesley T; Lee, Kristine E; Soliman, Elsayed Z; Klein, Ronald; Klein, Barbara E K

2017-03-01

To determine the incidence and determinants of developing abnormalities on the 12-lead electrocardiogram (ECG) in persons with type 1 diabetes. We evaluated the distribution of ECG abnormalities and risk factors for developing new abnormalities in 266 (mean age = 44 years ± 9.0; 50 % female) people with type 1 diabetes from the Wisconsin Epidemiologic Study of Diabetic Retinopathy. This analysis included participants with complete ECG data from study visit 5 (2000-2001) and follow-up ECGs from study visit 7 (2012-2014). ECG abnormalities were classified as major and minor according to Minnesota Code Classification. At baseline, 94 (35 %) participants had at least one ECG abnormality, including 13 major ECG abnormalities. At follow-up, 117 (44 %) participants developed at least one new ECG abnormality, including 35 new major ECG abnormalities. In a multivariable logistic regression model, older age (per 5-year increase: OR = 1.31, 95 % CI = 1.08, 1.60) was associated with the development of at least one new ECG abnormality, while serum HDL cholesterol (per 10-unit increase: OR = 0.98, 95 % CI = 0.96, 1.00) was protective against developing new ECG abnormalities. The development of new ECG abnormalities is common in type 1 diabetes. Older age and HDL cholesterol are independent risk factors for developing new ECG abnormalities. Further research is needed to determine whether routine ECG screening is indicated in people with type 1 diabetes to identify those with underlying subclinical coronary heart disease.

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

PubMed

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

2012-03-01

We assessed the relationship between brain structure and function in 10 individuals with specific language impairment (SLI), compared to six unaffected siblings, and 16 unrelated control participants with typical language. Voxel-based morphometry indicated that grey matter in the SLI group, relative to controls, was increased in the left inferior frontal cortex and decreased in the right caudate nucleus and superior temporal cortex bilaterally. The unaffected siblings also showed reduced grey matter in the caudate nucleus relative to controls. In an auditory covert naming task, the SLI group showed reduced activation in the left inferior frontal cortex, right putamen, and in the superior temporal cortex bilaterally. Despite spatially coincident structural and functional abnormalities in frontal and temporal areas, the relationships between structure and function in these regions were different. These findings suggest multiple structural and functional abnormalities in SLI that are differently associated with receptive and expressive language processing. Copyright © 2011 Elsevier Inc. All rights reserved.

Abnormal uterine bleeding unrelated to structural uterine abnormalities: management in the perimenopausal period.

PubMed

Sabbioni, Lorenzo; Zanetti, Isabella; Orlandini, Cinzia; Petraglia, Felice; Luisi, Stefano

2017-02-01

Abnormal uterine bleeding (AUB) is one of the commonest health problems encountered by women and a frequent phenomenon during menopausal transition. The clinical management of AUB must follow a standardized classification system to obtain the better diagnostic pathway and the optimal therapy. The PALM-COEIN classification system has been approved by the International Federation of Gynecology and Obstetrics (FIGO); it recognizes structural causes of AUB, which can be measured visually with imaging techniques or histopathology, and non-structural entities such as coagulopathies, ovulatory dysfunctions, endometrial and iatrogenic causes and disorders not yet classified. In this review we aim to evaluate the management of nonstructural causes of AUB during the menopausal transition, when commonly women experience changes in menstrual bleeding patterns and unexpected bleedings which affect their quality of life.

A Syndromic Neurodevelopmental Disorder Caused by De Novo Variants in EBF3.

PubMed

Chao, Hsiao-Tuan; Davids, Mariska; Burke, Elizabeth; Pappas, John G; Rosenfeld, Jill A; McCarty, Alexandra J; Davis, Taylor; Wolfe, Lynne; Toro, Camilo; Tifft, Cynthia; Xia, Fan; Stong, Nicholas; Johnson, Travis K; Warr, Coral G; Yamamoto, Shinya; Adams, David R; Markello, Thomas C; Gahl, William A; Bellen, Hugo J; Wangler, Michael F; Malicdan, May Christine V

2017-01-05

Early B cell factor 3 (EBF3) is a member of the highly evolutionarily conserved Collier/Olf/EBF (COE) family of transcription factors. Prior studies on invertebrate and vertebrate animals have shown that EBF3 homologs are essential for survival and that loss-of-function mutations are associated with a range of nervous system developmental defects, including perturbation of neuronal development and migration. Interestingly, aristaless-related homeobox (ARX), a homeobox-containing transcription factor critical for the regulation of nervous system development, transcriptionally represses EBF3 expression. However, human neurodevelopmental disorders related to EBF3 have not been reported. Here, we describe three individuals who are affected by global developmental delay, intellectual disability, and expressive speech disorder and carry de novo variants in EBF3. Associated features seen in these individuals include congenital hypotonia, structural CNS malformations, ataxia, and genitourinary abnormalities. The de novo variants affect a single conserved residue in a zinc finger motif crucial for DNA binding and are deleterious in a fly model. Our findings indicate that mutations in EBF3 cause a genetic neurodevelopmental syndrome and suggest that loss of EBF3 function might mediate a subset of neurologic phenotypes shared by ARX-related disorders, including intellectual disability, abnormal genitalia, and structural CNS malformations. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Diffusion tensor imaging study of pediatric patients with congenital hydrocephalus: 1-year postsurgical outcomes.

PubMed

Mangano, Francesco T; Altaye, Mekibib; McKinstry, Robert C; Shimony, Joshua S; Powell, Stephanie K; Phillips, Jannel M; Barnard, Holly; Limbrick, David D; Holland, Scott K; Jones, Blaise V; Dodd, Jonathan; Simpson, Sarah; Mercer, Deanna; Rajagopal, Akila; Bidwell, Sarah; Yuan, Weihong

2016-09-01

OBJECTIVE The purpose of this study was to investigate white matter (WM) structural abnormalities using diffusion tensor imaging (DTI) in children with hydrocephalus before CSF diversionary surgery (including ventriculoperitoneal shunt insertion and endoscopic third ventriculostomy) and during the course of recovery after surgery in association with neuropsychological and behavioral outcome. METHODS This prospective study included 54 pediatric patients with congenital hydrocephalus (21 female, 33 male; age range 0.03-194.5 months) who underwent surgery and 64 normal controls (30 female, 34 male; age range 0.30-197.75 months). DTI and neurodevelopmental outcome data were collected once in the control group and 3 times (preoperatively and at 3 and 12 months postoperatively) in the patients with hydrocephalus. DTI measures, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) values were extracted from the genu of the corpus callosum (gCC) and the posterior limb of internal capsule (PLIC). Group analysis was performed first cross-sectionally to quantify DTI abnormalities at 3 time points by comparing the data obtained in the hydrocephalus group for each of the 3 time points to data obtained in the controls. Longitudinal comparisons were conducted pairwise between different time points in patients whose data were acquired at multiple time points. Neurodevelopmental data were collected and analyzed using the Adaptive Behavior Assessment System, Second Edition, and the Bayley Scales of Infant Development, Third Edition. Correlation analyses were performed between DTI and behavioral measures. RESULTS Significant DTI abnormalities were found in the hydrocephalus patients in both the gCC (lower FA and higher MD, AD, and RD) and the PLIC (higher FA, lower AD and RD) before surgery. The DTI measures in the gCC remained mostly abnormal at 3 and 12 months after surgery. The DTI abnormalities in the PLIC were significant in FA and AD at 3 months after surgery but did not persist when tested at 12 months after surgery. Significant longitudinal DTI changes in the patients with hydrocephalus were found in the gCC when findings at 3 and 12 months after surgery were compared. In the PLIC, trend-level longitudinal changes were observed between preoperative findings and 3-month postoperative findings, as well as between 3- and 12-month postoperative findings. Significant correlation between DTI and developmental outcome was found at all 3 time points. Notably, a significant correlation was found between DTI in the PLIC at 3 months after surgery and developmental outcome at 12 months after surgery. CONCLUSIONS The data showed significant WM abnormality based on DTI in both the gCC and the PLIC in patients with congenital hydrocephalus before surgery, and the abnormalities persisted in both the gCC and the PLIC at 3 months after surgery. The DTI values remained significantly abnormal in the gCC at 12 months after surgery. Longitudinal analysis showed signs of recovery in both WM structures between different time points. Combined with the significant correlation found between DTI and neuropsychological measures, the findings of this study suggest that DTI can serve as a sensitive imaging biomarker for underlying neuroanatomical changes and postsurgical developmental outcome and even as a predictor for future outcomes.

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.

Aircraft Abnormal Conditions Detection, Identification, and Evaluation Using Innate and Adaptive Immune Systems Interaction

NASA Astrophysics Data System (ADS)

Al Azzawi, Dia

Abnormal flight conditions play a major role in aircraft accidents frequently causing loss of control. To ensure aircraft operation safety in all situations, intelligent system monitoring and adaptation must rely on accurately detecting the presence of abnormal conditions as soon as they take place, identifying their root cause(s), estimating their nature and severity, and predicting their impact on the flight envelope. Due to the complexity and multidimensionality of the aircraft system under abnormal conditions, these requirements are extremely difficult to satisfy using existing analytical and/or statistical approaches. Moreover, current methodologies have addressed only isolated classes of abnormal conditions and a reduced number of aircraft dynamic parameters within a limited region of the flight envelope. This research effort aims at developing an integrated and comprehensive framework for the aircraft abnormal conditions detection, identification, and evaluation based on the artificial immune systems paradigm, which has the capability to address the complexity and multidimensionality issues related to aircraft systems. Within the proposed framework, a novel algorithm was developed for the abnormal conditions detection problem and extended to the abnormal conditions identification and evaluation. The algorithm and its extensions were inspired from the functionality of the biological dendritic cells (an important part of the innate immune system) and their interaction with the different components of the adaptive immune system. Immunity-based methodologies for re-assessing the flight envelope at post-failure and predicting the impact of the abnormal conditions on the performance and handling qualities are also proposed and investigated in this study. The generality of the approach makes it applicable to any system. Data for artificial immune system development were collected from flight tests of a supersonic research aircraft within a motion-based flight simulator. The abnormal conditions considered in this work include locked actuators (stabilator, aileron, rudder, and throttle), structural damage of the wing, horizontal tail, and vertical tail, malfunctioning sensors, and reduced engine effectiveness. The results of applying the proposed approach to this wide range of abnormal conditions show its high capability in detecting the abnormal conditions with zero false alarms and very high detection rates, correctly identifying the failed subsystem and evaluating the type and severity of the failure. The results also reveal that the post-failure flight envelope can be reasonably predicted within this framework.

Structural Brain Abnormalities in Successfully Treated HIV Infection: Associations With Disease and Cerebrospinal Fluid Biomarkers.

PubMed

van Zoest, Rosan A; Underwood, Jonathan; De Francesco, Davide; Sabin, Caroline A; Cole, James H; Wit, Ferdinand W; Caan, Matthan W A; Kootstra, Neeltje A; Fuchs, Dietmar; Zetterberg, Henrik; Majoie, Charles B L M; Portegies, Peter; Winston, Alan; Sharp, David J; Gisslén, Magnus; Reiss, Peter

2017-12-27

Brain structural abnormalities have been reported in persons living with human immunodeficiency virus (HIV; PLWH) who are receiving suppressive combination antiretroviral therapy (cART), but their pathophysiology remains unclear. We investigated factors associated with brain tissue volumes and white matter microstructure (fractional anisotropy) in 134 PLWH receiving suppressive cART and 79 comparable HIV-negative controls, aged ≥45 years, from the Comorbidity in Relation to AIDS cohort, using multimodal neuroimaging and cerebrospinal fluid biomarkers. Compared with controls, PLWH had lower gray matter volumes (-13.7 mL; 95% confidence interval, -25.1 to -2.2) and fractional anisotropy (-0.0073; 95% confidence interval, -.012 to -.0024), with the largest differences observed in those with prior clinical AIDS. Hypertension and the soluble CD14 concentration in cerebrospinal fluid were associated with lower fractional anisotropy. These associations were independent of HIV serostatus (Pinteraction = .32 and Pinteraction = .59, respectively) and did not explain the greater abnormalities in brain structure in relation to HIV infection. The presence of lower gray matter volumes and more white matter microstructural abnormalities in well-treated PLWH partly reflect a combination of historical effects of AIDS, as well as the more general influence of systemic factors, such as hypertension and ongoing neuroinflammation. Additional mechanisms explaining the accentuation of brain structure abnormalities in treated HIV infection remain to be identified. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Ablation of Mrds1/Ofcc1 Induces Hyper-γ-Glutamyl Transpeptidasemia without Abnormal Head Development and Schizophrenia-Relevant Behaviors in Mice

PubMed Central

Ohnishi, Tetsuo; Yamada, Kazuo; Watanabe, Akiko; Ohba, Hisako; Sakaguchi, Toru; Honma, Yota; Iwayama, Yoshimi; Toyota, Tomoko; Maekawa, Motoko; Watanabe, Kazutada; Detera-Wadleigh, Sevilla D.; Wakana, Shigeharu; Yoshikawa, Takeo

2011-01-01

Mutations in the Opo gene result in eye malformation in medaka fish. The human ortholog of this gene, MRDS1/OFCC1, is a potentially causal gene for orofacial cleft, as well as a susceptibility gene for schizophrenia, a devastating mental illness. Based on this evidence, we hypothesized that this gene could perform crucial functions in the development of head and brain structures in vertebrates. To test this hypothesis, we created Mrds1/Ofcc1-null mice. Mice were examined thoroughly using an abnormality screening system referred to as “the Japan Mouse Clinic”. No malformations of the head structure, eye or other parts of the body were apparent in these knockout mice. However, the mutant mice showed a marked increase in serum γ-glutamyl transpeptidase (GGT), a marker for liver damage, but no abnormalities in other liver-related measurements. We also performed a family-based association study on the gene in schizophrenia samples of Japanese origin. We found five single nucleotide polymorphisms (SNPs) located across the gene that showed significant transmission distortion, supporting a prior report of association in a Caucasian cohort. However, the knockout mice showed no behavioral phenotypes relevant to schizophrenia. In conclusion, disruption of the Mrds1/Ofcc1 gene elicits asymptomatic hyper-γ-glutamyl-transpeptidasemia in mice. However, there were no phenotypes to support a role for the gene in the development of eye and craniofacial structures in vertebrates. These results prompt further examination of the gene, including its putative contribution to hyper-γ-glutamyl transpeptidasemia and schizophrenia. PMID:22242126

Brain Structure and Function Associated with a History of Sport Concussion: A Multi-Modal Magnetic Resonance Imaging Study.

PubMed

Churchill, Nathan; Hutchison, Michael; Richards, Doug; Leung, General; Graham, Simon; Schweizer, Tom A

2017-02-15

There is growing concern about the potential long-term consequences of sport concussion for young, currently active athletes. However, there remains limited information about brain abnormalities associated with a history of concussion and how they relate to clinical factors. In this study, advanced MRI was used to comprehensively describe abnormalities in brain structure and function associated with a history of sport concussion. Forty-three athletes (21 male, 22 female) were recruited from interuniversity teams at the beginning of the season, including 21 with a history of concussion and 22 without prior concussion; both groups also contained a balanced sample of contact and noncontact sports. Multi-modal MRI was used to evaluate abnormalities in brain structure and function. Athletes with a history of concussion showed frontal decreases in brain volume and blood flow. However, they also demonstrated increased posterior cortical volume and elevated markers of white matter microstructure. A greater number of prior concussions was associated with more extensive decreases in cerebral blood flow and insular volume, whereas recovery time from most recent concussion was correlated with reduced frontotemporal volume. White matter showed limited correlations with clinical factors, predominantly in the anterior corona radiata. This study provides the first evidence of the long-term effects of concussion on gray matter volume, blood flow, and white matter microstructure within a single athlete cohort. This was examined for a mixture of male and female athletes in both contact and noncontact sports, demonstrating the relevance of these findings for the overall sporting community.

Optic nerve head component responses of the multifocal electroretinogram in MS.

PubMed

Frohman, Teresa C; Beh, Shin Chien; Saidha, Shiv; Schnurman, Zane; Conger, Darrel; Conger, Amy; Ratchford, John N; Lopez, Carmen; Galetta, Steven L; Calabresi, Peter A; Balcer, Laura J; Green, Ari J; Frohman, Elliot M

2013-08-06

To employ a novel stimulation paradigm in order to elicit multifocal electroretinography (mfERG)-induced optic nerve head component (ONHC) responses, believed to be contingent upon the transformation in electrical transmission properties of retinal ganglion cell axons from membrane to saltatory conduction mechanisms, as they traverse the lamina cribrosa and obtain oligodendrocyte myelin. We further sought to characterize abnormalities in ONHC responses in eyes from patients with multiple sclerosis (MS). In 10 normal subjects and 7 patients with MS (including eyes with and without a history of acute optic neuritis), we utilized a novel mfERG stimulation paradigm that included interleaved global flashes in order to elicit the ONHC responses from 103 retinal patches of pattern-reversal stimulation. The number of abnormal or absent ONHC responses was significantly increased in MS patient eyes compared to normal subject eyes (p < 0.001, by general estimating equation modeling, and accounting for age and within-subject, intereye correlations). Studying the relationship between ONHC abnormalities and alterations in validated structural and functional measures of the visual system may facilitate the ability to dissect and characterize the pathobiological mechanisms that contribute to tissue damage in MS, and may have utility to detect and monitor neuroprotective or restorative effects of novel therapies.

Auditory hedonic phenotypes in dementia: A behavioural and neuroanatomical analysis

PubMed Central

Fletcher, Phillip D.; Downey, Laura E.; Golden, Hannah L.; Clark, Camilla N.; Slattery, Catherine F.; Paterson, Ross W.; Schott, Jonathan M.; Rohrer, Jonathan D.; Rossor, Martin N.; Warren, Jason D.

2015-01-01

Patients with dementia may exhibit abnormally altered liking for environmental sounds and music but such altered auditory hedonic responses have not been studied systematically. Here we addressed this issue in a cohort of 73 patients representing major canonical dementia syndromes (behavioural variant frontotemporal dementia (bvFTD), semantic dementia (SD), progressive nonfluent aphasia (PNFA) amnestic Alzheimer's disease (AD)) using a semi-structured caregiver behavioural questionnaire and voxel-based morphometry (VBM) of patients' brain MR images. Behavioural responses signalling abnormal aversion to environmental sounds, aversion to music or heightened pleasure in music (‘musicophilia’) occurred in around half of the cohort but showed clear syndromic and genetic segregation, occurring in most patients with bvFTD but infrequently in PNFA and more commonly in association with MAPT than C9orf72 mutations. Aversion to sounds was the exclusive auditory phenotype in AD whereas more complex phenotypes including musicophilia were common in bvFTD and SD. Auditory hedonic alterations correlated with grey matter loss in a common, distributed, right-lateralised network including antero-mesial temporal lobe, insula, anterior cingulate and nucleus accumbens. Our findings suggest that abnormalities of auditory hedonic processing are a significant issue in common dementias. Sounds may constitute a novel probe of brain mechanisms for emotional salience coding that are targeted by neurodegenerative disease. PMID:25929717

High Incidence of Progressive Postnatal Cerebellar Enlargement in Costello Syndrome: Brain Overgrowth Associated with HRAS Mutations as the Likely Cause of Structural Brain and Spinal Cord Abnormalities

PubMed Central

Gripp, Karen W.; Hopkins, Elisabeth; Doyle, Daniel; Dobyns, William B.

2010-01-01

Costello syndrome is a rasopathy caused by germline mutations in the proto-oncogene HRAS. Its presentation includes failure-to-thrive with macrocephaly, characteristic facial features, hypertrophic cardiomyopathy, papillomata, malignant tumors, and cognitive impairment. In a systematic review we found absolute or relative macrocephaly (100%), ventriculomegaly (50%), and other abnormalities on brain and spinal cord imaging studies in 27/28 individuals. Posterior fossa crowding with cerebellar tonsillar herniation (CBTH) was noted in 27/28 (96%), and in 10/17 (59%) with serial studies posterior fossa crowding progressed. Sequelae of posterior fossa crowding and CBTH included hydrocephalus requiring shunt or ventriculostomy (25%), Chiari 1 malformation (32%) and syrinx formation (25%). Our data reveal macrocephaly with progressive frontal bossing and CBTH, documenting an ongoing process rather than a static congenital anomaly. Comparison of images obtained in young infants to subsequent studies demonstrated postnatal development of posterior fossa crowding. This process of evolving megalencephaly and cerebellar enlargement is in keeping with mouse model data, delineating abnormal genesis of neurons and glia, resulting in an increased number of astrocytes and enlarged brain volume. In Costello syndrome and macrocephaly-capillary malformation syndrome disproportionate brain growth is the main factor resulting in postnatal CBTH and Chiari 1 malformation. PMID:20425820

Aberrant Global and Regional Topological Organization of the Fractional Anisotropy-weighted Brain Structural Networks in Major Depressive Disorder

PubMed Central

Chen, Jian-Huai; Yao, Zhi-Jian; Qin, Jiao-Long; Yan, Rui; Hua, Ling-Ling; Lu, Qing

2016-01-01

Background: Most previous neuroimaging studies have focused on the structural and functional abnormalities of local brain regions in major depressive disorder (MDD). Moreover, the exactly topological organization of networks underlying MDD remains unclear. This study examined the aberrant global and regional topological patterns of the brain white matter networks in MDD patients. Methods: The diffusion tensor imaging data were obtained from 27 patients with MDD and 40 healthy controls. The brain fractional anisotropy-weighted structural networks were constructed, and the global network and regional nodal metrics of the networks were explored by the complex network theory. Results: Compared with the healthy controls, the brain structural network of MDD patients showed an intact small-world topology, but significantly abnormal global network topological organization and regional nodal characteristic of the network in MDD were found. Our findings also indicated that the brain structural networks in MDD patients become a less strongly integrated network with a reduced central role of some key brain regions. Conclusions: All these resulted in a less optimal topological organization of networks underlying MDD patients, including an impaired capability of local information processing, reduced centrality of some brain regions and limited capacity to integrate information across different regions. Thus, these global network and regional node-level aberrations might contribute to understanding the pathogenesis of MDD from the view of the brain network. PMID:26960371

Cardiac structure and function in relation to cardiovascular risk factors in Chinese

PubMed Central

2012-01-01

Background Cardiac structure and function are well-studied in Western countries. However, epidemiological data is still scarce in China. Methods Our study was conducted in the framework of cardiovascular health examinations for the current and retired employees of a factory and their family members. According to the American Society of Echocardiography recommendations, we performed echocardiography to evaluate cardiac structure and function, including left atrial volume, left ventricular hypertrophy and diastolic dysfunction. Results The 843 participants (43.0 years) included 288 (34.2%) women, and 191 (22.7%) hypertensive patients, of whom 82 (42.9%) took antihypertensive drugs. The prevalence of left atrial enlargement, left ventricular hypertrophy and concentric remodeling was 2.4%, 5.0% and 12.7%, respectively. The prevalence of mild and moderate-to-severe left ventricular diastolic dysfunction was 14.2% and 3.3%, respectively. The prevalence of these cardiac abnormalities significantly (P ≤ 0.002) increased with age, except for the moderate-to-severe left ventricular diastolic dysfunction. After adjustment for age, gender, body height and body weight, left atrial enlargement was associated with plasma glucose (P = 0.009), and left ventricular hypertrophy and diastolic dysfunction were significantly associated with systolic and diastolic blood pressure (P ≤ 0.03), respectively. Conclusions The prevalence of cardiac structural and functional abnormalities increased with age in this Chinese population. Current drinking and plasma glucose had an impact on left atrial enlargement, whereas systolic and diastolic blood pressures were major correlates for left ventricular hypertrophy and diastolic dysfunction, respectively. PMID:23035836

Inflammation and premature aging in advanced chronic kidney disease.

PubMed

Kooman, Jeroen P; Dekker, Marijke J; Usvyat, Len A; Kotanko, Peter; van der Sande, Frank M; Schalkwijk, Casper G; Shiels, Paul G; Stenvinkel, Peter

2017-10-01

Systemic inflammation in end-stage renal disease is an established risk factor for mortality and a catalyst for other complications, which are related to a premature aging phenotype, including muscle wasting, vascular calcification, and other forms of premature vascular disease, depression, osteoporosis, and frailty. Uremic inflammation is also mechanistically related to mechanisms involved in the aging process, such as telomere shortening, mitochondrial dysfunction, and altered nutrient sensing, which can have a direct effect on cellular and tissue function. In addition to uremia-specific causes, such as abnormalities in the phosphate-Klotho axis, there are remarkable similarities between the pathophysiology of uremic inflammation and so-called "inflammaging" in the general population. Potentially relevant, but still somewhat unexplored in this respect, are abnormal or misplaced protein structures, as well as abnormalities in tissue homeostasis, which evoke danger signals through damage-associated molecular patterns, as well as the senescence-associated secretory phenotype. Systemic inflammation, in combination with the loss of kidney function, can impair the resilience of the body to external and internal stressors by reduced functional and structural tissue reserves, and by impairing normal organ crosstalk, thus providing an explanation for the greatly increased risk of homeostatic breakdown in this population. In this review, the relationship between uremic inflammation and a premature aging phenotype, as well as potential causes and consequences, are discussed. Copyright © 2017 the American Physiological Society.

The Non-Peptide Vasopressin V1b Receptor Antagonist, SSR149415, Ameliorates Spermatogenesis Function in a Mouse Model of Chronic Social Defeat Stress.

PubMed

Wang, Bin; Zhou, Jian; Zhuang, Yan-Yan; Wang, Liang-Liang; Pu, Jin-Xian; Huang, Yu-Hua; Xia, Fei; Lv, Jin-Xing

2017-11-01

To determine the effects of SSR149415 on testis and spermatogenesis in male mice subjected to chronic social defeat stress, C57BL/6 male mice were divided into two groups: Control and Stress. Then Stress group was subdivided into four subgroups administered water, SSR149415 (1 mg/kg/day), SSR149415 (10 mg/kg/day), SSR149415 (30 mg/kg/day), respectively. The behavioral alterations revealed by social interaction test and open field test were measured. The physical indices, including body weight and gonad weight (testis and epididymis) as well as testis/body weight and cauda epididymis/body weight were detected. Serum hormones, including testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were determined. Sperm count and abnormality as well as testicular histology structure were assessed. The germ cells apoptosis were also evaluated. Chronic social defeat stress-induced behavioral abnormality, as well as gonad atrophy (testis and epididymis) was significantly alleviated in stressed male mice exposed to SSR149415. Regressed serum testosterone levels and elevated serum FSH and LH levels exhibited by stressed male mice were observably reversed following SSR149415 administration. Chronic social defeat stress-induced damage in testicular histology structure and semen quality were also improved after SSR149415 administration. In addition, SSR149415 significantly reversed chronic social defeat stress-induced germ cells apoptosis. Overall, we provide clear evidence indicating the amelioration of chronic social defeat stress-induced behavioral abnormality and testicular dysfunction via SSR149415, promoting the development of drug-directed therapy against this disease. J. Cell. Biochem. 118: 3891-3898, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

IFT25, an intraflagellar transporter protein dispensable for ciliogenesis in somatic cells, is essential for sperm flagella formation.

PubMed

Liu, Hong; Li, Wei; Zhang, Yong; Zhang, Zhengang; Shang, Xuejun; Zhang, Ling; Zhang, Shiyang; Li, Yanwei; Somoza, Andres V; Delpi, Brandon; Gerton, George L; Foster, James A; Hess, Rex A; Pazour, Gregory J; Zhang, Zhibing

2017-05-01

Intraflagellar transport (IFT) is a conserved mechanism essential for the assembly and maintenance of most eukaryotic cilia and flagella. However, IFT25, a component of the IFT complex, is not required for the formation of cilia in somatic tissues. In mice, the gene is highly expressed in the testis, and its expression is upregulated during the final phase when sperm flagella are formed. To investigate the role of IFT25 in sperm flagella formation, the gene was specifically disrupted in male germ cells. All homozygous knockout mice survived to adulthood and did not show any gross abnormalities. However, all homozygous knockout males were completely infertile. Sperm numbers were reduced and these sperm were completely immotile. Multiple morphological abnormalities were observed in sperm, including round heads, short and bent tails, with some tails showing branched flagella and others with frequent abnormal thicknesses, as well as swollen tips of the tail. Transmission electron microscopy revealed that flagellar accessory structures, including the fibrous sheath and outer dense fibers, were disorganized, and most sperm had also lost the "9+2" microtubule structure. In the testis, IFT25 forms a complex with other IFT proteins. In Ift25 knockout testes, IFT27, an IFT25 binding partner, was missing, and IFT20 and IFT81 levels were also reduced. Our findings suggest that IFT25, although not necessary for the formation of cilia in somatic cells, is indispensable for sperm flagellum formation and male fertility in mice. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please journals.permissions@oup.com.

The Roles of Glutathione Peroxidases during Embryo Development

PubMed Central

Ufer, Christoph; Wang, Chi Chiu

2011-01-01

Embryo development relies on the complex interplay of the basic cellular processes including proliferation, differentiation, and apoptotic cell death. Precise regulation of these events is the basis for the establishment of embryonic structures and the organ development. Beginning with fertilization of the oocyte until delivery the developing embryo encounters changing environmental conditions such as varying levels of oxygen, which can give rise to reactive oxygen species (ROS). These challenges are met by the embryo with metabolic adaptations and by an array of anti-oxidative mechanisms. ROS can be deleterious by modifying biological molecules including lipids, proteins, and nucleic acids and may induce abnormal development or even embryonic lethality. On the other hand ROS are vital players of various signaling cascades that affect the balance between cell growth, differentiation, and death. An imbalance or dysregulation of these biological processes may generate cells with abnormal growth and is therefore potentially teratogenic and tumorigenic. Thus, a precise balance between processes generating ROS and those decomposing ROS is critical for normal embryo development. One tier of the cellular protective system against ROS constitutes the family of selenium-dependent glutathione peroxidases (GPx). These enzymes reduce hydroperoxides to the corresponding alcohols at the expense of reduced glutathione. Of special interest within this protein family is the moonlighting enzyme glutathione peroxidase 4 (Gpx4). This enzyme is a scavenger of lipophilic hydroperoxides on one hand, but on the other hand can be transformed into an enzymatically inactive cellular structural component. GPx4 deficiency – in contrast to all other GPx family members – leads to abnormal embryo development and finally produces a lethal phenotype in mice. This review is aimed at summarizing the current knowledge on GPx isoforms during embryo development and tumor development with an emphasis on GPx4. PMID:21847368

The Roles of Glutathione Peroxidases during Embryo Development.

PubMed

Ufer, Christoph; Wang, Chi Chiu

2011-01-01

Embryo development relies on the complex interplay of the basic cellular processes including proliferation, differentiation, and apoptotic cell death. Precise regulation of these events is the basis for the establishment of embryonic structures and the organ development. Beginning with fertilization of the oocyte until delivery the developing embryo encounters changing environmental conditions such as varying levels of oxygen, which can give rise to reactive oxygen species (ROS). These challenges are met by the embryo with metabolic adaptations and by an array of anti-oxidative mechanisms. ROS can be deleterious by modifying biological molecules including lipids, proteins, and nucleic acids and may induce abnormal development or even embryonic lethality. On the other hand ROS are vital players of various signaling cascades that affect the balance between cell growth, differentiation, and death. An imbalance or dysregulation of these biological processes may generate cells with abnormal growth and is therefore potentially teratogenic and tumorigenic. Thus, a precise balance between processes generating ROS and those decomposing ROS is critical for normal embryo development. One tier of the cellular protective system against ROS constitutes the family of selenium-dependent glutathione peroxidases (GPx). These enzymes reduce hydroperoxides to the corresponding alcohols at the expense of reduced glutathione. Of special interest within this protein family is the moonlighting enzyme glutathione peroxidase 4 (Gpx4). This enzyme is a scavenger of lipophilic hydroperoxides on one hand, but on the other hand can be transformed into an enzymatically inactive cellular structural component. GPx4 deficiency - in contrast to all other GPx family members - leads to abnormal embryo development and finally produces a lethal phenotype in mice. This review is aimed at summarizing the current knowledge on GPx isoforms during embryo development and tumor development with an emphasis on GPx4.

Expanding the SHOC2 mutation associated phenotype of Noonan syndrome with loose anagen hair: structural brain anomalies and myelofibrosis.

PubMed

Gripp, Karen W; Zand, Dina J; Demmer, Laurie; Anderson, Carol E; Dobyns, William B; Zackai, Elaine H; Denenberg, Elizabeth; Jenny, Kim; Stabley, Deborah L; Sol-Church, Katia

2013-10-01

Noonan syndrome is a heterogenous rasopathy typically presenting with short stature, characteristic facial features, cardiac abnormalities including pulmonic valve stenosis, ASD and hypertrophic cardiomyopathy (HCM), cryptorchidism, ectodermal abnormalities, and learning differences. The phenotype is variable, and limited genotype phenotype correlation exists with SOS1 mutations often associated with normal cognition and stature, RAF1 mutations entailing a high HCM risk, and certain PTPN11 mutations predisposing to juvenile myelomonocytic leukemia. The recently identified SHOC2 mutation (p.Ser2Gly) causes Noonan syndrome with loose anagen hair. We report five patients with this mutation. All had skin hyperpigmentation, sparse light colored hair, increased fine wrinkles, ligamentous laxity, developmental delay, and 4/4 had a structural cardiac anomaly. Hypotonia and macrocephaly occurred in 4/5 (80%); 3/5 (60%) had polyhydramnios, increased birth weight or required use of a feeding tube. Distinctive brain abnormalities included relative megalencephaly and enlarged subarachnoid spaces suggestive of benign external hydrocephalus, and a relatively small posterior fossa as indicated by a vertical tentorium. The combination of a large brain with a small posterior fossa likely resulted in the high rate of cerebellar tonsillar ectopia (3/4; 75%). Periventricular nodular heterotopia was seen in one patient with a thick and dysplastic corpus callosum. We report on the first hematologic neoplasm, myelofibrosis, in a 2-year-old patient with SHOC2 mutation. Myelofibrosis is exceedingly rare in children and young adults. The absence of a somatic JAK2 mutation, seen in the majority of patients with myelofibrosis, is noteworthy as it suggests that germline or somatic SHOC2 mutations are causally involved in myelofibrosis. Copyright © 2013 Wiley Periodicals, Inc.

Sequencing of a Patient with Balanced Chromosome Abnormalities and Neurodevelopmental Disease Identifies Disruption of Multiple High Risk Loci by Structural Variation

PubMed Central

Blake, Jonathon; Riddell, Andrew; Theiss, Susanne; Gonzalez, Alexis Perez; Haase, Bettina; Jauch, Anna; Janssen, Johannes W. G.; Ibberson, David; Pavlinic, Dinko; Moog, Ute; Benes, Vladimir; Runz, Heiko

2014-01-01

Balanced chromosome abnormalities (BCAs) occur at a high frequency in healthy and diseased individuals, but cost-efficient strategies to identify BCAs and evaluate whether they contribute to a phenotype have not yet become widespread. Here we apply genome-wide mate-pair library sequencing to characterize structural variation in a patient with unclear neurodevelopmental disease (NDD) and complex de novo BCAs at the karyotype level. Nucleotide-level characterization of the clinically described BCA breakpoints revealed disruption of at least three NDD candidate genes (LINC00299, NUP205, PSMD14) that gave rise to abnormal mRNAs and could be assumed as disease-causing. However, unbiased genome-wide analysis of the sequencing data for cryptic structural variation was key to reveal an additional submicroscopic inversion that truncates the schizophrenia- and bipolar disorder-associated brain transcription factor ZNF804A as an equally likely NDD-driving gene. Deep sequencing of fluorescent-sorted wild-type and derivative chromosomes confirmed the clinically undetected BCA. Moreover, deep sequencing further validated a high accuracy of mate-pair library sequencing to detect structural variants larger than 10 kB, proposing that this approach is powerful for clinical-grade genome-wide structural variant detection. Our study supports previous evidence for a role of ZNF804A in NDD and highlights the need for a more comprehensive assessment of structural variation in karyotypically abnormal individuals and patients with neurocognitive disease to avoid diagnostic deception. PMID:24625750

More Technology, Better Learning Resources, Better Learning? Lessons from Adopting Virtual Microscopy in Undergraduate Medical Education

PubMed Central

Helle, Laura; Nivala, Markus; Kronqvist, Pauliina

2013-01-01

The adoption of virtual microscopy at the University of Turku, Finland, created a unique real-world laboratory for exploring ways of reforming the learning environment. The purpose of this study was to evaluate the students' reactions and the impact of a set of measures designed to boost an experimental group's understanding of abnormal histology through an emphasis on knowledge of normal cells and tissues. The set of measures included (1) digital resources to review normal structures and an entrance examination for enforcement, (2) digital course slides highlighting normal and abnormal tissues, and (3) self-diagnostic quizzes. The performance of historical controls was used as a baseline, as previous students had never been exposed to the above-mentioned measures. The students' understanding of normal histology was assessed in the beginning of the module to determine the impact of the first set of measures, whereas that of abnormal histology was assessed at the end of the module to determine the impact of the whole set of measures. The students' reactions to the instructional measures were assessed by course evaluation data. Additionally, four students were interviewed. Results confirmed that the experimental group significantly outperformed the historical controls in understanding normal histology. The students held favorable opinions on the idea of emphasizing normal structures. However, with regards to abnormal histology, the historical controls outperformed the experimental group. In conclusion, allowing students access to high-quality digitized materials and boosting prerequisite skills are clearly not sufficient to boost final competence. Instead, the solution may lie in making students externally accountable for their learning throughout their training. Anat Sci Educ 6: 73–80. © 2012 American Association of Anatomists. PMID:22930425

Brain magnetic resonance imaging findings in Smith-Lemli-Opitz syndrome.

PubMed

Lee, Ryan W Y; Conley, Sandra K; Gropman, Andrea; Porter, Forbes D; Baker, Eva H

2013-10-01

Smith-Lemli-Opitz syndrome (SLOS) is a neurodevelopmental disorder caused by inborn errors of cholesterol metabolism resulting from mutations in 7-dehydrocholesterol reductase (DHCR7). There are only a few studies describing the brain imaging findings in SLOS. This study examines the prevalence of magnetic resonance imaging (MRI) abnormalities in the largest cohort of patients with SLOS to date. Fifty-five individuals with SLOS (27 M, 28 F) between age 0.17 years and 25.4 years (mean = 6.2, SD = 5.8) received a total of 173 brain MRI scans (mean = 3.1 per subject) on a 1.5T GE scanner between September 1998 and December 2003, or on a 3T Philips scanner between October 2010 and September 2012; all exams were performed at the Clinical Center of the National Institutes of Health. We performed a retrospective review of these imaging studies for both major and minor brain anomalies. Aberrant MRI findings were observed in 53 of 55 (96%) SLOS patients, with abnormalities of the septum pellucidum the most frequent (42/55, 76%) finding. Abnormalities of the corpus callosum were found in 38 of 55 (69%) patients. Other findings included cerebral atrophy, cerebellar atrophy, colpocephaly, white matter lesions, arachnoid cysts, Dandy-Walker variant, and type I Chiari malformation. Significant correlations were observed when comparing MRI findings with sterol levels and somatic malformations. Individuals with SLOS commonly have anomalies involving the midline and para-midline structures of the brain. Further studies are required to examine the relationship between structural brain abnormalities and neurodevelopmental disability in SLOS. © 2013 The Authors. American Journal of Medical Genetics Part A Published by U.S. Government Work.

More technology, better learning resources, better learning? Lessons from adopting virtual microscopy in undergraduate medical education.

PubMed

Helle, Laura; Nivala, Markus; Kronqvist, Pauliina

2013-01-01

The adoption of virtual microscopy at the University of Turku, Finland, created a unique real-world laboratory for exploring ways of reforming the learning environment. The purpose of this study was to evaluate the students' reactions and the impact of a set of measures designed to boost an experimental group's understanding of abnormal histology through an emphasis on knowledge of normal cells and tissues. The set of measures included (1) digital resources to review normal structures and an entrance examination for enforcement, (2) digital course slides highlighting normal and abnormal tissues, and (3) self-diagnostic quizzes. The performance of historical controls was used as a baseline, as previous students had never been exposed to the above-mentioned measures. The students' understanding of normal histology was assessed in the beginning of the module to determine the impact of the first set of measures, whereas that of abnormal histology was assessed at the end of the module to determine the impact of the whole set of measures. The students' reactions to the instructional measures were assessed by course evaluation data. Additionally, four students were interviewed. Results confirmed that the experimental group significantly outperformed the historical controls in understanding normal histology. The students held favorable opinions on the idea of emphasizing normal structures. However, with regards to abnormal histology, the historical controls outperformed the experimental group. In conclusion, allowing students access to high-quality digitized materials and boosting prerequisite skills are clearly not sufficient to boost final competence. Instead, the solution may lie in making students externally accountable for their learning throughout their training. Copyright © 2012 American Association of Anatomists.

Abnormal Eye Movements in Creutzfeldt-Jakob Disease

NASA Technical Reports Server (NTRS)

Grant, Michael P.; Cohen, Mark; Petersen, Robert B.; Halmagyi, G. Michael; McDougall, Alan; Tusa, Ronald J.; Leigh, R. John

1993-01-01

We report 3 patients with autopsy-proven Creutzfeldt-Jakob disease who, early in their course, developed abnormal eye movements that included periodic alternating nystagmus and slow vertical saccades. These findings suggested involvement of the cerebellar nodulus and uvula, and the brainstem reticular formation, respectively. Cerebellar ataxia was also an early manifestation and, in one patient, a frontal lobe brain biopsy was normal at a time when ocular motor and cerebellar signs were conspicuous. As the disease progressed, all saccades and quick phases of nystagmus were lost, but periodic alternating gaze deviation persisted. At autopsy, 2 of the 3 patients had pronounced involvement of the cerebellum, especially of the midline structures. Creutzfeldt-Jakob disease should be considered in patients with subacute progressive neurological disease when cognitive changes are overshadowed by ocular motor findings or ataxia.

Positive identification by a skull with multiple epigenetic traits and abnormal structure of the neurocranium, viscerocranium, and the skeleton.

PubMed

Kuharić, Josip; Kovacic, Natasa; Marusic, Petar; Marusic, Ana; Petrovecki, Vedrana

2011-05-01

Wormian bones are small ossicles appearing within the cranial sutures in more than 40% of skulls, most commonly at the lambdoid suture and pterion. During the skeletal analysis of an unidentified male war victim, we observed multiple wormian bones and a patent metopic suture. Additionally, the right elbow was deformed, probably as a consequence of an old trauma. The skull was analyzed by cranial measurements and computerized tomography, revealing the presence of cranial deformities including hyperbrachicrania, localized reduction in hemispheral widths, increased cranial capacity, and sclerosis of the viscerocranium. Besides unique anatomical features and their anthropological value, such skeletal abnormalities also have a forensic value as the evidence to support the final identification of the victim. © 2011 American Academy of Forensic Sciences.

Developmental origins of brain disorders: roles for dopamine

PubMed Central

Money, Kelli M.; Stanwood, Gregg D.

2013-01-01

Neurotransmitters and neuromodulators, such as dopamine, participate in a wide range of behavioral and cognitive functions in the adult brain, including movement, cognition, and reward. Dopamine-mediated signaling plays a fundamental neurodevelopmental role in forebrain differentiation and circuit formation. These developmental effects, such as modulation of neuronal migration and dendritic growth, occur before synaptogenesis and demonstrate novel roles for dopaminergic signaling beyond neuromodulation at the synapse. Pharmacologic and genetic disruptions demonstrate that these effects are brain region- and receptor subtype-specific. For example, the striatum and frontal cortex exhibit abnormal neuronal structure and function following prenatal disruption of dopamine receptor signaling. Alterations in these processes are implicated in the pathophysiology of neuropsychiatric disorders, and emerging studies of neurodevelopmental disruptions may shed light on the pathophysiology of abnormal neuronal circuitry in neuropsychiatric disorders. PMID:24391541

Structural Image Analysis of the Brain in Neuropsychology Using Magnetic Resonance Imaging (MRI) Techniques.

PubMed

Bigler, Erin D

2015-09-01

Magnetic resonance imaging (MRI) of the brain provides exceptional image quality for visualization and neuroanatomical classification of brain structure. A variety of image analysis techniques provide both qualitative as well as quantitative methods to relate brain structure with neuropsychological outcome and are reviewed herein. Of particular importance are more automated methods that permit analysis of a broad spectrum of anatomical measures including volume, thickness and shape. The challenge for neuropsychology is which metric to use, for which disorder and the timing of when image analysis methods are applied to assess brain structure and pathology. A basic overview is provided as to the anatomical and pathoanatomical relations of different MRI sequences in assessing normal and abnormal findings. Some interpretive guidelines are offered including factors related to similarity and symmetry of typical brain development along with size-normalcy features of brain anatomy related to function. The review concludes with a detailed example of various quantitative techniques applied to analyzing brain structure for neuropsychological outcome studies in traumatic brain injury.

A prospective evaluation of 68 patients suffering blunt chest trauma for evidence of cardiac injury.

PubMed

Helling, T S; Duke, P; Beggs, C W; Crouse, L J

1989-07-01

The prevalence and significance of cardiac injury following blunt chest trauma is largely unknown. Although electrocardiography (ECG) and creatinine phosphokinase isoenzyme (CPK-MB) determination have traditionally been used in determining cardiac injury, recent developments in two-dimensional echocardiography (ECHO) as a noninvasive diagnostic tool have led to its use in detecting structural cardiac damage following trauma. In an attempt to determine the occurrence and consequences of cardiac injury we prospectively evaluated 68 patients at one institution using ECHO, serial ECG, and serial CPK-MB determinations in the first 3 days following hospital admission. Patients were selected who had evidence of blunt chest injury on examination or by mechanism of injury. The mean age of the 68 patients was 36.3 +/- 19.6 years and the mean Injury Severity Score, 21.5 +/- 11.6. Forty-nine patients (72%) were found to have an abnormal ECHO, ECG, or CPK-MB (greater than 3%). Eighteen patients (26%) had abnormal ECHOs consisting of seven right ventricular contusions, three left ventricular contusions, three contusions of both chambers, four pericardial effusions, and one small ventricular septal defect. Only three contusions were associated with elevated CPK-MB and seven with abnormal ECGs. Abnormalities of ECG included 18 patients with S-T, T wave changes, axis shifts (11 patients), and bundle branch or hemiblocks (10 patients). No patient died or experienced serious morbidity as a result of their cardiac injury, including 12 patients who underwent surgical procedures with general anesthesia within 30 days of admission.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessing cardiac physical examination skills using simulation technology and real patients: a comparison study.

PubMed

Hatala, Rose; Issenberg, S Barry; Kassen, Barry; Cole, Gary; Bacchus, C Maria; Scalese, Ross J

2008-06-01

High-stakes assessments of doctors' physical examination skills often employ standardised patients (SPs) who lack physical abnormalities. Simulation technology provides additional opportunities to assess these skills by mimicking physical abnormalities. The current study examined the relationship between internists' cardiac physical examination competence as assessed with simulation technology compared with that assessed with real patients (RPs). The cardiac physical examination skills and bedside diagnostic accuracy of 28 internists were assessed during an objective structured clinical examination (OSCE). The OSCE included 3 modalities of cardiac patients: RPs with cardiac abnormalities; SPs combined with computer-based, audio-video simulations of auscultatory abnormalities, and a cardiac patient simulator (CPS) manikin. Four cardiac diagnoses and their associated cardiac findings were matched across modalities. At each station, 2 examiners independently rated a participant's physical examination technique and global clinical competence. Two investigators separately scored diagnostic accuracy. Inter-rater reliability between examiners for global ratings (GRs) ranged from 0.75-0.78 for the different modalities. Although there was no significant difference between participants' mean GRs for each modality, the correlations between participants' performances on each modality were low to modest: RP versus SP, r = 0.19; RP versus CPS, r = 0.22; SP versus CPS, r = 0.57 (P < 0.01). Methodological limitations included variability between modalities in the components contributing to examiners' GRs, a paucity of objective outcome measures and restricted case sampling. No modality provided a clear 'gold standard' for the assessment of cardiac physical examination competence. These limitations need to be addressed before determining the optimal patient modality for high-stakes assessment purposes.

Abnormal Neural Connectivity in Schizophrenia and fMRI-Brain-Computer Interface as a Potential Therapeutic Approach

PubMed Central

Ruiz, Sergio; Birbaumer, Niels; Sitaram, Ranganatha

2012-01-01

Considering that single locations of structural and functional abnormalities are insufficient to explain the diverse psychopathology of schizophrenia, new models have postulated that the impairments associated with the disease arise from a failure to integrate the activity of local and distributed neural circuits: the “abnormal neural connectivity hypothesis.” In the last years, new evidence coming from neuroimaging have supported and expanded this theory. However, despite the increasing evidence that schizophrenia is a disorder of neural connectivity, so far there are no treatments that have shown to produce a significant change in brain connectivity, or that have been specifically designed to alleviate this problem. Brain-Computer Interfaces based on real-time functional Magnetic Resonance Imaging (fMRI-BCI) are novel techniques that have allowed subjects to achieve self-regulation of circumscribed brain regions. In recent studies, experiments with this technology have resulted in new findings suggesting that this methodology could be used to train subjects to enhance brain connectivity, and therefore could potentially be used as a therapeutic tool in mental disorders including schizophrenia. The present article summarizes the findings coming from hemodynamics-based neuroimaging that support the abnormal connectivity hypothesis in schizophrenia, and discusses a new approach that could address this problem. PMID:23525496

Brain white matter changes associated with urological chronic pelvic pain syndrome: multisite neuroimaging from a MAPP case-control study.

PubMed

Huang, Lejian; Kutch, Jason J; Ellingson, Benjamin M; Martucci, Katherine T; Harris, Richard E; Clauw, Daniel J; Mackey, Sean; Mayer, Emeran A; Schaeffer, Anthony J; Apkarian, A Vania; Farmer, Melissa A

2016-12-01

Clinical phenotyping of urological chronic pelvic pain syndromes (UCPPSs) in men and women have focused on end organ abnormalities to identify putative clinical subtypes. Initial evidence of abnormal brain function and structure in male pelvic pain has necessitated large-scale, multisite investigations into potential UCPPS brain biomarkers. We present the first evidence of regional white matter (axonal) abnormalities in men and women with UCPPS, compared with positive (irritable bowel syndrome, IBS) and healthy controls. Epidemiological and neuroimaging data were collected from participants with UCPPS (n = 52), IBS (n = 39), and healthy sex- and age-matched controls (n = 61). White matter microstructure, measured as fractional anisotropy (FA), was examined by diffusion tensor imaging. Group differences in regional FA positively correlated with pain severity, including segments of the right corticospinal tract and right anterior thalamic radiation. Increased corticospinal FA was specific and sensitive to UCPPS, positively correlated with pain severity, and reflected sensory (not affective) features of pain. Reduced anterior thalamic radiation FA distinguished patients with IBS from those with UCPPS and controls, suggesting greater microstructural divergence from normal tract organization. Findings confirm that regional white matter abnormalities characterize UCPPS and can distinguish between visceral diagnoses, suggesting that regional axonal microstructure is either altered with ongoing pain or predisposes its development.

Brain white matter changes associated with urological chronic pelvic pain syndrome: Multi-site neuroimaging from a MAPP case-control study

PubMed Central

Huang, Lejian; Kutch, Jason J.; Ellingson, Benjamin M.; Martucci, Katherine T.; Harris, Richard E.; Clauw, Daniel J.; Mackey, Sean; Mayer, Emeran A.; Schaeffer, Anthony J.; Apkarian, A. Vania; Farmer, Melissa A.

2016-01-01

Clinical phenotyping of urological chronic pelvic pain syndromes (UCPPS) in men and women has focused on end-organ abnormalities to identify putative clinical subtypes. Initial evidence of abnormal brain function and structure in male pelvic pain has necessitated large-scale, multi-site investigations into potential UCPPS brain biomarkers. We present the first evidence of regional white matter (axonal) abnormalities in men and women with UCPPS, compared to positive (irritable bowel syndrome, IBS) and healthy controls. Epidemiological and neuroimaging data was collected from participants with UCPPS (n=52), IBS (n=39), and healthy, sex- and age-matched controls (n=61). White matter microstructure, measured as fractional anisotropy (FA), was examined with diffusion tensor imaging (DTI). Group differences in regional FA positively correlated with pain severity, including segments of the right corticospinal tract and right anterior thalamic radiation. Increased corticospinal FA was specific and sensitive to UCPPS, positively correlated with pain severity, and reflected sensory (not affective) features of pain. Reduced anterior thalamic radiation FA distinguished IBS from UCPPS patients and controls, suggesting greater microstructural divergence from normal tract organization. Findings confirm that regional white matter abnormalities characterize UCPPS and can distinguish between visceral diagnoses, suggesting that regional axonal microstructure is either altered with ongoing pain or predisposes its development. PMID:27842046

Abnormal endocrine pancreas function at birth in cystic fibrosis ferrets

PubMed Central

Olivier, Alicia K.; Yi, Yaling; Sun, Xingshen; Sui, Hongshu; Liang, Bo; Hu, Shanming; Xie, Weiliang; Fisher, John T.; Keiser, Nicholas W.; Lei, Diana; Zhou, Weihong; Yan, Ziying; Li, Guiying; Evans, Turan I.A.; Meyerholz, David K.; Wang, Kai; Stewart, Zoe A.; Norris, Andrew W.; Engelhardt, John F.

2012-01-01

Diabetes is a common comorbidity in cystic fibrosis (CF) that worsens prognosis. The lack of an animal model for CF-related diabetes (CFRD) has made it difficult to dissect how the onset of pancreatic pathology influences the emergence of CFRD. We evaluated the structure and function of the neonatal CF endocrine pancreas using a new CFTR-knockout ferret model. Although CF kits are born with only mild exocrine pancreas disease, progressive exocrine and endocrine pancreatic loss during the first months of life was associated with pancreatic inflammation, spontaneous hyperglycemia, and glucose intolerance. Interestingly, prior to major exocrine pancreas disease, CF kits demonstrated significant abnormalities in blood glucose and insulin regulation, including diminished first-phase and accentuated peak insulin secretion in response to glucose, elevated peak glucose levels following glucose challenge, and variably elevated insulin and C-peptide levels in the nonfasted state. Although there was no difference in lobular insulin and glucagon expression between genotypes at birth, significant alterations in the frequencies of small and large islets were observed. Newborn cultured CF islets demonstrated dysregulated glucose-dependent insulin secretion in comparison to controls, suggesting intrinsic abnormalities in CF islets. These findings demonstrate that early abnormalities exist in the regulation of insulin secretion by the CF endocrine pancreas. PMID:22996690

Association between serum levels of the proinflammatory protein S100A8/A9 and clinical and structural characteristics of patients with established knee, hip, and hand osteoarthritis.

PubMed

Mahler, E A M; Zweers, M C; van Lent, P L; Blom, A B; van den Hoogen, F H; van den Berg, W B; Roth, J; Vogl, T; Bijlsma, J W J; van den Ende, C H M; den Broeder, A A

2015-01-01

To explore the association between S100A8/A9 serum levels with clinical and structural characteristics of patients with established knee, hip, or hand osteoarthritis (OA). A cross-sectional exploratory study was conducted with 162 OA patients. Measures for pain, stiffness, and function included the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) questionnaire or the Australian Canadian Osteoarthritis Hand (AUSCAN) Index and for structural abnormalities, osteophytes and joint space narrowing grades. The association between S100A8/A9 and clinical or structural characteristics was analysed using linear regression or logistic regression where appropriate. The mean age of the OA patients was 56 years, 71% were female, and 61% had a Kellgren and Lawrence (K&L) score ≥ 2. The serum S100A8/A9 level did not differ between knee, hip, and hand OA patients and no association was found between serum S100A8/A9 and clinical characteristics. The serum S100A8/A9 level was negatively associated with the sum score of osteophytes after adjusting for sex and body mass index (BMI) [adjusted β -0.015, 95% confidence interval (CI) -0.030 to 0.001, p = 0.062] and positively associated with erythrocyte sedimentation rate (ESR) > 12 mm/h (adjusted OR 1.002, 95% CI 1.000-1.004 p = 0.049) for each increase in S100A8/A9 of 1 ng/mL. For hand OA patients, a negative association of S100A8/A9 with sum score of joint space narrowing was found (adjusted β -0.007, 95% CI -0.016 to 0.001, p = 0.099). The results from this cross-sectional exploratory study do not support an important role for serum S100A8/A9 levels as a biomarker for clinical and structural characteristics in established knee, hip, and hand OA patients. The inverse association with structural abnormalities and the positive association with ESR may reflect inflammatory synovial processes in patients with OA before structural abnormalities occur.

Diabetes-induced mechanophysiological changes in the small intestine and colon

PubMed Central

Zhao, Mirabella; Liao, Donghua; Zhao, Jingbo

2017-01-01

The disorders of gastrointestinal (GI) tract including intestine and colon are common in the patients with diabetes mellitus (DM). DM induced intestinal and colonic structural and biomechanical remodeling in animals and humans. The remodeling is closely related to motor-sensory abnormalities of the intestine and colon which are associated with the symptoms frequently encountered in patients with DM such as diarrhea and constipation. In this review, firstly we review DM-induced histomorphological and biomechanical remodeling of intestine and colon. Secondly we review motor-sensory dysfunction and how they relate to intestinal and colonic abnormalities. Finally the clinical consequences of DM-induced changes in the intestine and colon including diarrhea, constipation, gut microbiota change and colon cancer are discussed. The final goal is to increase the understanding of DM-induced changes in the gut and the subsequent clinical consequences in order to provide the clinicians with a better understanding of the GI disorders in diabetic patients and facilitates treatments tailored to these patients. PMID:28694926

Cellular and molecular effects of developmental exposure to diethylstilbestrol: implications for other environmental estrogens.

PubMed Central

Newbold, R

1995-01-01

Concerns have been raised regarding the role of environmental and dietary estrogens as possible contributors to an increased incidence of various abnormalities in estrogen-target tissues of both sexes. These abnormalities include breast cancer, endometriosis, fibroids, and uterine adenocarcinoma in females, as well as alterations in sex differentiation, decreased sperm concentrations, benign prostatic hyperplasia, prostatic cancer, testicular cancer, and reproductive problems in males. Whether these concerns are valid remains to be determined; however, studies with the potent synthetic estrogen diethylstilbestrol (DES) suggest that exogenous estrogen exposure during critical stages of development can result in permanent cellular and molecular alterations in the exposed organism. These alterations manifest themselves in the female and male as structural, functional, or long-term pathological changes including neoplasia. Although DES has potent estrogenic activity, it may be used as a model compound to study the effects of weaker environmental estrogens, many of which may fit into the category of endocrine disruptors. PMID:8593881

Cortical and subcortical gray matter bases of cognitive deficits in REM sleep behavior disorder.

PubMed

Rahayel, Shady; Postuma, Ronald B; Montplaisir, Jacques; Génier Marchand, Daphné; Escudier, Frédérique; Gaubert, Malo; Bourgouin, Pierre-Alexandre; Carrier, Julie; Monchi, Oury; Joubert, Sven; Blanc, Frédéric; Gagnon, Jean-François

2018-05-15

To investigate cortical and subcortical gray matter abnormalities underlying cognitive impairment in patients with REM sleep behavior disorder (RBD) with or without mild cognitive impairment (MCI). Fifty-two patients with RBD, including 17 patients with MCI, were recruited and compared to 41 controls. All participants underwent extensive clinical assessments, neuropsychological examination, and 3-tesla MRI acquisition of T1 anatomical images. Vertex-based cortical analyses of volume, thickness, and surface area were performed to investigate cortical abnormalities between groups, whereas vertex-based shape analysis was performed to investigate subcortical structure surfaces. Correlations were performed to investigate associations between cortical and subcortical metrics, cognitive domains, and other markers of neurodegeneration (color discrimination, olfaction, and autonomic measures). Patients with MCI had cortical thinning in the frontal, cingulate, temporal, and occipital cortices, and abnormal surface contraction in the lenticular nucleus and thalamus. Patients without MCI had cortical thinning restricted to the frontal cortex. Lower patient performance in cognitive domains was associated with cortical and subcortical abnormalities. Moreover, impaired performance on olfaction, color discrimination, and autonomic measures was associated with thinning in the occipital lobe. Cortical and subcortical gray matter abnormalities are associated with cognitive status in patients with RBD, with more extensive patterns in patients with MCI. Our results highlight the importance of distinguishing between subgroups of patients with RBD according to cognitive status in order to better understand the neurodegenerative process in this population. © 2018 American Academy of Neurology.

Impaired functional but preserved structural connectivity in limbic white matter tracts in youth with conduct disorder or oppositional defiant disorder plus psychopathic traits.

PubMed

Finger, Elizabeth Carrie; Marsh, Abigail; Blair, Karina Simone; Majestic, Catherine; Evangelou, Iordanis; Gupta, Karan; Schneider, Marguerite Reid; Sims, Courtney; Pope, Kayla; Fowler, Katherine; Sinclair, Stephen; Tovar-Moll, Fernanda; Pine, Daniel; Blair, Robert James

2012-06-30

Youths with conduct disorder or oppositional defiant disorder and psychopathic traits (CD/ODD+PT) are at high risk of adult antisocial behavior and psychopathy. Neuroimaging studies demonstrate functional abnormalities in orbitofrontal cortex and the amygdala in both youths and adults with psychopathic traits. Diffusion tensor imaging in psychopathic adults demonstrates disrupted structural connectivity between these regions (uncinate fasiculus). The current study examined whether functional neural abnormalities present in youths with CD/ODD+PT are associated with similar white matter abnormalities. Youths with CD/ODD+PT and comparison participants completed 3.0 T diffusion tensor scans and functional magnetic resonance imaging scans. Diffusion tensor imaging did not reveal disruption in structural connections within the uncinate fasiculus or other white matter tracts in youths with CD/ODD+PT, despite the demonstration of disrupted amygdala-prefrontal functional connectivity in these youths. These results suggest that disrupted amygdala-frontal white matter connectivity as measured by fractional anisotropy is less sensitive than imaging measurements of functional perturbations in youths with psychopathic traits. If white matter tracts are intact in youths with this disorder, childhood may provide a critical window for intervention and treatment, before significant structural brain abnormalities solidify. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Transvaginal Ultrasound for the Diagnosis of Abnormal Uterine Bleeding.

PubMed

Wheeler, Karen C; Goldstein, Steven R

2017-03-01

Transvaginal ultrasound is the first-line imaging test for the evaluation of abnormal uterine bleeding in both premenopausal and postmenopausal women. Transvaginal ultrasound can be used to diagnose structural causes of abnormal bleeding such as polyps, adenomyosis, leiomyomas, hyperplasia, and malignancy, and can also be beneficial in making the diagnosis of ovulatory dysfunction. Traditional 2-dimensional imaging is often enhanced by the addition of 3-dimension imaging with coronal reconstruction and saline infusion sonohysterography. In this article we discuss specific ultrasound findings and technical considerations useful in the diagnosis of abnormal uterine bleeding.

Characterization of tumor microvascular structure and permeability: comparison between magnetic resonance imaging and intravital confocal imaging

NASA Astrophysics Data System (ADS)

Reitan, Nina Kristine; Thuen, Marte; Goa, Pa˚L. Erik; de Lange Davies, Catharina

2010-05-01

Solid tumors are characterized by abnormal blood vessel organization, structure, and function. These abnormalities give rise to enhanced vascular permeability and may predict therapeutic responses. The permeability and architecture of the microvasculature in human osteosarcoma tumors growing in dorsal window chambers in athymic mice were measured by confocal laser scanning microscopy (CLSM) and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Dextran (40 kDa) and Gadomer were used as molecular tracers for CLSM and DCE-MRI, respectively. A significant correlation was found between permeability indicators. The extravasation rate Ki as measured by CLSM correlated positively with DCE-MRI parameters, such as the volume transfer constant Ktrans and the initial slope of the contrast agent concentration-time curve. This demonstrates that these two techniques give complementary information. Extravasation was further related to microvascular structure and was found to correlate with the fractal dimension and vascular density. The structural parameter values that were obtained from CLSM images were higher for abnormal tumor vasculature than for normal vessels.

Multifaceted impairments in impulsivity and brain structural abnormalities in opioid dependence and abstinence.

PubMed

Tolomeo, S; Gray, S; Matthews, K; Steele, J D; Baldacchino, A

2016-10-01

Chronic opioid exposure, as a treatment for a variety of disorders or as drug of misuse, is common worldwide, but behavioural and brain abnormalities remain under-investigated. Only a small percentage of patients who receive methadone maintenance treatment (MMT) for previous heroin misuse eventually achieve abstinence and studies on such patients are rare. The Cambridge Neuropsychological Test Automated Battery and T1 weighted magnetic resonance imaging (MRI) were used to study a cohort of 122 male individuals: a clinically stable opioid-dependent patient group receiving MMT (n = 48), an abstinent previously MMT maintained group (ABS) (n = 24) and healthy controls (n = 50). Stable MMT participants deliberated longer and placed higher bets earlier in the Cambridge Gambling Task (CGT) and showed impaired strategic planning compared with healthy controls. In contrast, ABS participants showed impairment in choosing the least likely outcome, delay aversion and risk adjustment on the CGT, and exhibited non-planning impulsivity compared with controls. MMT patients had widespread grey matter reductions in the orbitomedial prefrontal cortex, caudate, putamen and globus pallidus. In contrast, ABS participants showed midbrain-thalamic grey matter reductions. A higher methadone dose at the time of scanning was associated with a smaller globus pallidus in the MMT group. Our findings support an interpretation of heightened impulsivity in patients receiving MMT. Widespread structural brain abnormalities in the MMT group and reduced brain structural abnormality with abstinence suggest benefit of cessation of methadone intake. We suggest that a longitudinal study is required to determine whether abstinence improves abnormalities, or patients who achieve abstinence have reduced abnormalities before methadone cessation.

Brain Metabolism during Hallucination-Like Auditory Stimulation in Schizophrenia

PubMed Central

Horga, Guillermo; Fernández-Egea, Emilio; Mané, Anna; Font, Mireia; Schatz, Kelly C.; Falcon, Carles; Lomeña, Francisco; Bernardo, Miguel; Parellada, Eduard

2014-01-01

Auditory verbal hallucinations (AVH) in schizophrenia are typically characterized by rich emotional content. Despite the prominent role of emotion in regulating normal perception, the neural interface between emotion-processing regions such as the amygdala and auditory regions involved in perception remains relatively unexplored in AVH. Here, we studied brain metabolism using FDG-PET in 9 remitted patients with schizophrenia that previously reported severe AVH during an acute psychotic episode and 8 matched healthy controls. Participants were scanned twice: (1) at rest and (2) during the perception of aversive auditory stimuli mimicking the content of AVH. Compared to controls, remitted patients showed an exaggerated response to the AVH-like stimuli in limbic and paralimbic regions, including the left amygdala. Furthermore, patients displayed abnormally strong connections between the amygdala and auditory regions of the cortex and thalamus, along with abnormally weak connections between the amygdala and medial prefrontal cortex. These results suggest that abnormal modulation of the auditory cortex by limbic-thalamic structures might be involved in the pathophysiology of AVH and may potentially account for the emotional features that characterize hallucinatory percepts in schizophrenia. PMID:24416328

Exploratory analysis of diffusion tensor imaging in children with attention deficit hyperactivity disorder: evidence of abnormal white matter structure.

PubMed

Pastura, Giuseppe; Doering, Thomas; Gasparetto, Emerson Leandro; Mattos, Paulo; Araújo, Alexandra Prüfer

2016-06-01

Abnormalities in the white matter microstructure of the attentional system have been implicated in the aetiology of attention deficit hyperactivity disorder (ADHD). Diffusion tensor imaging (DTI) is a promising magnetic resonance imaging (MRI) technology that has increasingly been used in studies of white matter microstructure in the brain. The main objective of this work was to perform an exploratory analysis of white matter tracts in a sample of children with ADHD versus typically developing children (TDC). For this purpose, 13 drug-naive children with ADHD of both genders underwent MRI using DTI acquisition methodology and tract-based spatial statistics. The results were compared to those of a sample of 14 age- and gender-matched TDC. Lower fractional anisotropy was observed in the splenium of the corpus callosum, right superior longitudinal fasciculus, bilateral retrolenticular part of the internal capsule, bilateral inferior fronto-occipital fasciculus, left external capsule and posterior thalamic radiation (including right optic radiation). We conclude that white matter tracts in attentional and motor control systems exhibited signs of abnormal microstructure in this sample of drug-naive children with ADHD.

MRI anatomy of schizophrenia.

PubMed

McCarley, R W; Wible, C G; Frumin, M; Hirayasu, Y; Levitt, J J; Fischer, I A; Shenton, M E

1999-05-01

Structural magnetic resonance imaging (MRI) data have provided much evidence in support of our current view that schizophrenia is a brain disorder with altered brain structure, and consequently involving more than a simple disturbance in neurotransmission. This review surveys 118 peer-reviewed studies with control group from 1987 to May 1998. Most studies (81%) do not find abnormalities of whole brain/intracranial contents, while lateral ventricle enlargement is reported in 77%, and third ventricle enlargement in 67%. The temporal lobe was the brain parenchymal region with the most consistently documented abnormalities. Volume decreases were found in 62% of 37 studies of whole temporal lobe, and in 81% of 16 studies of the superior temporal gyrus (and in 100% with gray matter separately evaluated). Fully 77% of the 30 studies of the medial temporal lobe reported volume reduction in one or more of its constituent structures (hippocampus, amygdala, parahippocampal gyrus). Despite evidence for frontal lobe functional abnormalities, structural MRI investigations less consistently found abnormalities, with 55% describing volume reduction. It may be that frontal lobe volume changes are small, and near the threshold for MRI detection. The parietal and occipital lobes were much less studied; about half of the studies showed positive findings. Most studies of cortical gray matter (86%) found volume reductions were not diffuse, but more pronounced in certain areas. About two thirds of the studies of subcortical structures of thalamus, corpus callosum and basal ganglia (which tend to increase volume with typical neuroleptics), show positive findings, as do almost all (91%) studies of cavum septi pellucidi (CSP). Most data were consistent with a developmental model, but growing evidence was compatible also with progressive, neurodegenerative features, suggesting a "two-hit" model of schizophrenia, for which a cellular hypothesis is discussed. The relationship of clinical symptoms to MRI findings is reviewed, as is the growing evidence suggesting structural abnormalities differ in affective (bipolar) psychosis and schizophrenia.

Kidney biopsy

MedlinePlus

... normal structure. What Abnormal Results Mean An abnormal result means there are changes in the kidney tissue. This may be due to: Infection Poor blood flow through the kidney Connective tissue diseases such as systemic lupus erythematosus Other diseases that may be affecting the ...

Genetics Home Reference: Wolf-Hirschhorn syndrome

MedlinePlus

... syndrome include skin changes such as mottled or dry skin, skeletal abnormalities such as abnormal ... also cause abnormalities of the eyes, heart, genitourinary tract, and brain. A condition called ...

Hyporesponsive reward anticipation in the basal ganglia following severe institutional deprivation early in life.

PubMed

Mehta, Mitul A; Gore-Langton, Emma; Golembo, Nicole; Colvert, Emma; Williams, Steven C R; Sonuga-Barke, Edmund

2010-10-01

Severe deprivation in the first few years of life is associated with multiple difficulties in cognition and behavior. However, the brain basis for these difficulties is poorly understood. Structural and functional neuroimaging studies have implicated limbic system structures as dysfunctional, and one functional imaging study in a heterogeneous group of maltreated individuals has confirmed the presence of abnormalities in the basal ganglia. Based on these studies and known dopaminergic abnormalities from studies in experimental animals using social isolation, we used a task of monetary reward anticipation to examine the functional integrity of brain regions previously shown to be implicated in reward processing. Our sample included a group of adolescents (n = 12) who had experienced global deprivation early in their lives in Romania prior to adoption into UK families. In contrast to a nonadopted comparison group (n = 11), the adoptees did not recruit the striatum during reward anticipation despite comparable performance accuracy and latency. These results show, for the first time, an association between early institutional deprivation and brain reward systems in humans and highlight potential neural vulnerabilities resulting from such exposures.

Neuroimaging of Cerebrovascular Disease in the Aging Brain

PubMed Central

Gupta, Ajay; Nair, Sreejit; Schweitzer, Andrew D.; Kishore, Sirish; Johnson, Carl E.; Comunale, Joseph P.; Tsiouris, Apostolos J.; Sanelli, Pina C.

2012-01-01

Cerebrovascular disease remains a significant public health burden with its greatest impact on the elderly population. Advances in neuroimaging techniques allow detailed and sophisticated evaluation of many manifestations of cerebrovascular disease in the brain parenchyma as well as in the intracranial and extracranial vasculature. These tools continue to contribute to our understanding of the multifactorial processes that occur in the age-dependent development of cerebrovascular disease. Structural abnormalities related to vascular disease in the brain and vessels have been well characterized with CT and MRI based techniques. We review some of the pathophysiologic mechanisms in the aging brain and cerebral vasculature and the related structural abnormalities detectable on neuroimaging, including evaluation of age-related white matter changes, atherosclerosis of the cerebral vasculature, and cerebral infarction. In addition, newer neuroimaging techniques, such as diffusion tensor imaging, perfusion techniques, and assessment of cerebrovascular reserve, are also reviewed, as these techniques can detect physiologic alterations which complement the morphologic changes that cause cerebrovascular disease in the aging brain.Further investigation of these advanced imaging techniques has potential application to the understanding and diagnosis of cerebrovascular disease in the elderly. PMID:23185721

Adverse Pregnancy Outcomes after Abnormal First Trimester Screening for Aneuploidy

PubMed Central

Goetzl, Laura

2010-01-01

Women with abnormal first trimester screening but with a normal karyotype are at risk for adverse pregnancy outcomes. A nuchal translucency >3.5mm is associated with an increased risk of subsequent pregnancy loss, fetal infection, fetal heart abnormalities and other structural abnormalities. Abnormal first trimester analytes are also associated with adverse pregnancy outcomes but the predictive value is less impressive. As a single marker, PAPP-A <1st%ile has a good predictive value for subsequent fetal growth restriction. Women with PAPP-A<5th%ile should undergo subsequent risk assessment with routine MSAFP screening with the possible addition of uterine artery PI assessment in the midtrimester. PMID:20638576

MEG-guided analysis of 7T-MRI in patients with epilepsy.

PubMed

Colon, A J; Osch, M J P van; Buijs, M; Grond, J V D; Hillebrand, A; Schijns, O; Wagner, G J; Ossenblok, P; Hofman, P; Buchem, M A V; Boon, P

2018-05-26

To study possible detection of structural abnormalities on 7T MRI that were not detected on 3T MRI and estimate the added value of MEG-guidance. For abnormalities found, analysis of convergence between clinical, MEG and 7T MRI localization of suspected epileptogenic foci. In adult patients with well-documented localization-related epilepsy in whom a previous 3T MRI did not demonstrate an epileptogenic lesion but MEG indicated a plausible epileptogenic focus, 7T MRI was performed. Based on semiologic data, visual analysis of the 7T images was performed as well as based on prior MEG results. Correlation with other data from the patient charts, for as far as these were available, was analysed. To establish the level of concordance between the three observers the generalized or Fleiss kappa was calculated. In 3/19 patients abnormalities that, based on semiology, could plausibly represent an epileptogenic lesion were detected using 7T MRI. In an additional 3/19 an abnormality was detected after MEG-guidance. However, in these later cases there was no concordance among the three observers with regard to the presence of a structural abnormality. In one of these three cases intracranial recording was performed, proving the possible abnormality on 7T MRI to be the epileptogenic focus. In 32% of patients 7T MRI showed abnormalities that could indicate an epileptogenic lesion whereas previous 3T MRI did not, especially when visual inspection was guided by the presence of focal interictal MEG abnormalities. Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

The onset and evolution of fatigue-induced abnormal grain growth in nanocrystalline Ni–Fe

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

Furnish, T. A.; Mehta, A.; Van Campen, D.

Conventional structural metals suffer from fatigue-crack initiation through dislocation activity which forms persistent slip bands leading to notch-like extrusions and intrusions. Ultrafine-grained and nanocrystalline metals can potentially exhibit superior fatigue-crack initiation resistance by suppressing these cumulative dislocation activities. Prior studies on these metals have confirmed improved high-cycle fatigue performance. In the case of nano-grained metals, analyses of subsurface crack initiation sites have indicated that the crack nucleation is associated with abnormally large grains. But, these post-mortem analyses have led to only speculation about when abnormal grain growth occurs (e.g., during fatigue, after crack initiation, or during crack growth). In thismore » study, a recently developed synchrotron X-ray diffraction technique was used to detect the onset and progression of abnormal grain growth during stress-controlled fatigue loading. Our study provides the first direct evidence that the grain coarsening is cyclically induced and occurs well before final fatigue failure—our results indicate that the first half of the fatigue life was spent prior to the detectable onset of abnormal grain growth, while the second half was spent coarsening the nanocrystalline structure and cyclically deforming the abnormally large grains until crack initiation. Post-mortem fractography, coupled with cycle-dependent diffraction data, provides the first details regarding the kinetics of this abnormal grain growth process during high-cycle fatigue testing. Finally, precession electron diffraction images collected in a transmission electron microscope after the in situ fatigue experiment also confirm the X-ray evidence that the abnormally large grains contain substantial misorientation gradients and sub-grain boundaries.« less

The onset and evolution of fatigue-induced abnormal grain growth in nanocrystalline Ni–Fe

DOE PAGES

Furnish, T. A.; Mehta, A.; Van Campen, D.; ...

2016-10-11

Conventional structural metals suffer from fatigue-crack initiation through dislocation activity which forms persistent slip bands leading to notch-like extrusions and intrusions. Ultrafine-grained and nanocrystalline metals can potentially exhibit superior fatigue-crack initiation resistance by suppressing these cumulative dislocation activities. Prior studies on these metals have confirmed improved high-cycle fatigue performance. In the case of nano-grained metals, analyses of subsurface crack initiation sites have indicated that the crack nucleation is associated with abnormally large grains. But, these post-mortem analyses have led to only speculation about when abnormal grain growth occurs (e.g., during fatigue, after crack initiation, or during crack growth). In thismore » study, a recently developed synchrotron X-ray diffraction technique was used to detect the onset and progression of abnormal grain growth during stress-controlled fatigue loading. Our study provides the first direct evidence that the grain coarsening is cyclically induced and occurs well before final fatigue failure—our results indicate that the first half of the fatigue life was spent prior to the detectable onset of abnormal grain growth, while the second half was spent coarsening the nanocrystalline structure and cyclically deforming the abnormally large grains until crack initiation. Post-mortem fractography, coupled with cycle-dependent diffraction data, provides the first details regarding the kinetics of this abnormal grain growth process during high-cycle fatigue testing. Finally, precession electron diffraction images collected in a transmission electron microscope after the in situ fatigue experiment also confirm the X-ray evidence that the abnormally large grains contain substantial misorientation gradients and sub-grain boundaries.« less

[Brain structure analysis for patients with antisocial personality disorder by MRI].

PubMed

Jiang, Weixiong; Liao, Jian; Liu, Huasheng; Huang, Renzhi; Li, Yongfan; Wang, Wei

2015-02-01

To investigate the structural abnormalities of brain in patients with antisocial personality disorder (ASPD) but without alcoholism and drug abuse. Volunteers from Hunan Reformatory (n=36) and the matched healthy subjects (n=26) were examined by high-spatial resolution magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Voxel-based morphometry and fractional anisotropy (FA) maps were generated for each subject to reveal structural abnormalities in patients with ASPD. Compared with the healthy controls, ASPD patients showed significantly higher gray matter volumes in the inferior parietal lobule (P≤0.001, uncorrected), white matter volumes in the precuneus (P≤0.001, uncorrected), FA in the left lingual gyrus, bilateral precuneus, right superior frontal gyrus and right middle temporal gyrus (P≤0.01, uncorrected). Our results revealed the abnormal neuroanatomical features in ASPD patients, which might be related to the external behavioral traits in ASPD patients.

Added Value of Including Entire Brain on Body Imaging With FDG PET/MRI.

PubMed

Franceschi, Ana M; Matthews, Robert; Bangiyev, Lev; Relan, Nand; Chaudhry, Ammar; Franceschi, Dinko

2018-05-24

FDG PET/MRI examination of the body is routinely performed from the skull base to the mid thigh. Many types of brain abnormalities potentially could be detected on PET/MRI if the head was included. The objective of this study was therefore to identify and characterize brain findings incidentally detected on PET/MRI of the body with the head included. We retrospectively identified 269 patients with FDG PET/MRI whole-body scans that included the head. PET/MR images of the brain were reviewed by a nuclear medicine physician and neuroradiologist, first individually and then concurrently. Both PET and MRI findings were identified, including abnormal FDG uptake, standardized uptake value, lesion size, and MRI signal characteristics. For each patient, relevant medical history and prior imaging were reviewed. Of the 269 subjects, 173 were women and 96 were men (mean age, 57.4 years). Only the initial PET/MR image of each patient was reviewed. A total of 37 of the 269 patients (13.8%) had abnormal brain findings noted on the PET/MRI whole-body scan. Sixteen patients (5.9%) had vascular disease, nine patients (3.3%) had posttherapy changes, and two (0.7%) had benign cystic lesions in the brain. Twelve patients (4.5%) had serious nonvascular brain abnormalities, including cerebral metastasis in five patients and pituitary adenomas in two patients. Only nine subjects (3.3%) had a new neurologic or cognitive symptom suggestive of a brain abnormality. Routine body imaging with FDG PET/MRI of the area from the skull base to the mid thigh may miss important brain abnormalities when the head is not included. The additional brain abnormalities identified on whole-body imaging may provide added clinical value to the management of oncology patients.

Dissection of the complex genetic basis of craniofacial anomalies using haploid genetics and interspecies hybrids in Nasonia wasps

PubMed Central

Werren, John H.; Cohen, Lorna B.; Gadau, Juergen; Ponce, Rita; Baudry, Emmanuelle; Lynch, Jeremy A.

2016-01-01

The animal head is a complex structure where numerous sensory, structural and alimentary structures are concentrated and integrated, and its ontogeny requires precise and delicate interactions among genes, cells, and tissues. Thus, it is perhaps unsurprising that craniofacial abnormalities are among the most common birth defects in people, or that these defects have a complex genetic basis involving interactions among multiple loci. Developmental processes that depend on such epistatic interactions become exponentially more difficult to study in diploid organisms as the number of genes involved increases. Here, we present hybrid haploid males of the wasp species pair Nasonia vitripennis and Nasonia giraulti, which have distinct male head morphologies, as a genetic model of craniofacial development that possesses the genetic advantages of haploidy, along with many powerful genomic tools. Viable, fertile hybrids can be made between the species, and quantitative trail loci related to shape differences have been identified. In addition, a subset of hybrid males show head abnormalities, including clefting at the midline and asymmetries. Crucially, epistatic interactions among multiple loci underlie several developmental differences and defects observed in the F2 hybrid males. Furthermore, we demonstrate an introgression of a chromosomal region from N. giraulti into N. vitripennis that shows an abnormality in relative eye size, which maps to a region containing a major QTL for this trait. Therefore, the genetic sources of head morphology can, in principle, be identified by positional cloning. Thus, Nasonia is well positioned to be a uniquely powerful model invertebrate system with which to probe both development and complex genetics of craniofacial patterning and defects. PMID:26721604

Detection of structural and numerical chomosomal abnormalities by ACM-FISH analysis in sperm of oligozoospermic infertility patients

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

Schmid, T E; Brinkworth, M H; Hill, F

Modern reproductive technologies are enabling the treatment of infertile men with severe disturbances of spermatogenesis. The possibility of elevated frequencies of genetically and chromosomally defective sperm has become an issue of concern with the increased usage of intracytoplasmic sperm injection (ICSI), which can enable men with severely impaired sperm production to father children. Several papers have been published about aneuploidy in oligozoospermic patients, but relatively little is known about chromosome structural aberrations in the sperm of these patients. We examined sperm from infertile, oligozoospermic individuals for structural and numerical chromosomal abnormalities using a multicolor ACM FISH assay that utilizes DNAmore » probes specific for three regions of chromosome 1 to detect human sperm that carry numerical chromosomal abnormalities plus two categories of structural aberrations: duplications and deletions of 1pter and 1cen, and chromosomal breaks within the 1cen-1q12 region. There was a significant increase in the average frequencies of sperm with duplications and deletions in the infertility patients compared with the healthy concurrent controls. There was also a significantly elevated level of breaks within the 1cen-1q12 region. There was no evidence for an increase in chromosome-1 disomy, or in diploidy. Our data reveal that oligozoospermia is associated with chromosomal structural abnormalities suggesting that, oligozoospermic men carry a higher burden of transmissible, chromosome damage. The findings raise the possibility of elevated levels of transmissible chromosomal defects following ICSI treatment.« less

Tensor-based morphometry of cannabis use on brain structure in individuals at elevated genetic risk of schizophrenia.

PubMed

Welch, K A; Moorhead, T W; McIntosh, A M; Owens, D G C; Johnstone, E C; Lawrie, S M

2013-10-01

Schizophrenia is associated with various brain structural abnormalities, including reduced volume of the hippocampi, prefrontal lobes and thalami. Cannabis use increases the risk of schizophrenia but reports of brain structural abnormalities in the cannabis-using population have not been consistent. We used automated image analysis to compare brain structural changes over time in people at elevated risk of schizophrenia for familial reasons who did and did not use cannabis. Magnetic resonance imaging (MRI) scans were obtained from subjects at high familial risk of schizophrenia at entry to the Edinburgh High Risk Study (EHRS) and approximately 2 years later. Differential grey matter (GM) loss in those exposed (n=23) and not exposed to cannabis (n=32) in the intervening period was compared using tensor-based morphometry (TBM). Cannabis exposure was associated with significantly greater loss of right anterior hippocampal (pcorrected=0.029, t=3.88) and left superior frontal lobe GM (pcorrected=0.026, t=4.68). The former finding remained significant even after the exclusion of individuals who had used other drugs during the inter-scan interval. Using an automated analysis of longitudinal data, we demonstrate an association between cannabis use and GM loss in currently well people at familial risk of developing schizophrenia. This observation may be important in understanding the link between cannabis exposure and the subsequent development of schizophrenia.

In vivo laser confocal microscopy findings of a cornea with osteogenesis imperfecta.

PubMed

Kobayashi, Akira; Higashide, Tomomi; Yokogawa, Hideaki; Yamazaki, Natsuko; Masaki, Toshinori; Sugiyama, Kazuhisa

2014-01-01

To report the in vivo laser confocal microscopy findings of a cornea with osteogenesis imperfecta (OI) with special attention to the abnormality of Bowman's layer and sub-Bowman's fibrous structures (K-structures). Two patients (67-year-old male and his 26-year-old son) with OI type I were included in this study. Slit lamp biomicroscopic and in vivo laser confocal microscopic examinations were performed for both patients. Central corneal thickness and central endothelial cell density were also measured. Although the corneas looked clear with normal endothelial density for both eyes in both patients, they were quite thin (386 μm oculus dexter (OD) (the right eye) and 384 μm oculus sinister (OS) (the left eye) in the father and 430 μm OD and 425 μm OS in the son). In both patients, slit lamp biomicroscopic and in vivo laser confocal microscopic examination showed similar results. Anterior corneal mosaics produced by rubbing the eyelid under fluorescein were completely absent in both eyes. In vivo laser confocal microscopy revealed an absent or atrophic Bowman's layer; a trace of a presumed Bowman's layer and/or basement membrane was barely visible with high intensity. Additionally, K-structures were completely absent in both eyes. The absence of K-structures and fluorescein anterior corneal mosaics strongly suggested an abnormality of Bowman's layer in these OI patients.

The genetic basis of developmental abnormalities in interpopulation hybrids of the moss Ceratodon purpureus.

PubMed

McDaniel, Stuart F; Willis, John H; Shaw, A Jonathan

2008-07-01

Divergent populations are intrinsically reproductively isolated when hybrids between them either fail to develop properly or do not produce viable offspring. Intrinsic isolation may result from Dobzhansky-Muller (DM) incompatibilities, in which deleterious interactions among genes or gene products lead to developmental problems or underdominant chromosome structure differences between the parents. These mechanisms can be tested by studying marker segregation patterns in a hybrid mapping population. Here we examine the genetic basis of abnormal development in hybrids between two geographically distant populations of the moss Ceratodon purpureus. Approximately half of the hybrid progeny exhibited a severely reduced growth rate in early gametophyte development. We identified four unlinked quantitative trait loci (QTL) that interacted asymmetrically to cause the abnormal development phenotype. This pattern is consistent with DM interactions. We also found an excess of recombination between three marker pairs in the abnormally developing progeny, relative to that estimated in the normal progeny. This suggests that structural differences in these regions contribute to hybrid breakdown. Two QTL coincided with inferred structural differences, consistent with recent theory suggesting that rearrangements may harbor population divergence alleles. These observations suggest that multiple complex genetic factors contribute to divergence among populations of C. purpureus.

Can pharmacological and psychological treatment change brain structure and function in PTSD? A systematic review.

PubMed

Thomaes, Kathleen; Dorrepaal, Ethy; Draijer, Nel; Jansma, Elise P; Veltman, Dick J; van Balkom, Anton J

2014-03-01

While there is evidence of clinical improvement of posttraumatic stress disorder (PTSD) with treatment, its neural underpinnings are insufficiently clear. Moreover, it is unknown whether similar neurophysiological changes occur in PTSD specifically after child abuse, given its enduring nature and the developmental vulnerability of the brain during childhood. We systematically reviewed PTSD treatment effect studies on structural and functional brain changes from PubMed, EMBASE, PsycINFO, PILOTS and the Cochrane Library. We included studies on adults with (partial) PTSD in Randomized Controlled Trials (RCT) or pre-post designs (excluding case studies) on pharmacotherapy and psychotherapy. Risk of bias was evaluated independently by two raters. Brain coordinates and effect sizes were standardized for comparability. We included 15 studies (6 RCTs, 9 pre-post), four of which were on child abuse. Results showed that pharmacotherapy improved structural abnormalities (i.e., increased hippocampus volume) in both adult-trauma and child abuse related PTSD (3 pre-post studies). Functional changes were found to distinguish between groups. Adult-trauma PTSD patients showed decreased amygdala and increased dorsolateral prefrontal activations post-treatment (4 RCTs, 5 pre-post studies). In one RCT, child abuse patients showed no changes in the amygdala, but decreased dorsolateral prefrontal, dorsal anterior cingulate and insula activation post-treatment. In conclusion, pharmacotherapy may reduce structural abnormalities in PTSD, while psychotherapy may decrease amygdala activity and increase prefrontal, dorsal anterior cingulate and hippocampus activations, that may relate to extinction learning and re-appraisal. There is some evidence for a distinct activation pattern in child abuse patients, which clearly awaits further empirical testing. Copyright © 2013 Elsevier Ltd. All rights reserved.

Oligodendroglial Alterations and the Role of Microglia in White Matter Injury: Relevance to Schizophrenia

PubMed Central

Chew, Li-Jin; Fusar-Poli, Paolo; Schmitz, Thomas

2015-01-01

Schizophrenia is a chronic and debilitating mental illness characterized by a broad range of abnormal behaviors, including delusions and hallucinations, impaired cognitive function, as well as mood disturbances and social withdrawal. Due to the heterogeneous nature of the disease, the causes of schizophrenia are very complex; its etiology is believed to involve multiple brain regions and the connections between them, and includes alterations in both gray and white matter regions. The onset of symptoms varies with age and severity, and there is some debate over a degenerative or developmental etiology. Longitudinal magnetic resonance imaging studies have detected progressive gray matter loss in the first years of disease, suggesting neurodegeneration; but there is also increasing recognition of a temporal association between clinical complications at birth and disease onset that supports a neurodevelopmental origin. Presently, neuronal abnormalities in schizophrenia are better understood than alterations in myelin-producing cells of the brain, the oligodendrocytes, which are the predominant constituents of white matter structures. Proper white matter development and its structural integrity critically impacts brain connectivity, which affects sensorimotor coordination and cognitive ability. Evidence of defective white matter growth and compromised white matter integrity has been found in individuals at high risk of psychosis, and decreased numbers of mature oligodendrocytes are detected in schizophrenia patients. Inflammatory markers, including proinflammatory cytokines and chemokines, are also associated with psychosis. A relationship between risk of psychosis, white matter defects and prenatal inflammation is being established. Animal models of perinatal brain injury are successful in producing white matter damage in the brain, typified by hypomyelination and/or dysmyelination, impaired motor coordination and prepulse inhibition of the acoustic startle reflex, recapitulating structural and functional characteristics observed in schizophrenia. In addition, elevated expression of inflammation-related genes in brain tissue and increased production of cytokines by blood cells from patients with schizophrenia indicate immunological dysfunction and abnormal inflammatory responses, which are also important underlying features in experimental models. Microglia, resident immune defenders of the central nervous system, play important roles in the development and protection of neural cells, but can contribute to injury under pathological conditions. This article discusses oligodendroglial changes in schizophrenia and focuses on microglial activity in the context of the disease, in neonatal brain injury and in various experimental models of white matter damage. These include disorders associated with premature birth, and animal models of perinatal bacterial and viral infection, oxygen deprivation (hypoxia) and excess (hyperoxia), and elevated systemic proinflammatory cytokine levels. We briefly review the effects of treatment with antipsychotic and anti-inflammatory agents in models of perinatal brain injury, and comment on the therapeutic potential of these strategies. By understanding the neurobiological basis of oligodendroglial abnormalities in schizophrenia, it is hoped that patients will benefit from the availability of targeted and more efficacious treatment options. PMID:23446060

Association of recurrent pregnancy loss with chromosomal abnormalities and hereditary thrombophilias.

PubMed

Ocak, Z; Özlü, T; Ozyurt, O

2013-06-01

Recurrent pregnancy loss (RPL) which is generally known as >3 consecutive pregnancy losses before 20 weeks' gestation is seen in 0.5-2% of women. To evaluate the association of parental and fetal chromosomal abnormalities with recurrent pregnancy loss in our area and to analyze the frequency of three types of hereditary thrombophilia's; (MTHFR C677T polymorphisms, FV Leiden G1691A mutation and Prothrombin (factor II) G20210A mutation) in these female patients. The present case-control retrospective study was performed between February 2007 and December 2011 on 495 couples, who had two or more consecutive pregnancy losses before 20 weeks' gestation. We used conventional cytogenetic analysis and polymerase chain reaction-restriction fragment length polymorphism. Parental chromosomal abnormality was detected in 28 cases (2.8% of all cases, 5.7% of the couples) most of which (92.9%) were structural abnormalities. All of the structural abnormalities were balanced chromosomal translocations. Chromosomal analysis performed from the abortion materials detected a major chromosomal abnormality in 31.9% of the cases. The most frequently observed alteration in the hereditary thrombophilia genes was heterozygote mutation for the MTHFR C677T polymorphisms (n=55). Balanced translocations are the most commonly detected chromosomal abnormalities in couples being evaluated for recurrent pregnancy loss and these patients are the best candidates for offering prenatal genetic diagnosis by the help of which there is a possibility of obtaining a better reproductive outcome.

Practical approach to the gastrointestinal manifestations of cystic fibrosis.

PubMed

Bolia, Rishi; Ooi, Chee Y; Lewindon, Peter; Bishop, Jonathan; Ranganathan, Sarath; Harrison, Jo; Ford, Kristyn; van der Haak, Natalie; Oliver, Mark R

2018-05-16

Cystic fibrosis (CF) is the most common, life-shortening, genetic illness affecting children in Australia and New Zealand. The genetic abnormality results in abnormal anion transport across the apical membrane of epithelial cells in a number of organs, including the lungs, gastrointestinal tract, liver and genito-urinary tract. Thus, CF is a multi-system disorder that requires a multi-disciplinary approach. Respiratory disease is the predominant cause of both morbidity and mortality in patients with CF. However, there are significant and clinically relevant gastrointestinal, liver, pancreatic and nutritional manifestations that must be detected and managed in a timely and structured manner. The aim of this review is to provide evidence-based information and clinical algorithms to guide the nutritional and gastrointestinal management of patients with CF. © 2018 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

Ophthalmic pathology of Nance-Horan syndrome: case report and review of the literature.

PubMed

Ding, Xiaoyan; Patel, Mrinali; Herzlich, Alexandra A; Sieving, Pamela C; Chan, Chi-Chao

2009-09-01

Nance-Horan syndrome (NHS) is a rare X-linked disorder typified by dense congenital central cataracts, microcornea, anteverted and simplex pinnae, brachymetacarpalia, and numerous dental anomalies due in most cases to a mutation in the NHS gene. We present a case of clinical manifestation and ocular pathology in a patient with NHS. This article also reviews and discusses the relevant literature. Classic and novel ocular pathological findings of a young male with NHS are described, including congenital cataracts, infantile glaucoma, scleral staphyloma, and severe retinal cystoid degeneration. We report a new pathological finding of severe retinal cystoid degeneration in this NHS patient and confirm abnormal development of the anterior chamber angle structure. These findings, coupled with our analysis of the available NHS literature, provide new understanding of the histopathological basis of ocular abnormalities and vision loss in NHS.

Urologic evaluation of urinary tract infection in pregnancy.

PubMed

Diokno, A C; Compton, A; Seski, J; Vinson, R

1986-01-01

Thirty-three antepartum patients with urinary tract infections underwent urologic evaluation as soon as the infection had been successfully treated. The evaluation included history of voiding habits, cystometry, urethral calibration and cystourethroscopy. A second phase of the urologic evaluation included an excretory urogram and repeat cystometry 10-12 weeks postpartum. Sixty percent had a history of infrequent voiding, and 90% of them had a bladder capacity greater than 450 mL. Forty-one percent of the patients had a normal bladder capacity (less than 450 mL), and 85% of this group did not have any history of infrequent voiding. The radiographic evaluation postpartum in 18 of 33 patients revealed major abnormalities in 50%. These abnormalities were seen as often and were as significant in women with asymptomatic bacteriuria as in those who presented with acute pyelonephritis. The results suggest that the large bladder seen in pregnant women may be secondary to the chronic, unphysiologic habit of infrequent voiding. Furthermore, this study reinforced the fact that most pregnant women with urinary tract infection have preexisting chronic bladder or renal abnormalities that predispose them to infection. Those at risk should be identified early through a careful history and urinalysis to determine which ones need urinary prophylaxis during pregnancy. Postpartum urologic investigation should be carried out to identify any structural or functional problems; understanding them is helpful in present and future management.

Chromosomal abnormalities are associated with aging and cancer

Cancer.gov

Two new studies have found that large structural abnormalities in chromosomes, some of which have been associated with increased risk of cancer, can be detected in a small fraction of people without a prior history of cancer. The studies found that these

Service Member Suicide and Readiness: An Analysis

DTIC Science & Technology

2017-05-25

Young Adults,” Journal of Abnormal Psychology 118 (2009): 634-46. 180 L. C. Hawkley et al., “From Social Structural Factors to Perceptions of...Suicidality Relate Even When Everything but the Kitchen Sink is Covaried.” Journal of Abnormal Psychology 114, no. 2 (May 2005): 291-303. Joiner, Thomas E...Adults.” Journal of Abnormal Psychology 118, no. 3 (2009): 634-46. Joint Publication (JP) 1-02, Department of Defense Dictionary of Military and

The impact of additional cytogenetic abnormalities at diagnosis and during therapy with tyrosine kinase inhibitors in Chronic Myeloid Leukaemia.

PubMed

Crisan, A M; Coriu, D; Arion, C; Colita, A; Jardan, C

2015-01-01

Chronic Myeloid Leukemia's (CML) treatment was optimized since the development of tyrosine kinase inhibitors (TKI) and an increased overall survival during TKI was noticed. During the TKI era, protocols for assessing response and resistance to treatment were developed. Additional chromosomal abnormalities (ACAs) are strongly associated with disease progression but their prognostic impact and influence on treatment response are yet to be defined. The aim of this study was to analyze the impact of ACAs on time to achieve complete cytogenetic response (CCyR), treatment and overall survival. Since 2005 until 2013, the data from the Hematology and Bone Marrow Transplantation Department of Fundeni Clinical Institute was collected. In this observational retrospective single centre study, 28 CML patients with ACAs at diagnosis and during TKI treatment were included. From ACAs at diagnosis group, the most frequent major route ACAs were trisomy 8, trisomy 19 and second Philadelphia (Ph) chromosome and the most frequent minor route ACAs were monosomies and structural abnormalities (inversions and translocations). From the ACAs during the TKI group, the most frequent major route cytogenetic abnormalities in Ph positive and negative cells were trisomy 8, trisomy 19 and second Ph chromosome and the most frequent minor route cytogenetic abnormalities in Ph positive and negative cells were marker chromosomes and structural abnormalities (inversions, translocations and dicentric chromosomes). In both groups, the time to CCyR was longer and long-term results were inferior in comparison with standard patients but the differences were not significant and in accordance to published data. The 12 months follow-up after the study's end showed that 26 patients were alive and in long-term CCyR and 2 deaths were reported. CML = Chronic Myeloid Leukemia, BCR-ABL1 = Break Cluster Region - Abelson gene, TKI = tyrosine kinase inhibitor treatment, ACAs = additional cytogenetic abnormalities, CCyR = complete cytogenetic response, PCyR = partial cytogenetic response, mCyR = minor cytogenetic response, MMR = major molecular response, HSCT = hematopoietic stem cell transplant, HLA = human leukocyte antigens, CP = chronic phase, AP = accelerated phase, BP = blast phase, OS = overall survival, CBA = chromosome banding analysis, +8 = trisomy 8, i(17q) = isochromosome (17q), +Ph = second Philadelphia chromosome, -7 = monosomy 7, -17 = monosomy 17, +17 = trisomy 17, -21 = monosomy 21, +21 = trisomy 21, -Y = loss of Y chromosome, ELN = European LeukemiaNet, IMA600 = Imatinib 600 mg daily, IMA400 = Imatinib 400 mg daily, NILO600 = Nilotinib 600 mg daily, DASA100 = Dasatinib 100mg daily, DASA140 = Dasatinib 140 mg daily.

Abnormal branching and regression of the notochord and its relationship to foregut abnormalities.

PubMed

Vleesch Dubois, V N; Quan Qi, B; Beasley, S W; Williams, A

2002-04-01

An abnormally positioned notochord has been reported in embryos that develop foregut abnormalities, vertebral defects and other abnormalities of the VATER association. This study examines the patterns of regression of the abnormal notochord in the rat model of the VATER association and investigates the relationship between developmental abnormalities of the notochord and those of the vertebra and foregut. Timed-pregnant Sprague-Dawley rats were given daily intraperitoneal injections of 1.75 mg/kg adriamycin on gestational days 6 - 9 inclusive. Rats were sacrificed between days 14 and 20 and their embryos harvested, histologically sectioned and stained and examined serially. The location and appearance of the degenerating notochord and its relationship to regional structural defects were analysed. All 26 embryos exposed to adriamycin developed foregut abnormalities and had an abnormal notochord. The notochord disappeared by a process of apoptotic degeneration that lagged behind that of the normal embryo: the notochord persisted in the abnormal embryo beyond day 17, whereas in the normal rat it had already disappeared. Similarly, formation of the nucleus pulposus was delayed. Vertebral abnormalities occurred when the notochord was ventrally-positioned. The notochord disappears during day 16 in the normal embryo whereas abnormal branches of the notochord persist until day 19 in the adriamycin-treated embryo. Degeneration of the notochord is dominated by apoptosis. An excessively ventrally-placed notochord is closely associated with abnormalities of the vertebral column, especially hemivertebrae.

Critical review of the developmental toxicity and teratogenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin: Recent advances toward understanding the mechanism

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

Couture, L.A.; Abbott, B.D.; Birnbaum, L.S.

1990-01-01

A specific teratogenic response is elicited in the mouse as a result of exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin). The characteristic spectrum of structural malformations induced in mice following exposure to TCDD and structurally-related congeners is highly reproducible and includes both hydronephrosis and cleft palate. In addition, prenatal exposure to TCDD has been shown to induce thymic hypoplasia. The three abnormalities occur at doses well below those producing maternal or embryo/fetal toxicity, and are among the most sensitive indicators of dioxin toxicity. In all other laboratory species tested, TCDD causes maternal and embryo/fetal toxicity, but does not induce a significant increasemore » in the incidence of structural abnormalities even at toxic dose levels. Developmental toxicity occurs in a similar dose range across species, however, mice are particularly susceptible to development of TCDD-induced terata. Recent experiments using an organ culture were an attempt to address the issue of species and organ differences in sensitivity to TCDD. Human palatal shelves were examined in this in vitro system, and were found to approximate the rat in terms of sensitivity for induction of cleft palate.« less

Abnormal Labyrinthine Zone in the Hectd1-null Placenta

PubMed Central

Sarkar, Anjali A.; Sabatino, Julia A.; Sugrue, Kelsey F.; Zohn, Irene E.

2016-01-01

Introduction The labyrinthine zone of the placenta is where exchange of nutrients and waste occurs between maternal and fetal circulations. Proper development of the placental labyrinth is essential for successful growth of the developing fetus and abnormalities in placental development are associated with intrauterine growth restriction (IUGR), preeclampsia and fetal demise. Our previous studies demonstrate that Hectd1 is essential for development of the junctional and labyrinthine zones of the placenta. Here we further characterize labyrinthine zone defects in the Hectd1 mutant placenta. Methods The structure of the mutant placenta was compared to wildtype littermates using histological methods. The expression of cell type specific markers was examined by immunohistochemistry and in situ hybridization. Results Hectd1 is expressed in the labyrinthine zone throughout development and the protein is enriched in syncytiotrophoblast layer type I cells (SynT-I) and Sinusoidal Trophoblast Giant cells (S-TGCs) in the mature placenta. Mutation of Hectd1 results in pale placentas with frequent hemorrhages along with gross abnormalities in the structure of the labyrinthine zone including a smaller overall volume and a poorly elaborated fetal vasculature that contain fewer fetal blood cells. Examination of molecular markers of labyrinthine trophoblast cell types reveals increased Dlx3 positive cells and Syna positive SynT-I cells, along with decreased Hand1 and Ctsq positive sinusoidal trophoblast giant cells (S-TGCs). Discussion Together these defects indicate that Hectd1 is required for development of the labyrinthine zone or the mouse placenta. PMID:26907377

Abnormal labyrinthine zone in the Hectd1-null placenta.

PubMed

Sarkar, Anjali A; Sabatino, Julia A; Sugrue, Kelsey F; Zohn, Irene E

2016-02-01

The labyrinthine zone of the placenta is where exchange of nutrients and waste occurs between maternal and fetal circulations. Proper development of the placental labyrinth is essential for successful growth of the developing fetus and abnormalities in placental development are associated with intrauterine growth restriction (IUGR), preeclampsia and fetal demise. Our previous studies demonstrate that Hectd1 is essential for development of the junctional and labyrinthine zones of the placenta. Here we further characterize labyrinthine zone defects in the Hectd1 mutant placenta. The structure of the mutant placenta was compared to wildtype littermates using histological methods. The expression of cell type specific markers was examined by immunohistochemistry and in situ hybridization. Hectd1 is expressed in the labyrinthine zone throughout development and the protein is enriched in syncytiotrophoblast layer type I cells (SynT-I) and Sinusoidal Trophoblast Giant cells (S-TGCs) in the mature placenta. Mutation of Hectd1 results in pale placentas with frequent hemorrhages along with gross abnormalities in the structure of the labyrinthine zone including a smaller overall volume and a poorly elaborated fetal vasculature that contain fewer fetal blood cells. Examination of molecular markers of labyrinthine trophoblast cell types reveals increased Dlx3 positive cells and Syna positive SynT-I cells, along with decreased Hand1 and Ctsq positive sinusoidal trophoblast giant cells (S-TGCs). Together these defects indicate that Hectd1 is required for development of the labyrinthine zonethe mouse placenta. Copyright © 2015 Elsevier Ltd. All rights reserved.

Direct voxel-based comparisons between grey matter shrinkage and glucose hypometabolism in chronic alcoholism.

PubMed

Ritz, Ludivine; Segobin, Shailendra; Lannuzel, Coralie; Boudehent, Céline; Vabret, François; Eustache, Francis; Beaunieux, Hélène; Pitel, Anne L

2016-09-01

Alcoholism is associated with widespread brain structural abnormalities affecting mainly the frontocerebellar and the Papez's circuits. Brain glucose metabolism has received limited attention, and few studies used regions of interest approach and showed reduced global brain metabolism predominantly in the frontal and parietal lobes. Even though these studies have examined the relationship between grey matter shrinkage and hypometabolism, none has performed a direct voxel-by-voxel comparison between the degrees of structural and metabolic abnormalities. Seventeen alcoholic patients and 16 control subjects underwent both structural magnetic resonance imaging and (18)F-2-fluoro-deoxy-glucose-positron emission tomography examinations. Structural abnormalities and hypometabolism were examined in alcoholic patients compared with control subjects using two-sample t-tests. Then, these two patterns of brain damage were directly compared with a paired t-test. Compared to controls, alcoholic patients had grey matter shrinkage and hypometabolism in the fronto-cerebellar circuit and several nodes of Papez's circuit. The direct comparison revealed greater shrinkage than hypometabolism in the cerebellum, cingulate cortex, thalamus and hippocampus and parahippocampal gyrus. Conversely, hypometabolism was more severe than shrinkage in the dorsolateral, premotor and parietal cortices. The distinct profiles of abnormalities found within the Papez's circuit, the fronto-cerebellar circuit and the parietal gyrus in chronic alcoholism suggest the involvement of different pathological mechanisms. © The Author(s) 2015.

Direct voxel-based comparisons between grey matter shrinkage and glucose hypometabolism in chronic alcoholism

PubMed Central

Ritz, Ludivine; Segobin, Shailendra; Lannuzel, Coralie; Boudehent, Céline; Vabret, François; Eustache, Francis; Beaunieux, Hélène

2015-01-01

Alcoholism is associated with widespread brain structural abnormalities affecting mainly the frontocerebellar and the Papez’s circuits. Brain glucose metabolism has received limited attention, and few studies used regions of interest approach and showed reduced global brain metabolism predominantly in the frontal and parietal lobes. Even though these studies have examined the relationship between grey matter shrinkage and hypometabolism, none has performed a direct voxel-by-voxel comparison between the degrees of structural and metabolic abnormalities. Seventeen alcoholic patients and 16 control subjects underwent both structural magnetic resonance imaging and 18F-2-fluoro-deoxy-glucose-positron emission tomography examinations. Structural abnormalities and hypometabolism were examined in alcoholic patients compared with control subjects using two-sample t-tests. Then, these two patterns of brain damage were directly compared with a paired t-test. Compared to controls, alcoholic patients had grey matter shrinkage and hypometabolism in the fronto-cerebellar circuit and several nodes of Papez’s circuit. The direct comparison revealed greater shrinkage than hypometabolism in the cerebellum, cingulate cortex, thalamus and hippocampus and parahippocampal gyrus. Conversely, hypometabolism was more severe than shrinkage in the dorsolateral, premotor and parietal cortices. The distinct profiles of abnormalities found within the Papez’s circuit, the fronto-cerebellar circuit and the parietal gyrus in chronic alcoholism suggest the involvement of different pathological mechanisms. PMID:26661206

Improved detection rate of structural abnormalities in the first trimester using an extended examination protocol.

PubMed

Iliescu, D; Tudorache, S; Comanescu, A; Antsaklis, P; Cotarcea, S; Novac, L; Cernea, N; Antsaklis, A

2013-09-01

To assess the potential of first-trimester sonography in the detection of fetal abnormalities using an extended protocol that is achievable with reasonable resources of time, personnel and ultrasound equipment. This was a prospective two-center 2-year study of 5472 consecutive unselected pregnant women examined at 12 to 13 + 6 gestational weeks. Women were examined using an extended morphogenetic ultrasound protocol that, in addition to the basic evaluation, involved a color Doppler cardiac sweep and identification of early contingent markers for major abnormalities. The prevalence of lethal and severe malformations was 1.39%. The first-trimester scan identified 40.6% of the cases detected overall and 76.3% of major structural defects. The first-trimester detection rate (DR) for major congenital heart disease (either isolated or associated with extracardiac abnormalities) was 90% and that for major central nervous system anomalies was 69.5%. In fetuses with increased nuchal translucency (NT), the first-trimester DR for major anomalies was 96%, and in fetuses with normal NT it was 66.7%. Most (67.1%) cases with major abnormalities presented with normal NT. A detailed first-trimester anomaly scan using an extended protocol is an efficient screening method to detect major fetal structural abnormalities in low-risk pregnancies. It is feasible at 12 to 13 + 6 weeks with ultrasound equipment and personnel already used for routine first-trimester screening. Rate of detection of severe malformations is greater in early- than in mid-pregnancy and on postnatal evaluation. Early heart investigation could be improved by an extended protocol involving use of color Doppler. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.

Disruption of Ah Receptor Signaling during Mouse Development Leads to Abnormal Cardiac Structure and Function in the Adult

PubMed Central

Carreira, Vinicius S.; Fan, Yunxia; Kurita, Hisaka; Wang, Qin; Ko, Chia-I; Naticchioni, Mindi; Jiang, Min; Koch, Sheryl; Zhang, Xiang; Biesiada, Jacek; Medvedovic, Mario; Xia, Ying; Rubinstein, Jack; Puga, Alvaro

2015-01-01

The Developmental Origins of Health and Disease (DOHaD) Theory proposes that the environment encountered during fetal life and infancy permanently shapes tissue physiology and homeostasis such that damage resulting from maternal stress, poor nutrition or exposure to environmental agents may be at the heart of adult onset disease. Interference with endogenous developmental functions of the aryl hydrocarbon receptor (AHR), either by gene ablation or by exposure in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent AHR ligand, causes structural, molecular and functional cardiac abnormalities and altered heart physiology in mouse embryos. To test if embryonic effects progress into an adult phenotype, we investigated whether Ahr ablation or TCDD exposure in utero resulted in cardiac abnormalities in adult mice long after removal of the agent. Ten-months old adult Ahr -/- and in utero TCDD-exposed Ahr +/+ mice showed sexually dimorphic abnormal cardiovascular phenotypes characterized by echocardiographic findings of hypertrophy, ventricular dilation and increased heart weight, resting heart rate and systolic and mean blood pressure, and decreased exercise tolerance. Underlying these effects, genes in signaling networks related to cardiac hypertrophy and mitochondrial function were differentially expressed. Cardiac dysfunction in mouse embryos resulting from AHR signaling disruption seems to progress into abnormal cardiac structure and function that predispose adults to cardiac disease, but while embryonic dysfunction is equally robust in males and females, the adult abnormalities are more prevalent in females, with the highest severity in Ahr -/- females. The findings reported here underscore the conclusion that AHR signaling in the developing heart is one potential target of environmental factors associated with cardiovascular disease. PMID:26555816

Recurrent abnormalities in conifer cones and the evolutionary origins of flower-like structures.

PubMed

Rudall, Paula J; Hilton, Jason; Vergara-Silva, Francisco; Bateman, Richard M

2011-03-01

Conifer cones are reproductive structures that are typically of restricted growth and either exclusively pollen-bearing (male) or exclusively ovule-bearing (female). Here, we review two common spontaneous developmental abnormalities of conifer cones: proliferated cones, in which the apex grows vegetatively, and bisexual cones, which possess both male and female structures. Emerging developmental genetic data, combined with evidence from comparative morphology, ontogeny and palaeobotany, provide new insights into the evolution of both cones and flowers, and prompt novel strategies for understanding seed-plant evolution. Copyright © 2010 Elsevier Ltd. All rights reserved.

Approaching a network connectivity-driven classification of the psychosis continuum: a selective review and suggestions for future research.

PubMed

Schmidt, André; Diwadkar, Vaibhav A; Smieskova, Renata; Harrisberger, Fabienne; Lang, Undine E; McGuire, Philip; Fusar-Poli, Paolo; Borgwardt, Stefan

2014-01-01

Brain changes in schizophrenia evolve along a dynamic trajectory, emerging before disease onset and proceeding with ongoing illness. Recent investigations have focused attention on functional brain interactions, with experimental imaging studies supporting the disconnection hypothesis of schizophrenia. These studies have revealed a broad spectrum of abnormalities in brain connectivity in patients, particularly for connections integrating the frontal cortex. A critical point is that brain connectivity abnormalities, including altered resting state connectivity within the fronto-parietal (FP) network, are already observed in non-help-seeking individuals with psychotic-like experiences. If we consider psychosis as a continuum, with individuals with psychotic-like experiences at the lower and psychotic patients at the upper ends, individuals with psychotic-like experiences represent a key population for investigating the validity of putative biomarkers underlying the onset of psychosis. This paper selectively addresses the role played by FP connectivity in the psychosis continuum, which includes patients with chronic psychosis, early psychosis, clinical high risk, genetic high risk, as well as the general population with psychotic experiences. We first discuss structural connectivity changes among the FP pathway in each domain in the psychosis continuum. This may provide a basis for us to gain an understanding of the subsequent changes in functional FP connectivity. We further indicate that abnormal FP connectivity may arise from glutamatergic disturbances of this pathway, in particular from abnormal NMDA receptor-mediated plasticity. In the second part of this paper we propose some concepts for further research on the use of network connectivity in the classification of the psychosis continuum. These concepts are consistent with recent efforts to enhance the role of data in driving the diagnosis of psychiatric spectrum diseases.

Approaching a network connectivity-driven classification of the psychosis continuum: a selective review and suggestions for future research

PubMed Central

Schmidt, André; Diwadkar, Vaibhav A.; Smieskova, Renata; Harrisberger, Fabienne; Lang, Undine E.; McGuire, Philip; Fusar-Poli, Paolo; Borgwardt, Stefan

2015-01-01

Brain changes in schizophrenia evolve along a dynamic trajectory, emerging before disease onset and proceeding with ongoing illness. Recent investigations have focused attention on functional brain interactions, with experimental imaging studies supporting the disconnection hypothesis of schizophrenia. These studies have revealed a broad spectrum of abnormalities in brain connectivity in patients, particularly for connections integrating the frontal cortex. A critical point is that brain connectivity abnormalities, including altered resting state connectivity within the fronto-parietal (FP) network, are already observed in non-help-seeking individuals with psychotic-like experiences. If we consider psychosis as a continuum, with individuals with psychotic-like experiences at the lower and psychotic patients at the upper ends, individuals with psychotic-like experiences represent a key population for investigating the validity of putative biomarkers underlying the onset of psychosis. This paper selectively addresses the role played by FP connectivity in the psychosis continuum, which includes patients with chronic psychosis, early psychosis, clinical high risk, genetic high risk, as well as the general population with psychotic experiences. We first discuss structural connectivity changes among the FP pathway in each domain in the psychosis continuum. This may provide a basis for us to gain an understanding of the subsequent changes in functional FP connectivity. We further indicate that abnormal FP connectivity may arise from glutamatergic disturbances of this pathway, in particular from abnormal NMDA receptor-mediated plasticity. In the second part of this paper we propose some concepts for further research on the use of network connectivity in the classification of the psychosis continuum. These concepts are consistent with recent efforts to enhance the role of data in driving the diagnosis of psychiatric spectrum diseases. PMID:25628553

Sex differences of gray matter morphology in cortico-limbic-striatal neural system in major depressive disorder.

PubMed

Kong, Lingtao; Chen, Kaiyuan; Womer, Fay; Jiang, Wenyan; Luo, Xingguang; Driesen, Naomi; Liu, Jie; Blumberg, Hilary; Tang, Yanqing; Xu, Ke; Wang, Fei

2013-06-01

Sex differences are observed in both epidemiological and clinical aspects of major depressive disorder (MDD). The cortico-limbic-striatal neural system, including the prefrontal cortex, amygdala, hippocampus, and striatum, have shown sexually dimorphic morphological features and have been implicated in the dysfunctional regulation of mood and emotion in MDD. In this study, we utilized a whole-brain, voxel-based approach to examine sex differences in the regional distribution of gray matter (GM) morphological abnormalities in medication-naïve participants with MDD. Participants included 29 medication-naïve individuals with MDD (16 females and 13 males) and 33 healthy controls (HC) (17 females and 16 males). Gray matter morphology of the cortico-limbic-striatal neural system was examined using voxel-based morphometry analyzes of high-resolution structural magnetic resonance imaging scans. The main effect of diagnosis and interaction effect of diagnosis by sex on GM morphology were statistically significant (p < 0.05, corrected) in the left ventral prefrontal cortex, right amygdala, right hippocampus and bilateral caudate when comparing the MDD and HC groups. Posthoc analyzes showed that females with MDD had significant GM decreases in limbic regions (p < 0.05, corrected), compared to female HC; while males with MDD demonstrated significant GM reduction in striatal regions, (p < 0.05, corrected), compared to HC males. The observed sex-related patterns of abnormalities within the cortico-limbic-strial neural system, such as predominant prefrontal-limbic abnormalities in MDD females vs. predominant prefrontal-striatal abnormalities in MDD males, suggest differences in neural circuitry that may mediate sex differences in the clinical presentation of MDD and potential targets for sex-differentiated treatment of the disorder. Copyright © 2013 Elsevier Ltd. All rights reserved.

Abnormal frontal theta oscillations underlie the cognitive flexibility deficits in children with high-functioning autism spectrum disorders.

PubMed

Yeung, Michael K; Han, Yvonne M Y; Sze, Sophia L; Chan, Agnes S

2016-03-01

Deficits in cognitive flexibility have been suggested to underlie the repetitive and stereotyped behavior in individuals with autism spectrum disorders (ASD). Because cognitive flexibility is primarily mediated by the frontal lobe, where structural and functional abnormalities have been extensively found in these individuals, it is conceivable that their deficits in cognitive flexibility are related to abnormal activations of the frontal lobe. The present study investigates cognitive flexibility and its underlying neurophysiological activities as indicated by theta oscillations in children with ASD. Twenty-five children with high-functioning ASD and 25 IQ- and age-matched typically developing (TD) children were subjected to neuropsychological assessments on cognitive flexibility and electroencephalography recordings. The children with ASD performed significantly worse than the TD children across the tasks of cognitive flexibility, including the modified Wisconsin Card Sorting Test (WCST). These children also demonstrated a reduced increase of the theta power localized in multiple brain regions, including various sectors of the frontal lobe at the late stage (i.e., 600 ms-900 ms poststimulus interval) but not the early stage (i.e., 250 ms-550 ms poststimulus interval) of the performance of the modified WCST. The suppressed late frontal theta activities were further shown to be significantly correlated with a poorer performance on the cognitive flexibility measures. Our findings suggest that abnormal activations of multiple cortical regions, especially the frontal lobe, form the neural basis of the cognitive flexibility deficits in children with ASD. In addition, we found an EEG marker of cognitive flexibility which could be used to monitor treatment outcomes objectively. (c) 2016 APA, all rights reserved).

Acromegalic arthropathy in various stages of the disease: an MRI study.

PubMed

Claessen, K M J A; Canete, A Navas; de Bruin, P W; Pereira, A M; Kloppenburg, M; Kroon, H M; Biermasz, N R

2017-06-01

Arthropathy is a prevalent and invalidating complication of acromegaly with a characteristic radiographic phenotype. We aimed to further characterize cartilage and bone abnormalities associated with acromegalic arthropathy using magnetic resonance imaging (MRI). Twenty-six patients (23% women, mean age 56.8 ± 13.4 years), with active ( n  = 10) and controlled acromegaly ( n  = 16) underwent a 3.0 T MRI of the right knee. Osteophytes, cartilage defects, bone marrow lesions and subchondral cysts were assessed by the Knee Osteoarthritis Scoring System (KOSS) method. Cartilage thickness and cartilage T2 relaxation times, in which higher values reflect increased water content and/or structural changes, were measured. Twenty-five controls (52% women, mean age: 59.6 ± 8.0 years) with primary knee OA were included for comparison. Both in active and controlled acromegaly, structural OA defects were highly prevalent, with thickest cartilage and highest cartilage T2 relaxation times in the active patients. When compared to primary OA subjects, patients with acromegaly seem to have less cysts (12% vs 48%, P  = 0.001) and bone marrow lesions (15% vs 80%, P  = 0.006), but comparable prevalence of osteophytosis and cartilage defects. Patients with acromegaly had 31% thicker total joint cartilage ( P  < 0.001) with higher cartilage T2 relaxation times at all measured sites than primary OA subjects ( P  < 0.01). Patients with active acromegaly have a high prevalence of structural OA abnormalities in combination with thick joint cartilage. In addition, T2 relaxation times of cartilage are high in active patients, indicating unhealthy cartilage with increased water content, which is (partially) reversible by adequate treatment. Patients with acromegaly have a different distribution of structural OA abnormalities visualized by MRI than primary OA subjects, especially of cartilage defects. © 2017 European Society of Endocrinology.

Right ventricular outflow tract high-density endocardial unipolar voltage mapping in patients with Brugada syndrome: evidence for electroanatomical abnormalities.

PubMed

Letsas, Konstantinos P; Efremidis, Michael; Vlachos, Konstantinos; Georgopoulos, Stamatis; Karamichalakis, Nikolaos; Asvestas, Dimitrios; Valkanas, Kosmas; Korantzopoulos, Panagiotis; Liu, Tong; Sideris, Antonios

2017-05-02

Epicardial structural abnormalities at the right ventricular outflow tract (RVOT) may provide the arrhythmia substrate in Brugada syndrome (BrS). Electroanatomical endocardial unipolar voltage mapping is an emerging tool that accurately identifies epicardial abnormalities in different clinical settings. This study investigated whether endocardial unipolar voltage mapping of the RVOT detects electroanatomical abnormalities in patients with BrS. Ten asymptomatic patients (8 males, 34.5 ± 11.2 years) with spontaneous type 1 ECG pattern of BrS and negative late gadolinium enhancement-cardiac magnetic resonance imaging (LGE-c-MRI) underwent high-density endocardial electroanatomical mapping (>800 points). Using a cut-off of 1 mV and 4 mV for normal bipolar and unipolar voltage, respectively, derived from 20 control patients without structural heart disease established by LGE-c-MRI, the extend of low-voltage areas within the RVOT was estimated using a specific calculation software. The mean RVOT area presenting low-voltage bipolar signals in BrS patients was 3.4 ± 1.7 cm2 (range 1.5-7 cm2). A significantly greater area of abnormal unipolar signals was identified (12.6 ± 4.6 cm2 [range 7-22 cm2], P: 0.001). Both bipolar and unipolar electroanatomical abnormalities were mainly located at the free wall of the RVOT. The mean RVOT activation time was significantly prolonged in BrS patients compared to control population (86.4 ± 16.5 vs. 63.4 ± 9.7 ms, P < 0.001). Isochronal mapping demonstrated lines of conduction slowing within the RVOT in 8/10 BrS patients. Wide areas of endocardial unipolar voltage abnormalities that possibly reflect epicardial structural abnormalities are identified at the RVOT of BrS patients. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Structural MRI biomarkers of shared pathogenesis in autism spectrum disorder and epilepsy.

PubMed

Blackmon, Karen

2015-06-01

Etiological factors that contribute to a high comorbidity between autism spectrum disorder (ASD) and epilepsy are the subject of much debate. Does epilepsy cause ASD or are there common underlying brain abnormalities that increase the risk of developing both disorders? This review summarizes evidence from quantitative MRI studies to suggest that abnormalities of brain structure are not necessarily the consequence of ASD and epilepsy but are antecedent to disease expression. Abnormal gray and white matter volumes are present prior to onset of ASD and evident at the time of onset in pediatric epilepsy. Aberrant brain growth trajectories are also common in both disorders, as evidenced by blunted gray matter maturation and white matter maturation. Although the etiological factors that explain these abnormalities are unclear, high heritability estimates for gray matter volume and white matter microstructure demonstrate that genetic factors assert a strong influence on brain structure. In addition, histopathological studies of ASD and epilepsy brain tissue reveal elevated rates of malformations of cortical development (MCDs), such as focal cortical dysplasia and heterotopias, which supports disruption of neuronal migration as a contributing factor. Although MCDs are not always visible on MRI with conventional radiological analysis, quantitative MRI detection methods show high sensitivity to subtle malformations in epilepsy and can be potentially applied to MCD detection in ASD. Such an approach is critical for establishing quantitative neuroanatomic endophenotypes that can be used in genetic research. In the context of emerging drug treatments for seizures and autism symptoms, such as rapamycin and rapalogs, in vivo neuroimaging markers of subtle structural brain abnormalities could improve sample stratification in human clinical trials and potentially extend the range of patients that might benefit from treatment. This article is part of a Special Issue entitled "Autism and Epilepsy". Copyright © 2015 Elsevier Inc. All rights reserved.

Atypical sulcal anatomy in young children with autism spectrum disorder

PubMed Central

Auzias, G.; Viellard, M.; Takerkart, S.; Villeneuve, N.; Poinso, F.; Fonséca, D. Da; Girard, N.; Deruelle, C.

2014-01-01

Autism spectrum disorder is associated with an altered early brain development. However, the specific cortical structure abnormalities underlying this disorder remain largely unknown. Nonetheless, atypical cortical folding provides lingering evidence of early disruptions in neurodevelopmental processes and identifying changes in the geometry of cortical sulci is of primary interest for characterizing these structural abnormalities in autism and their evolution over the first stages of brain development. Here, we applied state-of-the-art sulcus-based morphometry methods to a large highly-selective cohort of 73 young male children of age spanning from 18 to 108 months. Moreover, such large cohort was selected through extensive behavioral assessments and stringent inclusion criteria for the group of 59 children with autism. After manual labeling of 59 different sulci in each hemisphere, we computed multiple shape descriptors for each single sulcus element, hereby separating the folding measurement into distinct factors such as the length and depth of the sulcus. We demonstrated that the central, intraparietal and frontal medial sulci showed a significant and consistent pattern of abnormalities across our different geometrical indices. We also found that autistic and control children exhibited strikingly different relationships between age and structural changes in brain morphology. Lastly, the different measures of sulcus shapes were correlated with the CARS and ADOS scores that are specific to the autistic pathology and indices of symptom severity. Inherently, these structural abnormalities are confined to regions that are functionally relevant with respect to cognitive disorders in ASD. In contrast to those previously reported in adults, it is very unlikely that these abnormalities originate from general compensatory mechanisms unrelated to the primary pathology. Rather, they most probably reflect an early disruption on developmental trajectory that could be part of the primary pathology. PMID:24936410

Deficits in Neurite Density Underlie White Matter Structure Abnormalities in First-Episode Psychosis.

PubMed

Rae, Charlotte L; Davies, Geoff; Garfinkel, Sarah N; Gabel, Matt C; Dowell, Nicholas G; Cercignani, Mara; Seth, Anil K; Greenwood, Kathryn E; Medford, Nick; Critchley, Hugo D

2017-11-15

Structural abnormalities across multiple white matter tracts are recognized in people with early psychosis, consistent with dysconnectivity as a neuropathological account of symptom expression. We applied advanced neuroimaging techniques to characterize microstructural white matter abnormalities for a deeper understanding of the developmental etiology of psychosis. Thirty-five first-episode psychosis patients, and 19 healthy controls, participated in a quantitative neuroimaging study using neurite orientation dispersion and density imaging, a multishell diffusion-weighted magnetic resonance imaging technique that distinguishes white matter fiber arrangement and geometry from changes in neurite density. Fractional anisotropy (FA) and mean diffusivity images were also derived. Tract-based spatial statistics compared white matter structure between patients and control subjects and tested associations with age, symptom severity, and medication. Patients with first-episode psychosis had lower regional FA in multiple commissural, corticospinal, and association tracts. These abnormalities predominantly colocalized with regions of reduced neurite density, rather than aberrant fiber bundle arrangement (orientation dispersion index). There was no direct relationship with active symptoms. FA decreased and orientation dispersion index increased with age in patients, but not control subjects, suggesting accelerated effects of white matter geometry change. Deficits in neurite density appear fundamental to abnormalities in white matter integrity in early psychosis. In the first application of neurite orientation dispersion and density imaging in psychosis, we found that processes compromising axonal fiber number, density, and myelination, rather than processes leading to spatial disruption of fiber organization, are implicated in the etiology of psychosis. This accords with a neurodevelopmental origin of aberrant brain-wide structural connectivity predisposing individuals to psychosis. Copyright © 2017 Society of Biological Psychiatry. All rights reserved.

Medial temporal lobe structure and cognition in individuals with schizophrenia and in their non-psychotic siblings.

PubMed

Karnik-Henry, Meghana S; Wang, Lei; Barch, Deanna M; Harms, Michael P; Campanella, Carolina; Csernansky, John G

2012-07-01

Medial temporal lobe (MTL) structures play a central role in episodic memory. Prior studies suggest that individuals with schizophrenia have deficits in episodic memory as well as structural abnormalities of the medial temporal lobe (MTL). While correlations have been reported between MTL volume loss and episodic memory deficits in such individuals, it is not clear whether such correlations reflect the influence of the disease state or of underlying genetic influences that might contribute to risk. We used high resolution magnetic resonance imaging and probabilistic algorithms for image analysis to determine whether MTL structure, episodic memory performance and the relationship between the two differed among groups of 47 healthy control subjects, 50 control siblings, 39 schizophrenia subjects, and 33 siblings of schizophrenia subjects. High-dimensional large deformation brain mapping was used to obtain volume measures of the hippocampus. Cortical distance mapping was used to obtain volume and thickness measures of the parahippocampal gyrus (PHG) and its substructures: the entorhinal cortex (ERC), the perirhinal cortex (PRC), and the parahippocampal cortex (PHC). Neuropsychological data was used to establish an episodic memory domain score for each subject. Both schizophrenia subjects and their siblings displayed abnormalities in episodic memory performance. Siblings of individuals with schizophrenia, and to a lesser extent, individuals with schizophrenia themselves, displayed abnormalities in measures of MTL structure (volume loss or cortical thinning) as compared to control groups. Further, we observed correlations between structural measures and memory performance in both schizophrenia subjects and their siblings, but not in their respective control groups. These findings suggest that disease-specific genetic factors present in both patients and their relatives may be responsible for correlated abnormalities of MTL structure and memory impairment. The observed attenuated effect of such factors on MTL structure in individuals with schizophrenia may be due to non-genetic influences related to the development and progression of the disease on global brain structure and cognitive processing. Copyright © 2012 Elsevier B.V. All rights reserved.

Genetic disruption of CYP26B1 severely affects development of neural crest derived head structures, but does not compromise hindbrain patterning.

PubMed

Maclean, Glenn; Dollé, Pascal; Petkovich, Martin

2009-03-01

Cyp26b1 encodes a cytochrome-P450 enzyme that catabolizes retinoic acid (RA), a vitamin A derived signaling molecule. We have examined Cyp26b1(-/-) mice and report that mutants exhibit numerous abnormalities in cranial neural crest cell derived tissues. At embryonic day (E) 18.5 Cyp26b1(-/-) animals exhibit a truncated mandible, abnormal tooth buds, reduced ossification of calvaria, and are missing structures of the maxilla and nasal process. Some of these abnormalities may be due to defects in formation of Meckel's cartilage, which is truncated with an unfused distal region at E14.5 in mutant animals. Despite the severe malformations, we did not detect any abnormalities in rhombomere segmentation, or in patterning and migration of anterior hindbrain derived neural crest cells. Abnormal migration of neural crest cells toward the posterior branchial arches was observed, which may underlie defects in larynx and hyoid development. These data suggest different periods of sensitivity of anterior and posterior hindbrain neural crest derivatives to elevated levels of RA in the absence of CYP26B1. (c) 2009 Wiley-Liss, Inc.

Copper pyrithione, a booster biocide, induces abnormal muscle and notochord architecture in zebrafish embryogenesis.

PubMed

Almond, Kelly M; Trombetta, Louis D

2017-09-01

The metal pyrithiones, principally zinc (ZnPT) and copper (CuPT), are replacing tributyltin (TBT) as antifouling agents. Zebrafish embryos were exposed within the first hour after fertilization to 12 and 64 µg/L of CuPT for 24 h. Morphological abnormalities in notochord and muscle architecture were observed at 96 h post fertilization (hpf). TEM revealed abnormal electron dense deposits in the notochord sheath and muscle fiber degeneration in animals treated with 12 µg/L of CuPT. Embryos that were exposed to 64 µg/L of CuPT displayed severe muscle fiber degeneration including abnormal A and I band patterning and altered z disk arrangement. Abnormalities in the notochord sheath, swelling of the mitochondria and numerous lipid whorls were also noted. Total antioxidant capacity was significantly decreased in embryos exposed to 12 and 64 µg/L of CuPT. Acridine orange staining revealed an increase in apoptosis particularly in the brain, eye, heart and tail regions of both treatment groups. Apoptosis was confirmed with an increase in caspase 3/7 activity in both treatment groups. Severe alternations in primary motor neuron axon extensions, slow tonic muscle fibers and fast twitch fibers were observed in CuPT treated embryos. There was a significant upregulation in sonic hedgehog and myod1 expression at 24 hpf in the 12 µg/L treatment group. Exposed zebrafish embryos showed ultra-structural hallmarks of peroxidative injury and cell death via apoptosis. These changes question the use of copper pyrithione as an antifouling agent.

Abnormal mitochondrial respiration in failed human myocardium.

PubMed

Sharov, V G; Todor, A V; Silverman, N; Goldstein, S; Sabbah, H N

2000-12-01

Chronic heart failure (HF) is associated with morphologic abnormalities of cardiac mitochondria including hyperplasia, reduced organelle size and compromised structural integrity. In this study, we examined whether functional abnormalities of mitochondrial respiration are also present in myocardium of patients with advanced HF. Mitochondrial respiration was examined using a Clark electrode in an oxygraph cell containing saponin-skinned muscle bundles obtained from myocardium of failed explanted human hearts due to ischemic (ICM, n=9) or idiopathic dilated (IDC, n=9) cardiomyopathy. Myocardial specimens from five normal donor hearts served as controls (CON). Basal respiratory rate, respiratory rate after addition of the substrates glutamate and malate (V(SUB)), state 3 respiration (after addition of ADP, V(ADP)) and respiration after the addition of atractyloside (V(AT)) were measured in scar-free muscle bundles obtained from the subendocardial (ENDO) and subepicardial (EPI) thirds of the left ventricular (LV) free wall, interventricular septum and right ventricular (RV) free wall. There were no differences in basal and substrate-supported respiration between CON and HF regardless of etiology. V(ADP)was significantly depressed both in ICM and IDC compared to CON in all the regions studied. The respiratory control ratio, V(ADP)/V(AT), was also significantly decreased in HF compared to CON. In both ICM and IDC, V(ADP)was significantly lower in ENDO compared to EPI. The results indicate that mitochondrial respiration is abnormal in the failing human heart. The findings support the concept of low myocardial energy production in HF via oxidative phosphorylation, an abnormality with a potentially impact on global cardiac performance. Copyright 2000 Academic Press.

Mitral valve regurgitation

MedlinePlus

... to help prevent blood clots in people with atrial fibrillation Drugs that help control uneven or abnormal heartbeats ... that may develop include: Abnormal heart rhythms , including atrial fibrillation and possibly more serious, or even life-threatening ...

Sluggish cognitive tempo in abnormal child psychology: an historical overview and introduction to the special section.

PubMed

Becker, Stephen P; Marshall, Stephen A; McBurnett, Keith

2014-01-01

There has recently been a resurgence of interest in Sluggish Cognitive Tempo (SCT) as an important construct in the field of abnormal child psychology. Characterized by drowsiness, daydreaming, lethargy, mental confusion, and slowed thinking/behavior, SCT has primarily been studied as a feature of Attention-Deficit/Hyperactivity Disorder (ADHD), and namely the predominately inattentive subtype/presentation. Although SCT is strongly associated with ADHD inattention, research increasingly supports the possibility that SCT is distinct from ADHD or perhaps a different mental health condition altogether, with unique relations to child and adolescent psychosocial adjustment. This introductory article to the Special Section on SCT provides an historical overview of the SCT construct and briefly describes the contributions of the eight empirical papers included in the Special Section. Given the emerging importance of SCT for abnormal psychology and clinical science, there is a clear need for additional studies that examine (1) the measurement, structure, and multidimensional nature of SCT, (2) SCT as statistically distinct from not only ADHD-inattention but also other psychopathologies (particularly depression and anxiety), (3) genetic and environmental contributions to the development of SCT symptoms, and (4) functional impairments associated with SCT. This Special Section brings together papers to advance the current knowledge related to these issues as well as to spur research in this exciting and expanding area of abnormal psychology.

Arthroscopic and magnetic resonance image appearance and reconstruction of the anterior talofibular ligament in cases of apparent functional ankle instability.

PubMed

Takao, Masato; Innami, Ken; Matsushita, Takashi; Uchio, Yuji; Ochi, Mitsuo

2008-08-01

Many patients report feeling functional ankle instability, despite having no clinically demonstrable lateral instability. Some patients who experience functional instability of the ankle have substantial abnormalities of the anterior talofibular ligament despite having apparently normal lateral laxity in clinical examination. Case series; Level of evidence, 4. Fourteen patients who had functional ankle instability after sprain, despite having no clinically demonstrable lateral instability, were included in this study. All subjects underwent standard stress radiography, magnetic resonance imaging, and ankle arthroscopy. These patients were treated with anatomical reconstruction of the anterior talofibular ligament. Arthroscopic assessment revealed 3 cases with no ligamentous structure with scar tissue, 9 cases with partial ligament tears and scar tissue on the disrupted anterior talofibular ligament fiber, and 2 cases of abnormal course of the ligament at the fibular or talar attachment. Magnetic resonance imaging revealed the following: 5 cases of discontinuity of the anterior talofibular ligament, 2 cases of narrowing of the anterior talofibular ligament, 4 cases of high-intensity lesion in the anterior talofibular ligament, and 3 normal cases. The mean American Orthopaedic Foot and Ankle Society Ankle Hindfoot scale score was 66.2 +/- 3.2 points at preoperation and 92.3 +/- 4.4 points 2 years after surgery. All patients in this study with functional ankle instability, despite their having no demonstrable abnormal lateral laxity, had morphologic ligamentous abnormality on arthroscopic assessment.

Periventricular Nodular Heterotopia: Detection of Abnormal Microanatomic Fiber Structures with Whole-Brain Diffusion MR Imaging Tractography.

PubMed

Farquharson, Shawna; Tournier, J-Donald; Calamante, Fernando; Mandelstam, Simone; Burgess, Rosemary; Schneider, Michal E; Berkovic, Samuel F; Scheffer, Ingrid E; Jackson, Graeme D; Connelly, Alan

2016-12-01

Purpose To investigate whether it is possible in patients with periventricular nodular heterotopia (PVNH) to detect abnormal fiber projections that have only previously been reported in the histopathology literature. Materials and Methods Whole-brain diffusion-weighted (DW) imaging data from 14 patients with bilateral PVNH and 14 age- and sex-matched healthy control subjects were prospectively acquired by using 3.0-T magnetic resonance (MR) imaging between August 1, 2008, and December 5, 2012. All participants provided written informed consent. The DW imaging data were processed to generate whole-brain constrained spherical deconvolution (CSD)-based tractography data and super-resolution track-density imaging (TDI) maps. The tractography data were overlaid on coregistered three-dimensional T1-weighted images to visually assess regions of heterotopia. A panel of MR imaging researchers independently assessed each case and indicated numerically (no = 1, yes = 2) as to the presence of abnormal fiber tracks in nodular tissue. The Fleiss κ statistical measure was applied to assess the reader agreement. Results Abnormal fiber tracks emanating from one or more regions of heterotopia were reported by all four readers in all 14 patients with PVNH (Fleiss κ = 1). These abnormal structures were not visible on the tractography data from any of the control subjects and were not discernable on the conventional T1-weighted images of the patients with PVNH. Conclusion Whole-brain CSD-based fiber tractography and super-resolution TDI mapping reveals abnormal fiber projections in nodular tissue suggestive of abnormal organization of white matter (with abnormal fibers both within nodules and projecting to the surrounding white matter) in patients with bilateral PVNH. © RSNA, 2016.

The association of foot arch posture and prior history of shoulder or elbow surgery in elite-level baseball pitchers.

PubMed

Feigenbaum, Luis A; Roach, Kathryn E; Kaplan, Lee D; Lesniak, Bryson; Cunningham, Sean

2013-11-01

Case-control. The specific aim of this study was to examine the association between abnormal foot arch postures and a history of shoulder or elbow surgery in baseball pitchers. Pitching a baseball generates forces throughout the musculoskeletal structures of the upper and lower limbs. Structures such as the longitudinal arch of the foot are adaptable to stresses over time. Repeated pitching-related stresses may contribute to acquiring abnormal foot arch postures. Inversely, congenitally abnormal foot arch posture may lead to altered stresses of the upper limb during pitching. A convenience sample of 77 pitchers was recruited from a Division I university team and a professional baseball franchise. Subjects who had a history of shoulder or elbow surgery to the pitching arm were classified as cases. Subjects who met the criteria for classification of pes planus or pes cavus based on longitudinal arch angle were classified as having abnormal foot arch posture. Odds ratios were calculated to examine the association between abnormal foot arch posture and pitching-arm injury requiring surgery. Twenty-three subjects were classified as cases. The odds of being a case were 3.4 (95% confidence interval: 1.2, 9.6; P = .02) times greater for subjects with abnormal foot arch posture and 2.9 (95% confidence interval: 1.0, 8.1; P = .04) times greater for subjects with abnormal foot posture on the lunge leg. Abnormal foot arch posture and a surgical history in the pitching shoulder or elbow may be associated. Because the foot and its arches are adaptable and change over time, the pathomechanics of this association should be further explored.

Neuroanatomical Abnormalities in Violent Individuals with and without a Diagnosis of Schizophrenia.

PubMed

Del Bene, Victor A; Foxe, John J; Ross, Lars A; Krakowski, Menahem I; Czobor, Pal; De Sanctis, Pierfilippo

2016-01-01

Several structural brain abnormalities have been associated with aggression in patients with schizophrenia. However, little is known about shared and distinct abnormalities underlying aggression in these subjects and non-psychotic violent individuals. We applied a region-of-interest volumetric analysis of the amygdala, hippocampus, and thalamus bilaterally, as well as whole brain and ventricular volumes to investigate violent (n = 37) and non-violent chronic patients (n = 26) with schizophrenia, non-psychotic violent (n = 24) as well as healthy control subjects (n = 24). Shared and distinct volumetric abnormalities were probed by analysis of variance with the factors violence (non-violent versus violent) and diagnosis (non-psychotic versus psychotic), adjusted for substance abuse, age, academic achievement and negative psychotic symptoms. Patients showed elevated vCSF volume, smaller left hippocampus and smaller left thalamus volumes. This was particularly the case for non-violent individuals diagnosed with schizophrenia. Furthermore, patients had reduction in right thalamus size. With regard to left amygdala, we found an interaction between violence and diagnosis. More specifically, we report a double dissociation with smaller amygdala size linked to violence in non-psychotic individuals, while for psychotic patients smaller size was linked to non-violence. Importantly, the double dissociation appeared to be mostly driven by substance abuse. Overall, we found widespread morphometric abnormalities in subcortical regions in schizophrenia. No evidence for shared volumetric abnormalities in individuals with a history of violence was found. Finally, left amygdala abnormalities in non-psychotic violent individuals were largely accounted for by substance abuse. This might be an indication that the association between amygdala reduction and violence is mediated by substance abuse. Our results indicate the importance of structural abnormalities in aggressive individuals.

Lysosomal abnormalities in hereditary spastic paraplegia types SPG15 and SPG11

PubMed Central

Renvoisé, Benoît; Chang, Jaerak; Singh, Rajat; Yonekawa, Sayuri; FitzGibbon, Edmond J; Mankodi, Ami; Vanderver, Adeline; Schindler, Alice B; Toro, Camilo; Gahl, William A; Mahuran, Don J; Blackstone, Craig; Pierson, Tyler Mark

2014-01-01

Objective Hereditary spastic paraplegias (HSPs) are among the most genetically diverse inherited neurological disorders, with over 70 disease loci identified (SPG1-71) to date. SPG15 and SPG11 are clinically similar, autosomal recessive disorders characterized by progressive spastic paraplegia along with thin corpus callosum, white matter abnormalities, cognitive impairment, and ophthalmologic abnormalities. Furthermore, both have been linked to early-onset parkinsonism. Methods We describe two new cases of SPG15 and investigate cellular changes in SPG15 and SPG11 patient-derived fibroblasts, seeking to identify shared pathogenic themes. Cells were evaluated for any abnormalities in cell division, DNA repair, endoplasmic reticulum, endosomes, and lysosomes. Results Fibroblasts prepared from patients with SPG15 have selective enlargement of LAMP1-positive structures, and they consistently exhibited abnormal lysosomal storage by electron microscopy. A similar enlargement of LAMP1-positive structures was also observed in cells from multiple SPG11 patients, though prominent abnormal lysosomal storage was not evident. The stabilities of the SPG15 protein spastizin/ZFYVE26 and the SPG11 protein spatacsin were interdependent. Interpretation Emerging studies implicating these two proteins in interactions with the late endosomal/lysosomal adaptor protein complex AP-5 are consistent with shared abnormalities in lysosomes, supporting a converging mechanism for these two disorders. Recent work with Zfyve26−/− mice revealed a similar phenotype to human SPG15, and cells in these mice had endolysosomal abnormalities. SPG15 and SPG11 are particularly notable among HSPs because they can also present with juvenile parkinsonism, and this lysosomal trafficking or storage defect may be relevant for other forms of parkinsonism associated with lysosomal dysfunction. PMID:24999486

Functional disorders of the anus and rectum

PubMed Central

Whitehead, W; Wald, A; Diamant, N; Enck, P; Pemberton, J; Rao, S

1999-01-01

In this report the functional anorectal disorders, the etiology of which is currently unknown or related to the abnormal functioning of normally innervated and structurally intact muscles, are discussed. These disorders include functional fecal incontinence, functional anorectal pain, including levator ani syndrome and proctalgia fugax, and pelvic floor dyssynergia. The epidemiology of each disorder is defined and discussed, their pathophysiology is summarized and diagnostic approaches and treatment are suggested. Some suggestions for the direction of future research on these disorders are also given.


Keywords: fecal incontinence; pelvic floor dyssynergia; anismus; proctalgia fugax; levator ani syndrome; constipation; Rome II PMID:10457046

Structural brain abnormalities in Cushing's syndrome.

PubMed

Bauduin, Stephanie E E C; van der Wee, Nic J A; van der Werff, Steven J A

2018-05-08

Alongside various physical symptoms, patients with Cushing's disease and Cushing's syndrome display a wide variety of neuropsychiatric and cognitive symptoms, which are indicative of involvement of the central nervous system. The aim of this review is to provide an overview of the structural brain abnormalities that are associated with Cushing's disease and Cushing's syndrome and their relation to behavioral and cognitive symptomatology. In this review, we discuss the gray matter structural abnormalities found in patients with active Cushing's disease and Cushing's syndrome, the reversibility and persistence of these changes and the white matter structural changes related to Cushing's syndrome. Recent findings are of particular interest because they provide more detailed information on localization of the structural changes as well as possible insights into the underlying biological processes. Active Cushing's disease and Cushing's syndrome is related to volume reductions of the hippocampus and in a prefrontal region involving the anterior cingulate cortex (ACC) and medial frontal gyrus (MFG). Whilst there are indications that the reductions in hippocampal volume are partially reversible, the changes in the ACC and MFG appear to be more persistent. In contrast to the volumetric findings, changes in white matter connectivity are typically widespread involving multiple tracts.

Cortico-Striatal-Thalamic Loop Circuits of the Salience Network: A Central Pathway in Psychiatric Disease and Treatment.

PubMed

Peters, Sarah K; Dunlop, Katharine; Downar, Jonathan

2016-01-01

The salience network (SN) plays a central role in cognitive control by integrating sensory input to guide attention, attend to motivationally salient stimuli and recruit appropriate functional brain-behavior networks to modulate behavior. Mounting evidence suggests that disturbances in SN function underlie abnormalities in cognitive control and may be a common etiology underlying many psychiatric disorders. Such functional and anatomical abnormalities have been recently apparent in studies and meta-analyses of psychiatric illness using functional magnetic resonance imaging (fMRI) and voxel-based morphometry (VBM). Of particular importance, abnormal structure and function in major cortical nodes of the SN, the dorsal anterior cingulate cortex (dACC) and anterior insula (AI), have been observed as a common neurobiological substrate across a broad spectrum of psychiatric disorders. In addition to cortical nodes of the SN, the network's associated subcortical structures, including the dorsal striatum, mediodorsal thalamus and dopaminergic brainstem nuclei, comprise a discrete regulatory loop circuit. The SN's cortico-striato-thalamo-cortical loop increasingly appears to be central to mechanisms of cognitive control, as well as to a broad spectrum of psychiatric illnesses and their available treatments. Functional imbalances within the SN loop appear to impair cognitive control, and specifically may impair self-regulation of cognition, behavior and emotion, thereby leading to symptoms of psychiatric illness. Furthermore, treating such psychiatric illnesses using invasive or non-invasive brain stimulation techniques appears to modulate SN cortical-subcortical loop integrity, and these effects may be central to the therapeutic mechanisms of brain stimulation treatments in many psychiatric illnesses. Here, we review clinical and experimental evidence for abnormalities in SN cortico-striatal-thalamic loop circuits in major depression, substance use disorders (SUD), anxiety disorders, schizophrenia and eating disorders (ED). We also review emergent therapeutic evidence that novel invasive and non-invasive brain stimulation treatments may exert therapeutic effects by normalizing abnormalities in the SN loop, thereby restoring the capacity for cognitive control. Finally, we consider a series of promising directions for future investigations on the role of SN cortico-striatal-thalamic loop circuits in the pathophysiology and treatment of psychiatric disorders.

Unique double de novo structural rearrangements for chromosome 11 with 46,XX,del(11)(q13q23)/46,XX,inv dup(11)(q13q23) in an infant with minor congenital abnormalities and delayed development

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

Tharapel, A.T.; Zhao, J.; Smith, M.E.

1994-09-01

Reported here is a patient with two most unusual structural rearrangements, both involving chromosome 11. The first cell line showed an interstitial deletion of a chromosome 11 with a 46,XX,del(11)(q13q23) chromosome complement. In the second cell line, one of the chromosome 11s had a duplication for the exact region, (11)(q13q23), that was deleted in the first cell line. This duplication also appeared to be inverted with karyotype 46,XX,inv dup(11)(q13q23). Interestingly, chromosome analysis did not reveal a normal cell line and the two abnormal cell lines were present in a 1:1 ratio. Parental chromosome analyses showed normal karyotypes. The patient wasmore » referred for genetic evaluation because of developmental delay. Minor congenital anomalies presented on physical examination included: weight and height at or below the 5th percentile, microcephaly, downward slanting palpebral fissures, severe clinodactyly of one toe, bilateral short fifth fingers and a broad based gait. Results of the MRI and urine metabolic screen were normal. Two hypotheses are advanced to explain the origin of the abnormality. It is most likely that the abnormality arose as a postzygotic event at the very early zygotic division. During the first DNA synthesis after fertilization and before the zygotic division, DNA synthesis errors could result in two chromatids, one with a deletion and the other with a duplication. It is also possible that after the DNA synthesis prior to the first cell division, the chromatids of the same chromosome 11 for unknown reasons were involved in uneven double somatic crossing over events resulting in deleted and duplicated chromatids, respectively. The 1:1 cell ratio found in the patient and the apparent non-existence of a normal cell line further suggest that the origin of the abnormality was post-zygotic.« less

Cortico-Striatal-Thalamic Loop Circuits of the Salience Network: A Central Pathway in Psychiatric Disease and Treatment

PubMed Central

Peters, Sarah K.; Dunlop, Katharine; Downar, Jonathan

2016-01-01

The salience network (SN) plays a central role in cognitive control by integrating sensory input to guide attention, attend to motivationally salient stimuli and recruit appropriate functional brain-behavior networks to modulate behavior. Mounting evidence suggests that disturbances in SN function underlie abnormalities in cognitive control and may be a common etiology underlying many psychiatric disorders. Such functional and anatomical abnormalities have been recently apparent in studies and meta-analyses of psychiatric illness using functional magnetic resonance imaging (fMRI) and voxel-based morphometry (VBM). Of particular importance, abnormal structure and function in major cortical nodes of the SN, the dorsal anterior cingulate cortex (dACC) and anterior insula (AI), have been observed as a common neurobiological substrate across a broad spectrum of psychiatric disorders. In addition to cortical nodes of the SN, the network’s associated subcortical structures, including the dorsal striatum, mediodorsal thalamus and dopaminergic brainstem nuclei, comprise a discrete regulatory loop circuit. The SN’s cortico-striato-thalamo-cortical loop increasingly appears to be central to mechanisms of cognitive control, as well as to a broad spectrum of psychiatric illnesses and their available treatments. Functional imbalances within the SN loop appear to impair cognitive control, and specifically may impair self-regulation of cognition, behavior and emotion, thereby leading to symptoms of psychiatric illness. Furthermore, treating such psychiatric illnesses using invasive or non-invasive brain stimulation techniques appears to modulate SN cortical-subcortical loop integrity, and these effects may be central to the therapeutic mechanisms of brain stimulation treatments in many psychiatric illnesses. Here, we review clinical and experimental evidence for abnormalities in SN cortico-striatal-thalamic loop circuits in major depression, substance use disorders (SUD), anxiety disorders, schizophrenia and eating disorders (ED). We also review emergent therapeutic evidence that novel invasive and non-invasive brain stimulation treatments may exert therapeutic effects by normalizing abnormalities in the SN loop, thereby restoring the capacity for cognitive control. Finally, we consider a series of promising directions for future investigations on the role of SN cortico-striatal-thalamic loop circuits in the pathophysiology and treatment of psychiatric disorders. PMID:28082874

Neonatal Pulmonary MRI of Bronchopulmonary Dysplasia Predicts Short-term Clinical Outcomes.

PubMed

Higano, Nara S; Spielberg, David R; Fleck, Robert J; Schapiro, Andrew H; Walkup, Laura L; Hahn, Andrew D; Tkach, Jean A; Kingma, Paul S; Merhar, Stephanie L; Fain, Sean B; Woods, Jason C

2018-05-23

Bronchopulmonary dysplasia (BPD) is a serious neonatal pulmonary condition associated with premature birth, but the underlying parenchymal disease and trajectory are poorly characterized. The current NICHD/NHLBI definition of BPD severity is based on degree of prematurity and extent of oxygen requirement. However, no clear link exists between initial diagnosis and clinical outcomes. We hypothesized that magnetic resonance imaging (MRI) of structural parenchymal abnormalities will correlate with NICHD-defined BPD disease severity and predict short-term respiratory outcomes. Forty-two neonates (20 severe BPD, 6 moderate, 7 mild, 9 non-BPD controls; 40±3 weeks post-menstrual age) underwent quiet-breathing structural pulmonary MRI (ultrashort echo-time and gradient echo) in a NICU-sited, neonatal-sized 1.5T scanner, without sedation or respiratory support unless already clinically prescribed. Disease severity was scored independently by two radiologists. Mean scores were compared to clinical severity and short-term respiratory outcomes. Outcomes were predicted using univariate and multivariable models including clinical data and scores. MRI scores significantly correlated with severities and predicted respiratory support at NICU discharge (P<0.0001). In multivariable models, MRI scores were by far the strongest predictor of respiratory support duration over clinical data, including birth weight and gestational age. Notably, NICHD severity level was not predictive of discharge support. Quiet-breathing neonatal pulmonary MRI can independently assess structural abnormalities of BPD, describe disease severity, and predict short-term outcomes more accurately than any individual standard clinical measure. Importantly, this non-ionizing technique can be implemented to phenotype disease and has potential to serially assess efficacy of individualized therapies.

Recurrent wheeze and cough in young children: is it asthma?

PubMed Central

Ng, Mark Chung Wai; How, Choon How

2014-01-01

A clinical diagnosis of asthma is often considered when a child presents with recurrent cough, wheeze and breathlessness. However, there are many other causes of wheeze in a young child. These range from recurrent viral infections to chronic suppurative lung disease, gastro-oesophageal reflux disease and rare structural abnormalities. Arriving at a diagnosis includes taking into consideration the symptomatology, triggers, atopic features, family history, absence of red flags and therapeutic trial, where indicated. PMID:24862744

Meiotic abnormalities

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

NONE

1993-12-31

Chapter 19, describes meiotic abnormalities. These include nondisjunction of autosomes and sex chromosomes, genetic and environmental causes of nondisjunction, misdivision of the centromere, chromosomally abnormal human sperm, male infertility, parental age, and origin of diploid gametes. 57 refs., 2 figs., 1 tab.

Striatal Circuits as a Common Node for Autism Pathophysiology

PubMed Central

Fuccillo, Marc V.

2016-01-01

Autism spectrum disorders (ASD) are characterized by two seemingly unrelated symptom domains—deficits in social interactions and restrictive, repetitive patterns of behavioral output. Whether the diverse nature of ASD symptomatology represents distributed dysfunction of brain networks or abnormalities within specific neural circuits is unclear. Striatal dysfunction is postulated to underlie the repetitive motor behaviors seen in ASD, and neurological and brain-imaging studies have supported this assumption. However, as our appreciation of striatal function expands to include regulation of behavioral flexibility, motivational state, goal-directed learning, and attention, we consider whether alterations in striatal physiology are a central node mediating a range of autism-associated behaviors, including social and cognitive deficits that are hallmarks of the disease. This review investigates multiple genetic mouse models of ASD to explore whether abnormalities in striatal circuits constitute a common pathophysiological mechanism in the development of autism-related behaviors. Despite the heterogeneity of genetic insult investigated, numerous genetic ASD models display alterations in the structure and function of striatal circuits, as well as abnormal behaviors including repetitive grooming, stereotypic motor routines, deficits in social interaction and decision-making. Comparative analysis in rodents provides a unique opportunity to leverage growing genetic association data to reveal canonical neural circuits whose dysfunction directly contributes to discrete aspects of ASD symptomatology. The description of such circuits could provide both organizing principles for understanding the complex genetic etiology of ASD as well as novel treatment routes. Furthermore, this focus on striatal mechanisms of behavioral regulation may also prove useful for exploring the pathogenesis of other neuropsychiatric diseases, which display overlapping behavioral deficits with ASD. PMID:26903795

[Monilethrix--rare syndrome of structural hair abnormalities].

PubMed

Brzezińska-Wcisło, L; Bogdanowski, T; Szeremeta-Bazylewicz, G; Pierzchała, E

1999-11-01

Monilethrix is a rare structural disorder of hair. Characteristic abnormalities in the form of alternating thinning and fusiform thickening are observed in most of hair shafts that we call beaded hair. Macroscopic estimation shows lustreless, dry, rough, fragile hair. Trichological examination usually reveals a considerable percentage of anagenic hair. According to our own experiences and literature data systemic therapy (vitamins) and topical treatment (desquamative ointments) are not effective sufficiently. Spontaneous regression of symptoms often appears with time. Five cases of familial occurrence of monilethrix have been presented.

Eyeblink Conditioning Deficits Indicate Timing and Cerebellar Abnormalities in Schizophrenia

ERIC Educational Resources Information Center

Brown, S.M.; Kieffaber, P.D.; Carroll, C.A.; Vohs, J.L.; Tracy, J.A.; Shekhar, A.; O'Donnell, B.F.; Steinmetz, J.E.; Hetrick, W.P.

2005-01-01

Accumulating evidence indicates that individuals with schizophrenia manifest abnormalities in structures (cerebellum and basal ganglia) and neurotransmitter systems (dopamine) linked to internal-timing processes. A single-cue tone delay eyeblink conditioning paradigm comprised of 100 learning and 50 extinction trials was used to examine cerebellar…

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…

Congenital sensory neuropathy

PubMed Central

Barry, J. E.; Hopkins, I. J.; Neal, B. W.

1974-01-01

Two infants with sporadic congenital sensory neuropathy are described. The criteria of generalized lack of superficial sensory appreciation, hypotonia, areflexia, together with histological evidence of abnormalities of sensory neural structures in skin and peripheral nerves have been met. No abnormality of motor or autonomic nerves was shown. ImagesFIG. PMID:4131674

Abnormal characteristics of binary molecular clusters in DMSO–ethanol mixtures under external electric fields

NASA Astrophysics Data System (ADS)

Wu, Zhiyan; Huang, Kama

2018-05-01

For the nonlinearly phenomena on the dielectric properties of dimethyl sulfoxide (DMSO)-ethanol mixtures under a low intensity microwave field, we propose a conjecture that there exist some abnormal molecular clusters. To interpret the mechanism of abnormal phenomena and confirm our conjecture about the existence of abnormal molecular clusters, an in-depth investigation about the structure evolutions of (DMSO)m(C2H5OH)n (m = 0-4; n = 0-4; m + n ≤ 4) molecular clusters induced by external electric fields has been given by using density functional theory. The results show that there exist some binary molecular clusters with large cluster radii in mixtures, and some of them are unstable under exposure of electric fields. It implies that the existence of certain abnormal molecular clusters in DMSO-ethanol mixtures results in their abnormality of dielectric properties.

High prevalence of brain pathology in violent prisoners: a qualitative CT and MRI scan study.

PubMed

Schiltz, Kolja; Witzel, Joachim G; Bausch-Hölterhoff, Josef; Bogerts, Bernhard

2013-10-01

The aim of this study was to determine the frequency and extent of brain anomalies in a large sample of incarcerated violent offenders not previously considered neuropsychiatrically ill, in comparison with non-violent offenders and non-offending controls. MRI and CT brain scans from 287 male prison inmates (162 violent and 125 non-violent) not diagnosed as mentally ill before that were obtained due to headache, vertigo or psychological complaints during imprisonment were assessed and compared to 52 non-criminal controls. Brain scans were rated qualitatively with respect to evidence of structural brain damage. Each case received a semiquantitative rating of "normal" (=0), "questionably abnormal" (=1) or "definitely abnormal" (=2) for the lateral ventricles, frontal/parietal cortex and medial temporal structures bilaterally as well as third ventricle. Overall, offenders displayed a significantly higher rate of morphological abnormality, with the violent offenders scoring significantly higher than non-violent offenders and controls. This difference was statistically detectable for frontal/parietal cortex, medial temporal structures, third ventricle and the left but not the right lateral ventricle. The remarkable prevalence of brain pathology in convicted violent prisoners detectable by neuroradiological routine assessment not only highlights the importance of frontal and temporal structures in the control of social, and specifically of violent behaviour, but also raises questions on the legal culpability of violent offenders with brain abnormalities. The high proportion of undetected presence of structural brain damage emphasizes the need that in violent criminals, the comprehensive routine neuropsychiatric assessment usually performed in routine forensic psychiatric expertises should be complemented with brain imaging.

Association of Weight and Body Composition on Cardiac Structure and Function in the Atherosclerosis Risk in Communities (ARIC) Study

PubMed Central

Bello, Natalie A.; Cheng, Susan; Claggett, Brian; Shah, Amil; Ndumele, Chiadi E.; Roca, Gabriela Querejeta; Santos, Angela B.S.; Gupta, Deepak; Vardeny, Orly; Aguilar, David; Folsom, Aaron R.; Butler, Kenneth R.; Kitzman, Dalane W.; Coresh, Josef; Solomon, Scott D.

2016-01-01

Background Obesity increases cardiovascular risk. However, the extent to which various measures of body composition are associated with abnormalities in cardiac structure and function, independent of comorbidities commonly affecting obese individuals, is not clear. This study sought to examine the relationship of body mass index (BMI), waist circumference (WC), and percent body fat (BF) with conventional and advanced measures of cardiac structure and function. Methods and Results We studied 4343 participants of the Atherosclerosis Risk in Communities Study who were aged 69-82 years, free of coronary heart disease and heart failure, and underwent comprehensive echocardiography. Increasing BMI, WC, and BF were associated with greater left ventricular (LV) mass and left atrial volume indexed to height2.7 in both men and women (P<0.001). In women, all three measures were associated with abnormal LV geometry, and increasing WC and BF were associated with worse global longitudinal strain, a measure of left ventricular systolic function. In both sexes, increasing BMI was associated with greater right ventricular (RV) end-diastolic area and worse RV fractional area change (P≤0.001). We observed similar associations for both waist circumference and percent body fat. Conclusions In a large, biracial cohort of older adults free of clinically overt coronary heart disease or heart failure, obesity was associated with subclinical abnormalities in cardiac structure in both men and women and with adverse left ventricular remodeling and impaired left ventricular systolic function in women. These data highlight the association of obesity and subclinical abnormalities of cardiac structure and function, particularly in women. PMID:27512104

Reaction trajectory revealed by a joint analysis of protein data bank.

PubMed

Ren, Zhong

2013-01-01

Structural motions along a reaction pathway hold the secret about how a biological macromolecule functions. If each static structure were considered as a snapshot of the protein molecule in action, a large collection of structures would constitute a multidimensional conformational space of an enormous size. Here I present a joint analysis of hundreds of known structures of human hemoglobin in the Protein Data Bank. By applying singular value decomposition to distance matrices of these structures, I demonstrate that this large collection of structural snapshots, derived under a wide range of experimental conditions, arrange orderly along a reaction pathway. The structural motions along this extensive trajectory, including several helical transformations, arrive at a reverse engineered mechanism of the cooperative machinery (Ren, companion article), and shed light on pathological properties of the abnormal homotetrameric hemoglobins from α-thalassemia. This method of meta-analysis provides a general approach to structural dynamics based on static protein structures in this post genomics era.

Reaction Trajectory Revealed by a Joint Analysis of Protein Data Bank

PubMed Central

Ren, Zhong

2013-01-01

Structural motions along a reaction pathway hold the secret about how a biological macromolecule functions. If each static structure were considered as a snapshot of the protein molecule in action, a large collection of structures would constitute a multidimensional conformational space of an enormous size. Here I present a joint analysis of hundreds of known structures of human hemoglobin in the Protein Data Bank. By applying singular value decomposition to distance matrices of these structures, I demonstrate that this large collection of structural snapshots, derived under a wide range of experimental conditions, arrange orderly along a reaction pathway. The structural motions along this extensive trajectory, including several helical transformations, arrive at a reverse engineered mechanism of the cooperative machinery (Ren, companion article), and shed light on pathological properties of the abnormal homotetrameric hemoglobins from α-thalassemia. This method of meta-analysis provides a general approach to structural dynamics based on static protein structures in this post genomics era. PMID:24244274

Investigation of defect-induced abnormal body current in fin field-effect-transistors

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

Liu, Kuan-Ju; Tsai, Jyun-Yu; Lu, Ying-Hsin

2015-08-24

This letter investigates the mechanism of abnormal body current at the linear region in n-channel high-k/metal gate stack fin field effect transistors. Unlike body current, which is generated by impact ionization at high drain voltages, abnormal body current was found to increase with decreasing drain voltages. Notably, the unusual body leakage only occurs in three-dimensional structure devices. Based on measurements under different operation conditions, the abnormal body current can be attributed to fin surface defect-induced leakage current, and the mechanism is electron tunneling to the fin via the defects, resulting in holes left at the body terminal.

Connectivity and functional profiling of abnormal brain structures in pedophilia

PubMed Central

Poeppl, Timm B.; Eickhoff, Simon B.; Fox, Peter T.; Laird, Angela R.; Rupprecht, Rainer; Langguth, Berthold; Bzdok, Danilo

2015-01-01

Despite its 0.5–1% lifetime prevalence in men and its general societal relevance, neuroimaging investigations in pedophilia are scarce. Preliminary findings indicate abnormal brain structure and function. However, no study has yet linked structural alterations in pedophiles to both connectional and functional properties of the aberrant hotspots. The relationship between morphological alterations and brain function in pedophilia as well as their contribution to its psychopathology thus remain unclear. First, we assessed bimodal connectivity of structurally altered candidate regions using meta-analytic connectivity modeling (MACM) and resting-state correlations employing openly accessible data. We compared the ensuing connectivity maps to the activation likelihood estimation (ALE) maps of a recent quantitative meta-analysis of brain activity during processing of sexual stimuli. Second, we functionally characterized the structurally altered regions employing meta-data of a large-scale neuroimaging database. Candidate regions were functionally connected to key areas for processing of sexual stimuli. Moreover, we found that the functional role of structurally altered brain regions in pedophilia relates to nonsexual emotional as well as neurocognitive and executive functions, previously reported to be impaired in pedophiles. Our results suggest that structural brain alterations affect neural networks for sexual processing by way of disrupted functional connectivity, which may entail abnormal sexual arousal patterns. The findings moreover indicate that structural alterations account for common affective and neurocognitive impairments in pedophilia. The present multi-modal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia. PMID:25733379

Connectivity and functional profiling of abnormal brain structures in pedophilia.

PubMed

Poeppl, Timm B; Eickhoff, Simon B; Fox, Peter T; Laird, Angela R; Rupprecht, Rainer; Langguth, Berthold; Bzdok, Danilo

2015-06-01

Despite its 0.5-1% lifetime prevalence in men and its general societal relevance, neuroimaging investigations in pedophilia are scarce. Preliminary findings indicate abnormal brain structure and function. However, no study has yet linked structural alterations in pedophiles to both connectional and functional properties of the aberrant hotspots. The relationship between morphological alterations and brain function in pedophilia as well as their contribution to its psychopathology thus remain unclear. First, we assessed bimodal connectivity of structurally altered candidate regions using meta-analytic connectivity modeling (MACM) and resting-state correlations employing openly accessible data. We compared the ensuing connectivity maps to the activation likelihood estimation (ALE) maps of a recent quantitative meta-analysis of brain activity during processing of sexual stimuli. Second, we functionally characterized the structurally altered regions employing meta-data of a large-scale neuroimaging database. Candidate regions were functionally connected to key areas for processing of sexual stimuli. Moreover, we found that the functional role of structurally altered brain regions in pedophilia relates to nonsexual emotional as well as neurocognitive and executive functions, previously reported to be impaired in pedophiles. Our results suggest that structural brain alterations affect neural networks for sexual processing by way of disrupted functional connectivity, which may entail abnormal sexual arousal patterns. The findings moreover indicate that structural alterations account for common affective and neurocognitive impairments in pedophilia. The present multimodal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia. © 2015 Wiley Periodicals, Inc.

Adenotonsillar hypertrophy as a risk factor of dentofacial abnormality in Korean children.

PubMed

Kim, Dong-Kyu; Rhee, Chae Seo; Yun, Pil-Young; Kim, Jeong-Whun

2015-11-01

No studies for the role of adenotonsillar hypertrophy in development of dentofacial abnormalities have been performed in Asian pediatric population. Thus, we aimed to investigate the relationship between adenotonsillar hypertrophy and dentofacial abnormalities in Korean children. The present study included consecutive children who visited a pediatric clinic for sleep-disordered breathing due to habitual mouth breathing, snoring or sleep apnea. Their palatine tonsils and adenoids were graded by oropharyngeal endoscopy and lateral cephalometry. Anterior open bite, posterior crossbite, and Angle's class malocclusions were evaluated for dentofacial abnormality. The receiver-operating characteristic curve analysis was used to identify age cutoffs to predict dentofacial abnormality. A total of 1,083 children were included. The presence of adenotonsillar hypertrophy was significantly correlated with the prevalence of dentofacial abnormality [adjusted odds ratio = 4.587, 95% CI (2.747-7.658)] after adjusting age, sex, body mass index, allergy, and Korean version of obstructive sleep apnea-18 score. The cutoff age associated with dentofacial abnormality was 5.5 years (sensitivity = 75.5%, specificity = 67%) in the children with adenotonsillar hypertrophy and 6.5 years (sensitivity = 70.6%, specificity = 57%) in those without adenotonsillar hypertrophy. In conclusion, adenotonsillar hypertrophy may be a risk factor for dentofacial abnormalities in Korean children and early surgical intervention could be considered with regards to dentofacial abnormality.

Functional Brain Network Abnormalities during Verbal Working Memory Performance in Adolescents and Young Adults with Dyslexia

ERIC Educational Resources Information Center

Wolf, Robert Christian; Sambataro, Fabio; Lohr, Christina; Steinbrink, Claudia; Martin, Claudia; Vasic, Nenad

2010-01-01

Behavioral and functional neuroimaging studies indicate deficits in verbal working memory (WM) and frontoparietal dysfunction in individuals with dyslexia. Additionally, structural brain abnormalities in dyslexics suggest a dysconnectivity of brain regions associated with phonological processing. However, little is known about the functional…

A structural abnormality associated with graded levels of thyroid hormone insufficiency: Dose dependent increases in heterotopia volume

EPA Science Inventory

A large number of environmental contaminants reduce circulating levels of thyroid hormone (TH), but clear markers of neurological insult associated with modest TH insufficiency are lacking. We have previously identified the presence of an abnormal cluster of misplaced neurons in ...

White matter microstructure and cognitive decline in metabolic syndrome: a review of diffusion tensor imaging.

PubMed

Alfaro, Freddy J; Gavrieli, Anna; Saade-Lemus, Patricia; Lioutas, Vasileios-Arsenios; Upadhyay, Jagriti; Novak, Vera

2018-01-01

Metabolic syndrome is a cluster of cardiovascular risk factors defined by the presence of abdominal obesity, glucose intolerance, hypertension and/or dyslipidemia. It is a major public health epidemic worldwide, and a known risk factor for the development of cognitive dysfunction and dementia. Several studies have demonstrated a positive association between the presence of metabolic syndrome and worse cognitive outcomes, however, evidence of brain structure pathology is limited. Diffusion tensor imaging has offered new opportunities to detect microstructural white matter changes in metabolic syndrome, and a possibility to detect associations between functional and structural abnormalities. This review analyzes the impact of metabolic syndrome on white matter microstructural integrity, brain structure abnormalities and their relationship to cognitive function. Each of the metabolic syndrome components exerts a specific signature of white matter microstructural abnormalities. Metabolic syndrome and its components exert both additive/synergistic, as well as, independent effects on brain microstructure thus accelerating brain aging and cognitive decline. Copyright © 2017 Elsevier Inc. All rights reserved.

Abnormal structural luteolysis in ovaries of the senescence accelerated mouse (SAM): expression of Fas ligand/Fas-mediated apoptosis signaling molecules in luteal cells.

PubMed

Kiso, Minako; Manabe, Noboru; Komatsu, Kohji; Shimabe, Munetake; Miyamoto, Hajime

2003-12-01

Senescence accelerated mouse-prone (SAMP) mice with a shortened life span show accelerated changes in many of the signs of aging and a shorter reproductive life span than SAM-resistant (SAMR) controls. We previously showed that functional regression (progesterone dissimilation) occurs in abnormally accumulated luteal bodies (aaLBs) of SAMP mice, but structural regression of luteal cells in aaLB is inhibited. A deficiency of luteal cell apoptosis causes the abnormal accumulation of LBs in SAMP ovaries. In the present study, to show the abnormality of Fas ligand (FasL)/Fas-mediated apoptosis signal transducing factors in the aaLBs of the SAMP ovaries, we assessed the changes in the expression of FasL, Fas, caspase-8 and caspase-3 mRNAs by reverse transcription-polymerase chain reaction, and in the expression and localization of FasL, Fas and activated caspase-3 proteins by Western blotting and immunohistochemistry, respectively, during the estrus cycle/luteolysis. These mRNAs and proteins were expressed in normal LBs of both SAMP and SAMR ovaries, but not at all or only in trace amounts in aaLBs of SAMP, indicating that structural regression is inhibited by blockage of the expression of these transducing factors in luteal cells of aaLBs in SAMP mice.

The ‘structure-function’ relationship in glaucoma – past thinking and current concepts

PubMed Central

Malik, Rizwan; Swanson, William H.; Garway-Heath, David F

2013-01-01

An understanding of the relationship between functional and structural measures in primary open angle glaucoma (POAG) is necessary for both grading the severity of disease and for understanding the natural history of the condition. This article outlines the current evidence for the nature of this relationship, and highlights the current mathematical models linking structure and function. Large clinical trials demonstrate that both structural and functional change are apparent in advanced stages of disease, while, at an individual level, detectable structural abnormality may precede functional abnormality in some patients whilst the converse in true in other patients. Although the exact nature of the ‘structure-function’ relationship in POAG is still the topic of scientific debate and the subject of continuing research, this article aims to provide the clinician with an understanding of the past concepts and contemporary thinking in relation to the structure-function relationship in POAG. PMID:22339936

Amniotic fluid-AFP in Down syndrome and other chromosome abnormalities.

PubMed

Crandall, B F; Matsumoto, M; Perdue, S

1988-05-01

80.2 Per cent of 111 Down syndrome pregnancies had anmiotic fluid (AF) alpha fetoprotein (AFP) levels on or below the median and 10.8 per cent at or below 0.5 MoM compared with 41.9 and 1.4 per cent of controls. These differences were even more striking when the gestational age was less than 18 weeks compared with greater than or equal to 18 weeks. No such association was seen for other chromosome abnormalities including trisomy 18,45,X and mosaics, 47,XXY,47,XXX, and other structural abnormalities and triploidy, even when high levels due to defects such as omphalocele and cystic hygroma were excluded. All cases of trisomy 13 and 80 per cent with 47,XYY had AF-AFP levels above the median. Selection of cases for karyotyping by a low level of AF-AFP would clearly fail to detect aneuploidies other than Down syndrome and is not recommended. A possible weak association between low maternal serum (MS) and AF-AFPs in Down syndrome was most evident at less than 18 weeks, suggesting that MS screening between 16 and 18 weeks may be the most informative time.

Esophageal symptoms and their lack of association with high-resolution manometry in systemic sclerosis patients.

PubMed

Arana-Guajardo, Ana Cecilia; Barrera-Torres, Gustavo; Villarreal-Alarcón, Miguel Ángel; Vega-Morales, David; Esquivel-Valerio, Jorge Antonio

2017-12-16

The esophageal involvement in systemic sclerosis (SSc) causes impact in the morbidity and mortality. High resolution manometry assesses esophageal involvement. Our aim was to categorize esophageal motor disorder in patients with SSc by HRM. We carried out an observational, descriptive and cross-sectional study. All patients underwent HRM as well as semi-structured interviews to assess frequency and severity of upper GI symptoms. Patients also completed the gastroesophageal reflux questionnaire (Carlsson-Dent). We included 19 patients with SSc, 1 with morphea, and 1 with scleroderma sine scleroderma. Dysphagia and heartburn were the most frequent symptoms (61% each). We found an abnormal HRM in 15 (71.4%) patients. We found no statistically significant association between clinical or demographic variables and an abnormal HRM, or between any upper GI symptom and HRM findings. We observed a high prevalence of esophageal symptoms and of HRM abnormalities. However, there was no clear association between symptomatology and HRM findings. HRM does not seem to accurately predict upper GI symptomatology. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Ophthalmic Pathology of Nance-Horan Syndrome: Case Report and Review of the Literature

PubMed Central

Ding, Xiaoyan; Patel, Mrinali; Herzlich, Alexandra A.; Sieving, Pamela C.; Chan, Chi-Chao

2009-01-01

Background Nance-Horan syndrome (NHS) is a rare X-linked disorder typified by dense congenital central cataracts, microcornea, anteverted and simplex pinnae, brachymetacarpalia, and numerous dental anomalies due in most cases to a mutation in the NHS gene. Material and Methods We present a case of clinical manifestation and ocular pathology in a patient with NHS. This article also reviews and discusses the relevant literature. Results Classic and novel ocular pathological findings of a young male with NHS are described, including congenital cataracts, infantile glaucoma, scleral staphyloma, and severe retinal cystoid degeneration. Conclusions We report a new pathological finding of severe retinal cystoid degeneration in this NHS patient and confirm abnormal development of the anterior chamber angle structure. These findings, coupled with our analysis of the available NHS literature, provide new understanding of the histopathological basis of ocular abnormalities and vision loss in NHS. PMID:19941417

Knockout of Foxp2 disrupts vocal development in mice.

PubMed

Castellucci, Gregg A; McGinley, Matthew J; McCormick, David A

2016-03-16

The FOXP2 gene is important for the development of proper speech motor control in humans. However, the role of the gene in general vocal behavior in other mammals, including mice, is unclear. Here, we track the vocal development of Foxp2 heterozygous knockout (Foxp2+/-) mice and their wildtype (WT) littermates from juvenile to adult ages, and observe severe abnormalities in the courtship song of Foxp2+/- mice. In comparison to their WT littermates, Foxp2+/- mice vocalized less, produced shorter syllable sequences, and possessed an abnormal syllable inventory. In addition, Foxp2+/- song also exhibited irregular rhythmic structure, and its development did not follow the consistent trajectories observed in WT vocalizations. These results demonstrate that the Foxp2 gene is critical for normal vocal behavior in juvenile and adult mice, and that Foxp2 mutant mice may provide a tractable model system for the study of the gene's role in general vocal motor control.

Dictyostelium RasG Is Required for Normal Motility and Cytokinesis, But Not Growth

PubMed Central

Tuxworth, Richard I.; Cheetham, Janet L.; Machesky, Laura M.; Spiegelmann, George B.; Weeks, Gerald; Insall, Robert H.

1997-01-01

RasG is the most abundant Ras protein in growing Dictyostelium cells and the closest relative of mammalian Ras proteins. We have generated null mutants in which expression of RasG is completely abolished. Unexpectedly, RasG − cells are able to grow at nearly wild-type rates. However, they exhibit defective cell movement and a wide range of defects in the control of the actin cytoskeleton, including a loss of cell polarity, absence of normal lamellipodia, formation of unusual small, punctate polymerized actin structures, and a large number of abnormally long filopodia. Despite their lack of polarity and abnormal cytoskeleton, mutant cells perform normal chemotaxis. However, rasG − cells are unable to perform normal cytokinesis, becoming multinucleate when grown in suspension culture. Taken together, these data suggest a principal role for RasG in coordination of cell movement and control of the cytoskeleton. PMID:9245789

Spectrum of magnetic resonance imaging findings in clinical glenohumeral instability

PubMed Central

Jana, Manisha; Srivastava, Deep Narayan; Sharma, Raju; Gamanagatti, Shivanand; Nag, Hiralal; Mittal, Ravi; Upadhyay, Ashish Dutt

2011-01-01

The glenohumeral joint is the most commonly dislocated joint in the body, and anterior instability is the most common type of shoulder instability. Depending on the etiology and the age of the patient, there may be associated injuries, for example, to the anterior-inferior labro-ligamentous structures (in young individuals with traumatic instability) or to the bony components (commoner in the elderly), which are best visualized using MRI and MR arthrography. Anterior instability is associated with a Bankart lesion and its variants and abnormalities of the anterior band of the inferior glenohumeral ligament (IGHL), whereas posterior instability is associated with reverse Bankart and reverse Hill-Sachs lesions. Cases of multidirectional instability often have no labral pathology on imaging but show specific osseous changes including increased chondrolabral retroversion. This article reviews the relevant anatomy in brief and describes the MRI findings in each type, with the imaging features of the common abnormalities. PMID:21799591

Magnetic resonance imaging in neuropsychiatric systemic lupus erythematosus: current state of the art and novel approaches.

PubMed

Postal, M; Lapa, A Tamires; Reis, F; Rittner, L; Appenzeller, S

2017-04-01

Systemic lupus erythematosus is a chronic, inflammatory, immune-mediated disease affecting 0.1% of the general population. Neuropsychiatric manifestations in systemic lupus erythematosus have been more frequently recognized and reported in recent years, occurring in up to 75% of patients during the disease course. Magnetic resonance imaging is known to be a useful tool for the detection of structural brain abnormalities in neuropsychiatric systemic lupus erythematosus patients because of the excellent soft-tissue contrast observed with MRI and the ability to acquire multiplanar images. In addition to conventional magnetic resonance imaging techniques to evaluate the presence of atrophy and white matter lesions, several different magnetic resonance imaging techniques have been used to identify microstructural or functional abnormalities. This review will highlight different magnetic resonance imaging techniques, including the advanced magnetic resonance imaging methods used to determine central nervous system involvement in systemic lupus erythematosus.

BDNF in fragile X syndrome.

PubMed

Castrén, Maija L; Castrén, Eero

2014-01-01

Fragile X syndrome (FXS) is a monogenic disorder that is caused by the absence of FMR1 protein (FMRP). FXS serves as an excellent model disorder for studies investigating disturbed molecular mechanisms and synapse function underlying cognitive impairment, autism, and behavioral disturbance. Abnormalities in dendritic spines and synaptic transmission in the brain of FXS individuals and mouse models for FXS indicate perturbations in the development, maintenance, and plasticity of neuronal network connectivity. However, numerous alterations are found during the early development in FXS, including abnormal differentiation of neural progenitors and impaired migration of newly born neurons. Several aspects of FMRP function are modulated by brain-derived neurotrophic factor (BDNF) signaling. Here, we review the evidence of the role for BDNF in the developing and adult FXS brain. This article is part of the Special Issue entitled 'BDNF Regulation of Synaptic Structure, Function, and Plasticity'. Copyright © 2013 Elsevier Ltd. All rights reserved.

Women's experiences of coping with pregnancy termination for fetal abnormality.

PubMed

Lafarge, Caroline; Mitchell, Kathryn; Fox, Pauline

2013-07-01

Pregnancy termination for fetal abnormality (TFA) can have significant psychological consequences. Most previous research has been focused on measuring the psychological outcomes of TFA, and little is known about the coping strategies involved. In this article, we report on women's coping strategies used during and after the procedure. Our account is based on experiences of 27 women who completed an online survey. We analyzed the data using interpretative phenomenological analysis. Coping comprised four structures, consistent across time points: support, acceptance, avoidance, and meaning attribution. Women mostly used adaptive coping strategies but reported inadequacies in aftercare, which challenged their resources. The study's findings indicate the need to provide sensitive, nondirective care rooted in the acknowledgment of the unique nature of TFA. Enabling women to reciprocate for emotional support, promoting adaptive coping strategies, highlighting the potential value of spending time with the baby, and providing long-term support (including during subsequent pregnancies) might promote psychological adjustment to TFA.

Cerebral morphology and functional sparing after prenatal frontal cortex lesions in rats.

PubMed

Kolb, B; Cioe, J; Muirhead, D

1998-03-01

Rats were given suction lesions of the presumptive frontal cortex on embryonic day 18 (E18) and subsequently tested, as adults, on tests of spatial navigation (Morris water task, radial arm maze), motor tasks (Whishaw reaching task, beam walking), and locomotor activity. Frontal cortical lesions at E18 affected cerebral morphogenesis, producing unusual morphological structures including abnormal patches of neurons in the cortex and white matter as well as neuronal bridges between the hemispheres. A small sample of E18 operates also had hydrocephaly. The animals with E18 lesions without hydrocephalus were behaviorally indistinguishable from littermate controls. The results demonstrate that animals with focal lesions of the presumptive frontal cortex have gross abnormalities in cerebral morphology but the lesions leave the functions normally subserved by the frontal cortex in adult rats unaffected. The results are discussed in the context of a hypothesis regarding the optimal times for functional recovery from cortical injury.

A case of probable autosomal recessive ectodermal dysplasia with corkscrew hairs and mental retardation in a family with tuberous sclerosis.

PubMed

Argenziano, G; Monsurrò, M R; Pazienza, R; Delfino, M

1998-02-01

We describe a woman with a probable autosomal recessive ectodermal dysplasia with corkscrew hairs and mental retardation in a family with tuberous sclerosis. Other findings included syndactyly, typical facies, dental abnormalities, dermatoglyphic hypoplasia, epidermal ridge sweat pore count slightly below normal, and keratosis pilaris. Clinical studies and genetic analysis excluded the diagnosis of tuberous sclerosis in our patient. We conclude that she has ectodermal dysplasia associated with mental retardation. This association has been described previously; it suggests the possible interrelationship of a community of ectodermal dysplasia syndromes with a distinctive structural hair abnormality (pili torti et canaliculi), variable midfacial malformations, limb defects, and other features such as mental retardation. The similarity of our patient to that described by Whiting et al. and Abramovits-Ackerman et al. suggests the autonomy of this syndrome.

AB INITIO Molecular Dynamics Simulations on Local Structure and Electronic Properties in Liquid Sb from 913 K to 1193 K

NASA Astrophysics Data System (ADS)

Hao, Qing-Hai; Li, Y. D.; Kong, Xiang-Shan; Liu, C. S.

2013-02-01

Ab initio molecular dynamics simulations on liquid Sb have been carried out at five different temperatures from 913 K to 1193 K. We have investigated the temperature dependence of structure properties including structural factor S(Q), pair correlation function g(r), bond-angle distribution function g3(θ), cluster properties and bond order parameter Q4 and Q6. A shoulder was reproduced in the high wave number side of the first peak in the S(Q) implying that the residual structure units of crystalline Sb remain in liquid Sb. There is a noticeable bend at around 1023 K in the temperature dependence of the first-peak height of S(Q), the cluster properties and bond order parameter Q4, respectively, indicating that an abnormal structural change may occur at 973-1023 K.

Dynamic changes of striatal and extrastriatal abnormalities in glutaric aciduria type I.

PubMed

Harting, Inga; Neumaier-Probst, Eva; Seitz, Angelika; Maier, Esther M; Assmann, Birgit; Baric, Ivo; Troncoso, Monica; Mühlhausen, Chris; Zschocke, Johannes; Boy, Nikolas P S; Hoffmann, Georg F; Garbade, Sven F; Kölker, Stefan

2009-07-01

In glutaric aciduria type I, an autosomal recessive disease of mitochondrial lysine, hydroxylysine and tryptophan catabolism, striatal lesions are characteristically induced by acute encephalopathic crises during a finite period of brain development (age 3-36 months). The frequency of striatal injury is significantly less in patients diagnosed as asymptomatic newborns by newborn screening. Most previous studies have focused on the onset and mechanism of striatal injury, whereas little is known about neuroradiological abnormalities in pre-symptomatically diagnosed patients and about dynamic changes of extrastriatal abnormalities. Thus, the major aim of the present retrospective study was to improve our understanding of striatal and extrastriatal abnormalities in affected individuals including those diagnosed by newborn screening. To this end, we systematically analysed magnetic resonance imagings (MRIs) in 38 patients with glutaric aciduria type I diagnosed before or after the manifestation of neurological symptoms. To identify brain regions that are susceptible to cerebral injury during acute encephalopathic crises, we compared the frequency of magnetic resonance abnormalities in patients with and without such crises. Major specific changes after encephalopathic crises were found in the putamen (P < 0.001), nucleus caudatus (P < 0.001), globus pallidus (P = 0.012) and ventricles (P = 0.001). Analysis of empirical cumulative distribution frequencies, however, demonstrated that isolated pallidal abnormalities did not significantly differ over time in both groups (P = 0.544) suggesting that isolated pallidal abnormalities are not induced by acute crises--in contrast to striatal abnormalities. The manifestation of motor disability was associated with signal abnormalities in putamen, caudate, pallidum and ventricles. In addition, we found a large number of extrastriatal abnormalities in patients with and without preceding encephalophatic crises. These abnormalities include widening of anterior temporal and sylvian CSF spaces, pseudocysts, signal changes of substantia nigra, nucleus dentatus, thalamus, tractus tegmentalis centralis and supratentorial white matter as well as signs of delayed maturation (myelination and gyral pattern). In contrast to the striatum, extrastriatal abnormalities were variable and could regress or even normalize with time. This includes widening of sylvian fissures, delayed maturation, pallidal signal changes and pseudocysts. Based on these results, we hypothesize that neuroradiological abnormalities and neurological symptoms in glutaric aciduria type I can be explained by overlaying episodes of cerebral alterations including maturational delay of the brain in utero, acute striatal injury during a vulnerable period in infancy and chronic progressive changes that may continue lifelong. This may have widespread consequences for the pathophysiological understanding of this disease, long-term outcomes and therapeutic considerations.

The clinical profile and pathophysiology of atrial fibrillation: relationships among clinical features, epidemiology, and mechanisms.

PubMed

Andrade, Jason; Khairy, Paul; Dobrev, Dobromir; Nattel, Stanley

2014-04-25

Atrial fibrillation (AF) is the most common arrhythmia (estimated lifetime risk, 22%-26%). The aim of this article is to review the clinical epidemiological features of AF and to relate them to underlying mechanisms. Long-established risk factors for AF include aging, male sex, hypertension, valve disease, left ventricular dysfunction, obesity, and alcohol consumption. Emerging risk factors include prehypertension, increased pulse pressure, obstructive sleep apnea, high-level physical training, diastolic dysfunction, predisposing gene variants, hypertrophic cardiomyopathy, and congenital heart disease. Potential risk factors are coronary artery disease, kidney disease, systemic inflammation, pericardial fat, and tobacco use. AF has substantial population health consequences, including impaired quality of life, increased hospitalization rates, stroke occurrence, and increased medical costs. The pathophysiology of AF centers around 4 general types of disturbances that promote ectopic firing and reentrant mechanisms, and include the following: (1) ion channel dysfunction, (2) Ca(2+)-handling abnormalities, (3) structural remodeling, and (4) autonomic neural dysregulation. Aging, hypertension, valve disease, heart failure, myocardial infarction, obesity, smoking, diabetes mellitus, thyroid dysfunction, and endurance exercise training all cause structural remodeling. Heart failure and prior atrial infarction also cause Ca(2+)-handling abnormalities that lead to focal ectopic firing via delayed afterdepolarizations/triggered activity. Neural dysregulation is central to atrial arrhythmogenesis associated with endurance exercise training and occlusive coronary artery disease. Monogenic causes of AF typically promote the arrhythmia via ion channel dysfunction, but the mechanisms of the more common polygenic risk factors are still poorly understood and under intense investigation. Better recognition of the clinical epidemiology of AF, as well as an improved appreciation of the underlying mechanisms, is needed to develop improved methods for AF prevention and management.

The Prevalence and Significance of Abnormal Vital Signs Prior to In-Hospital Cardiac Arrest

PubMed Central

Andersen, Lars W.; Kim, Won Young; Chase, Maureen; Berg, Katherine; Mortensen, Sharri J.; Moskowitz, Ari; Novack, Victor; Cocchi, Michael N.; Donnino, Michael W.

2015-01-01

Background Patients suffering in-hospital cardiac arrest often show signs of physiological deterioration before the event. The purpose of this study was to determine the prevalence of abnormal vital signs 1–4 hours before cardiac arrest, and to evaluate the association between these vital sign abnormalities and inhospital mortality. Methods We included adults from the Get With the Guidelines® - Resuscitation registry with an in-hospital cardiac arrest. We used two a priori definitions for vital signs: abnormal (heart rate (HR) ≤ 60 or ≥ 100 min−1, respiratory rate (RR) ≤ 10 or > 20 min−1 and systolic blood pressure (SBP) ≤ 90 mm Hg) and severely abnormal (HR ≤ 50 or ≥ 130 min−1, RR ≤ 8 or ≥ 30 min−1 and SBP ≤80 mm Hg). We evaluated the association between the number of abnormal vital signs and in-hospital mortality using a multivariable logistic regression model. Results 7,851 patients were included. Individual vital signs were associated with in-hospital mortality. The majority of patients (59.4%) had at least one abnormal vital sign 1–4 hours before the arrest and 13.4% had at least one severely abnormal sign. We found a step-wise increase in mortality with increasing number of abnormal vital signs within the abnormal (odds ratio (OR) 1.53 (CI: 1.42 – 1.64) and severely abnormal groups (OR 1.62 [CI: 1.38 – 1.90]). This remained in multivariable analysis (abnormal: OR 1.38 [CI: 1.28 – 1.48], and severely abnormal: OR 1.40 [CI: 1.18 – 1.65]). Conclusion Abnormal vital signs are prevalent 1–4 hours before in-hospital cardiac arrest on hospital wards. Inhospital mortality increases with increasing number of pre-arrest abnormal vital signs as well as increased severity of vital sign derangements. PMID:26362486

Prevalence of triangular fibrocartilage complex abnormalities regardless of symptoms rise with age: systematic review and pooled analysis.

PubMed

Chan, Jimmy J; Teunis, Teun; Ring, David

2014-12-01

Triangular fibrocartilage complex abnormalities seem to be more common with age, but the degree to which this is so, and the degree to which the presence of an abnormality is associated with symptoms, are topics of controversy. We wished to perform a systematic review to determine the prevalence of triangular fibrocartilage complex abnormalities, and to determine if the prevalence of abnormalities are greater with increasing age. In addition, we stratified age groups based on symptoms. We searched MEDLINE, EMBASE, and the Cochrane Library through August 15, 2013. Studies that reported triangular fibrocartilage complex abnormalities by age were included. Fifteen studies including 977 wrists met our criteria and reported a total of 368 (38%) triangular fibrocartilage complex abnormalities. Eight studies included symptomatic patients; the remainder studied cadavers (six studies) or asymptomatic volunteers (one study). Patients were divided into four age groups (< 30, 30-49, 50-69, and 70 years and older) for pooled analysis, comparing the proportions of patients with and without abnormalities between groups using chi-square analysis. We also evaluated the proportions after stratifying each age group by symptoms. Overall, the prevalence of triangular fibrocartilage complex abnormalities increased with age, from 27% (80/301) in patients younger than 30 years to 49% (130/265) in patients 70 years and older (p < 0.001), odds ratio (OR), 2.7, 95% CI, 1.9-3.8 (p < 0.001). In asymptomatic patients, triangular fibrocartilage complex prevalence abnormality increased from 15% (24/159) to 49% (129/263) in the same age groups (p < 0.001), OR, 5.4, 95% CI, 3.3-8.9 (p < 0.001). For symptomatic patients prevalence ranged from 39% (56/142) to 70% (14/20) in patients between 50 and 69 years old (p < 0.034), OR, 3.6, 95% CI, 1.3-9.9 (p < 0.014). Triangular fibrocartilage complex abnormalities are common in symptomatic and asymptomatic wrists, and they are increasingly common with age. As in all situations where abnormalities are so common that they may be incidental, we need (1) a reliable and accurate method for determining whether these abnormalities are the cause of symptoms; and (2) evidence that treatment of these abnormalities improves symptoms better than placebo. Level III, prognostic study. See the Instructions for Authors for a complete description of levels of evidence.

Thalamic alterations in preterm neonates and its relation to ventral striatum disturbances revealed by a combined shape and pose analysis

PubMed Central

Lao, Yi; Wang, Yalin; Shi, Jie; Ceschin, Rafael; Nelson, Marvin D.; Panigrahy, Ashok; Leporé, Natasha

2015-01-01

Finding the neuroanatomical correlates of prematurity is vital to understanding which structures are affected, and design efficient prevention andtreatment strategy. Converging results reveal that thalamic abnormalities are important indicators of prematurity. However, little is known about the localization of the disturbance within the subnuclei of the thalamus, or on the association of altered thalamic development with other deep gray matter disturbances. Here, using brain structural magnetic resonance imaging (MRI), we perform a novel combined shape and pose analysis of the thalamus and ventral striatum between 17 preterm and 19 term-born neonates. We detect statistically significant surface deformations and pose changes on the thalamus andventral striatum, successfully locating the alterations on specific regions such as the anterior and ventral-anterior thalamic nuclei, and for the first time, demonstrating the feasibility of using relative pose parameters as indicators for prematurity in neonates. We also perform a set of correlation analyses between the thalamus and the ventral striatum, based on the surface and pose results. Our methods show that regional abnormalities of the thalamus are associated with alterations of the ventral striatum, possibly due to disturbed development of sharedpre-frontal connectivity. More specifically, the significantly correlated regions in these two structures point to frontal-subcortical pathways including the dorsolateral prefrontal-subcortical circuit, the lateral orbitofrontal-subcortical circuit, the motor circuit, and the oculomotor circuit. These findings reveal new insight into potential subcortical structural covariatesfor poor neurodevelopmental outcomes in the preterm population. PMID:25366970

In vivo laser confocal microscopy findings of a cornea with osteogenesis imperfecta

PubMed Central

Kobayashi, Akira; Higashide, Tomomi; Yokogawa, Hideaki; Yamazaki, Natsuko; Masaki, Toshinori; Sugiyama, Kazuhisa

2014-01-01

Objective To report the in vivo laser confocal microscopy findings of a cornea with osteogenesis imperfecta (OI) with special attention to the abnormality of Bowman’s layer and sub-Bowman’s fibrous structures (K-structures). Patients and methods Two patients (67-year-old male and his 26-year-old son) with OI type I were included in this study. Slit lamp biomicroscopic and in vivo laser confocal microscopic examinations were performed for both patients. Central corneal thickness and central endothelial cell density were also measured. Results Although the corneas looked clear with normal endothelial density for both eyes in both patients, they were quite thin (386 μm oculus dexter (OD) (the right eye) and 384 μm oculus sinister (OS) (the left eye) in the father and 430 μm OD and 425 μm OS in the son). In both patients, slit lamp biomicroscopic and in vivo laser confocal microscopic examination showed similar results. Anterior corneal mosaics produced by rubbing the eyelid under fluorescein were completely absent in both eyes. In vivo laser confocal microscopy revealed an absent or atrophic Bowman’s layer; a trace of a presumed Bowman’s layer and/or basement membrane was barely visible with high intensity. Additionally, K-structures were completely absent in both eyes. Conclusion The absence of K-structures and fluorescein anterior corneal mosaics strongly suggested an abnormality of Bowman’s layer in these OI patients. PMID:24591812

Structural, Metabolic, and Functional Brain Abnormalities as a Result of Prenatal Exposure to Drugs of Abuse: Evidence from Neuroimaging

PubMed Central

Roussotte, Florence; Soderberg, Lindsay

2010-01-01

Prenatal exposure to alcohol and stimulants negatively affects the developing trajectory of the central nervous system in many ways. Recent advances in neuroimaging methods have allowed researchers to study the structural, metabolic, and functional abnormalities resulting from prenatal exposure to drugs of abuse in living human subjects. Here we review the neuroimaging literature of prenatal exposure to alcohol, cocaine, and methamphetamine. Neuroimaging studies of prenatal alcohol exposure have reported differences in the structure and metabolism of many brain systems, including in frontal, parietal, and temporal regions, in the cerebellum and basal ganglia, as well as in the white matter tracts that connect these brain regions. Functional imaging studies have identified significant differences in brain activation related to various cognitive domains as a result of prenatal alcohol exposure. The published literature of prenatal exposure to cocaine and methamphetamine is much smaller, but evidence is beginning to emerge suggesting that exposure to stimulant drugs in utero may be particularly toxic to dopamine-rich basal ganglia regions. Although the interpretation of such findings is somewhat limited by the problem of polysubstance abuse and by the difficulty of obtaining precise exposure histories in retrospective studies, such investigations provide important insights into the effects of drugs of abuse on the structure, function, and metabolism of the developing human brain. These insights may ultimately help clinicians develop better diagnostic tools and devise appropriate therapeutic interventions to improve the condition of children with prenatal exposure to drugs of abuse. PMID:20978945

Constitutional and acquired autosomal aneuploidy.

PubMed

Jackson-Cook, Colleen

2011-12-01

Chromosomal imbalances can result from numerical or structural anomalies. Numerical chromosomal abnormalities are often referred to as aneuploid conditions. This article focuses on the occurrence of constitutional and acquired autosomal aneuploidy in humans. Topics covered include frequency, mosaicism, phenotypic findings, and etiology. The article concludes with a consideration of anticipated advances that might allow for the development of screening tests and/or lead to improvements in our understanding and management of the role that aneuploidy plays in the aging process and acquisition of age-related and constitutional conditions.

Structural relationships between human erythrocyte sialoglycoproteins beta and gamma and abnormal sialoglycoproteins found in certain rare human erythrocyte variants lacking the Gerbich blood-group antigen(s).

PubMed Central

Reid, M E; Anstee, D J; Tanner, M J; Ridgwell, K; Nurse, G T

1987-01-01

The human erythrocyte membrane sialoglycoproteins beta and gamma are important for the maintenance of the discoid shape of the normal erythrocyte. In this paper we show that the human erythrocyte sialoglycoproteins beta and gamma (hereafter called beta and gamma) are structurally related. Rabbit antisera produced against purified beta and beta 1 and rendered specific to the cytoplasmic portion of these proteins also react with the cytoplasmic portion of gamma. Some human anti-Gerbich (Ge) sera react with the extracellular portion of both beta and gamma. This reactivity is shown to be directed towards a common epitope on beta and gamma. However, most anti-Ge sera do not react with beta, but react with an extracellular epitope only present on gamma. All individuals who lack the Ge antigens lack beta and gamma. In some cases abnormal sialoglycoproteins are present in the erythrocytes, and these are shown to be structurally related to beta and gamma. Rabbit antisera raised against the purified abnormal sialoglycoprotein from a Ge-negative erythrocyte type reacted with the cytoplasmic portion of both beta and gamma. Unlike normal beta and gamma, the abnormal sialoglycoproteins found in Ge-negative erythrocytes migrate as a diffuse band on SDS/polyacrylamide-gel electrophoresis. Studies using endoglycosidases suggest that the diffuse nature of these bands results from carbohydrate heterogeneity and that the abnormal sialoglycoproteins contain N-glycosidically linked oligosaccharides with repeating lactosamine units. Such polylactosamine chains are not present on normal beta or gamma. Images Fig. 1. Fig. 2. Fig. 3. PMID:2444210

The Role of Esophageal Hypersensitivity in Functional Esophageal Disorders.

PubMed

Farmer, Adam D; Ruffle, James K; Aziz, Qasim

2017-02-01

The Rome IV diagnostic criteria delineates 5 functional esophageal disorders which include functional chest pain, functional heartburn, reflux hypersensitivity, globus, and functional dysphagia. These are a heterogenous group of disorders which, despite having characteristic symptom profiles attributable to esophageal pathology, fail to demonstrate any structural, motility or inflammatory abnormalities on standard clinical testing. These disorders are associated with a marked reduction in patient quality of life, not least considerable healthcare resources. Furthermore, the pathophysiology of these disorders is incompletely understood. In this narrative review we provide the reader with an introductory primer to the structure and function of esophageal perception, including nociception that forms the basis of the putative mechanisms that may give rise to symptoms in functional esophageal disorders. We also discuss the provocative techniques and outcome measures by which esophageal hypersensitivity can be established.

Myocardial perfusion and left ventricular function indices assessed by gated myocardial perfusion SPECT in methamphetamine abusers.

PubMed

Dadpour, Bita; Dabbagh Kakhki, Vahid R; Afshari, Reza; Dorri-Giv, Masoumeh; Mohajeri, Seyed A R; Ghahremani, Somayeh

2016-12-01

Methamphetamine (MA) is associated with alterations of cardiac structure and function, although it is less known. In this study, we assessed possible abnormality in myocardial perfusion and left ventricular function using gated myocardial perfusion SPECT. Fifteen patients with MA abuse, on the basis of Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) MA dependency determined by Structured Clinical Interview for DSM-IV, underwent 2-day dipyridamole stress/rest Tc-sestamibi gated myocardial perfusion SPECT. An average daily dose of MA use was 0.91±1.1 (0.2-4) g. The duration of MA use was 3.4±2.1 (1-7) years. In visual and semiquantitative analyses, all patients had normal gated myocardial perfusion SPECT, with no perfusion defects. In all gated SPECT images, there was no abnormality in left ventricular wall motion and thickening. All summed stress scores and summed rest scores were below 3. Calculated left ventricular functional indices including the end-diastolic volume, end-systolic volume, and left ventricular ejection fraction were normal. Many cardiac findings because of MA mentioned in previous reports are less likely because of significant epicardial coronary artery stenosis.

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

PubMed

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

2017-05-01

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

Altered structural connectivity of cortico-striato-pallido-thalamic networks in Gilles de la Tourette syndrome.

PubMed

Worbe, Yulia; Marrakchi-Kacem, Linda; Lecomte, Sophie; Valabregue, Romain; Poupon, Fabrice; Guevara, Pamela; Tucholka, Alan; Mangin, Jean-François; Vidailhet, Marie; Lehericy, Stephane; Hartmann, Andreas; Poupon, Cyril

2015-02-01

Gilles de la Tourette syndrome is a childhood-onset syndrome characterized by the presence and persistence of motor and vocal tics. A dysfunction of cortico-striato-pallido-thalamo-cortical networks in this syndrome has been supported by convergent data from neuro-pathological, electrophysiological as well as structural and functional neuroimaging studies. Here, we addressed the question of structural integration of cortico-striato-pallido-thalamo-cortical networks in Gilles de la Tourette syndrome. We specifically tested the hypothesis that deviant brain development in Gilles de la Tourette syndrome could affect structural connectivity within the input and output basal ganglia structures and thalamus. To this aim, we acquired data on 49 adult patients and 28 gender and age-matched control subjects on a 3 T magnetic resonance imaging scanner. We used and further implemented streamline probabilistic tractography algorithms that allowed us to quantify the structural integration of cortico-striato-pallido-thalamo-cortical networks. To further investigate the microstructure of white matter in patients with Gilles de la Tourette syndrome, we also evaluated fractional anisotropy and radial diffusivity in these pathways, which are both sensitive to axonal package and to myelin ensheathment. In patients with Gilles de la Tourette syndrome compared to control subjects, we found white matter abnormalities in neuronal pathways connecting the cerebral cortex, the basal ganglia and the thalamus. Specifically, striatum and thalamus had abnormally enhanced structural connectivity with primary motor and sensory cortices, as well as paracentral lobule, supplementary motor area and parietal cortices. This enhanced connectivity of motor cortex positively correlated with severity of tics measured by the Yale Global Tics Severity Scale and was not influenced by current medication status, age or gender of patients. Independently of the severity of tics, lateral and medial orbito-frontal cortex, inferior frontal, temporo-parietal junction, medial temporal and frontal pole also had enhanced structural connectivity with the striatum and thalamus in patients with Gilles de la Tourette syndrome. In addition, the cortico-striatal pathways were characterized by elevated fractional anisotropy and diminished radial diffusivity, suggesting microstructural axonal abnormalities of white matter in Gilles de la Tourette syndrome. These changes were more prominent in females with Gilles de la Tourette syndrome compared to males and were not related to the current medication status. Taken together, our data showed widespread structural abnormalities in cortico-striato-pallido-thalamic white matter pathways in patients with Gilles de la Tourette, which likely result from abnormal brain development in this syndrome. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain.

Interpretation of normal anatomic structures on chest radiography: Comparison of Fuji Computed Radiography (FCR) 5501D with FCR 5000 and screen‐film system

PubMed Central

Nakashima, Kazuaki; Ashizawa, Kazuto; Ochi, Makoto; Hashmi, Rashid; Hayashi, Kuniaki; Gotoh, Shinichi; Honda, Sumihisa; Igarashi, Akito; Komaki, Takao

2003-01-01

The purpose of this study was to investigate the usefulness of Fuji Computed Radiography (FCR) 5501D by comparing it with FCR 5000 and a screen‐film system (S/F). Posteroanterior chest radiographs often patients with no abnormality on chest CT scans were obtained with FCR 5501D, FCR 5000, and S/F. Six observers (three radiologists and three radio‐technologists) evaluated the visibility of nine normal anatomic structures (including lungs, soft tissue, and bones) and overall visibility on each image. Observers scored using a five‐point scale on each structure. FCR 5000 showed a significantly higher score in soft tissue and bone structures, and overall visibility compared with S/F, but, there was no significant difference between them in the visibility of all four normal lung structures. Compared with S/F, the score for FCR 5501D was higher in eight of the nine normal structures, including three of the four lung structures (unobscured lung, retrocardiac lung, and subdiaphragmatic lung), and overall visibility. Compared with FCR 5000, the score for FCR 5501D was higher in three normal structures, including two of the four lung structures (unobscured lung and subdiaphragmatic lung), and overall visibility. FCR 5501D was the best among the three techniques to visualize normal anatomic structures, particularly the obscured and unobscured lung. © 2003 American College of Medical Physics. PACS number(s): 87.57.–s, 87.62.+n PMID:12540822

Abnormal prefrontal cortex resting state functional connectivity and severity of internet gaming disorder.

PubMed

Jin, Chenwang; Zhang, Ting; Cai, Chenxi; Bi, Yanzhi; Li, Yangding; Yu, Dahua; Zhang, Ming; Yuan, Kai

2016-09-01

Internet Gaming Disorder (IGD) among adolescents has become an important public concern and gained more and more attention internationally. Recent studies focused on IGD and revealed brain abnormalities in the IGD group, especially the prefrontal cortex (PFC). However, the role of PFC-striatal circuits in pathology of IGD remains unknown. Twenty-five adolescents with IGD and 21 age- and gender-matched healthy controls were recruited in our study. Voxel-based morphometric (VBM) and functional connectivity analysis were employed to investigate the abnormal structural and resting-state properties of several frontal regions in individuals with online gaming addiction. Relative to healthy comparison subjects, IGD subjects showed significant decreased gray matter volume in PFC regions including the bilateral dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC) and the right supplementary motor area (SMA) after controlling for age and gender effects. We chose these regions as the seeding areas for the resting-state analysis and found that IGD subjects showed decreased functional connectivity between several cortical regions and our seeds, including the insula, and temporal and occipital cortices. Moreover, significant decreased functional connectivity between some important subcortical regions, i.e., dorsal striatum, pallidum, and thalamus, and our seeds were found in the IGD group and some of those changes were associated with the severity of IGD. Our results revealed the involvement of several PFC regions and related PFC-striatal circuits in the process of IGD and suggested IGD may share similar neural mechanisms with substance dependence at the circuit level.

Model-based recovery of histological parameters from multispectral images of the colon

NASA Astrophysics Data System (ADS)

Hidovic-Rowe, Dzena; Claridge, Ela

2005-04-01

Colon cancer alters the macroarchitecture of the colon tissue. Common changes include angiogenesis and the distortion of the tissue collagen matrix. Such changes affect the colon colouration. This paper presents the principles of a novel optical imaging method capable of extracting parameters depicting histological quantities of the colon. The method is based on a computational, physics-based model of light interaction with tissue. The colon structure is represented by three layers: mucosa, submucosa and muscle layer. Optical properties of the layers are defined by molar concentration and absorption coefficients of haemoglobins; the size and density of collagen fibres; the thickness of the layer and the refractive indexes of collagen and the medium. Using the entire histologically plausible ranges for these parameters, a cross-reference is created computationally between the histological quantities and the associated spectra. The output of the model was compared to experimental data acquired in vivo from 57 histologically confirmed normal and abnormal tissue samples and histological parameters were extracted. The model produced spectra which match well the measured data, with the corresponding spectral parameters being well within histologically plausible ranges. Parameters extracted for the abnormal spectra showed the increase in blood volume fraction and changes in collagen pattern characteristic of the colon cancer. The spectra extracted from multi-spectral images of ex-vivo colon including adenocarcinoma show the characteristic features associated with normal and abnormal colon tissue. These findings suggest that it should be possible to compute histological quantities for the colon from the multi-spectral images.

Genomic Changes in Normal Breast Tissue in Women at Normal Risk or at High Risk for Breast Cancer

PubMed Central

Danforth, David N.

2016-01-01

Sporadic breast cancer develops through the accumulation of molecular abnormalities in normal breast tissue, resulting from exposure to estrogens and other carcinogens beginning at adolescence and continuing throughout life. These molecular changes may take a variety of forms, including numerical and structural chromosomal abnormalities, epigenetic changes, and gene expression alterations. To characterize these abnormalities, a review of the literature has been conducted to define the molecular changes in each of the above major genomic categories in normal breast tissue considered to be either at normal risk or at high risk for sporadic breast cancer. This review indicates that normal risk breast tissues (such as reduction mammoplasty) contain evidence of early breast carcinogenesis including loss of heterozygosity, DNA methylation of tumor suppressor and other genes, and telomere shortening. In normal tissues at high risk for breast cancer (such as normal breast tissue adjacent to breast cancer or the contralateral breast), these changes persist, and are increased and accompanied by aneuploidy, increased genomic instability, a wide range of gene expression differences, development of large cancerized fields, and increased proliferation. These changes are consistent with early and long-standing exposure to carcinogens, especially estrogens. A model for the breast carcinogenic pathway in normal risk and high-risk breast tissues is proposed. These findings should clarify our understanding of breast carcinogenesis in normal breast tissue and promote development of improved methods for risk assessment and breast cancer prevention in women. PMID:27559297

Congenital portosystemic shunts: prenatal manifestations with postnatal confirmation and follow-up.

PubMed

Han, Byoung Hee; Park, Sung Bin; Song, Mi Jin; Lee, Kyung Sang; Lee, Young-Ho; Ko, Sun Young; Lee, Yeon Kyung

2013-01-01

The purpose of this study was to evaluate prenatal sonographic findings that could be helpful for diagnosis of congenital intrahepatic portosystemic venous shunts and the follow-up results. Six neonates with congenital shunts between the portal vein and hepatic vein were enrolled in this study. Prenatal sonography was performed in 5 cases. We categorized the cases according to a previously published classification of intrahepatic portosystemic venous shunts and retrospectively reviewed the prenatal and postnatal sonographic examinations to identify findings that might be helpful for diagnosing shunts prenatally. Follow-up sonographic examinations were done until closure of the shunts. Clinical features were also determined. According to the original reports, intrahepatic portosystemic venous shunts were diagnosed by prenatal sonography in 2 of 5 cases. In the remaining 3 cases, there were suggestive abnormal findings on retrospective review, including an abnormal intrahepatic tubular structure, a prominent hepatic vein, and congestive heart failure. Postnatal sonography showed type 2 shunts in all 6 cases. In 1 case, there were 2 type 2 lesions between two branches of the left portal vein and the middle and left hepatic veins. On follow-up sonography, 5 of the 6 congenital shunts had spontaneously closed by 11 months of age. One case was treated with coil embolization during the neonatal period. Intrauterine growth restriction was the most commonly clinical feature prenatally. Findings such as an abnormal tubular structure, a prominent hepatic vein, and congestive heart failure can be important clues for identifying congenital intrahepatic portosystemic venous shunts on prenatal sonography. The use of prenatal and postnatal sonography is feasible for detection and evaluation of these shunts.

Prediction of vascular abnormalities on CT angiography in patients with acute headache.

PubMed

Alons, Imanda M E; Goudsmit, Ben F J; Jellema, Korné; van Walderveen, Marianne A A; Wermer, Marieke J H; Algra, Ale

2018-05-09

Patients with acute headache increasingly undergo CT-angiography (CTA) to evaluate underlying vascular causes. The aim of this study is to determine clinical and non-contrast CT (NCCT) criteria to select patients who might benefit from CTA. We retrospectively included patients with acute headache who presented to the emergency department of an academic medical center and large regional teaching hospital and underwent NCCT and CTA. We identified factors that increased the probability of finding a vascular abnormality on CTA, performed multivariable regression analyses and determined discrimination with the c-statistic. A total of 384 patients underwent NCCT and CTA due to acute headache. NCCT was abnormal in 194 patients. Among these, we found abnormalities in 116 cases of which 99 aneurysms. In the remaining 190 with normal NCCT we found abnormalities in 12 cases; four unruptured aneurysms, three cerebral venous thrombosis', two reversible cerebral vasoconstriction syndromes, two cervical arterial dissections and one cerebellar infarction. In multivariable analysis abnormal NCCT, lowered consciousness and presentation within 6 hr of headache onset were independently associated with abnormal CTA. The c-statistic of abnormal NCCT alone was 0.80 (95% CI: 0.75-0.80), that also including the other two variables was 0.84 (95% CI: 0.80-0.88). If NCCT was normal no other factors could help identify patients at risk for abnormalities. In patients with acute headache abnormal NCCT is the strongest predictor of a vascular abnormality on CTA. If NCCT is normal no other predictors increase the probability of finding an abnormality on CTA and diagnostic yield is low. © 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

Neural mechanisms of oculomotor abnormalities in the infantile strabismus syndrome.

PubMed

Walton, Mark M G; Pallus, Adam; Fleuriet, Jérome; Mustari, Michael J; Tarczy-Hornoch, Kristina

2017-07-01

Infantile strabismus is characterized by numerous visual and oculomotor abnormalities. Recently nonhuman primate models of infantile strabismus have been established, with characteristics that closely match those observed in human patients. This has made it possible to study the neural basis for visual and oculomotor symptoms in infantile strabismus. In this review, we consider the available evidence for neural abnormalities in structures related to oculomotor pathways ranging from visual cortex to oculomotor nuclei. These studies provide compelling evidence that a disturbance of binocular vision during a sensitive period early in life, whatever the cause, results in a cascade of abnormalities through numerous brain areas involved in visual functions and eye movements. Copyright © 2017 the American Physiological Society.

Primary Cortical Folding in the Human Newborn: An Early Marker of Later Functional Development

ERIC Educational Resources Information Center

Dubois, J.; Benders, M.; Borradori-Tolsa, C.; Cachia, A.; Lazeyras, F.; Leuchter, R. Ha-Vinh; Sizonenko, S. V.; Warfield, S. K.; Mangin, J. F.; Huppi, P. S.

2008-01-01

In the human brain, the morphology of cortical gyri and sulci is complex and variable among individuals, and it may reflect pathological functioning with specific abnormalities observed in certain developmental and neuropsychiatric disorders. Since cortical folding occurs early during brain development, these structural abnormalities might be…

Three-dimensional HDlive imaging of an umbilical cord cyst.

PubMed

Inubashiri, Eisuke; Nishiyama, Naomi; Tatedo, Sayuri; Minami, Hiina; Saitou, Atushi; Watanabe, Yukio; Sugawara, Masaki

2018-04-01

Umbilical cord cysts (UCC) are a rare congenital malformation. Previous reports have suggested that the second- and third-trimester UCC may be associated with other structural anomalies or chromosomal abnormalities. Therefore, high-quality imaging is clinically important for the antenatal diagnosis of UCC and to conduct a precise anatomical survey of intrauterine abnormalities. There have been few reports of antenatal diagnosis of UCC with the conventional two- and three-dimensional ultrasonography. In this report, we demonstrate the novel visual depiction of UCC in utero with three-dimensional HDlive imaging, which helps substantially with prenatal diagnosis. A case with an abnormal placental mass at 16 weeks and 5 days of gestation was observed in detail using HDlive. HDlive revealed very realistic images of the intrauterine abnormality: the oval lesion was smooth with regular contours and a homogenous wall at the site of cord insertion on the placenta. In addition, we confirmed the absent of umbilical cord, placental, and fetal structural anomalies. Here, we report a case wherein HDlive may have provided clinically valuable information for prenatal diagnosis of UCC and offered a potential advantage relative to the conventional US.

Progressive neurostructural changes in adolescent and adult patients with bipolar disorder.

PubMed

Lisy, Megan E; Jarvis, Kelly B; DelBello, Melissa P; Mills, Neil P; Weber, Wade A; Fleck, David; Strakowski, Stephen M; Adler, Caleb M

2011-06-01

Several lines of evidence suggest that bipolar disorder is associated with progressive changes in gray matter volume (GMV), particularly in brain structures involved in emotional regulation and expression. The majority of these studies however, have been cross-sectional in nature. In this study we compared baseline and follow-up scans in groups of bipolar disorder and healthy subjects. We hypothesized bipolar disorder subjects would demonstrate significant GMV changes over time. A total of 58 bipolar disorder and 48 healthy subjects participated in structural magnetic resonance imaging (MRI). Subjects were rescanned 3-34 months after their baseline MRI. MRI images were segmented, normalized to standard stereotactic space, and compared voxel-by-voxel using statistical parametrical mapping software (SPM2). A model was developed to investigate differences in GMV at baseline, and associated with time and episodes, as well as in comparison to healthy subjects. We observed increases in GMV in bipolar disorder subjects across several brain regions at baseline and over time, including portions of the prefrontal cortex as well as limbic and subcortical structures. Time-related changes differed to some degree between adolescent and adult bipolar disorder subjects. The interval between scans positively correlated with GMV increases in bipolar disorder subjects in portions of the prefrontal cortex, and both illness duration and number of depressive episodes were associated with increased GMV in subcortical and limbic structures. Our findings support suggestions that widely observed progressive neurofunctional changes in bipolar disorder patients may be related to structural brain abnormalities in anterior limbic structures. Abnormalities largely involve regions previously noted to be integral to emotional expression and regulation, and appear to vary by age. © 2011 John Wiley and Sons A/S.

Effects of Hatchery Rearing on the Structure and Function of Salmonid Mechanosensory Systems.

PubMed

Brown, Andrew D; Sisneros, Joseph A; Jurasin, Tyler; Coffin, Allison B

2016-01-01

This paper reviews recent studies on the effects of hatchery rearing on the auditory and lateral line systems of salmonid fishes. Major conclusions are that (1) hatchery-reared juveniles exhibit abnormal lateral line morphology (relative to wild-origin conspecifics), suggesting that the hatchery environment affects lateral line structure, perhaps due to differences in the hydrodynamic conditions of hatcheries versus natural rearing environments, and (2) hatchery-reared salmonids have a high proportion of abnormal otoliths, a condition associated with reduced auditory sensitivity and suggestive of inner ear dysfunction.

Grey matter abnormalities in children and adolescents with functional neurological symptom disorder.

PubMed

Kozlowska, Kasia; Griffiths, Kristi R; Foster, Sheryl L; Linton, James; Williams, Leanne M; Korgaonkar, Mayuresh S

2017-01-01

Functional neurological symptom disorder refers to the presence of neurological symptoms not explained by neurological disease. Although this disorder is presumed to reflect abnormal function of the brain, recent studies in adults show neuroanatomical abnormalities in brain structure . These structural brain abnormalities have been presumed to reflect long-term adaptations to the disorder, and it is unknown whether child and adolescent patients, with illness that is typically of shorter duration, show similar deficits or have normal brain structure. High-resolution, three-dimensional T1-weighted magnetic resonance images (MRIs) were acquired in 25 patients (aged 10-18 years) and 24 healthy controls. Structure was quantified in terms of grey matter volume using voxel-based morphometry. Post hoc, we examined whether regions of structural difference related to a measure of motor readiness to emotional signals and to clinical measures of illness duration, illness severity, and anxiety/depression. Patients showed greater volumes in the left supplementary motor area (SMA) and right superior temporal gyrus (STG) and dorsomedial prefrontal cortex (DMPFC) (corrected p < 0.05). Previous studies of adult patients have also reported alterations of the SMA. Greater SMA volumes correlated with faster reaction times in identifying emotions but not with clinical measures. The SMA, STG, and DMPFC are known to be involved in the perception of emotion and the modulation of motor responses. These larger volumes may reflect the early expression of an experience-dependent plasticity process associated with increased vigilance to others' emotional states and enhanced motor readiness to organize self-protectively in the context of the long-standing relational stress that is characteristic of this disorder.

Association of Weight and Body Composition on Cardiac Structure and Function in the ARIC Study (Atherosclerosis Risk in Communities).

PubMed

Bello, Natalie A; Cheng, Susan; Claggett, Brian; Shah, Amil M; Ndumele, Chiadi E; Roca, Gabriela Querejeta; Santos, Angela B S; Gupta, Deepak; Vardeny, Orly; Aguilar, David; Folsom, Aaron R; Butler, Kenneth R; Kitzman, Dalane W; Coresh, Josef; Solomon, Scott D

2016-08-01

Obesity increases cardiovascular risk. However, the extent to which various measures of body composition are associated with abnormalities in cardiac structure and function, independent of comorbidities commonly affecting obese individuals, is not clear. This study sought to examine the relationship between body mass index, waist circumference, and percent body fat with conventional and advanced measures of cardiac structure and function. We studied 4343 participants of the ARIC study (Atherosclerosis Risk in Communities) who were aged 69 to 82 years, free of coronary heart disease and heart failure, and underwent comprehensive echocardiography. Increasing body mass index, waist circumference, and body fat were associated with greater left ventricular (LV) mass and left atrial volume indexed to height(2.7) in both men and women (P<0.001). In women, all 3 measures were associated with abnormal LV geometry, and increasing waist circumference and body fat were associated with worse global longitudinal strain, a measure of LV systolic function. In both sexes, increasing body mass index was associated with greater right ventricular end-diastolic area and worse right ventricular fractional area change (P≤0.001). We observed similar associations for both waist circumference and percent body fat. In a large, biracial cohort of older adults free of clinically overt coronary heart disease or heart failure, obesity was associated with subclinical abnormalities in cardiac structure in both men and women and with adverse LV remodeling and impaired LV systolic function in women. These data highlight the association of obesity and subclinical abnormalities of cardiac structure and function, particularly in women. © 2016 American Heart Association, Inc.

Development of quantitative analysis method for stereotactic brain image: assessment of reduced accumulation in extent and severity using anatomical segmentation.

PubMed

Mizumura, Sunao; Kumita, Shin-ichiro; Cho, Keiichi; Ishihara, Makiko; Nakajo, Hidenobu; Toba, Masahiro; Kumazaki, Tatsuo

2003-06-01

Through visual assessment by three-dimensional (3D) brain image analysis methods using stereotactic brain coordinates system, such as three-dimensional stereotactic surface projections and statistical parametric mapping, it is difficult to quantitatively assess anatomical information and the range of extent of an abnormal region. In this study, we devised a method to quantitatively assess local abnormal findings by segmenting a brain map according to anatomical structure. Through quantitative local abnormality assessment using this method, we studied the characteristics of distribution of reduced blood flow in cases with dementia of the Alzheimer type (DAT). Using twenty-five cases with DAT (mean age, 68.9 years old), all of whom were diagnosed as probable Alzheimer's disease based on NINCDS-ADRDA, we collected I-123 iodoamphetamine SPECT data. A 3D brain map using the 3D-SSP program was compared with the data of 20 cases in the control group, who age-matched the subject cases. To study local abnormalities on the 3D images, we divided the whole brain into 24 segments based on anatomical classification. We assessed the extent of an abnormal region in each segment (rate of the coordinates with a Z-value that exceeds the threshold value, in all coordinates within a segment), and severity (average Z-value of the coordinates with a Z-value that exceeds the threshold value). This method clarified orientation and expansion of reduced accumulation, through classifying stereotactic brain coordinates according to the anatomical structure. This method was considered useful for quantitatively grasping distribution abnormalities in the brain and changes in abnormality distribution.

Calcified parenchymal central nervous system cysticercosis and clinical outcomes in epilepsy.

PubMed

Leon, Amanda; Saito, Erin K; Mehta, Bijal; McMurtray, Aaron M

2015-02-01

This study aimed to compare clinical outcomes including seizure frequency and psychiatric symptoms between patients with epilepsy with neuroimaging evidence of past brain parenchymal neurocysticercosis infection, patients with other structural brain lesions, and patients without structural neuroimaging abnormalities. The study included retrospective cross-sectional analysis of all patients treated for epilepsy in a community-based adult neurology clinic during a three-month period. A total of 160 patients were included in the analysis, including 63 with neuroimaging findings consistent with past parenchymal neurocysticercosis infection, 55 with structurally normal brain neuroimaging studies, and 42 with other structural brain lesions. No significant differences were detected between groups for either seizure freedom (46.03%, 50.91%, and 47.62%, respectively; p=0.944) or mean seizure frequency per month (mean=2.50, S.D.=8.1; mean=4.83, S.D.=17.64; mean=8.55, S.D.=27.31, respectively; p=0.267). Self-reported depressive symptoms were more prevalent in those with parenchymal neurocysticercosis than in the other groups (p=0.003). No significant differences were detected for prevalence of self-reported anxiety or psychotic symptoms. Calcified parenchymal neurocysticercosis results in refractory epilepsy about as often as other structural brain lesions. Depressive symptoms may be more common among those with epilepsy and calcified parenchymal neurocysticercosis; consequently, screening for depression may be indicated in this population. Published by Elsevier Inc.

Conceptualizing neurodevelopmental disorders through a mechanistic understanding of fragile X syndrome and Williams syndrome.

PubMed

Fung, Lawrence K; Quintin, Eve-Marie; Haas, Brian W; Reiss, Allan L

2012-04-01

The overarching goal of this review is to compare and contrast the cognitive-behavioral features of fragile X syndrome (FraX) and Williams syndrome and to review the putative neural and molecular underpinnings of these features. Information is presented in a framework that provides guiding principles for conceptualizing gene-brain-behavior associations in neurodevelopmental disorders. Abnormalities, in particular cognitive-behavioral domains with similarities in underlying neurodevelopmental correlates, occur in both FraX and Williams syndrome including aberrant frontostriatal pathways leading to executive function deficits, and magnocellular/dorsal visual stream, superior parietal lobe, inferior parietal lobe, and postcentral gyrus abnormalities contributing to deficits in visuospatial function. Compelling cognitive-behavioral and neurodevelopmental contrasts also exist in these two disorders, for example, aberrant amygdala and fusiform cortex structure and function occurring in the context of contrasting social behavioral phenotypes, and temporal cortical and cerebellar abnormalities potentially underlying differences in language function. Abnormal dendritic development is a shared neurodevelopmental morphologic feature between FraX and Williams syndrome. Commonalities in molecular machinery and processes across FraX and Williams syndrome occur as well - microRNAs involved in translational regulation of major synaptic proteins; scaffolding proteins in excitatory synapses; and proteins involved in axonal development. Although the genetic variations leading to FraX and Williams syndrome are different, important similarities and contrasts in the phenotype, neurocircuitry, molecular machinery, and cellular processes in these two disorders allow for a unique approach to conceptualizing gene-brain-behavior links occurring in neurodevelopmental disorders.

Brain Growth Across the Life Span in Autism: Age-Specific Changes in Anatomical Pathology

PubMed Central

Courchesne, Eric; Campbell, Kathleen; Solso, Stephanie

2014-01-01

Autism is marked by overgrowth of the brain at the earliest ages but not at older ages when decreases in structural volumes and neuron numbers are observed instead. This has lead to the theory of age-specific anatomic abnormalities in autism. Here we report age-related changes in brain size in autistic and typical subjects from 12 months to 50 years of age based on analyses of 586 longitudinal and cross-sectional MRI scans. This dataset is several times larger than the largest autism study to date. Results demonstrate early brain overgrowth during infancy and the toddler years in autistic boys and girls, followed by an accelerated rate of decline in size and perhaps degeneration from adolescence to late middle age in this disorder. We theorize that underlying these age-specific changes in anatomic abnormalities in autism there may also be age-specific changes in gene expression, molecular, synaptic, cellular and circuit abnormalities. A peak age for detecting and studying the earliest fundamental biological underpinnings of autism is prenatal life and the first three postnatal years. Studies of the older autistic brain may not address original causes but are essential to discovering how best to help the older aging autistic person. Lastly, the theory of age-specific anatomic abnormalities in autism has broad implications for a wide range of work on the disorder including the design, validation and interpretation of animal model, lymphocyte gene expression, brain gene expression, and genotype/CNV-anatomic phenotype studies. PMID:20920490

Neuropathology of leukoencephalopathy with brainstem and spinal cord involvement and high lactate caused by a homozygous mutation of DARS2.

PubMed

Yamashita, Sumimasa; Miyake, Noriko; Matsumoto, Naomichi; Osaka, Hitoshi; Iai, Mizue; Aida, Noriko; Tanaka, Yukichi

2013-04-01

We diagnosed three siblings from consanguineous east Asian parents with leukoencephalopathy with brainstem and spinal cord involvement and high lactate (LBSL) from characteristic MRI, MRS findings and a homozygous mutation in the DARS2 gene. The neurological symptoms of the three patients consisted of psychomotor developmental delay, cerebellar ataxia since infancy, spasticity in the initial phase and peripheral neuropathy in later stages. Their mental development was delayed, but did not deteriorate. MRI signal abnormalities included the same abnormalities reported previously but tended to be more extensive. Signal abnormalities in the cerebral and cerebellar white matter were homogeneous and confluent from early stages. In addition, other tract such as the central tegmental tract was involved. Furthermore, an atrophic change in the cerebral white matter was observed on follow-up in one case. Two of the patients were autopsied and neuropathological findings revealed characteristic vacuolar changes in the white matter of the cerebrum, cerebellum and the nerve tracts of the brain stem and spinal cord. The central myelin sheath showed intralamellar splitting by electron microscopy. These findings were consistent to a spongy degeneration in the diffuse white matter of the brain, or spongiform leukoencephalopathy. In addition, peripheral nerves showed both axonal degeneration and abnormal myelin structures. We discussed the relationship between deficits in mitochondrial aspartyl-tRNA synthetase activity and the neuropathology observed. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Hip1-related Mutant Mice Grow and Develop Normally but Have Accelerated Spinal Abnormalities and Dwarfism in the Absence of HIP1†

PubMed Central

Hyun, Teresa S.; Li, Lina; Oravecz-Wilson, Katherine I.; Bradley, Sarah V.; Provot, Melissa M.; Munaco, Anthony J.; Mizukami, Ikuko F.; Sun, Hanshi; Ross, Theodora S.

2004-01-01

In mice and humans, there are two known members of the Huntingtin interacting protein 1 (HIP1) family, HIP1 and HIP1-related (HIP1r). Based on structural and functional data, these proteins participate in the clathrin trafficking network. The inactivation of Hip1 in mice leads to spinal, hematopoietic, and testicular defects. To investigate the biological function of HIP1r, we generated a Hip1r mutant allele in mice. Hip1r homozygous mutant mice are viable and fertile without obvious morphological abnormalities. In addition, embryonic fibroblasts derived from these mice do not have gross abnormalities in survival, proliferation, or clathrin trafficking pathways. Altogether, this demonstrates that HIP1r is not necessary for normal development of the embryo or for normal adulthood and suggests that HIP1 or other functionally related members of the clathrin trafficking network can compensate for HIP1r absence. To test the latter, we generated mice deficient in both HIP1 and HIP1r. These mice have accelerated development of abnormalities seen in Hip1 -deficient mice, including kypholordosis and growth defects. The severity of the Hip1r/Hip1 double-knockout phenotype compared to the Hip1 knockout indicates that HIP1r partially compensates for HIP1 function in the absence of HIP1 expression, providing strong evidence that HIP1 and HIP1r have overlapping roles in vivo. PMID:15121852

Hip1-related mutant mice grow and develop normally but have accelerated spinal abnormalities and dwarfism in the absence of HIP1.

PubMed

Hyun, Teresa S; Li, Lina; Oravecz-Wilson, Katherine I; Bradley, Sarah V; Provot, Melissa M; Munaco, Anthony J; Mizukami, Ikuko F; Sun, Hanshi; Ross, Theodora S

2004-05-01

In mice and humans, there are two known members of the Huntingtin interacting protein 1 (HIP1) family, HIP1 and HIP1-related (HIP1r). Based on structural and functional data, these proteins participate in the clathrin trafficking network. The inactivation of Hip1 in mice leads to spinal, hematopoietic, and testicular defects. To investigate the biological function of HIP1r, we generated a Hip1r mutant allele in mice. Hip1r homozygous mutant mice are viable and fertile without obvious morphological abnormalities. In addition, embryonic fibroblasts derived from these mice do not have gross abnormalities in survival, proliferation, or clathrin trafficking pathways. Altogether, this demonstrates that HIP1r is not necessary for normal development of the embryo or for normal adulthood and suggests that HIP1 or other functionally related members of the clathrin trafficking network can compensate for HIP1r absence. To test the latter, we generated mice deficient in both HIP1 and HIP1r. These mice have accelerated development of abnormalities seen in Hip1 -deficient mice, including kypholordosis and growth defects. The severity of the Hip1r/Hip1 double-knockout phenotype compared to the Hip1 knockout indicates that HIP1r partially compensates for HIP1 function in the absence of HIP1 expression, providing strong evidence that HIP1 and HIP1r have overlapping roles in vivo.

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.

Brain structure and executive functions in children with cerebral palsy: a systematic review.

PubMed

Weierink, Lonneke; Vermeulen, R Jeroen; Boyd, Roslyn N

2013-05-01

This systematic review aimed to establish the current knowledge about brain structure and executive function (EF) in children with cerebral palsy (CP). Five databases were searched (up till July 2012). Six articles met the inclusion criteria, all included structural brain imaging though no functional brain imaging. Study quality was assessed using the STROBE checklist. All articles scored between 58.7% and 70.5% for quality (100% is the maximum score). The included studies all reported poorer performance on EF tasks for children with CP compared to children without CP. For the selected EF measures non-significant effect sizes were found for the CP group compared to a semi-control group (children without cognitive deficits but not included in a control group). This could be due to the small sample sizes, group heterogeneity and lack of comparison of the CP group to typically developing children. The included studies did not consider specific brain areas associated with EF performance. To conclude, there is a paucity of brain imaging studies focused on EF in children with CP, especially of studies that include functional brain imaging. Outcomes of the present studies are difficult to compare as each study included different EF measures and cortical abnormality measures. Copyright © 2013 Elsevier Ltd. All rights reserved.

Risk of Central Nervous System Decompression Sickness in Air Diving to No-Stop Limits

DTIC Science & Technology

2009-01-01

190 9 1 10 1. Weak, faint, vertigo 2. Heavy legs, abnormal gait 3. Vertigo and cardiorespiratory symptoms 4. Bilateral numbness and paresthesia ...original report," were included. 6. Pain in both feet, paresthesia 7. Hearing deficit, anisocoria, nystagmus, confusion, emotionally labile, abnormal...tandem gait 8. Scintillating scotoma, abnormal left foot dorsiflexion 9. Weakness, general left side paresthesia , numbness, abnormal gait 10. See

Synthetic lipids and their role in defining macromolecular assemblies.

PubMed

Parrill, Abby L

2015-10-01

Lipids have a variety of physiological roles, ranging from structural and biophysical contributions to membrane functions to signaling contributions in normal and abnormal physiology. This review highlights some of the contributions made by Robert Bittman to our understanding of lipid assemblies through the production of synthetic lipid analogs in the sterol, sphingolipid, and glycolipid classes. His contributions have included the development of a fluorescent cholesterol analog that shows strong functional analogies to cholesterol that has allowed live imaging of cholesterol distribution in living systems, to stereospecific synthetic approaches to both sphingolipid and glycolipid analogs crucial in defining the structure-activity relationships of lipid biological targets. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Non-invasive prenatal testing for fetal chromosomal abnormalities by low-coverage whole-genome sequencing of maternal plasma DNA: review of 1982 consecutive cases in a single center.

PubMed

Lau, T K; Cheung, S W; Lo, P S S; Pursley, A N; Chan, M K; Jiang, F; Zhang, H; Wang, W; Jong, L F J; Yuen, O K C; Chan, H Y C; Chan, W S K; Choy, K W

2014-03-01

To review the performance of non-invasive prenatal testing (NIPT) by low-coverage whole-genome sequencing of maternal plasma DNA at a single center. The NIPT result and pregnancy outcome of 1982 consecutive cases were reviewed. NIPT was based on low coverage (0.1×) whole-genome sequencing of maternal plasma DNA. All subjects were contacted for pregnancy and fetal outcome. Of the 1982 NIPT tests, a repeat blood sample was required in 23 (1.16%). In one case, a conclusive report could not be issued, probably because of an abnormal vanished twin fetus. NIPT was positive for common trisomies in 29 cases (23 were trisomy 21, four were trisomy 18 and two were trisomy 13); all were confirmed by prenatal karyotyping (specificity=100%). In addition, 11 cases were positive for sex-chromosomal abnormalities (SCA), and nine cases were positive for other aneuploidies or deletion/duplication. Fourteen of these 20 subjects agreed to undergo further investigations, and the abnormality was found to be of fetal origin in seven, confined placental mosaicism (CPM) in four, of maternal origin in two and not confirmed in one. Overall, 85.7% of the NIPT-suspected SCA were of fetal origin, and 66.7% of the other abnormalities were caused by CPM. Two of the six cases suspected or confirmed to have CPM were complicated by early-onset growth restriction requiring delivery before 34 weeks. Fetal outcome of the NIPT-negative cases was ascertained in 1645 (85.15%). Three chromosomal abnormalities were not detected by NIPT, including one case each of a balanced translocation, unbalanced translocation and triploidy. There were no known false negatives involving the common trisomies (sensitivity=100%). Low-coverage whole-genome sequencing of maternal plasma DNA was highly accurate in detecting common trisomies. It also enabled the detection of other aneuploidies and structural chromosomal abnormalities with high positive predictive value. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.

Evaluation of central nervous system in patients with glycogen storage disease type 1a.

PubMed

Aydemir, Yusuf; Gürakan, Figen; Saltık Temizel, İnci Nur; Demir, Hülya; Oğuz, Kader Karlı; Yalnızoğlu, Dilek; Topçu, Meral; Özen, Hasan; Yüce, Aysel

2016-01-01

We aimed to evaluate structure and functions of central nervous system (CNS) in children with glycogen storage disease (GSD) type 1a. Neurological examination, psychometric tests, electroencephalography (EEG), magnetic resonance imaging (MRI), visual evoked potentials (VEP) and brainstem auditory evoked potentials (BAEP) were performed. The results were compared between patients with good and poor metabolic control and healthy children. Twenty-three patients with GSD type 1a were studied. Twelve patients were in poor metabolic control group and 11 patients in good metabolic control group. Five patients had intellectual disability, 10 had EEG abnormalities, seven had abnormal VEP and two had abnormal BAEP results. MRI was abnormal in five patients. There was significant correlation between the number of hypoglycemic attacks and MRI abnormalities. Central nervous system may be affected in GSD type 1a even in patients with normal neurologic examination. Accumulation of abnormal results in patients with poor metabolic control supports the importance of metabolic control in GSD type 1a.

Brain structural correlates of sensory phenomena in patients with obsessive–compulsive disorder

PubMed Central

Subirà, Marta; Sato, João R.; Alonso, Pino; do Rosário, Maria C.; Segalàs, Cinto; Batistuzzo, Marcelo C.; Real, Eva; Lopes, Antonio C.; Cerrillo, Ester; Diniz, Juliana B.; Pujol, Jesús; Assis, Rachel O.; Menchón, José M.; Shavitt, Roseli G.; Busatto, Geraldo F.; Cardoner, Narcís; Miguel, Euripedes C.; Hoexter, Marcelo Q.; Soriano-Mas, Carles

2015-01-01

Background Sensory phenomena (SP) are uncomfortable feelings, including bodily sensations, sense of inner tension, “just-right” perceptions, feelings of incompleteness, or “urge-only” phenomena, which have been described to precede, trigger or accompany repetitive behaviours in individuals with obsessive–compulsive disorder (OCD). Sensory phenomena are also observed in individuals with tic disorders, and previous research suggests that sensorimotor cortex abnormalities underpin the presence of SP in such patients. However, to our knowledge, no studies have assessed the neural correlates of SP in patients with OCD. Methods We assessed the presence of SP using the University of São Paulo Sensory Phenomena Scale in patients with OCD and healthy controls from specialized units in São Paulo, Brazil, and Barcelona, Spain. All participants underwent a structural magnetic resonance examination, and brain images were examined using DARTEL voxel-based morphometry. We evaluated grey matter volume differences between patients with and without SP and healthy controls within the sensorimotor and premotor cortices. Results We included 106 patients with OCD and 87 controls in our study. Patients with SP (67% of the sample) showed grey matter volume increases in the left sensorimotor cortex in comparison to patients without SP and bilateral sensorimotor cortex grey matter volume increases in comparison to controls. No differences were observed between patients without SP and controls. Limitations Most patients were medicated. Participant recruitment and image acquisition were performed in 2 different centres. Conclusion We have identified a structural correlate of SP in patients with OCD involving grey matter volume increases within the sensorimotor cortex; this finding is in agreement with those of tic disorder studies showing that abnormal activity and volume increases within this region are associated with the urges preceding tic onset. PMID:25652753

Dandy-Walker syndrome and chromosomal abnormalities.

PubMed

Imataka, George; Yamanouchi, Hideo; Arisaka, Osamu

2007-12-01

Dandy-Walker syndrome (DWS) is a brain malformation of unknown etiology, but several reports have been published indicating that there is a causal relationship to various types of chromosomal abnormalities and malformation syndromes. In the present article, we present a bibliographical survey of several previously issued reports on chromosomal abnormalities associated with DWS, including our case of DWS found in trisomy 18. There are various types of chromosomal abnormalities associated with DWS; most of them are reported in chromosome 3, 9, 13 and 18. We also summarize some other chromosomal abnormalities and various congenital malformation syndromes.

Fetal MRI: head and neck.

PubMed

Mirsky, David M; Shekdar, Karuna V; Bilaniuk, Larissa T

2012-08-01

Abnormalities of the fetal head and neck may be seen in isolation or in association with central nervous system abnormalities, chromosomal abnormalities, and syndromes. Magnetic resonance imaging (MRI) plays an important role in detecting associated abnormalities of the brain as well as in evaluating for airway obstruction that may impact prenatal management and delivery planning. This article provides an overview of the common indications for MRI of the fetal head and neck, including abnormalities of the fetal skull and face, masses of the face and neck, and fetal goiter. Copyright © 2012 Elsevier Inc. All rights reserved.

Immune Abnormalities in Patients with Autism.

ERIC Educational Resources Information Center

Warren, Reed P.; And Others

1986-01-01

A study of 31 autistic patients (3-28 years old) has revealed several immune-system abnormalities, including decreased numbers of T lymphocytes and an altered ratio of helper-to-suppressor T cells. Immune-system abnormalities may be directly related to underlying biologic processes of autism or an indirect reflection of the actual pathologic…

Left ventricular eccentricity index measured with SPECT myocardial perfusion imaging: An additional parameter of adverse cardiac remodeling.

PubMed

Gimelli, Alessia; Liga, Riccardo; Clemente, Alberto; Marras, Gavino; Kusch, Annette; Marzullo, Paolo

2017-01-12

Single-photon emission computed-tomography (SPECT) allows the quantification of LV eccentricity index (EI), a measure of cardiac remodeling. We sought to evaluate the feasibility of EI measurement with SPECT myocardial perfusion imaging and its interactions with relevant LV functional and structural parameters. Four-hundred and fifty-six patients underwent myocardial perfusion imaging on a Cadmium-Zinc-Telluride (CZT) camera. The summed rest, stress, and difference scores were calculated. From rest images, the LV end-diastolic (EDV) and end-systolic volumes, ejection fraction (EF), and peak filling rate (PFR) were calculated. In every patient, the EI, ranging from 0 (sphere) to 1 (line), was computed using a dedicated software (QGS/QPS; Cedars-Sinai Medical Center). Three-hundred and thirty-eight/456 (74%) patients showed a normal EF (>50%), while 26% had LV systolic dysfunction. The EI was computed from CZT images with excellent reproducibility (interclass correlation coefficient: 0.99, 95% CI 0.98-0.99). More impaired EI values correlated with the presence of a more abnormal LV perfusion (P < .001), function (EF and PFR, P < .001), and structure (EDV, P < .001). On multivariate analysis, higher EDV (P < .001) and depressed EF (P = .014) values were independent predictors of abnormal EI. The evaluation of LV eccentricity is feasible on gated CZT images. Abnormal EI associates with significant cardiac structural and functional abnormalities.

The Nitrate-nitrite-NO pathway and its implications for Heart Failure and Preserved Ejection Fraction

PubMed Central

Chirinos, Julio A.; Zamani, Payman

2016-01-01

The pathogenesis of exercise intolerance in patients with heart failure and preserved ejection fraction (HFpEF) is likely multifactorial. In addition to cardiac abnormalities (diastolic dysfunction, abnormal contractile reserve, chronotropic incompetence), several peripheral abnormalities are likely to be involved. These include abnormal pulsatile hemodynamics, abnormal arterial vasodilatory responses to exercise, and abnormal peripheral O2 delivery, extraction and utilization. The nitrate-nitrite-NO pathway is emerging as a potential target to modify key physiologic abnormalities, including late systolic LV load from arterial wave reflections (which has deleterious short- and long-term consequences for the LV), arterial vasodilatory reserve, muscle O2 delivery, and skeletal muscle mitochondrial function. In a recently completed randomized trial, the administration of a single dose of exogenous inorganic nitrate has been shown exert various salutary arterial hemodynamic effects, ultimately leading to enhanced aerobic capacity in patients with HFpEF. These effects have the potential for both immediate improvements in exercise tolerance and for long-term “disease-modifying” effects. In this review, we provide an overview of key mechanistic contributors to exercise intolerance in HFpEF, and of the potential therapeutic role of drugs that target the nitrate-nitrite-NO pathway. PMID:26792295

Multi-disciplinary clinical study of Smith-Magenis syndrome (deletion 17p11.2)

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

Greenberg, F.; Lewis, R.A.; Potocki, L.

1996-03-29

Smith-Magenis syndrome (SMS) is a multiple congenital anomaly, mental retardation (MCA/MR) syndrome associated with deletion of chromosome 17 band p11.2. As part of a multi-disciplinary clinical, cytogenetic, and molecular approach to SMS, detailed clinical studies including radiographic neurologic, developmental, ophthalmologic, otolaryngologic, and audiologic evaluations were performed on 27 SMS patients. Significant findings include otolaryngologic abnormalities in 94%, eye abnormalities in 85%, sleep abnormalities (especially reduced REM sleep) in 75%, hearing impairment in 68% (approximately 65% conductive and 35% sensorineural), scoliosis in 65% brain abnormalities (predominantly ventriculomegaly) in 52%, cardiac abnormalities in at least 37%, renal anomalies (especially duplication of themore » collecting system) in 35%, low thyroxine levels in 29%, low immunoglobulin levels in 23%, and forearm abnormalities in 16%. The measured IQ ranged between 20-78, most patients falling in the moderate range of mental retardation at 40-54, although several patients scored in the mild or borderline range. The frequency of these many abnormalities in SMS suggests that patients should be evaluated thoroughly for associated complications both at the time of diagnosis and at least annually thereafter. 42 refs., 2 figs., 3 tabs.« 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

The Utility of Chromosomal Microarray Analysis in Developmental and Behavioral Pediatrics

ERIC Educational Resources Information Center

Beaudet, Arthur L.

2013-01-01

Chromosomal microarray analysis (CMA) has emerged as a powerful new tool to identify genomic abnormalities associated with a wide range of developmental disabilities including congenital malformations, cognitive impairment, and behavioral abnormalities. CMA includes array comparative genomic hybridization (CGH) and single nucleotide polymorphism…

Basement Membrane Defects in Genetic Kidney Diseases

PubMed Central

Chew, Christine; Lennon, Rachel

2018-01-01

The glomerular basement membrane (GBM) is a specialized structure with a significant role in maintaining the glomerular filtration barrier. This GBM is formed from the fusion of two basement membranes during development and its function in the filtration barrier is achieved by key extracellular matrix components including type IV collagen, laminins, nidogens, and heparan sulfate proteoglycans. The characteristics of specific matrix isoforms such as laminin-521 (α5β2γ1) and the α3α4α5 chain of type IV collagen are essential for the formation of a mature GBM and the restricted tissue distribution of these isoforms makes the GBM a unique structure. Detailed investigation of the GBM has been driven by the identification of inherited abnormalities in matrix proteins and the need to understand pathogenic mechanisms causing severe glomerular disease. A well-described hereditary GBM disease is Alport syndrome, associated with a progressive glomerular disease, hearing loss, and lens defects due to mutations in the genes COL4A3, COL4A4, or COL4A5. Other proteins associated with inherited diseases of the GBM include laminin β2 in Pierson syndrome and LMX1B in nail patella syndrome. The knowledge of these genetic mutations associated with GBM defects has enhanced our understanding of cell–matrix signaling pathways affected in glomerular disease. This review will address current knowledge of GBM-associated abnormalities and related signaling pathways, as well as discussing the advances toward disease-targeted therapies for patients with glomerular disease. PMID:29435440

Voxel-based morphometric multisite collaborative study on schizophrenia.

PubMed

Segall, Judith M; Turner, Jessica A; van Erp, Theo G M; White, Tonya; Bockholt, H Jeremy; Gollub, Randy L; Ho, Beng C; Magnotta, Vince; Jung, Rex E; McCarley, Robert W; Schulz, S Charles; Lauriello, John; Clark, Vince P; Voyvodic, James T; Diaz, Michele T; Calhoun, Vince D

2009-01-01

Regional gray matter (GM) abnormalities are well known to exist in patients with chronic schizophrenia. Voxel-based morphometry (VBM) has been previously used on structural magnetic resonance images (MRI) data to characterize these abnormalities. Two multisite schizophrenia studies, the Functional Biomedical Informatics Research Network and the Mind Clinical Imaging Consortium, which include 9 data collection sites, are evaluating the efficacy of pooling structural imaging data across imaging centers. Such a pooling of data could yield the increased statistical power needed to elucidate effects that may not be seen with smaller samples. VBM analyses were performed to evaluate the consistency of patient versus control gray matter concentration (GMC) differences across the study sites, as well as the effects of combining multisite data. Integration of data from both studies yielded a large sample of 503 subjects, including 266 controls and 237 patients diagnosed with schizophrenia, schizoaffective or schizophreniform disorder. The data were analyzed using the combined sample, as well as analyzing each of the 2 multisite studies separately. A consistent pattern of reduced relative GMC in schizophrenia patients compared with controls was found across all study sites. Imaging center-specific effects were evaluated using a region of interest analysis. Overall, the findings support the use of VBM in combined multisite studies. This analysis of schizophrenics and controls from around the United States provides continued supporting evidence for GM deficits in the temporal lobes, anterior cingulate, and frontal regions in patients with schizophrenia spectrum disorders.

Cortical thickness and folding deficits in conduct-disordered adolescents

PubMed Central

Hyatt, Christopher J.; Haney-Caron, Emily; Stevens, Michael C.

2012-01-01

Background Studies of pediatric conduct disorder (CD) have described frontal and temporal lobe structural abnormalities that parallel findings in antisocial adults. The purpose of this study was to examine previously unexplored cortical thickness and folding as markers for brain abnormalities in “pure CD”-diagnosed adolescents. Based on current fronto-temporal theories, we hypothesized that CD youth would have thinner cortex or less cortical folding in temporal and frontal lobes than control subjects. Methods We obtained T1-weighted brain structure images from n=24 control and n=19 CD participants aged 12–18 years, matched by overall gender and age. We measured group differences in cortical thickness and local gyrification index (regional cortical folding measure) using surface-based morphometry with clusterwise correction for multiple comparisons. Results CD participants, when compared with controls, showed both reduced cortical thickness and folding. Thinner cortex was located primarily in posterior brain regions, including left superior temporal and parietal lobes, temporoparietal junction and paracentral lobule, right superior temporal and parietal lobes, temporoparietal junction and precuneus. Folding deficits were located mainly in anterior brain regions and included left insula, ventro- and dorsomedial prefrontal, anterior cingulate and orbitofrontal cortices, temporal lobe, right superior frontal and parietal lobes and paracentral lobule. Conclusions Our findings generally agree with previous CD volumetric studies, but here show the unique contributions of cortical thickness and folding to gray matter reductions in pure CD in different brain regions. PMID:22209639

Prenatal and Neonatal Brain Structure and White Matter Maturation in Children at High Risk for Schizophrenia

PubMed Central

Gilmore, John H.; Kang, Chaeryon; Evans, Dianne D.; Wolfe, Honor M.; Smith, J. Keith; Lieberman, Jeffrey A.; Lin, Weili; Hamer, Robert M.; Styner, Martin; Gerig, Guido

2011-01-01

Objective Schizophrenia is a neurodevelopmental disorder associated with abnormalities of brain structure and white matter, although little is known about when these abnormalities arise. This study was conducted to identify structural brain abnormalities in the prenatal and neonatal periods associated with genetic risk for schizophrenia. Method Prenatal ultrasound scans and neonatal structural magnetic resonance imaging (MRI) and diffusion tensor imaging were prospectively obtained in the offspring of mothers with schizophrenia or schizoaffective disorder (N=26) and matched comparison mothers without psychiatric illness (N=26). Comparisons were made for prenatal lateral ventricle width and head circumference, for neonatal intracranial, CSF, gray matter, white matter, and lateral ventricle volumes, and for neonatal diffusion properties of the genu and splenium of the corpus callosum and corticospinal tracts. Results Relative to the matched comparison subjects, the offspring of mothers with schizophrenia did not differ in prenatal lateral ventricle width or head circumference. Overall, the high-risk neonates had nonsignificantly larger intracranial, CSF, and lateral ventricle volumes. Subgroup analysis revealed that male high-risk infants had significantly larger intracranial, CSF, total gray matter, and lateral ventricle volumes; the female high-risk neonates were similar to the female comparison subjects. There were no group differences in white matter diffusion tensor properties. Conclusions Male neonates at genetic risk for schizophrenia had several larger than normal brain volumes, while females did not. To the authors' knowledge, this study provides the first evidence, in the context of its limitations, that early neonatal brain development may be abnormal in males at genetic risk for schizophrenia. PMID:20516153

Structural Pituitary Abnormalities Associated With CHARGE Syndrome

PubMed Central

Gregory, Louise C.; Gevers, Evelien F.; Baker, Joanne; Kasia, Tessa; Chong, Kling; Josifova, Dragana J.; Caimari, Maria; Bilan, Frederic; McCabe, Mark J.

2013-01-01

Introduction: CHARGE syndrome is a multisystem disorder that, in addition to Kallmann syndrome/isolated hypogonadotrophic hypogonadism, has been associated with anterior pituitary hypoplasia (APH). However, structural abnormalities such as an ectopic posterior pituitary (EPP) have not yet been described in such patients. Objective: The aims of the study were: 1) to describe the association between CHARGE syndrome and a structurally abnormal pituitary gland; and 2) to investigate whether CHD7 variants, which are identified in 65% of CHARGE patients, are common in septo-optic dysplasia /hypopituitarism. Methods: We describe 2 patients with features of CHARGE and EPP. CHD7 was sequenced in these and other patients with septo-optic dysplasia/hypopituitarism. Results: EPP, APH, and GH, TSH, and probable LH/FSH deficiency were present in 1 patient, and EPP and APH with GH, TSH, LH/FSH, and ACTH deficiency were present in another patient, both of whom had features of CHARGE syndrome. Both had variations in CHD7 that were novel and undetected in control cohorts or in the international database of CHARGE patients, but were also present in their unaffected mothers. No CHD7 variants were detected in the patients with septo-optic dysplasia/hypopituitarism without additional CHARGE features. Conclusion: We report a novel association between CHARGE syndrome and structural abnormalities of the pituitary gland in 2 patients with variations in CHD7 that are of unknown significance. However, CHD7 mutations are an uncommon cause of septo-optic dysplasia or hypopituitarism. Our data suggest the need for evaluation of pituitary function/anatomy in patients with CHARGE syndrome. PMID:23526466

Identification and Treatment of Pathophysiological Comorbidities of Autism Spectrum Disorder to Achieve Optimal Outcomes

PubMed Central

Frye, Richard E.; Rossignol, Daniel A.

2016-01-01

Despite the fact that the prevalence of autism spectrum disorder (ASD) continues to rise, no effective medical treatments have become standard of care. In this paper we review some of the pathophysiological abnormalities associated with ASD and their potential associated treatments. Overall, there is evidence for some children with ASD being affected by seizure and epilepsy, neurotransmitter dysfunction, sleep disorders, metabolic abnormalities, including abnormalities in folate, cobalamin, tetrahydrobiopterin, carnitine, redox and mitochondrial metabolism, and immune and gastrointestinal disorders. Although evidence for an association between these pathophysiological abnormalities and ASD exists, the exact relationship to the etiology of ASD and its associated symptoms remains to be further defined in many cases. Despite these limitations, treatments targeting some of these pathophysiological abnormalities have been studied in some cases with high-quality studies, whereas treatments for other pathophysiological abnormalities have not been well studied in many cases. There are some areas of more promising treatments specific for ASD including neurotransmitter abnormalities, particularly imbalances in glutamate and acetylcholine, sleep onset disorder (with behavioral therapy and melatonin), and metabolic abnormalities in folate, cobalamin, tetrahydrobiopterin, carnitine, and redox pathways. There is some evidence for treatments of epilepsy and seizures, mitochondrial and immune disorders, and gastrointestinal abnormalities, particularly imbalances in the enteric microbiome, but further clinical studies are needed in these areas to better define treatments specific to children with ASD. Clearly, there are some promising areas of ASD research that could lead to novel treatments that could become standard of care in the future, but more research is needed to better define subgroups of children with ASD who are affected by specific pathophysiological abnormalities and the optimal treatments for these abnormalities. PMID:27330338

Abnormal/Emergency Situations. Impact of Unmanned Aircraft Systems Emergency and Abnormal Events on the National Airspace System

NASA Technical Reports Server (NTRS)

2006-01-01

Access 5 analyzed the differences between UAS and manned aircraft operations under five categories of abnormal or emergency situations: Link Failure, Lost Communications, Onboard System Failures, Control Station Failures and Abnormal Weather. These analyses were made from the vantage point of the impact that these operations have on the US air traffic control system, with recommendations for new policies and procedures included where appropriate.

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.

[Pedophilia--a review of literature, casuistics, doubts].

PubMed

Łucka, Izabela; Dziemian, Anna

2014-01-01

The main purpose of this article is presentation of several basic issues related to the phenomenon of child sexual molesters and recognition of pedophilia as a significant social problem. The article, supplemented by casuistic illustration showing adolescents with sexual behavior disorders is giving rise to the following question: do they progress in their inappropriate behaviors to grow into adult molesters or do they stop anywhere along the way of their development? Casuistry, in the intention of the authors, is the background for discussion about prevention of child sexual abuse. This article presents also a review of the current knowledge about child sexual molesters. The topics include: the definition of pedophilia itself, which varies in the literature depending on the types of activities, kinds of victims and the circumstances in which the perpetrator acts, through to the recognition of symptoms of pedophilia as well as its consequences. It includes both intra-familial and extra-familial child sexual abuse and their offenders. The more, that the history of child sexual abuse is associated with numerous long-term physical, psychological, behavioral, interpersonal and social effects on the victim. The examinations made among pedophilic molesters have shown structural and functional temporal-limbic abnormalities, including abnormalities in the amygdala and it is possible that the pedophilic inclinations are secondary to neurodevelopmental perturbations and other neuropsychiatric syndromes.

Possible involvement of rumination in gray matter abnormalities in persistent symptoms of major depression: an exploratory magnetic resonance imaging voxel-based morphometry study.

PubMed

Machino, Akihiko; Kunisato, Yoshihiko; Matsumoto, Tomoya; Yoshimura, Shinpei; Ueda, Kazutaka; Yamawaki, Yosuke; Okada, Go; Okamoto, Yasumasa; Yamawaki, Shigeto

2014-10-01

A recent meta-analysis of many magnetic resonance imaging (MRI) studies has identified brain regions with gray matter (GM) abnormalities in patients with major depressive disorder (MDD). A few studies addressing GM abnormalities in patients with treatment-resistant depression (TRD) have yielded inconsistent results. Moreover, although TRD patients tend to exhibit ruminative thoughts, it remains unclear whether rumination is related to GM abnormalities in such patients or not. We conducted structural MRI scans and voxel-based morphometry (VBM) to identify GM differences among 29 TRD patients and 29 healthy age-matched and sex-matched controls. A response style questionnaire was used to assess the respective degrees of rumination in TRD patients. Structural correlates of rumination were examined. TRD patients showed several regions with smaller GM volume than in healthy subjects: the left dorsal anterior cingulate cortex (ACC), right ventral ACC, right superior frontal gyrus, right cerebellum (Crus I), and cerebellar vermis. GM volumes in these regions did not correlate to rumination. However, whole-brain analysis revealed that rumination was positively correlated with the GM volume in the right superior temporal gyrus in TRD patients. Structural correlates of rumination were examined only in TRD patients. Our data provide additional evidence supporting the hypothesis that TRD patients show GM abnormalities compared with healthy subjects. Furthermore, this report is the first to describe a study identifying brain regions for which the GM volume is correlated with rumination in TRD patients. These results improve our understanding of the anatomical characteristics of TRD. Copyright © 2014 Elsevier B.V. All rights reserved.

Rapid Morphological Brain Abnormalities during Acute Methamphetamine Intoxication in the Rat. An Experimental study using Light and Electron Microscopy

PubMed Central

Sharma, Hari S.; Kiyatkin, Eugene A.

2009-01-01

This study describes morphological abnormalities of brain cells during acute methamphetamine (METH) intoxication in the rat and demonstrates the role of hyperthermia, disruption of the blood-brain barrier (BBB) and edema in their development. Rats with chronically implanted brain, muscle and skin temperature probes and an intravenous (iv) catheter were exposed to METH (9 mg/kg) at standard (23°C) and warm (29°C) ambient temperatures, allowing for the observation of hyperthermia ranging from mild to pathological levels (38–42°C). When brain temperature peaked or reached a level suggestive of possible lethality (>41.5°C), rats were injected with Evans blue (EB), rapidly anesthetized, perfused, and their brains were taken for further analyses. Four brain areas (cortex, hippocampus, thalamus and hypothalamus) were analyzed for EB extravasation, water and electrolyte (Na+, K+, Cl−) contents, immunostained for albumin and glial fibrillary acidic protein, and examined for neuronal, glial and axonal alterations using standard light and electron microscopy. These examinations revealed profound abnormalities in neuronal, glial, and endothelial cells, which were stronger with METH administered at 29°C than 23°C and tightly correlated with brain and body hyperthermia. These changes had some structural specificity, but in each structure they tightly correlated with increases in EB levels, the numbers of albumin-positive cells, and water and ion contents, suggesting leakage of the BBB, acutely developing brain edema, and serious shifts in brain ion homeostasis as leading factors underlying brain abnormalities. While most of these acute structural and functional abnormalities appear to be reversible, they could trigger subsequent cellular alterations in the brain and accelerate neurodegeneration—the most dangerous complication of chronic amphetamine-like drug abuse. PMID:18773954

Alkali-Metal-Mediated Magnesiations of an N-Heterocyclic Carbene: Normal, Abnormal, and "Paranormal" Reactivity in a Single Tritopic Molecule.

PubMed

Martínez-Martínez, Antonio J; Fuentes, M Ángeles; Hernán-Gómez, Alberto; Hevia, Eva; Kennedy, Alan R; Mulvey, Robert E; O'Hara, Charles T

2015-11-16

Herein the sodium alkylmagnesium amide [Na4Mg2(TMP)6(nBu)2] (TMP=2,2,6,6-tetramethylpiperidide), a template base as its deprotonating action is dictated primarily by its 12 atom ring structure, is studied with the common N-heterocyclic carbene (NHC) IPr [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]. Remarkably, magnesiation of IPr occurs at the para-position of an aryl substituent, sodiation occurs at the abnormal C4 position, and a dative bond occurs between normal C2 and sodium, all within a 20 atom ring structure accommodating two IPr(2-). Studies with different K/Mg and Na/Mg bimetallic bases led to two other magnesiated NHC structures containing two or three IPr(-) monoanions bound to Mg through abnormal C4 sites. Synergistic in that magnesiation can only work through alkali-metal mediation, these reactions add magnesium to the small cartel of metals capable of directly metalating a NHC. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

NEONATAL CEREBRAL MORPHOMETRY AND LATER RISK OF PERSISTENT INATTENTION/HYPERACTIVITY IN CHILDREN BORN VERY PRETERM

PubMed Central

Bora, Samudragupta; Pritchard, Verena E.; Chen, Zhe; Inder, Terrie E.; Woodward, Lianne J.

2014-01-01

Background Attention problems are among the most prevalent neurobehavioral morbidities affecting very preterm (VPT) born children. The first study aim was to document rates of persistent attention/hyperactivity problems from ages 4 to 9 years in a regional cohort of VPT born children. The second aim was to examine the extent to which persistent problems were related to cerebral white matter abnormality and structural development on neonatal MRI. Methods Data were drawn from a prospective longitudinal study of 110 VPT (≤32 weeks’ gestation) and 113 full-term (FT) children born from 1998 to 2000. At term equivalent, all VPT and 10 FT children underwent cerebral structural MRI, with scans analyzed qualitatively for white matter abnormalities and quantitatively for cortical and subcortical gray matter, myelinated and unmyelinated white matter, and cerebrospinal fluid volumes. At ages 4, 6, and 9 years, each child’s parent and teacher completed the Inattention/Hyperactivity subscale of the Strengths and Difficulties Questionnaire. Results VPT born children had a 5-fold increased risk of persistent attention/hyperactivity problems compared to FT children (13.1% vs. 2.8%; p=.002). No association was found between neonatal white matter abnormalities and later persistent inattention/hyperactivity risk (p≥.24). In contrast, measures of cerebral structural development including volumetric estimates of total cerebral tissue and cerebrospinal fluid relative to intracranial volume were associated with an increased risk of persistent attention/hyperactivity problems in VPT born children (p=.001). The dorsal prefrontal region showed the largest volumetric reduction (↓3.2–8.2ml). These brain-behavior associations persisted and in some cases, strengthened after covariate adjustment for postmenstrual age at MRI, sex, and family socioeconomic status. Conclusions Just over one in 10 VPT born children are subject to early onset and persistent attention/hyperactivity problems during childhood. These problems appear to reflect, at least in part, neonatal disturbances in cerebral growth and development rather than the effects of white matter injury. PMID:24438003

Method and system for providing work machine multi-functional user interface

DOEpatents

Hoff, Brian D [Peoria, IL; Akasam, Sivaprasad [Peoria, IL; Baker, Thomas M [Peoria, IL

2007-07-10

A method is performed to provide a multi-functional user interface on a work machine for displaying suggested corrective action. The process includes receiving status information associated with the work machine and analyzing the status information to determine an abnormal condition. The process also includes displaying a warning message on the display device indicating the abnormal condition and determining one or more corrective actions to handle the abnormal condition. Further, the process includes determining an appropriate corrective action among the one or more corrective actions and displaying a recommendation message on the display device reflecting the appropriate corrective action. The process may also include displaying a list including the remaining one or more corrective actions on the display device to provide alternative actions to an operator.

Assessment of abnormal brain structures and networks in major depressive disorder using morphometric and connectome analyses.

PubMed

Chen, Vincent Chin-Hung; Shen, Chao-Yu; Liang, Sophie Hsin-Yi; Li, Zhen-Hui; Tyan, Yeu-Sheng; Liao, Yin-To; Huang, Yin-Chen; Lee, Yena; McIntyre, Roger S; Weng, Jun-Cheng

2016-11-15

It is hypothesized that the phenomenology of major depressive disorder (MDD) is subserved by disturbances in the structure and function of brain circuits; however, findings of structural abnormalities using MRI have been inconsistent. Generalized q-sampling imaging (GQI) methodology provides an opportunity to assess the functional integrity of white matter tracts in implicated circuits. The study population was comprised of 16 outpatients with MDD (mean age 44.81±2.2 years) and 30 age- and gender-matched healthy controls (mean age 45.03±1.88 years). We excluded participants with any other primary mental disorder, substance use disorder, or any neurological illnesses. We used T1-weighted 3D MRI with voxel-based morphometry (VBM) and vertex-wise shape analysis, and GQI with voxel-based statistical analysis (VBA), graph theoretical analysis (GTA) and network-based statistical (NBS) analysis to evaluate brain structure and connectivity abnormalities in MDD compared to healthy controls correlates with clinical measures of depressive symptom severity, Hamilton Depression Rating Scale 17-item (HAMD) and Hospital Anxiety and Depression Scale (HADS). Using VBM and vertex-wise shape analyses, we found significant volumetric decreases in the hippocampus and amygdala among subjects with MDD (p<0.001). Using GQI, we found decreases in diffusion anisotropy in the superior longitudinal fasciculus and increases in diffusion probability distribution in the frontal lobe among subjects with MDD (p<0.01). In GTA and NBS analyses, we found several disruptions in connectivity among subjects with MDD, particularly in the frontal lobes (p<0.05). In addition, structural alterations were correlated with depressive symptom severity (p<0.01). Small sample size; the cross-sectional design did not allow us to observe treatment effects in the MDD participants. Our results provide further evidence indicating that MDD may be conceptualized as a brain disorder with abnormal circuit structure and connectivity. Copyright © 2016 Elsevier B.V. All rights reserved.

Use of an automated decision support tool optimizes clinicians' ability to interpret and appropriately respond to structured self-monitoring of blood glucose data.

PubMed

Rodbard, Helena W; Schnell, Oliver; Unger, Jeffrey; Rees, Christen; Amstutz, Linda; Parkin, Christopher G; Jelsovsky, Zhihong; Wegmann, Nathan; Axel-Schweitzer, Matthias; Wagner, Robin S

2012-04-01

We evaluated the impact of an automated decision support tool (DST) on clinicians' ability to identify glycemic abnormalities in structured self-monitoring of blood glucose (SMBG) data and then make appropriate therapeutic changes based on the glycemic patterns observed. In this prospective, randomized, controlled, multicenter study, 288 clinicians (39.6% family practice physicians, 37.9% general internal medicine physicians, and 22.6% nurse practitioners) were randomized to structured SMBG alone (STG; n = 72); structured SMBG with DST (DST; n = 72); structured SMBG with an educational DVD (DVD; n = 72); and structured SMBG with DST and the educational DVD (DST+DVD; n = 72). Clinicians analyzed 30 patient cases (type 2 diabetes), identified the primary abnormality, and selected the most appropriate therapy. A total of 222 clinicians completed all 30 patient cases with no major protocol deviations. Significantly more DST, DVD, and DST+DVD clinicians correctly identified the glycemic abnormality and selected the most appropriate therapeutic option compared with STG clinicians: 49, 51, and 55%, respectively, vs. 33% (all P < 0.0001) with no significant differences among DST, DVD, and DST+DVD clinicians. Use of structured SMBG, combined with the DST, the educational DVD, or both, enhances clinicians' ability to correctly identify significant glycemic patterns and make appropriate therapeutic decisions to address those patterns. Structured testing interventions using either the educational DVD or the DST are equally effective in improving data interpretation and utilization. The DST provides a viable alternative when comprehensive education is not feasible, and it may be integrated into medical practices with minimal training.

Clinical and molecular features of Joubert syndrome and related disorders

PubMed Central

Parisi, Melissa A.

2009-01-01

Joubert syndrome (JBTS; OMIM 213300) is a rare, autosomal recessive disorder characterized by a specific congenital malformation of the hindbrain and a broad spectrum of other phenotypic findings that is now known to be caused by defects in the structure and/or function of the primary cilium. The complex hindbrain malformation that is characteristic of JBTS can be identified on axial magnetic resonance imaging and is known as the molar tooth sign (MTS); other diagnostic criteria include intellectual disability, hypotonia, and often, abnormal respiratory pattern and/or abnormal eye movements. In addition, a broad spectrum of other anomalies characterize Joubert syndrome and related disorders (JSRD), and may include retinal dystrophy, ocular coloboma, oral frenulae and tongue tumors, polydactyly, cystic renal disease (including cystic dysplasia or juvenile nephronophthisis), and congenital hepatic fibrosis. The clinical course can be variable, but most children with this condition survive infancy to reach adulthood. At least 8 genes cause JSRD, with some genotype-phenotype correlations emerging, including the association between mutations in the MKS3 gene and hepatic fibrosis characteristic of the JSRD subtype known as COACH syndrome. Several of the causative genes for JSRD are implicated in other ciliary disorders, such as juvenile nephronophthisis and Meckel syndrome, illustrating the close association between these conditions and their overlapping clinical features that reflect a shared etiology involving the primary cilium. PMID:19876931

Grey matter volume and thickness abnormalities in young people with a history of childhood abuse.

PubMed

Lim, L; Hart, H; Mehta, M; Worker, A; Simmons, A; Mirza, K; Rubia, K

2018-04-01

Childhood abuse is associated with abnormalities in brain structure and function. Few studies have investigated abuse-related brain abnormalities in medication-naïve, drug-free youth that also controlled for psychiatric comorbidities by inclusion of a psychiatric control group, which is crucial to disentangle the effects of abuse from those associated with the psychiatric conditions. Cortical volume (CV), cortical thickness (CT) and surface area (SA) were measured in 22 age- and gender-matched medication-naïve youth (aged 13-20) exposed to childhood abuse, 19 psychiatric controls matched for psychiatric diagnoses and 27 healthy controls. Both region-of-interest (ROI) and whole-brain analyses were conducted. For the ROI analysis, the childhood abuse group compared with healthy controls only, had significantly reduced CV in bilateral cerebellum and reduced CT in left insula and right lateral orbitofrontal cortex (OFC). At the whole-brain level, relative to healthy controls, the childhood abuse group showed significantly reduced CV in left lingual, pericalcarine, precuneus and superior parietal gyri, and reduced CT in left pre-/postcentral and paracentral regions, which furthermore correlated with greater abuse severity. They also had increased CV in left inferior and middle temporal gyri relative to healthy controls. Abnormalities in the precuneus, temporal and precentral regions were abuse-specific relative to psychiatric controls, albeit at a more lenient level. Groups did not differ in SA. Childhood abuse is associated with widespread structural abnormalities in OFC-insular, cerebellar, occipital, parietal and temporal regions, which likely underlie the abnormal affective, motivational and cognitive functions typically observed in this population.

The Cerebellar Dysplasia of Chiari II Malformation as Revealed by Eye Movements

PubMed Central

Salman, Michael S.; Dennis, Maureen; Sharpe, James A.

2011-01-01

Introduction Chiari type II malformation (CII) is a developmental deformity of the hindbrain. We have previously reported that many patients with CII have impaired smooth pursuit, while few make inaccurate saccades or have an abnormal vestibulo-ocular reflex. In contrast, saccadic adaptation and visual fixation are normal. In this report, we correlate results from several eye movement studies with neuroimaging in CII. We present a model for structural changes within the cerebellum in CII. Methods Saccades, smooth pursuit, the vestibulo-ocular reflex, and visual fixation were recorded in 21 patients with CII, aged 8–19 years and 39 age-matched controls, using an infrared eye tracker. Qualitative and quantitative MRI data were correlated with eye movements in 19 CII patients and 28 controls. Results Nine patients with CII had abnormal eye movements. Smooth pursuit gain was subnormal in eight, saccadic accuracy abnormal in four, and vestibulo-ocular reflex gain abnormal in three. None had fixation instability. Patients with CII had a significantly smaller cerebellar volume than controls, and those with normal eye motion had an expanded midsagittal vermis compared to controls. However, patients with abnormal eye movements had a smaller (non-expanded) midsagittal vermis area, posterior fossa area and medial cerebellar volumes than CII patients with normal eye movements. Conclusions The deformity of CII affects the structure and function of the cerebellum selectively and differently in those with abnormal eye movements. We propose that the vermis can expand when compressed within a small posterior fossa in some CII patients, thus sparing its ocular motor functions. PMID:19960749

Cardiac troponin T is necessary for normal development in the embryonic chick heart.

PubMed

England, Jennifer; Pang, Kar Lai; Parnall, Matthew; Haig, Maria Isabel; Loughna, Siobhan

2016-09-01

The heart is the first functioning organ to develop during embryogenesis. The formation of the heart is a tightly regulated and complex process, and alterations to its development can result in congenital heart defects. Mutations in sarcomeric proteins, such as alpha myosin heavy chain and cardiac alpha actin, have now been associated with congenital heart defects in humans, often with atrial septal defects. However, cardiac troponin T (cTNT encoded by gene TNNT2) has not. Using gene-specific antisense oligonucleotides, we have investigated the role of cTNT in chick cardiogenesis. TNNT2 is expressed throughout heart development and in the postnatal heart. TNNT2-morpholino treatment resulted in abnormal atrial septal growth and a reduction in the number of trabeculae in the developing primitive ventricular chamber. External analysis revealed the development of diverticula from the ventricular myocardial wall which showed no evidence of fibrosis and still retained a myocardial phenotype. Sarcomeric assembly appeared normal in these treated hearts. In humans, congenital ventricular diverticulum is a rare condition, which has not yet been genetically associated. However, abnormal haemodynamics is known to cause structural defects in the heart. Further, structural defects, including atrial septal defects and congenital diverticula, have previously been associated with conduction anomalies. Therefore, to provide mechanistic insights into the effect that cTNT knockdown has on the developing heart, quantitative PCR was performed to determine the expression of the shear stress responsive gene NOS3 and the conduction gene TBX3. Both genes were differentially expressed compared to controls. Therefore, a reduction in cTNT in the developing heart results in abnormal atrial septal formation and aberrant ventricular morphogenesis. We hypothesize that alterations to the haemodynamics, indicated by differential NOS3 expression, causes these abnormalities in growth in cTNT knockdown hearts. In addition, the muscular diverticula reported here suggest a novel role for mutations of structural sarcomeric proteins in the pathogenesis of congenital cardiac diverticula. From these studies, we suggest TNNT2 is a gene worthy of screening for those with a congenital heart defect, particularly atrial septal defects and ventricular diverticula. © 2016 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.

Benign paroxysmal vertigo of childhood: diagnostic value of vestibular test and high stimulus rate auditory brainstem response test.

PubMed

Zhang, Daogong; Fan, Zhaomin; Han, Yuechen; Wang, Mingming; Xu, Lei; Luo, Jianfen; Ai, Yu; Wang, Haibo

2012-01-01

To investigate the diagnostic value of vestibular test and high stimulus rate auditory brainstem response (ABR) test and the possible mechanism responsible for benign paroxysmal vertigo of childhood (BPVC). Data of 56 patients with BPVC in vertigo clinic of our hospital from May 2007 to September 2008 were retrospectively analyzed in this study. Patients with BPVC were tested with pure tone audiometry, high stimulus rate auditory brainstem response test (ABR), transcranial Doppler sonography (TCD), bithermal caloric test, and VEMP. The results of the hearing and vestibular function test were compared and analyzed. There were 56 patients with BPVC, including 32 men, 24 women, aged 3-12 years old, with an average of 6.5 years. Among 56 cases of BPVC patients, the results of pure tone audiometry were all normal. High stimulus rate ABR was abnormal in 66.1% (37/56) of cases. TCD showed 57.1% abnormality in 56 cases, including faster flow rate in 28 cases and slower flow rate in 4 cases. High stimulus rate ABR and TCD were both abnormal in 48.2% (27/56) of cases. Bithermal caloric test was abnormal in 14.3% (8/56) of cases. VEMP showed 32.1% abnormality, including amplitude abnormality in 16 cases and latency abnormality in 2 cases. The abnormal rate of VEMP was much higher than that of caloric test. Vascular mechanisms might be involved in the pathogenesis of BPVC and there is strong evidence for close relationship between BPVC and migraine. High stimulus rate ABR is helpful in the diagnosis of BPVC. The inferior vestibular pathway is much more impaired than the superior vestibular pathway in BPVC. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Acute optic neuritis

PubMed Central

Galetta, Steven L.; Villoslada, Pablo; Levin, Netta; Shindler, Kenneth; Ishikawa, Hiroshi; Parr, Edward; Cadavid, Diego

2015-01-01

Idiopathic demyelinating optic neuritis (ON) most commonly presents as acute unilateral vision loss and eye pain and is frequently associated with multiple sclerosis. Although emphasis is often placed on the good recovery of high-contrast visual acuity, persistent deficits are frequently observed in other aspects of vision, including contrast sensitivity, visual field testing, color vision, motion perception, and vision-related quality of life. Persistent and profound structural and functional changes are often revealed by imaging and electrophysiologic techniques, including optical coherence tomography, visual-evoked potentials, and nonconventional MRI. These abnormalities can impair patients' abilities to perform daily activities (e.g., driving, working) so they have important implications for patients' quality of life. In this article, we review the sequelae from ON, including clinical, structural, and functional changes and their interrelationships. The unmet needs in each of these areas are considered and the progress made toward meeting those needs is examined. Finally, we provide an overview of past and present investigational approaches for disease modification in ON. PMID:26236761

Abnormal hippocampal functioning and impaired spatial navigation in depressed individuals: evidence from whole-head magnetoencephalography.

PubMed

Cornwell, Brian R; Salvadore, Giacomo; Colon-Rosario, Veronica; Latov, David R; Holroyd, Tom; Carver, Frederick W; Coppola, Richard; Manji, Husseini K; Zarate, Carlos A; Grillon, Christian

2010-07-01

Dysfunction of the hippocampus has long been suspected to be a key component of the pathophysiology of major depressive disorder. Despite evidence of hippocampal structural abnormalities in depressed patients, abnormal hippocampal functioning has not been demonstrated. The authors aimed to link spatial navigation deficits previously documented in depressed patients to abnormal hippocampal functioning using a virtual reality navigation task. Whole-head magnetoencephalography (MEG) recordings were collected while participants (19 patients diagnosed with major depressive disorder and 19 healthy subjects matched by gender and age) navigated a virtual Morris water maze to find a hidden platform; navigation to a visible platform served as a control condition. Behavioral measures were obtained to assess navigation performance. Theta oscillatory activity (4-8 Hz) was mapped across the brain on a voxel-wise basis using a spatial-filtering MEG source analysis technique. Depressed patients performed worse than healthy subjects in navigating to the hidden platform. Robust group differences in theta activity were observed in right medial temporal cortices during navigation, with patients exhibiting less engagement of the anterior hippocampus and parahippocampal cortices relative to comparison subjects. Left posterior hippocampal theta activity was positively correlated with individual performance within each group. Consistent with previous findings, depressed patients showed impaired spatial navigation. Dysfunction of right anterior hippocampus and parahippocampal cortices may underlie this deficit and stem from structural abnormalities commonly found in depressed patients.

Behaviour modification in the management of chronic habits of abnormal eye rubbing.

PubMed

McMonnies, Charles W

2009-04-01

To describe how and why many keratoconus patients do not comply with strong advice to control chronic habits of abnormal rubbing. To outline a behaviour modification approach for controlling chronic habits of abnormal rubbing. Common reasons for chronic habits of abnormal rubbing have been reviewed as a basis for specifying a behavioural modification approach to habit reversal. The methods described are organized into the classic behavioural modification structure of: (1) habit awareness, (2) competing responses, (3) development of motivation, and (4) social support. This structure is supported by the application of social influence principles to achieve optimum compliance. The use of take-home written information in the form of an Abnormal Rubbing Guide is the basis for the development of motivation. Family social support is based upon a widening of the responsibility for avoiding eye rubbing to all family members. Some patients will need minimal application of these principles with patient education being sufficient intervention to achieve habit reversal. For patients with strong provocation to rubbing and/or by having a well established rubbing habit, a greater exposure to the habit reversal program described is indicated. Successful habit reversal may slow the rate of ectasia progression. Prophylactic application of the methods described for patients who are at risk for developing keratoconus, or post-laser assisted in situ keratomileusis keratectasia, may show that some forms of keratectasia are preventable.

Primary cilia are increased in number and demonstrate structural abnormalities in human cancer.

PubMed

Yasar, Binnaz; Linton, Kim; Slater, Christian; Byers, Richard

2017-07-01

Primary cilia play an important role in the regulation of cell signalling pathways and are thought to have a role in cancer but have seldom been studied in human cancer samples. Primary cilia were visualised by dual immunofluorescence for anti-CROCC (ciliary rootlet coiled-coil) and anti-tubulin in a range of human cancers (including carcinomas of stomach, pancreas, prostate, lung and colon, lobular and ductal breast cancers and follicular lymphoma) and in matched normal tissue (stomach, pancreas, lung, large and small intestines, breast and reactive lymph nodes) samples using a tissue microarray; their frequency, association with proliferation, was measured by Ki-67 staining and their structure was analysed. Compared with normal tissues, primary cilia frequency was significantly elevated in adenocarcinoma of the lung (2.75% vs 1.85%, p=0.016), adenocarcinoma of the colon (3.80% vs 2.43%, respectively, p=0.017), follicular lymphoma (1.18% vs 0.83%, p=0.003) and pancreatic adenocarcinoma (7.00% vs 5.26%, p=0.002); there was no statistically significant difference compared with normal control tissue for gastric and prostatic adenocarcinomas or for lobular and ductal breast cancers. Additionally, structural abnormalities of primary cilia were identified in cancer tissues, including elongation of the axoneme, multiple basal bodies and branching of the axoneme. Ki-67 scores ranged from 0.7% to 78.4% and showed no statistically significant correlation with primary cilia frequency across all tissues (p=0.1501). The results show upregulation of primary cilia and the presence of structural defects in a wide range of human cancer tissue samples demonstrating association of dysregulation of primary cilia with human cancer. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Advances in understanding paternally transmitted Chromosomal Abnormalities

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

Marchetti, F; Sloter, E; Wyrobek, A J

2001-03-01

Multicolor FISH has been adapted for detecting the major types of chromosomal abnormalities in human sperm including aneuploidies for clinically-relevant chromosomes, chromosomal aberrations including breaks and rearrangements, and other numerical abnormalities. The various sperm FISH assays have been used to evaluate healthy men, men of advanced age, and men who have received mutagenic cancer therapy. The mouse has also been used as a model to investigate the mechanism of paternally transmitted genetic damage. Sperm FISH for the mouse has been used to detect chromosomally abnormal mouse sperm, while the PAINT/DAPI analysis of mouse zygotes has been used to evaluate themore » types of chromosomal defects that can be paternally transmitted to the embryo and their effects on embryonic development.« less

Abnormal hematologic findings in an African hedgehog (Atelerix albiventris) with gastrointestinal lymphosarcoma.

PubMed

Helmer, P J

2000-06-01

A 4-year-old African hedgehog (Atelerix albiventris) was examined for weight loss and hematochezia, and was subsequently diagnosed with gastrointestinal lymphosarcoma. Abnormal hematological findings included marked leukocytosis with lymphocytosis and atypical circulating lymphocytes. This report represents the first documentation of hemogram abnormalities associated with gastrointestinal lymphosarcoma in this species.

Structural and functional differences in the cingulate cortex relate to disease severity in anorexia nervosa

PubMed Central

Bär, Karl-Jürgen; de la Cruz, Feliberto; Berger, Sandy; Schultz, Carl Christoph; Wagner, Gerd

2015-01-01

Background The dysfunction of specific brain areas might account for the distortion of body image in patients with anorexia nervosa. The present study was designed to reveal brain regions that are abnormal in structure and function in patients with this disorder. We hypothesized, based on brain areas of altered activity in patients with anorexia nervosa and regions involved in pain processing, an interrelation of structural aberrations in the frontoparietal–cingulate network and aberrant functional activation during thermal pain processing in patients with the disorder. Methods We determined pain thresholds outside the MRI scanner in patients with anorexia nervosa and matched healthy controls. Thereafter, thermal pain stimuli were applied during fMRI imaging. Structural analyses with high-resolution structural T1-weighted volumes were performed using voxel-based morphometry and a surface-based approach. Results Twenty-six patients and 26 controls participated in our study, and owing to technical difficulties, 15 participants in each group were included in our fMRI analysis. Structural analyses revealed significantly decreased grey matter volume and cortical thickness in the frontoparietal–cingulate network in patients with anorexia nervosa. We detected an increased blood oxygen level–dependent signal in patients during the painful 45°C condition in the midcingulate and posterior cingulate cortex, which positively correlated with increased pain thresholds. Decreased grey matter and cortical thickness correlated negatively with pain thresholds, symptom severity and illness duration, but not with body mass index. Limitations The lack of a specific quantification of body image distortion is a limitation of our study. Conclusion This study provides further evidence for confined structural and functional brain abnormalities in patients with anorexia nervosa in brain regions that are involved in perception and integration of bodily stimuli. The association of structural and functional deviations with thermal thresholds as well as with clinical characteristics might indicate a common neuronal origin. PMID:25825813

Prenatal diagnosis of left isomerism with normal heart: a case report

PubMed Central

De Paola, Nico; Ermito, Santina; Nahom, Antonella; Dinatale, Angela; Pappalardo, Elisa Maria; Carrara, Sabina; Cavaliere, Alessandro; Brizzi, Cristiana

2009-01-01

Objective: Left isomerism, also called polysplenia, is a laterality disturbance associated with with paired leftsidedness viscera and multiple small spleens. Left isomerism, heart congenital abnormalities and gastrointestinal malformation are strongly associated. Methods: We present a case of prenatal diagnosis of left isomerism in a fetus with a structurally normal heart. Conclusion: Left isomerism syndrone may coesist with a structurally normal heart. If prenatal left isomerism is suspected, even in presence of a normal heart, is mandatory to esclude sign of gastrointestinal abnormalities, as late poly hy dramnios, and cardiac rhytm disturbance during the pregnancy and neonatal age. PMID:22439041

Determinants of parental decision to abort or continue after non-aneuploid ultrasound-detected fetal abnormalities.

PubMed

Pryde, P G; Isada, N B; Hallak, M; Johnson, M P; Odgers, A E; Evans, M I

1992-07-01

This study evaluated factors influencing the decision to abort after abnormalities in the karyotypically normal fetus were found through ultrasonography. We reviewed all pregnancies complicated by ultrasound-detected abnormalities managed on our service from April 1990 through August 1991 (N = 262). Cases with associated karyotypic abnormalities were excluded (N = 35), as were cases diagnosed after the legal gestational age limit for abortion (N = 68). The remaining 159 cases were stratified into prognosis groups of "severe," "uncertain," and "mild." The prognostic severity of the ultrasound abnormality strongly correlated with the decision to abort (P less than .0001). Rates of termination were 0, 12, and 66% in the "mild," "uncertain," and "severe" groups, respectively. The patients' age, gravidity, and parity, and the fetal gestational age at diagnosis did not differ significantly between the groups. 1) In non-aneuploid pregnancies with an ultrasound diagnosis of fetal abnormality, the major predictor of the decision to abort was the severity of fetal prognosis. 2) The gestational age at diagnosis was not an important variable in the decision to abort for fetal structural abnormalities. 3) Parents who had fetuses with abnormalities associated with uncertain prognoses usually opted to continue the pregnancy. This appeared to be particularly true for defects that were potentially correctable in utero or by neonatal intervention (even if investigational).

Methods and systems for detecting abnormal digital traffic

DOEpatents

Goranson, Craig A [Kennewick, WA; Burnette, John R [Kennewick, WA

2011-03-22

Aspects of the present invention encompass methods and systems for detecting abnormal digital traffic by assigning characterizations of network behaviors according to knowledge nodes and calculating a confidence value based on the characterizations from at least one knowledge node and on weighting factors associated with the knowledge nodes. The knowledge nodes include a characterization model based on prior network information. At least one of the knowledge nodes should not be based on fixed thresholds or signatures. The confidence value includes a quantification of the degree of confidence that the network behaviors constitute abnormal network traffic.

Cone Structure in Retinal Degeneration Associated with Mutations in the peripherin/RDS Gene

PubMed Central

Talcott, Katherine E.; Ratnam, Kavitha; Sundquist, Sanna M.; Lucero, Anya S.; Day, Shelley; Zhang, Yuhua; Roorda, Austin

2011-01-01

Purpose. To study cone photoreceptor structure and function associated with mutations in the second intradiscal loop region of peripherin/RDS. Methods. High-resolution macular images were obtained with adaptive optics scanning laser ophthalmoscopy and spectral domain optical coherence tomography in four patients with peripherin/RDS mutations and 27 age-similar healthy subjects. Measures of retinal structure and fundus autofluorescence (AF) were correlated with visual function, including best-corrected visual acuity (BCVA), kinetic and static perimetry, fundus-guided microperimetry, full-field electroretinography (ERG), and multifocal ERG. The coding regions of the peripherin/RDS gene were sequenced in each patient. Results. Heterozygous mutations in peripherin/RDS were predicted to affect protein structure in the second intradiscal domain in each patient (Arg172Trp, Gly208Asp, Pro210Arg and Cys213Tyr). BCVA was at least 20/32 in the study eye of each patient. Diffuse cone-greater-than-rod dysfunction was present in patient 1, while rod-greater-than-cone dysfunction was present in patient 4; macular outer retinal dysfunction was present in all patients. Macular AF was heterogeneous, and the photoreceptor-retinal pigment epithelial (RPE) junction layer showed increased reflectivity at the fovea in all patients except patient 1, who showed cone-rod dystrophy. Cone packing was irregular, and cone spacing was significantly increased (z-scores >2) at most locations throughout the central 4° in each patient. Conclusions. peripherin/RDS mutations produced diffuse AF abnormalities, disruption of the photoreceptor/RPE junction, and increased cone spacing, consistent with cone loss in the macula. The abnormalities observed suggest that the integrity of the second intradiscal domain of peripherin/RDS is critical for normal macular cone structure. PMID:21071739

Phenotypic, histological and proteomic analyses reveal multiple differences associated with chloroplast development in yellow and variegated variants from Camellia sinensis

PubMed Central

Ma, Chengying; Cao, Junxi; Li, Jianke; Zhou, Bo; Tang, Jinchi; Miao, Aiqing

2016-01-01

Leaf colour variation is observed in several plants. We obtained two types of branches with yellow and variegated leaves from Camellia sinensis. To reveal the mechanisms that underlie the leaf colour variations, combined morphological, histological, ionomic and proteomic analyses were performed using leaves from abnormal branches (variants) and normal branches (CKs). The measurement of the CIE-Lab coordinates showed that the brightness and yellowness of the variants were more intense than the CKs. When chloroplast profiles were analysed, HY1 (branch with yellow leaves) and HY2 (branch with variegated leaves) displayed abnormal chloroplast structures and a reduced number and size compared with the CKs, indicating that the abnormal chloroplast development might be tightly linked to the leaf colour variations. Moreover, the concentration of elemental minerals was different between the variants and the CKs. Furthermore, DEPs (differentially expressed proteins) were identified in the variants and the CKs by a quantitative proteomics analysis using the label-free approach. The DEPs were significantly involved in photosynthesis and included PSI, PSII, cytochrome b6/f complex, photosynthetic electron transport, LHC and F-type ATPase. Our results suggested that a decrease in the abundance of photosynthetic proteins might be associated with the changes of leaf colours in tea plants. PMID:27633059

Anatomical correlates of reward-seeking behaviours in behavioural variant frontotemporal dementia

PubMed Central

Sturm, Virginia E.; Seeley, William W.; Miller, Bruce L.; Kramer, Joel H.; Rosen, Howard J.

2014-01-01

Behavioural variant frontotemporal dementia is characterized by abnormal responses to primary reward stimuli such as food, sex and intoxicants, suggesting abnormal functioning of brain circuitry mediating reward processing. The goal of this analysis was to determine whether abnormalities in reward-seeking behaviour in behavioural variant frontotemporal dementia are correlated with atrophy in regions known to mediate reward processing. Review of case histories in 103 patients with behavioural variant frontotemporal dementia identified overeating or increased sweet food preference in 80 (78%), new or increased alcohol or drug use in 27 (26%), and hypersexuality in 17 (17%). For each patient, a primary reward-seeking score of 0–3 was created with 1 point given for each target behaviour (increased seeking of food, drugs, or sex). Voxel-based morphometry performed in 91 patients with available imaging revealed that right ventral putamen and pallidum atrophy correlated with higher reward-seeking scores. Each of the reward-related behaviours involved partially overlapping right hemisphere reward circuit regions including putamen, globus pallidus, insula and thalamus. These findings indicate that in some patients with behavioural variant frontotemporal dementia, low volume of subcortical reward-related structures is associated with increased pursuit of primary rewards, which may be a product of increased thalamocortical feedback. PMID:24740987

Neuroimaging studies of social cognition in schizophrenia.

PubMed

Fujiwara, Hironobu; Yassin, Walid; Murai, Toshiya

2015-05-01

Impaired social cognition is considered a core contributor to unfavorable psychosocial functioning in schizophrenia. Rather than being a unitary process, social cognition is a collection of multifaceted processes that recruit multiple brain structures, thus structural and functional neuroimaging techniques are ideal methodologies for revealing the underlying pathophysiology of impaired social cognition. Many neuroimaging studies have suggested that in addition to white-matter deficits, schizophrenia is associated with decreased gray-matter volume in multiple brain areas, especially fronto-temporal and limbic regions. However, few schizophrenia studies have examined associations between brain abnormalities and social cognitive disabilities. During the last decade, we have investigated structural brain abnormalities in schizophrenia using high-resolution magnetic resonance imaging, and our findings have been confirmed by us and others. By assessing different types of social cognitive abilities, structural abnormalities in multiple brain regions have been found to be associated with disabilities in social cognition, such as recognition of facial emotion, theory of mind, and empathy. These structural deficits have also been associated with alexithymia and quality of life in ways that are closely related to the social cognitive disabilities found in schizophrenia. Here, we overview a series of neuroimaging studies from our laboratory that exemplify current research into this topic, and discuss how it can be further tackled using recent advances in neuroimaging technology. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

Is there an association with constitutional structural chromosomal abnormalities and hematologic neoplastic process? A short review.

PubMed

Panani, Anna D

2009-04-01

The occasional observation of constitutional chromosomal abnormalities in patients with a malignant disease has led to a number of studies on their potential role in cancer development. Investigations of families with hereditary cancers and constitutional chromosomal abnormalities have been key observations leading to the molecular identification of specific genes implicated in tumorigenesis. Large studies have been reported on the incidence of constitutional chromosomal aberrations in patients with hematologic malignancies, but they could not confirm an increased risk for hematologic malignancy among carriers of structural chromosomal changes. However, it is of particular interest that constitutional structural aberrations with breakpoints similar to leukemia-associated specific breakpoints have been reported in patients with hematologic malignancies. Because of insufficient data, it remains still unclear if these aberrations represent random events or are associated with malignancy. There has been a substantial discussion about mechanisms involved in constitutional structural chromosomal changes in the literature. The documentation of more patients with constitutional structural chromosomal changes could be of major importance. Most importantly, the molecular investigation of chromosomal regions involved in rearrangements could give useful information on the genetic events underlying constitutional anomalies, contributing to isolation of genes important in the development of the neoplastic process. Regarding constitutional anomalies in patients with hematologic disorders, a survey of the cytogenetic data of our cytogenetics unit is herein also presented.

BRAIN ABNORMALITIES IN YOUNG ADULTS AT GENETIC RISK FOR AUTOSOMAL DOMINANT ALZHEIMER’S DISEASE: A CROSS-SECTIONAL STUDY

PubMed Central

Reiman, Eric M.; Quiroz, Yakeel T.; Fleisher, Adam S.; Chen, Kewei; Velez-Pardo, Carlos; Jimenez-Del-Rio, Marlene; Fagan, Anne M.; Shah, Aarti R.; Alvarez, Sergio; Arbelaez, Andrés; Giraldo, Margarita; Acosta-Baena, Natalia; Sperling, Reisa A.; Dickerson, Brad; Stern, Chantal E.; Tirado, Victoria; Munoz, Claudia; Reiman, Rebecca A.; Huentelman, Matthew J.; Alexander, Gene E.; Langbaum, Jessica B.S.; Kosik, Kenneth S.; Tariot, Pierre N.; Lopera, Francisco

2013-01-01

Summary Background We previously detected functional brain imaging abnormalities in young adults at genetic risk for late-onset Alzheimer’s disease (AD). Here, we sought to characterize structural and functional magnetic resonance imaging (MRI), cerebrospinal fluid (CSF), and plasma biomarker abnormalities in young adults at risk for autosomal dominant early-onset AD. Biomarker measurements were characterized and compared in presenilin 1 (PSEN1) E280A mutation carriers and non-carriers from the world’s largest known autosomal dominant early-onset AD kindred, more than two decades before the carriers’ estimated median age of 44 at the onset of mild cognitive impairment (MCI) and before their estimated age of 28 at the onset of amyloid-β (Aβ) plaque deposition. Methods Biomarker data for this cross-sectional study were acquired in Antioquia, Colombia between July and August, 2010. Forty-four participants from the Colombian Alzheimer’s Prevention Initiative (API) Registry had structural MRIs, functional MRIs during associative memory encoding/novel viewing and control tasks, and cognitive assessments. They included 20 mutation carriers and 24 non-carriers, who were cognitively normal, 18-26 years old and matched for their gender, age, and educational level. Twenty of the participants, including 10 mutation carriers and 10 non-carriers, had lumbar punctures and venipunctures. Primary outcome measures included task-dependent hippocampal/parahippocampal activations and precuneus/posterior cingulate deactivations, regional gray matter reductions, CSF Aβ1-42, total tau and phospho-tau181 levels, and plasma Aβ1-42 levels and Aβ1-42/Aβ1-40 ratios. Structural and functional MRI data were compared using automated brain mapping algorithms and AD-related search regions. Cognitive and fluid biomarkers were compared using Mann-Whitney tests. Findings The mutation carrier and non-carrier groups did not differ significantly in their dementia ratings, neuropsychological test scores, or proportion of apolipoprotein E (APOE) ε4 carriers. Compared to the non-carriers, carriers had higher CSF Aβ1-42 levels (p=0·008), plasma Aβ1-42 levels (p=0·01), and plasma Aβ1-42/Aβ1-40 ratios (p=0·001), consistent with Aβ1-42 overproduction. They also had greater hippocampal/parahippocampal activations (as low as p=0·008, after correction for multiple comparisons), less precuneus/posterior cingulate deactivations (as low as p=0·001, after correction), less gray matter in several regions (p-values <0·005, uncorrected, and corrected p=0·008 in the parietal search region), similar to findings in the later preclinical and clinical stages of autosomal dominant and late-onset AD. Interpretation Young adults at genetic risk for autosomal dominant AD have functional and structural MRI abnormalities, along with CSF and plasma biomarker findings consistent with Aβ1-42 over-production. While the extent to which the underlying brain changes are progressive or developmental remain to be determined, this study demonstrates the earliest known biomarker changes in cognitively normal people at genetic risk for autosomal dominant AD. Funding Banner Alzheimer’s Foundation, Nomis Foundation, Anonymous Foundation, Forget Me Not Initiative, Boston University Department of Psychology, Colciencias (1115-408-20512, 1115-545-31651), National Institute on Aging (R01 AG031581, P30 AG19610, UO1 AG024904, RO1 AG025526, RF1AG041705), National Institute of Neurological Disorders and Stroke (F31-NS078786) and state of Arizona. PMID:23137948

Imaging functional and structural brain connectomics in attention-deficit/hyperactivity disorder.

PubMed

Cao, Miao; Shu, Ni; Cao, Qingjiu; Wang, Yufeng; He, Yong

2014-12-01

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopment disorders in childhood. Clinically, the core symptoms of this disorder include inattention, hyperactivity, and impulsivity. Previous studies have documented that these behavior deficits in ADHD children are associated with not only regional brain abnormalities but also changes in functional and structural connectivity among regions. In the past several years, our understanding of how ADHD affects the brain's connectivity has been greatly advanced by mapping topological alterations of large-scale brain networks (i.e., connectomes) using noninvasive neurophysiological and neuroimaging techniques (e.g., electroencephalograph, functional MRI, and diffusion MRI) in combination with graph theoretical approaches. In this review, we summarize the recent progresses of functional and structural brain connectomics in ADHD, focusing on graphic analysis of large-scale brain systems. Convergent evidence suggests that children with ADHD had abnormal small-world properties in both functional and structural brain networks characterized by higher local clustering and lower global integrity, suggesting a disorder-related shift of network topology toward regular configurations. Moreover, ADHD children showed the redistribution of regional nodes and connectivity involving the default-mode, attention, and sensorimotor systems. Importantly, these ADHD-associated alterations significantly correlated with behavior disturbances (e.g., inattention and hyperactivity/impulsivity symptoms) and exhibited differential patterns between clinical subtypes. Together, these connectome-based studies highlight brain network dysfunction in ADHD, thus opening up a new window into our understanding of the pathophysiological mechanisms of this disorder. These works might also have important implications on the development of imaging-based biomarkers for clinical diagnosis and treatment evaluation in ADHD.

The relationship of impulsivity and cortical thickness in depressed and non-depressed adolescents.

PubMed

Fradkin, Yuli; Khadka, Sabin; Bessette, Katie L; Stevens, Michael C

2017-10-01

Major Depressive Disorder (MDD) is recognized to be heterogeneous in terms of brain structure abnormality findings across studies, which might reflect previously unstudied traits that confer variability to neuroimaging measurements. The purpose of this study was to examine the relationships between different types of trait impulsivity and MDD diagnosis on adolescent brain structure. We predicted that adolescents with depression who were high on trait impulsivity would have more abnormal cortical structure than depressed patients or non-MDD who were low on impulsivity. We recruited 58 subjects, including 29 adolescents (ages 12-19) with a primary DSM-IV diagnosis of MDD and a history of suicide attempt and 29 demographically-matched healthy control participants. Our GLM-based analyses sought to describe differences in the linear relationships between cortical thickness and impulsivity trait levels. As hypothesized, we found significant moderation effects in rostral middle frontal gyrus and right paracentral lobule cortical thickness for different subscales of the Barratt Impulsiveness Scale. However, although these brain-behavior relationships differed between diagnostic study groups, they were not simple additive effects as we had predicted. For the middle frontal gyrus, non-MDD participants showed a strong positive association between cortical thickness and BIS-11 Motor scores, while MDD-diagnosed participants showed a negative association. For Non-Planning Impulsiveness, paracentral lobule cortical thickness was observed with greater impulsivity in MDD, but no association was found for controls. In conclusion, the findings confirm that dimensions of impulsivity have discrete neural correlates, and show that relationships between impulsivity and brain structure are expressed differently in adolescents with MDD compared to non-MDD.

The Relationship of Intellectual Functioning and Cognitive Performance to Brain Structure in Schizophrenia

PubMed Central

Wang, Lei; Gama, Clarissa S.; Barch, Deanna M.

2017-01-01

Abstract Background: Schizophrenia (SZ) is often characterized by cognitive and intellectual impairment. However, there is much heterogeneity across individuals, suggesting different trajectories of the illness. Recent findings have shown brain volume differences across subgroups of individuals with psychosis (SZ and bipolar disorder), such that those with intellectual and cognitive impairments presented evidence of early cerebral disruption, while those with cognitive but not intellectual impairments showed evidence of progressive brain abnormalities. Our aim was to investigate the relations of cognition and intellectual functioning with brain structure abnormalities in a sample of SZ compared to unaffected individuals. Methods: 92 individuals with SZ and 94 healthy controls part of the Northwestern University Schizophrenia Data and Software Tool (NUSDAST) underwent neuropsychological assessment and structural magnetic resonance imaging (MRI). Individuals with SZ were divided into subgroups according their estimated premorbid crystallized intellectual (ePMC-IQ) and cognitive performance. Brain volumes differences were investigated across groups. Results: SZ with ePMC-IQ and cognitive impairments had reduced total brain volume (TBV), intracranial volume (ICV), TBV corrected for ICV, and cortical gray matter volume, as well as reduced cortical thickness, and insula volumes. SZ with cognitive impairment but intact ePMC-IQ showed only reduced cortical gray matter volume and cortical thickness. Conclusions: These data provide additional evidence for heterogeneity in SZ. Impairments in cognition associated with reduced ePMC-IQ were related to evidence of broad brain structural alterations, including suggestion of early cerebral disruption. In contrast, impaired cognitive functioning in the context of more intact intellectual functioning was associated with cortical alterations that may reflect neurodegeneration. PMID:27369471

The effect of alcohol use on human adolescent brain structures and systems.

PubMed

Squeglia, Lindsay M; Jacobus, Joanna; Tapert, Susan F

2014-01-01

This article reviews the neurocognitive and neuroimaging literature regarding the effect of alcohol use on human adolescent brain structure and function. Adolescents who engage in heavy alcohol use, even at subdiagnostic levels, show differences in brain structure, function, and behavior when compared with non-drinking controls. Preliminary longitudinal studies have helped disentangle premorbid factors from consequences associated with drinking. Neural abnormalities and cognitive disadvantages both appear to predate drinking, particularly in youth who have a family history of alcoholism, and are directly related to the neurotoxic effect of alcohol use. Binge drinking and withdrawal and hangover symptoms have been associated with the greatest neural abnormalities during adolescence, particularly in frontal, parietal, and temporal regions. © 2014 Elsevier B.V. All rights reserved.

Discriminative analysis of schizophrenia using support vector machine and recursive feature elimination on structural MRI images.

PubMed

Lu, Xiaobing; Yang, Yongzhe; Wu, Fengchun; Gao, Minjian; Xu, Yong; Zhang, Yue; Yao, Yongcheng; Du, Xin; Li, Chengwei; Wu, Lei; Zhong, Xiaomei; Zhou, Yanling; Fan, Ni; Zheng, Yingjun; Xiong, Dongsheng; Peng, Hongjun; Escudero, Javier; Huang, Biao; Li, Xiaobo; Ning, Yuping; Wu, Kai

2016-07-01

Structural abnormalities in schizophrenia (SZ) patients have been well documented with structural magnetic resonance imaging (MRI) data using voxel-based morphometry (VBM) and region of interest (ROI) analyses. However, these analyses can only detect group-wise differences and thus, have a poor predictive value for individuals. In the present study, we applied a machine learning method that combined support vector machine (SVM) with recursive feature elimination (RFE) to discriminate SZ patients from normal controls (NCs) using their structural MRI data. We first employed both VBM and ROI analyses to compare gray matter volume (GMV) and white matter volume (WMV) between 41 SZ patients and 42 age- and sex-matched NCs. The method of SVM combined with RFE was used to discriminate SZ patients from NCs using significant between-group differences in both GMV and WMV as input features. We found that SZ patients showed GM and WM abnormalities in several brain structures primarily involved in the emotion, memory, and visual systems. An SVM with a RFE classifier using the significant structural abnormalities identified by the VBM analysis as input features achieved the best performance (an accuracy of 88.4%, a sensitivity of 91.9%, and a specificity of 84.4%) in the discriminative analyses of SZ patients. These results suggested that distinct neuroanatomical profiles associated with SZ patients might provide a potential biomarker for disease diagnosis, and machine-learning methods can reveal neurobiological mechanisms in psychiatric diseases.

Therapeutic Role of Hematopoietic Stem Cells in Autism Spectrum Disorder-Related Inflammation

PubMed Central

Siniscalco, Dario; Bradstreet, James Jeffrey; Antonucci, Nicola

2013-01-01

Autism and autism spectrum disorders (ASDs) are heterogeneous, severe neuro-developmental disorders with core symptoms of dysfunctions in social interactions and communication skills, restricted interests, repetitive – stereotypic verbal and non-verbal behaviors. Biomolecular evidence points to complex gene-environmental interactions in ASDs. Several biochemical processes are associated with ASDs: oxidative stress (including endoplasmic reticulum stress), decreased methylation capacity, limited production of glutathione; mitochondrial dysfunction, intestinal dysbiosis, increased toxic metal burden, and various immune abnormalities. The known immunological disorders include: T-lymphocyte populations and function, gene expression changes in monocytes, several autoimmune-related findings, high levels of N-acetylgalactosaminidase (which precludes macrophage activation), and primary immune deficiencies. These immunological observations may result in minicolumn structural changes in the brain, as well as, abnormal immune mediation of synaptic functions. Equally, these immune dysregulations serve as the rationale for immune-directed interventions such as hematopoietic stem cells (HSCs), which are pivotal in controlling chronic inflammation and in the restoration of immunological balance. These properties make them intriguing potential agents for ASD treatments. This prospective review will focus on the current state-of-the-art knowledge and challenges intrinsic in the application of HSCs for ASD-related immunological disorders. PMID:23772227

Social isolation stress induces ATF-7 phosphorylation and impairs silencing of the 5-HT 5B receptor gene

PubMed Central

Maekawa, Toshio; Kim, Seungjoon; Nakai, Daisuke; Makino, Chieko; Takagi, Tsuyoshi; Ogura, Hiroo; Yamada, Kazuyuki; Chatton, Bruno; Ishii, Shunsuke

2010-01-01

Many symptoms induced by isolation rearing of rodents may be relevant to neuropsychiatric disorders, including depression. However, identities of transcription factors that regulate gene expression in response to chronic social isolation stress remain elusive. The transcription factor ATF-7 is structurally related to ATF-2, which is activated by various stresses, including inflammatory cytokines. Here, we report that Atf-7-deficient mice exhibit abnormal behaviours and increased 5-HT receptor 5B (Htr5b) mRNA levels in the dorsal raphe nuclei. ATF-7 silences the transcription of Htr5B by directly binding to its 5′-regulatory region, and mediates histone H3-K9 trimethylation via interaction with the ESET histone methyltransferase. Isolation-reared wild-type (WT) mice exhibit abnormal behaviours that resemble those of Atf-7-deficient mice. Upon social isolation stress, ATF-7 in the dorsal raphe nucleus is phosphorylated via p38 and is released from the Htr5b promoter, leading to the upregulation of Htr5b. Thus, ATF-7 may have a critical role in gene expression induced by social isolation stress. PMID:19893493

New Perspectives on Osteogenesis Imperfecta

PubMed Central

Forlino, Antonella; Cabral, Wayne A.; Barnes, Aileen M.; Marini, Joan C.

2012-01-01

A new paradigm has emerged for osteogenesis imperfecta (OI) as a collagen-related disorder. The more prevalent autosomal dominant forms of OI are caused by primary defects in type I collagen, while autosomal recessive forms are caused by deficiency of proteins which interact with type I procollagen for post-translational modification and/or folding. Factors contributing to the mechanism of dominant OI include intracellular stress, disruption of interactions between collagen and non-collagenous proteins, compromised matrix structure, abnormal cell-cell and cell-matrix interactions and tissue mineralization. Recessive OI is caused by deficiency of any of the three components of the collagen prolyl 3-hydroxylation complex; absence of 3-hydroxylation is associated with increased modification of the collagen helix, supporting delayed collagen folding. Other causes of recessive OI include deficiency of collagen chaperones, FKBP65 or HSP47. Murine models are crucial to uncovering the common pathways in dominant and recessive OI bone dysplasia. Clinical management of OI is multidiscipinary, encompassing substantial progress in physical rehabilitation and surgical procedures, managment of hearing, dental and pulmonary abnormalities, as well as drugs such as bisphosphonates and rGH. Novel treatments using cell therapy or new drug regimens hold promise for the future. PMID:21670757

A Cross-Sectional and Follow-Up Functional MRI Study with a Working Memory Task in Adolescent Anorexia Nervosa

ERIC Educational Resources Information Center

Castro-Fornieles, Josefina; Caldu, Xavier; Andres-Perpina, Susana; Lazaro, Luisa; Bargallo, Nuria; Falcon, Carles; Plana, Maria Teresa; Junque, Carme

2010-01-01

Structural and functional brain abnormalities have been described in anorexia nervosa (AN). The objective of this study was to examine whether there is abnormal regional brain activation during a working memory task not associated with any emotional stimuli in adolescent patients with anorexia and to detect possible changes after weight recovery.…

Molecular analysis of abnormal hemoglobins in beta chain in Aegean region of Turkey and first reports of hemoglobin Andrew-Minneapolis and Hb Hinsdale from Turkey.

PubMed

Aykut, Ayça; Onay, Hüseyin; Durmaz, Asude; Karaca, Emin; Vergin, Canan; Aydınok, Yeşim; Özkınay, Ferda

2015-07-01

The Agean is one of the regions in Turkey where thalassemias and abnormal hemoglobins (Hbs) are prevalent. Combined heterozygosity of thalassemia mutations with a variety of structural Hb variants lead to an extremely wide spectrum of clinical and hematological phenotypes which is of importance for prenatal diagnosis. One hundred and seventeen patients and carriers diagnosed by hemoglobin electrophoresis (HPLC), at risk for abnormal hemoglobinopathies were screened for mutational analysis of the beta-globin gene. The full coding the 5' UTR, and the 3' UTR sequences of beta-globin gene (GenBank accession no. U01317) were amplified and sequenced. In this study, a total of 118 (12.24%) structural Hb variant alleles were identified in 1341 mutated beta-chain alleles in Medical Genetics Department of Ege University between January 2006 and November 2013. Here, we report the mutation spectrum of abnormal Hbs associated with the beta-globin gene in Aegean region of Turkey. In the present study, the Hb Hinsdale and Hb Andrew-Minneapolis variants are demonstrated for the first time in the Turkish population.

NOVEL PRERETINAL HAIR PIN-LIKE VESSEL IN RETINAL ASTROCYTIC HAMARTOMA WITH VITREOUS HEMORRHAGE.

PubMed

Soeta, Megumi; Arai, Yusuke; Takahashi, Hidenori; Fujino, Yujiro; Tanabe, Tatsuro; Inoue, Yuji; Kawashima, Hidetoshi

2018-01-01

To report a case of retinal astrocytic hamartoma with vitreous hemorrhage and a hair pin-like vessel adhering to a posterior vitreous membrane. A 33-year-old man with a retinal astrocytic hamartoma presented with vitreous hemorrhage 5 times. Multimodal imaging, including fundus photography, fluorescein angiography, optical coherence tomography, and B-mode ultrasonography. Multimodal imaging demonstrated a novel hair pin-like vessel that adhered to the posterior vitreous membrane. Some cases of retinal astrocytic hamartoma with vitreous hemorrhage may be related to structure abnormalities of tumor vessels.

Malformations of cortical development: 3T magnetic resonance imaging features

PubMed Central

Battal, Bilal; Ince, Selami; Akgun, Veysel; Kocaoglu, Murat; Ozcan, Emrah; Tasar, Mustafa

2015-01-01

Malformation of cortical development (MCD) is a term representing an inhomogeneous group of central nervous system abnormalities, referring particularly to embriyological aspect as a consequence of any of the three developmental stages, i.e., cell proliferation, cell migration and cortical organization. These include cotical dysgenesis, microcephaly, polymicrogyria, schizencephaly, lissencephaly, hemimegalencephaly, heterotopia and focal cortical dysplasia. Since magnetic resonance imaging is the modality of choice that best identifies the structural anomalies of the brain cortex, we aimed to provide a mini review of MCD by using 3T magnetic resonance scanner images. PMID:26516429

Nuclear states with anomalously large radius (size isomers)

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

Ogloblin, A. A.; Demyanova, A. S., E-mail: a.s.demyanova@bk.ru; Danilov, A. N.

2016-07-15

Methods of determination of the nuclear excited state radii are discussed together with the recently obtained data on the states of some light nuclei having abnormally large radii (size isomers). It is shown that such states include excited neutron-halo states in {sup 9}Be, {sup 11}Be, and {sup 13}C and some alpha-cluster states in {sup 12}C, {sup 11}B, and {sup 13}C. Among the latter ones, there is the well-known Hoyle state in {sup 12}C—the structure of this state exhibit rudimentary features of alpha-particle states.

Neurobiological correlates of cognitions in fear and anxiety: a cognitive-neurobiological information-processing model.

PubMed

Hofmann, Stefan G; Ellard, Kristen K; Siegle, Greg J

2012-01-01

We review likely neurobiological substrates of cognitions related to fear and anxiety. Cognitive processes are linked to abnormal early activity reflecting hypervigilance in subcortical networks involving the amygdala, hippocampus, and insular cortex, and later recruitment of cortical regulatory resources, including activation of the anterior cingulate cortex and prefrontal cortex to implement avoidant response strategies. Based on this evidence, we present a cognitive-neurobiological information-processing model of fear and anxiety, linking distinct brain structures to specific stages of information processing of perceived threat.

[Role of BoBs technology in early missed abortion chorionic villi].

PubMed

Li, Z Y; Liu, X Y; Peng, P; Chen, N; Ou, J; Hao, N; Zhou, J; Bian, X M

2018-05-25

Objective: To investigate the value of bacterial artificial chromosome-on-beads (BoBs) technology in the genetic analysis of early missed abortion chorionic villi. Methods: Early missed abortion chorionic villi were detected with both conventional karyotyping method and BoBs technology in Peking Union Medical Hospital from July 2014 to March 2015. Compared the results of BoBs with conventional karyotyping analysis to evaluate the sensitivity, specificity and accuracy of this new method. Results: (1) A total of 161 samples were tested successfully in the technology of BoBs, 131 samples were tested successfully in the method of conventional karyotyping. (2) All of the cases obtained from BoBs results in (2.7±0.6) days and obtained from conventional karyotyping results in (22.5±1.9) days. There was significant statistical difference between the two groups ( t= 123.315, P< 0.01) . (3) Out of 161 cases tested in BoBs, 85 (52.8%, 85/161) cases had the abnormal chromosomes, including 79 cases chromosome number abnormality, 4 cases were chromosome segment deletion, 2 cases mosaic. Out of 131 cases tested successfully in conventional karyotyping, 79 (60.3%, 79/131) cases had the abnormal chromosomes including 62 cases chromosome number abnormality, 17 cases other chromosome number abnormality, and the rate of chromosome abnormality between two methods was no significant differences ( P =0.198) . (4) Conventional karyotyping results were served as the gold standard, the accuracy of BoBs for abnormal chromosomes was 82.4% (108/131) , analysed the normal chromosomes (52 cases) and chromosome number abnormality (62 cases) tested in conventional karyotyping, the accuracy of BoBs for chromosome number abnormality was 94.7% (108/114) . Conclusion: BoBs is a rapid reliable and easily operated method to test early missed abortion chorionic villi chromosomal abnormalities.

Visual impairment evaluation in 119 children with congenital Zika syndrome.

PubMed

Ventura, Liana O; Ventura, Camila V; Dias, Natália de C; Vilar, Isabelle G; Gois, Adriana L; Arantes, Tiago E; Fernandes, Luciene C; Chiang, Michael F; Miller, Marilyn T; Lawrence, Linda

2018-06-01

To assess visual impairment in a large sample of infants with congenital Zika syndrome (CZS) and to compare with a control group using the same assessment protocol. The study group was composed of infants with confirmed diagnosis of CZS. Controls were healthy infants matched for age, sex, and socioeconomic status. All infants underwent comprehensive ophthalmologic evaluation including visual acuity, visual function assessment, and visual developmental milestones. The CZS group included 119 infants; the control group, 85 infants. At examination, the mean age of the CZS group was 8.5 ± 1.2 months (range, 6-13 months); of the controls, 8.4 ± 1.8 months (range, 5-12 months; P = 0.598). Binocular Teller Acuity Card (TAC) testing was abnormal in 107 CZS infants and in 4 controls (89.9% versus 5% [P < 0.001]). In the study group, abnormal monocular TAC results were more frequent in eyes with funduscopic alterations (P = 0.008); however, 104 of 123 structurally normal eyes (84.6%) also presented abnormal TAC results. Binocular contrast sensitivity was reduced in 87 of 107 CZS infants and in 8 of 80 controls (81.3% versus 10% [P < 0.001]). The visual development milestones were less achieved by infants with CZS compared to controls (P < 0.001). Infants with CZS present with severe visual impairment. A protocol for assessment of the ocular findings, visual acuity, and visual developmental milestones tested against age-matched controls is suggested. Copyright © 2018 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

R6/2 Huntington's disease mice develop early and progressive abnormal brain metabolism and seizures.

PubMed

Cepeda-Prado, Efrain; Popp, Susanna; Khan, Usman; Stefanov, Dimitre; Rodríguez, Jorge; Menalled, Liliana B; Dow-Edwards, Diana; Small, Scott A; Moreno, Herman

2012-05-09

A hallmark feature of Huntington's disease pathology is the atrophy of brain regions including, but not limited to, the striatum. Though MRI studies have identified structural CNS changes in several Huntington's disease (HD) mouse models, the functional consequences of HD pathology during the progression of the disease have yet to be investigated using in vivo functional MRI (fMRI). To address this issue, we first established the structural and functional MRI phenotype of juvenile HD mouse model R6/2 at early and advanced stages of disease. Significantly higher fMRI signals [relative cerebral blood volumes (rCBVs)] and atrophy were observed in both age groups in specific brain regions. Next, fMRI results were correlated with electrophysiological analysis, which showed abnormal increases in neuronal activity in affected brain regions, thus identifying a mechanism accounting for the abnormal fMRI findings. [(14)C] 2-deoxyglucose maps to investigate patterns of glucose utilization were also generated. An interesting mismatch between increases in rCBV and decreases in glucose uptake was observed. Finally, we evaluated the sensitivity of this mouse line to audiogenic seizures early in the disease course. We found that R6/2 mice had an increased susceptibility to develop seizures. Together, these findings identified seizure activity in R6/2 mice and show that neuroimaging measures sensitive to oxygen metabolism can be used as in vivo biomarkers, preceding the onset of an overt behavioral phenotype. Since fMRI-rCBV can also be obtained in patients, we propose that it may serve as a translational tool to evaluate therapeutic responses in humans and HD mouse models.

Metabolic consequences of stress during childhood and adolescence.

PubMed

Pervanidou, Panagiota; Chrousos, George P

2012-05-01

Stress, that is, the state of threatened or perceived as threatened homeostasis, is associated with activation of the stress system, mainly comprised by the hypothalamic-pituitary-adrenal axis and the arousal/sympathetic nervous systems. The stress system normally functions in a circadian manner and interacts with other systems to regulate a variety of behavioral, endocrine, metabolic, immune, and cardiovascular functions. However, the experience of acute intense physical or emotional stress, as well as of chronic stress, may lead to the development of or may exacerbate several psychologic and somatic conditions, including anxiety disorders, depression, obesity, and the metabolic syndrome. In chronically stressed individuals, both behavioral and neuroendocrine mechanisms promote obesity and metabolic abnormalities: unhealthy lifestyles in conjunction with dysregulation of the stress system and increased secretion of cortisol, catecholamines, and interleukin-6, with concurrently elevated insulin concentrations, lead to development of central obesity, insulin resistance, and the metabolic syndrome. Fetal life, childhood, and adolescence are particularly vulnerable periods of life to the effects of intense acute or chronic stress. Similarly, these life stages are crucial for the later development of behavioral, metabolic, and immune abnormalities. Developing brain structures and functions related to stress regulation, such as the amygdala, the hippocampus, and the mesocorticolimbic system, are more vulnerable to the effects of stress compared with mature structures in adults. Moreover, chronic alterations in cortisol secretion in children may affect the timing of puberty, final stature, and body composition, as well as cause early-onset obesity, metabolic syndrome, and type 2 diabetes mellitus. The understanding of stress mechanisms leading to metabolic abnormalities in early life may lead to more effective prevention and intervention strategies of obesity-related health problems. Copyright © 2012 Elsevier Inc. All rights reserved.

[Automated hematology analysers and spurious counts Part 3. Haemoglobin, red blood cells, cell count and indices, reticulocytes].

PubMed

Godon, Alban; Genevieve, Franck; Marteau-Tessier, Anne; Zandecki, Marc

2012-01-01

Several situations lead to abnormal haemoglobin measurement or to abnormal red blood cells (RBC) counts, including hyperlipemias, agglutinins and cryoglobulins, haemolysis, or elevated white blood cells (WBC) counts. Mean (red) cell volume may be also subject to spurious determination, because of agglutinins (mainly cold), high blood glucose level, natremia, anticoagulants in excess and at times technological considerations. Abnormality related to one measured parameter eventually leads to abnormal calculated RBC indices: mean cell haemoglobin content is certainly the most important RBC parameter to consider, maybe as important as flags generated by the haematology analysers (HA) themselves. In many circumstances, several of the measured parameters from cell blood counts (CBC) may be altered, and the discovery of a spurious change on one parameter frequently means that the validity of other parameters should be considered. Sensitive flags allow now the identification of several spurious counts, but only the most sophisticated HA have optimal flagging, and simpler ones, especially those without any WBC differential scattergram, do not share the same capacity to detect abnormal results. Reticulocytes are integrated into the CBC in many HA, and several situations may lead to abnormal counts, including abnormal gating, interference with intraerythrocytic particles, erythroblastosis or high WBC counts.

Electrocardiogram

MedlinePlus

... history of heart disease in the family Normal Results Normal test results include: Heart rate: 60 to ... minute Heart rhythm: Consistent and even What Abnormal Results Mean Abnormal ECG results may be a sign ...

Anoscopy

MedlinePlus

... What Abnormal Results Mean Abnormal results may include: Abscess Fissures Foreign object in the anus Hemorrhoids Infection ... Wechter, MD, FACS, general surgery practice specializing in breast cancer, Virginia Mason Medical Center, Seattle, WA. Also ...

Evaluation of Esophageal Motility Utilizing the Functional Lumen Imaging Probe.

PubMed

Carlson, Dustin A; Kahrilas, Peter J; Lin, Zhiyue; Hirano, Ikuo; Gonsalves, Nirmala; Listernick, Zoe; Ritter, Katherine; Tye, Michael; Ponds, Fraukje A; Wong, Ian; Pandolfino, John E

2016-12-01

Esophagogastric junction (EGJ) distensibility and distension-mediated peristalsis can be assessed with the functional lumen imaging probe (FLIP) during a sedated upper endoscopy. We aimed to describe esophageal motility assessment using FLIP topography in patients presenting with dysphagia. In all, 145 patients (aged 18-85 years, 54% female) with dysphagia that completed upper endoscopy with a 16-cm FLIP assembly and high-resolution manometry (HRM) were included. HRM was analyzed according to the Chicago Classification of esophageal motility disorders; major esophageal motility disorders were considered "abnormal". FLIP studies were analyzed using a customized program to calculate the EGJ-distensibility index (DI) and generate FLIP topography plots to identify esophageal contractility patterns. FLIP topography was considered "abnormal" if EGJ-DI was <2.8 mm 2 /mm Hg or contractility pattern demonstrated absent contractility or repetitive, retrograde contractions. HRM was abnormal in 111 (77%) patients: 70 achalasia (19 type I, 39 type II, and 12 type III), 38 EGJ outflow obstruction, and three jackhammer esophagus. FLIP topography was abnormal in 106 (95%) of these patients, including all 70 achalasia patients. HRM was "normal" in 34 (23%) patients: five ineffective esophageal motility and 29 normal motility. In all, 17 (50%) had abnormal FLIP topography including 13 (37%) with abnormal EGJ-DI. FLIP topography provides a well-tolerated method for esophageal motility assessment (especially to identify achalasia) at the time of upper endoscopy. FLIP topography findings that are discordant with HRM may indicate otherwise undetected abnormalities of esophageal function, thus FLIP provides an alternative and complementary method to HRM for evaluation of non-obstructive dysphagia.

Abnormal hematologic findings in an African hedgehog (Atelerix albiventris) with gastrointestinal lymphosarcoma.

PubMed Central

Helmer, P J

2000-01-01

A 4-year-old African hedgehog (Atelerix albiventris) was examined for weight loss and hematochezia, and was subsequently diagnosed with gastrointestinal lymphosarcoma. Abnormal hematological findings included marked leukocytosis with lymphocytosis and atypical circulating lymphocytes. This report represents the first documentation of hemogram abnormalities associated with gastrointestinal lymphosarcoma in this species. PMID:10857034

Movement Disorders and Other Motor Abnormalities in Adults With 22q11.2 Deletion Syndrome

PubMed Central

Boot, Erik; Butcher, Nancy J; van Amelsvoort, Thérèse AMJ; Lang, Anthony E; Marras, Connie; Pondal, Margarita; Andrade, Danielle M; Fung, Wai Lun Alan; Bassett, Anne S

2015-01-01

Movement abnormalities are frequently reported in children with 22q11.2 deletion syndrome (22q11.2DS), but knowledge in this area is scarce in the increasing adult population. We report on five individuals illustrative of movement disorders and other motor abnormalities in adults with 22q11.2DS. In addition to an increased susceptibility to neuropsychiatric disorders, seizures, and early-onset Parkinson disease, the underlying brain dysfunction associated with 22q11.2DS may give rise to an increased vulnerability to multiple movement abnormalities, including those influenced by medications. Movement abnormalities may also be secondary to treatable endocrine diseases and congenital musculoskeletal abnormalities. We propose that movement abnormalities may be common in adults with 22q11.2DS and discuss the implications and challenges important to clinical practice. PMID:25684639

[Chromosome study on chronic lymphocytic leukemia using CpG-oligodeoxynucleotide as immunostimulant agent].

PubMed

Wu, Yafang; Xue, Yongquan; Chen, Suning; Yao, Li; Jiang, Hui; Zhang, Jun; Shen, Juan; Pan, Jinlan; Wang, Yong; Bai, Shuxiao

2010-02-01

To investigate whether CpG-oligodeoxynucleotide (CpG-ODN) can improve the detection rate of the karyotypic abnormalities in chronic lymphocytic leukemia (CLL). The bone marrow (BM) or peripheral blood (PB) cells from 57 cases of CLL were collected and cultured with CpG-ODN DSP30+interleukin-2 (IL-2), phytohemagglutinin (PHA), pokeweed (PWM) or IL-2, respectively. Five days later cells were harvested for chromosome preparation. Karyotypic analysis was done using R banding technique. Panel fluorescence in situ hybridization (FISH) was carried out on 19 cases of CLL with normal karyotypes using the following probes: Cen12, D13S25, Rb1, ATM, p53, MYB and IgH. Genomic DNA from 21 cases of them was extracted from BM or PB leukocytes. The immunoglobulin variable heavy chain (IgVH) was amplified by polymerase chain reaction (PCR) and sequenced. CD38 and ZAP70 expressions in the leukemic cells were determined by flow cytometry (FCM). The detection rate of karyotypic abnormalities in the CpG-ODN+IL-2 group (43.85%) was obviously higher than that in the PHA (15.09%), PWM (17.31%) and IL-2 (3.13%) groups (P<0.01). Fifty-two types of karyotypic abnormalities were found. Among them, trisomy12 (+12) or +12 with other abnormalities were the most common, while translocations were the most frequent structural abnormalities including 3 unbalanced and 11 balanced translocations, among them 7 had rearrangements involving 14q32. Thirteen cases showed one or more abnormalities on FISH including trisomy 12 and p53 deletion each in one case, IgH rearrangement and partial deletion each in one case, 13q14.3 deletion in 11 cases of which 5 cases also had Rb1 deletion, 1 case had Rb1 partial deletion. No case with ATM or MYB deletions was found. PCR detected IgVH mutations in 10/21 cases. FCM showed 10/45 cases were CD38 positive, but 35 /45 were CD38 negative, 11/27 cases expressed ZAP70, but 16/27 did not. Among the 26 cases examined for CD38 and ZAP70 expressions simultaneously, 5 cases were CD38+ZAP70+, 13 were CD38-ZAP70-, 6 were CD38-ZAP70+, and 2 were CD38+ZAP70-, respectively. Statistic analysis showed a correlation between complex karyotype and IgVH without mutation, but no association between karyotype and CD38 or ZAP70 expression was observed. CpG-ODN immunostimulation can obviously raise the detection rate of abnormal karyotypes, especially translocations in CLL. FISH is an important complement to conventional karyotypic analysis. The combination of both methods can provide more comprehensive genetic information for CLL.

The hydration structure at yttria-stabilized cubic zirconia (110)-water interface with sub-Ångström resolution

DOE PAGES

Hou, Binyang; Kim, Seunghyun; Kim, Taeho; ...

2016-06-15

The interfacial hydration structure of yttria-stabilized cubic zirconia (110) surface in contact with water was determined with ~0.5 Å resolution by high-resolution X-ray reflectivity measurement. The terminal layer shows a reduced electron density compared to the following substrate lattice layers, which indicates there are additional defects generated by metal depletion as well as intrinsic oxygen vacancies, both of which are apparently filled by water species. Above this top surface layer, two additional adsorbed layers are observed forming a characteristic interfacial hydration structure. The first adsorbed layer shows abnormally high density as pure water and likely includes metal species, whereas themore » second layer consists of pure water. The observed interfacial hydration structure seems responsible for local equilibration of the defective surface in water and eventually regulating the long-term degradation processes. As a result, the multitude of water interactions with the zirconia surface results in the complex but highly ordered interfacial structure constituting the reaction front.« less

A Systematic Review and Meta-analysis of Neuroimaging in Oppositional Defiant Disorder (ODD) and Conduct Disorder (CD) Taking Attention-Deficit Hyperactivity Disorder (ADHD) Into Account.

PubMed

Noordermeer, Siri D S; Luman, Marjolein; Oosterlaan, Jaap

2016-03-01

Oppositional defiant disorder (ODD) and conduct disorder (CD) are common behavioural disorders in childhood and adolescence and are associated with brain abnormalities. This systematic review and meta-analysis investigates structural (sMRI) and functional MRI (fMRI) findings in individuals with ODD/CD with and without attention-deficit hyperactivity disorder (ADHD). Online databases were searched for controlled studies, resulting in 12 sMRI and 17 fMRI studies. In line with current models on ODD/CD, studies were classified in hot and cool executive functioning (EF). Both the meta-analytic and narrative reviews showed evidence of smaller brain structures and lower brain activity in individuals with ODD/CD in mainly hot EF-related areas: bilateral amygdala, bilateral insula, right striatum, left medial/superior frontal gyrus, and left precuneus. Evidence was present in both structural and functional studies, and irrespective of the presence of ADHD comorbidity. There is strong evidence that abnormalities in the amygdala are specific for ODD/CD as compared to ADHD, and correlational studies further support the association between abnormalities in the amygdala and ODD/CD symptoms. Besides the left precuneus, there was no evidence for abnormalities in typical cool EF related structures, such as the cerebellum and dorsolateral prefrontal cortex. Resulting areas are associated with emotion-processing, error-monitoring, problem-solving and self-control; areas associated with neurocognitive and behavioural deficits implicated in ODD/CD. Our findings confirm the involvement of hot, and to a smaller extent cool, EF associated brain areas in ODD/CD, and support an integrated model for ODD/CD (e.g. Blair, Development and Psychopathology, 17(3), 865-891, 2005).

Orbitofrontal volumes in early adolescence predict initiation of cannabis use: a 4-year longitudinal and prospective study.

PubMed

Cheetham, Ali; Allen, Nicholas B; Whittle, Sarah; Simmons, Julian G; Yücel, Murat; Lubman, Dan I

2012-04-15

There is growing evidence that long-term, heavy cannabis use is associated with alterations in regional brain volumes. Although these changes are frequently attributed to the neurotoxic effects of cannabis, it is possible that some abnormalities might predate use and represent markers of vulnerability. To date, no studies have examined whether structural brain abnormalities are present before the onset of cannabis use. This study aims to determine whether adolescents who have initiated cannabis use early (i.e., before age 17 years) show premorbid structural abnormalities in the amygdala, hippocampus, orbitofrontal cortex, and anterior cingulate cortex. Participants (n = 121) were recruited from primary schools in Melbourne, Australia, as part of a larger study examining adolescent emotional development. Participants underwent structural magnetic resonance imaging at age 12 years and were assessed for cannabis use 4 years later, at age 16 years. At the follow-up assessment, 28 participants had commenced using cannabis (16 female subjects [57%]), and 93 had not (43 female subjects [46%]). Smaller orbitofrontal cortex volumes at age 12 years predicted initiation of cannabis use by age 16 years. The volumes of other regions (amygdala, hippocampus, and anterior cingulate cortex) did not predict later cannabis use. These findings suggest that structural abnormalities in the orbitofrontal cortex might contribute to risk for cannabis exposure. Although the results have important implications for understanding neurobiological predictors of cannabis use, further research is needed to understand their relationship with heavier patterns of use in adulthood as well as later abuse of other substances. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Computer-Aided Classification of Visual Ventilation Patterns in Patients with Chronic Obstructive Pulmonary Disease at Two-Phase Xenon-Enhanced CT

PubMed Central

Yoon, Soon Ho; Jung, Julip; Hong, Helen; Park, Eun Ah; Lee, Chang Hyun; Lee, Youkyung; Jin, Kwang Nam; Choo, Ji Yung; Lee, Nyoung Keun

2014-01-01

Objective To evaluate the technical feasibility, performance, and interobserver agreement of a computer-aided classification (CAC) system for regional ventilation at two-phase xenon-enhanced CT in patients with chronic obstructive pulmonary disease (COPD). Materials and Methods Thirty-eight patients with COPD underwent two-phase xenon ventilation CT with resulting wash-in (WI) and wash-out (WO) xenon images. The regional ventilation in structural abnormalities was visually categorized into four patterns by consensus of two experienced radiologists who compared the xenon attenuation of structural abnormalities with that of adjacent normal parenchyma in the WI and WO images, and it served as the reference. Two series of image datasets of structural abnormalities were randomly extracted for optimization and validation. The proportion of agreement on a per-lesion basis and receiver operating characteristics on a per-pixel basis between CAC and reference were analyzed for optimization. Thereafter, six readers independently categorized the regional ventilation in structural abnormalities in the validation set without and with a CAC map. Interobserver agreement was also compared between assessments without and with CAC maps using multirater κ statistics. Results Computer-aided classification maps were successfully generated in 31 patients (81.5%). The proportion of agreement and the average area under the curve of optimized CAC maps were 94% (75/80) and 0.994, respectively. Multirater κ value was improved from moderate (κ = 0.59; 95% confidence interval [CI], 0.56-0.62) at the initial assessment to excellent (κ = 0.82; 95% CI, 0.79-0.85) with the CAC map. Conclusion Our proposed CAC system demonstrated the potential for regional ventilation pattern analysis and enhanced interobserver agreement on visual classification of regional ventilation. PMID:24843245

Computer-aided classification of visual ventilation patterns in patients with chronic obstructive pulmonary disease at two-phase xenon-enhanced CT.

PubMed

Yoon, Soon Ho; Goo, Jin Mo; Jung, Julip; Hong, Helen; Park, Eun Ah; Lee, Chang Hyun; Lee, Youkyung; Jin, Kwang Nam; Choo, Ji Yung; Lee, Nyoung Keun

2014-01-01

To evaluate the technical feasibility, performance, and interobserver agreement of a computer-aided classification (CAC) system for regional ventilation at two-phase xenon-enhanced CT in patients with chronic obstructive pulmonary disease (COPD). Thirty-eight patients with COPD underwent two-phase xenon ventilation CT with resulting wash-in (WI) and wash-out (WO) xenon images. The regional ventilation in structural abnormalities was visually categorized into four patterns by consensus of two experienced radiologists who compared the xenon attenuation of structural abnormalities with that of adjacent normal parenchyma in the WI and WO images, and it served as the reference. Two series of image datasets of structural abnormalities were randomly extracted for optimization and validation. The proportion of agreement on a per-lesion basis and receiver operating characteristics on a per-pixel basis between CAC and reference were analyzed for optimization. Thereafter, six readers independently categorized the regional ventilation in structural abnormalities in the validation set without and with a CAC map. Interobserver agreement was also compared between assessments without and with CAC maps using multirater κ statistics. Computer-aided classification maps were successfully generated in 31 patients (81.5%). The proportion of agreement and the average area under the curve of optimized CAC maps were 94% (75/80) and 0.994, respectively. Multirater κ value was improved from moderate (κ = 0.59; 95% confidence interval [CI], 0.56-0.62) at the initial assessment to excellent (κ = 0.82; 95% CI, 0.79-0.85) with the CAC map. Our proposed CAC system demonstrated the potential for regional ventilation pattern analysis and enhanced interobserver agreement on visual classification of regional ventilation.

Indirect gonioscopy system for imaging iridocorneal angle of eye

NASA Astrophysics Data System (ADS)

Perinchery, Sandeep M.; Fu, Chan Yiu; Baskaran, Mani; Aung, Tin; Murukeshan, V. M.

2017-08-01

Current clinical optical imaging systems do not provide sufficient structural information of trabecular meshwork (TM) in the iridocorneal angle (ICA) of the eye due to their low resolution. Increase in the intraocular pressure (IOP) can occur due to the abnormalities in TM, which could subsequently lead to glaucoma. Here, we present an indirect gonioscopy based imaging probe with significantly improved visualization of structures in the ICA including TM region, compared to the currently available tools. Imaging quality of the developed system was tested in porcine samples. Improved direct high quality visualization of the TM region through this system can be used for Laser trabeculoplasty, which is a primary treatment of glaucoma. This system is expected to be used complementary to angle photography and gonioscopy.

Anterior lens epithelium in cataract patients with retinitis pigmentosa - scanning and transmission electron microscopy study.

PubMed

Andjelic, Sofija; Drašlar, Kazimir; Hvala, Anastazija; Hawlina, Marko

2017-05-01

In retinitis pigmentosa (RP) patients, relatively minor lens opacity in central part of posterior pole of the lens may cause disproportionate functional symptoms requiring cataract operation. To investigate the possible structural reasons for this opacity development, we studied the structure of the lens epithelium of patients with RP. The anterior lens capsule (aLC: basement membrane and associated lens epithelial cells, LECs) was obtained from cataract surgery and prepared for scanning and transmission electron microscopy (SEM and TEM). Both SEM and TEM show a number of abnormal features in the anterior lens epithelium of cataract patients with RP. The abnormalities appear mainly as holes, thinning and degradation of the epithelium, with the dimensions from <1 μm to more than 50 μm. Other types of holes in size up to 20 μm were seen that may be formed by gradual stretching of the lens epithelium. Another type of abnormalities was cracks that were seen between adjacent LECs, with dimensions 0.1-2 μm × up to 10 μm. Abnormal structural features were observed in the anterior lens epithelium that may cause water influx into the lens. This may lead to clouding along the water clefts leading towards the posterior pole in the RP cataractous lens. We suggest that the lens epithelium has a role in the development of the cataract in patients with RP. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Generalized epilepsy syndromes and callosal thickness: Differential effects between patients with juvenile myoclonic epilepsy and those with generalized tonic-clonic seizures alone.

PubMed

Anastasopoulou, Stavroula; Kurth, Florian; Luders, Eileen; Savic, Ivanka

2017-01-01

The definition of two well-studied genetic generalized epilepsy syndromes (GGE) - juvenile myoclonic epilepsy (JME) and epilepsy with generalized tonic-clonic seizures alone (GTCS) - suggests the absence of structural cerebral abnormalities. Nevertheless, there are various reports of such abnormalities (especially in JME), where effects mainly occur within thalamus and mesial prefrontal regions. This raises the question of whether JME is particularly linked to midline structure abnormalities, which may also involve the corpus callosum. We studied callosal morphology in a well-matched sample of 22 JME patients, 15 GTCS patients, and 42 controls (CTL) for all of whom we obtained T1-weighted data on a 3T MRI scanner. More specifically, we measured callosal thickness at 100 equidistant points across the callosal surface, and subsequently compared the three groups (JME, GTCS, and CTL) against each other. Significant differences between JME patients and controls were observed within the callosal genu, anterior midbody, and isthmus, with thinner regions in JME patients. There were no significant differences between GTCS patients and controls, and also not between JME patients and GTCS patients. The present outcomes point to callosal abnormalities in JME patients suggesting an impairment of interhemisperic communication between prefrontal, motor, parietal and temporal cortices. These findings further support the notion that structural aberrations are present and differentiated across GGE syndromes, with significant callosal deviations from normality in JME. Copyright © 2016 Elsevier B.V. All rights reserved.

A critical role of solute carrier 22a14 in sperm motility and male fertility in mice

PubMed Central

Maruyama, Shin-ya; Ito, Momoe; Ikami, Yuusuke; Okitsu, Yu; Ito, Chizuru; Toshimori, Kiyotaka; Fujii, Wataru; Yogo, Keiichiro

2016-01-01

We previously identified solute carrier 22a14 (Slc22a14) as a spermatogenesis-associated transmembrane protein in mice. Although Slc22a14 is a member of the organic anion/cation transporter family, its expression profile and physiological role have not been elucidated. Here, we show that Slc22a14 is crucial for sperm motility and male fertility in mice. Slc22a14 is expressed specifically in male germ cells, and mice lacking the Slc22a14 gene show severe male infertility. Although the overall differentiation of sperm was normal, Slc22a14−/− cauda epididymal spermatozoa showed reduced motility with abnormal flagellar bending. Further, the ability to migrate into the female reproductive tract and fertilise the oocyte were also impaired in Slc22a14−/− spermatozoa. The abnormal flagellar bending was thought to be partly caused by osmotic cell swelling since osmotic challenge or membrane permeabilisation treatment alleviated the tail abnormality. In addition, we found structural abnormalities in Slc22a14−/− sperm cells: the annulus, a ring-like structure at the mid-piece–principal piece junction, was disorganised, and expression and localisation of septin 4, an annulus component protein that is essential for the annulus formation, was also impaired. Taken together, our results demonstrated that Slc22a14 plays a pivotal role in normal flagellar structure, motility and fertility in mouse spermatozoa. PMID:27811987

Achondroplasia-hypochondroplasia complex and abnormal pulmonary anatomy.

PubMed

Bober, Michael B; Taylor, Megan; Heinle, Robert; Mackenzie, William

2012-09-01

Achondroplasia and hypochondroplasia are two of the most common forms of skeletal dysplasia. They are both caused by activating mutations in FGFR3 and are inherited in an autosomal dominant manner. Our patient was born to parents with presumed achondroplasia, and found on prenatal testing to have p.G380R and p.N540K FGFR3 mutations. In addition to having typical problems associated with both achondroplasia and hypochondroplasia, our patient had several atypical findings including: abnormal lobulation of the lungs with respiratory insufficiency, C1 stenosis, and hypoglycemia following a Nissen fundoplication. After his reflux and aspiration were treated, the persistence of the tachypnea and increased respiratory effort indicated this was not the primary source of the respiratory distress. Our subsequent hypothesis was that primary restrictive lung disease was the cause of his respiratory distress. A closer examination of his chest circumference did not support this conclusion either. Following his death, an autopsy found the right lung had 2 lobes while the left lung had 3 lobes. A literature review demonstrates that other children with achondroplasia-hypochondroplasia complex have been described with abnormal pulmonary function and infants with thanatophoric dysplasia have similar abnormal pulmonary anatomy. We hypothesize that there may be a primary pulmonary phenotype associated with FGFR3-opathies, unrelated to chest size which leads to the consistent finding of increased respiratory signs and symptoms in these children. Further observation of respiratory status, combined with the macroscopic and microscopic analysis of pulmonary branching anatomy and alveolar structure in this patient population will be important to explore this hypothesis. Copyright © 2012 Wiley Periodicals, Inc.

Complex Anatomic Abnormalities of the Lower Leg Muscles and Tendons Associated With Phocomelia: A Case Report.

PubMed

Hodo, Thomas; Hamrick, Mark; Melenevsky, Yulia

Musculoskeletal anatomy is widely known to have components that stray from the norm in the form of variant muscle and tendon presence, absence, origin, insertion, and bifurcation. Although these variant muscles and tendons might be deemed incidental and insignificant findings by most, they can be important contributors to pathologic physiology or, more importantly, an option for effective treatment. In the present case report, we describe a patient with phocomelia and Müllerian abnormalities secondary to in utero thalidomide exposure. The patient had experienced recurrent bilateral foot pain accompanied by numbness, stiffness, swelling, and longstanding pes planus. These symptoms persisted despite conservative treatment with orthotics, steroids, and nonsteroidal anti-inflammatory drugs. Radiographic imaging showed dysmorphic and degenerative changes of the ankle and foot joints. Further investigation with magnetic resonance imaging revealed complex anatomic abnormalities, including the absence of the posterior tibialis and peroneus brevis, lateralization of the peroneus longus, and the presence of a variant anterior compartment muscle. The variant structure was likely a previously described anterior compartment variant, anterior fibulocalcaneus, and might have been a source of the recurrent pain. Also, the absence of the posterior tibialis might have caused the pes planus in the present patient, considering that posterior tibialis tendon dysfunction is the most common cause of acquired pes planus. Although thalidomide infrequently affects the lower extremities, its effects on growth and development were likely the cause of this rare array of anatomic abnormalities and resulting ankle and foot pathologic features. Copyright © 2017 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Conceptualizing neurodevelopmental disorders through a mechanistic understanding of fragile X syndrome and Williams syndrome

PubMed Central

Fung, Lawrence K.; Quintin, Eve-Marie; Haas, Brian W.

2013-01-01

Purpose of review The overarching goal of this review is to compare and contrast the cognitive-behavioral features of fragile X syndrome (FraX) and Williams syndrome and to review the putative neural and molecular underpinnings of these features. Information is presented in a framework that provides guiding principles for conceptualizing gene-brain-behavior associations in neurodevelopmental disorders. Recent findings Abnormalities, in particular cognitive-behavioral domains with similarities in underlying neurodevelopmental correlates, occur in both FraX and Williams syndrome including aberrant frontostriatal pathways leading to executive function deficits, and magnocellular/dorsal visual stream, superior parietal lobe, inferior parietal lobe, and postcentral gyrus abnormalities contributing to deficits in visuospatial function. Compelling cognitive–behavioral and neurodevelopmental contrasts also exist in these two disorders, for example, aberrant amygdala and fusiform cortex structure and function occurring in the context of contrasting social behavioral phenotypes, and temporal cortical and cerebellar abnormalities potentially underlying differences in language function. Abnormal dendritic development is a shared neurodevelopmental morphologic feature between FraX and Williams syndrome. Commonalities in molecular machinery and processes across FraX and Williams syndrome occur as well – microRNAs involved in translational regulation of major synaptic proteins; scaffolding proteins in excitatory synapses; and proteins involved in axonal development. Summary Although the genetic variations leading to FraX and Williams syndrome are different, important similarities and contrasts in the phenotype, neurocircuitry, molecular machinery, and cellular processes in these two disorders allow for a unique approach to conceptualizing gene–brain–behavior links occurring in neurodevelopmental disorders. PMID:22395002

Intact anger recognition in depression despite aberrant visual facial information usage.

PubMed

Clark, Cameron M; Chiu, Carina G; Diaz, Ruth L; Goghari, Vina M

2014-08-01

Previous literature has indicated abnormalities in facial emotion recognition abilities, as well as deficits in basic visual processes in major depression. However, the literature is unclear on a number of important factors including whether or not these abnormalities represent deficient or enhanced emotion recognition abilities compared to control populations, and the degree to which basic visual deficits might impact this process. The present study investigated emotion recognition abilities for angry versus neutral facial expressions in a sample of undergraduate students with Beck Depression Inventory-II (BDI-II) scores indicative of moderate depression (i.e., ≥20), compared to matched low-BDI-II score (i.e., ≤2) controls via the Bubbles Facial Emotion Perception Task. Results indicated unimpaired behavioural performance in discriminating angry from neutral expressions in the high depressive symptoms group relative to the minimal depressive symptoms group, despite evidence of an abnormal pattern of visual facial information usage. The generalizability of the current findings is limited by the highly structured nature of the facial emotion recognition task used, as well as the use of an analog sample undergraduates scoring high in self-rated symptoms of depression rather than a clinical sample. Our findings suggest that basic visual processes are involved in emotion recognition abnormalities in depression, demonstrating consistency with the emotion recognition literature in other psychopathologies (e.g., schizophrenia, autism, social anxiety). Future research should seek to replicate these findings in clinical populations with major depression, and assess the association between aberrant face gaze behaviours and symptom severity and social functioning. Copyright © 2014 Elsevier B.V. All rights reserved.

Podocyte Depletion in Thin GBM and Alport Syndrome.

PubMed

Wickman, Larysa; Hodgin, Jeffrey B; Wang, Su Q; Afshinnia, Farsad; Kershaw, David; Wiggins, Roger C

2016-01-01

The proximate genetic cause of both Thin GBM and Alport Syndrome (AS) is abnormal α3, 4 and 5 collagen IV chains resulting in abnormal glomerular basement membrane (GBM) structure/function. We previously reported that podocyte detachment rate measured in urine is increased in AS, suggesting that podocyte depletion could play a role in causing progressive loss of kidney function. To test this hypothesis podometric parameters were measured in 26 kidney biopsies from 21 patients aged 2-17 years with a clinic-pathologic diagnosis including both classic Alport Syndrome with thin and thick GBM segments and lamellated lamina densa [n = 15] and Thin GBM cases [n = 6]. Protocol biopsies from deceased donor kidneys were used as age-matched controls. Podocyte depletion was present in AS biopsies prior to detectable histologic abnormalities. No abnormality was detected by light microscopy at <30% podocyte depletion, minor pathologic changes (mesangial expansion and adhesions to Bowman's capsule) were present at 30-50% podocyte depletion, and FSGS was progressively present above 50% podocyte depletion. eGFR did not change measurably until >70% podocyte depletion. Low level proteinuria was an early event at about 25% podocyte depletion and increased in proportion to podocyte depletion. These quantitative data parallel those from model systems where podocyte depletion is the causative event. This result supports a hypothesis that in AS podocyte adherence to the GBM is defective resulting in accelerated podocyte detachment causing progressive podocyte depletion leading to FSGS-like pathologic changes and eventual End Stage Kidney Disease. Early intervention to reduce podocyte depletion is projected to prolong kidney survival in AS.

Functional connectivity abnormalities and associated cognitive deficits in fetal alcohol Spectrum disorders (FASD).

PubMed

Wozniak, Jeffrey R; Mueller, Bryon A; Mattson, Sarah N; Coles, Claire D; Kable, Julie A; Jones, Kenneth L; Boys, Christopher J; Lim, Kelvin O; Riley, Edward P; Sowell, Elizabeth R

2017-10-01

Consistent with well-documented structural and microstructural abnormalities in prenatal alcohol exposure (PAE), recent studies suggest that functional connectivity (FC) may also be disrupted. We evaluated whole-brain FC in a large multi-site sample, examined its cognitive correlates, and explored its potential to objectively identify neurodevelopmental abnormality in individuals without definitive dysmorphic features. Included were 75 children with PAE and 68 controls from four sites. All participants had documented heavy prenatal alcohol exposure. All underwent a formal evaluation of physical anomalies and dysmorphic facial features. MRI data were collected using modified matched protocols on three platforms (Siemens, GE, and Philips). Resting-state FC was examined using whole-brain graph theory metrics to characterize each individual's connectivity. Although whole-brain FC metrics did not discriminate prenatally-exposed from unexposed overall, atypical FC (> 1 standard deviation from the grand mean) was significantly more common (2.7 times) in the PAE group vs. In a subset of 55 individuals (PAE and controls) whose dysmorphology examination could not definitively characterize them as either Fetal Alcohol Syndrome (FAS) or non-FAS, atypical FC was seen in 27 % of the PAE group, but 0 % of controls. Across participants, a 1 % difference in local network efficiency was associated with a 36 point difference in global cognitive functioning. Whole-brain FC metrics have potential to identify individuals with objective neurodevelopmental abnormalities from prenatal alcohol exposure. When applied to individuals unable to be classified as FAS or non-FAS from dysmorphology alone, these measures separate prenatally-exposed from non-exposed with high specificity.

Brain growth across the life span in autism: age-specific changes in anatomical pathology.

PubMed

Courchesne, Eric; Campbell, Kathleen; Solso, Stephanie

2011-03-22

Autism is marked by overgrowth of the brain at the earliest ages but not at older ages when decreases in structural volumes and neuron numbers are observed instead. This has led to the theory of age-specific anatomic abnormalities in autism. Here we report age-related changes in brain size in autistic and typical subjects from 12 months to 50 years of age based on analyses of 586 longitudinal and cross-sectional MRI scans. This dataset is several times larger than the largest autism study to date. Results demonstrate early brain overgrowth during infancy and the toddler years in autistic boys and girls, followed by an accelerated rate of decline in size and perhaps degeneration from adolescence to late middle age in this disorder. We theorize that underlying these age-specific changes in anatomic abnormalities in autism, there may also be age-specific changes in gene expression, molecular, synaptic, cellular, and circuit abnormalities. A peak age for detecting and studying the earliest fundamental biological underpinnings of autism is prenatal life and the first three postnatal years. Studies of the older autistic brain may not address original causes but are essential to discovering how best to help the older aging autistic person. Lastly, the theory of age-specific anatomic abnormalities in autism has broad implications for a wide range of work on the disorder including the design, validation, and interpretation of animal model, lymphocyte gene expression, brain gene expression, and genotype/CNV-anatomic phenotype studies. Copyright © 2010 Elsevier B.V. All rights reserved.

Cardiac abnormalities in patients with mitochondrial DNA mutation 3243A>G.

PubMed

Majamaa-Voltti, Kirsi; Peuhkurinen, Keijo; Kortelainen, Marja-Leena; Hassinen, Ilmo E; Majamaa, Kari

2002-08-01

Tissues that depend on aerobic energy metabolism suffer most in diseases caused by mutations in mitochondrial DNA (mtDNA). Cardiac abnormalities have been described in many cases, but their frequency and clinical spectrum among patients with mtDNA mutations is unknown. Thirty-nine patients with the 3243A>G mtDNA mutation were examined, methods used included clinical evaluation, electrocardiogram, Holter recording and echocardiography. Autopsy reports on 17 deceased subjects were also reviewed. The degree of 3243A>G mutation heteroplasmy was determined using an Apa I restriction fragment analysis. Better hearing level (BEHL0.5-4 kHz) was used as a measure of the clinical severity of disease. Left ventricular hypertrophy (LVH) was diagnosed in 19 patients (56%) by echocardiography and in six controls (15%) giving an odds ratio of 7.5 (95% confidence interval; 1.74-67). The dimensions of the left ventricle suggested a concentric hypertrophy. Left ventricular systolic or diastolic dysfunction was observed in 11 patients. Holter recording revealed frequent ventricular extrasystoles (>10/h) in five patients. Patients with LVH differed significantly from those without LVH in BEHL0.5-4 kHz, whereas the contribution of age or the degree of the mutant heteroplasmy in skeletal muscle to the risk of LVH was less remarkable. Structural and functional abnormalities of the heart were common in patients with 3243A>G. The risk of LVH was related to the clinical severity of the phenotype, and to a lesser degree to age, suggesting that patients presenting with any symptoms from the mutation should also be evaluated for cardiac abnormalities.

Population-based prevalence of abnormal cervical cytology findings and local risk factors in Ibadan, Nigeria: implications for cervical cancer control programs and human papilloma virus immunization.

PubMed

Thomas, J O; Ojemakinde, K O; Ajayi, I O; Omigbodun, A O; Fawole, O I; Oladepo, O

2012-01-01

To investigate the prevalence of abnormal cervical cytological findings and local risk factors in Ibadan, Nigeria. All women aged ≥15 years in each household in Idikan, Ibadan, were invited to participate in a population-based study. Structured questionnaires were administered to all consenting women. Conventional cervical Papanicolaou smears obtained from sexually active women were classified using the 2001 Bethesda system. The diagnoses were correlated with sociodemographic data and risk factors. Of 2,870 women aged ≥15 years estimated to live in Idikan, 1,204 sexually active women consented to pelvic examination and cervical smears. Results were available for 1,104 women (mean age: 39.8 years). Mean ages at menarche, first sexual intercourse and first pregnancy were 16.1, 20.3 and 20.7 years, respectively. Cytological results were categorized into atypical squamous cells of undetermined significance and atypical glandular cells 22 (1.99%); low-grade 43 (3.89%) and high-grade squamous intraepithelial lesions (HSIL) 17 (1.54%); invasive cancer 2 (0.18%) and normal 593 (53.8%) and reactive changes 427 (38.7%). The prevalence of epithelial abnormalities is 7.6%. Significant host-related factors in those with HSIL and invasive cancer included older age (mean 56.2 years), high parity and gravidity, lack of formal education and being divorced (p < 0.05). This study provides prevalence data and local risk factors for abnormal cervical cytology in a Nigerian population, which will be useful for planning future cervical cancer control programs. Copyright © 2012 S. Karger AG, Basel.