Abnormal pulmonary function in adults with sickle cell anemia.

PubMed

Klings, Elizabeth S; Wyszynski, Diego F; Nolan, Vikki G; Steinberg, Martin H

2006-06-01

Pulmonary complications of sickle cell anemia (Hb-SS) commonly cause morbidity, yet few large studies of pulmonary function tests (PFTs) in this population have been reported. PFTs (spirometry, lung volumes, and diffusion capacity for carbon monoxide [DLCO]) from 310 adults with Hb-SS were analyzed to determine the pattern of pulmonary dysfunction and their association with other systemic complications of sickle cell disease. Raw PFT data were compared with predicted values. Each subject was subclassified into one of five groups: obstructive physiology, restrictive physiology, mixed obstructive/restrictive physiology, isolated low DLCO, or normal. The association between laboratory data of patients with decreased DLCO or restrictive physiology and those of normal subjects was assessed by multivariate linear regression. Normal PFTs were present in only 31 of 310 (10%) patients. Overall, adults with Hb-SS were characterized by decreased total lung capacities (70.2 +/- 14.7% predicted) and DLCO (64.5 +/- 19.9%). The most common PFT patterns were restrictive physiology (74%) and isolated low DLCO (13%). Decreased DLCO was associated with thrombocytosis (p = 0.05), with hepatic dysfunction (elevated alanine aminotransferase; p = 0.07), and a trend toward renal dysfunction (elevated blood urea nitrogen and creatinine; p = 0.05 and 0.07, respectively). Pulmonary function is abnormal in 90% of adult patients with Hb-SS. Common abnormalities include restrictive physiology and decreased DLCO. Decreased DLCO may indicate more severe sickle vasculopathy characterized by impaired hepatic and renal function.

Sleep Deprivation Reveals Altered Brain Perfusion Patterns in Somnambulism

PubMed Central

Dang-Vu, Thien Thanh; Zadra, Antonio; Labelle, Marc-Antoine; Petit, Dominique; Soucy, Jean-Paul; Montplaisir, Jacques

2015-01-01

Background Despite its high prevalence, relatively little is known about the pathophysiology of somnambulism. Increasing evidence indicates that somnambulism is associated with functional abnormalities during wakefulness and that sleep deprivation constitutes an important drive that facilitates sleepwalking in predisposed patients. Here, we studied the neural mechanisms associated with somnambulism using Single Photon Emission Computed Tomography (SPECT) with 99mTc-Ethylene Cysteinate Dimer (ECD), during wakefulness and after sleep deprivation. Methods Ten adult sleepwalkers and twelve controls with normal sleep were scanned using 99mTc-ECD SPECT in morning wakefulness after a full night of sleep. Eight of the sleepwalkers and nine of the controls were also scanned during wakefulness after a night of total sleep deprivation. Between-group comparisons of regional cerebral blood flow (rCBF) were performed to characterize brain activity patterns during wakefulness in sleepwalkers. Results During wakefulness following a night of total sleep deprivation, rCBF was decreased bilaterally in the inferior temporal gyrus in sleepwalkers compared to controls. Conclusions Functional neural abnormalities can be observed during wakefulness in somnambulism, particularly after sleep deprivation and in the inferior temporal cortex. Sleep deprivation thus not only facilitates the occurrence of sleepwalking episodes, but also uncovers patterns of neural dysfunction that characterize sleepwalkers during wakefulness. PMID:26241047

Arterial spin labelling reveals an abnormal cerebral perfusion pattern in Parkinson's disease.

PubMed

Melzer, Tracy R; Watts, Richard; MacAskill, Michael R; Pearson, John F; Rüeger, Sina; Pitcher, Toni L; Livingston, Leslie; Graham, Charlotte; Keenan, Ross; Shankaranarayanan, Ajit; Alsop, David C; Dalrymple-Alford, John C; Anderson, Tim J

2011-03-01

There is a need for objective imaging markers of Parkinson's disease status and progression. Positron emission tomography and single photon emission computed tomography studies have suggested patterns of abnormal cerebral perfusion in Parkinson's disease as potential functional biomarkers. This study aimed to identify an arterial spin labelling magnetic resonance-derived perfusion network as an accessible, non-invasive alternative. We used pseudo-continuous arterial spin labelling to measure cerebral grey matter perfusion in 61 subjects with Parkinson's disease with a range of motor and cognitive impairment, including patients with dementia and 29 age- and sex-matched controls. Principal component analysis was used to derive a Parkinson's disease-related perfusion network via logistic regression. Region of interest analysis of absolute perfusion values revealed that the Parkinson's disease pattern was characterized by decreased perfusion in posterior parieto-occipital cortex, precuneus and cuneus, and middle frontal gyri compared with healthy controls. Perfusion was preserved in globus pallidus, putamen, anterior cingulate and post- and pre-central gyri. Both motor and cognitive statuses were significant factors related to network score. A network approach, supported by arterial spin labelling-derived absolute perfusion values may provide a readily accessible neuroimaging method to characterize and track progression of both motor and cognitive status in Parkinson's disease.

Abnormalities of keratinocyte maturation and differentiation in keratosis palmoplantaris striata. Immunohistochemical and ultrastructural study before and during etretinate therapy.

PubMed

Fartasch, M; Vigneswaran, N; Diepgen, T L; Hornstein, O P

1990-06-01

Keratoderma striatum (Brünauer-Fuhs type) with linear keratotic elevations on the palms and small islets (areata form) on the soles is a rare form of palmoplantar keratoderma (PPK). An immunohistochemical and ultrastructural study has been performed to characterize the altered keratinization and maturation patterns in this disease before and during complete clinical remission on therapy with etretinate. Anticytokeratin antibody KL1 showed no significant difference in reaction pattern either between healthy controls and PPK or following therapy. Earlier expression of both filaggrin and involucrin was found in PPK in comparison with the controls. During etretinate therapy the filaggrin pattern returned to normal, whereas the altered involucrin pattern was not influenced. Ultrastructural investigations before treatment revealed tightly packed tonofibrils (TF) and large masses of keratohyalin (KH) granules with abnormal configuration. During therapy the TF and KH granules were reduced in number and size. KH granules now showed frayed borders. Moreover, a transitional cell zone, focal parakeratosis with lipid droplets, and dyskeratotic cells became apparent. The normalization of filaggrin pattern accompanying the clinical remission of these lesions implies a role of this keratinocyte differentiation protein in the pathogenesis of these lesions. Since etretinate is assumed to act at a very late stage of epidermal differentiation, there was no influence on the altered expression of involucrin during etretinate therapy. Despite the clinical remission, fine structural abnormalities persisted, indicating that the deviations from the normal keratinocyte differentiation program in PKK occur very early.

Predictive factors for the occurrence of idiopathic menorrhagia: evidence for a hereditary trait.

PubMed

Kuzmina, Natalia; Palmblad, Jan; Mints, Miriam

2011-01-01

The aim of the present study was to assess predictive factors for occurrence of idiopathic menorrhagia (IM), a disease characterized by abnormal endometrial blood vessel morphology. It was hypothesized that IM exhibits familial clustering (suggesting inheritance) and is associated with other vascular abnormalities, primarily cutaneous hemangiomas. Women with IM (n=152) and healthy, regularly menstruating (n=56) women answered a questionnaire concerning menstrual pattern, susceptibility to bleeding and family history of abnormal gynecological bleeding. Factor analysis with principal component extraction was used to separate predictive factors that may be associated with IM. A total of 35 different items were analyzed. A strong association was found between IM and a family history of heavy menstrual bleeding (r=0.68), but not with cutaneous vascular abnormalities. Our results revealed that a family history of heavy menstrual bleeding may have the highest predictive value for the diagnosis of IM, indicating a hereditary trait.

T wave abnormalities, high body mass index, current smoking and high lipoprotein (a) levels predict the development of major abnormal Q/QS patterns 20 years later. A population-based study

PubMed Central

Moller, Christina Strom; Byberg, Liisa; Sundstrom, Johan; Lind, Lars

2006-01-01

Background Most studies on risk factors for development of coronary heart disease (CHD) have been based on the clinical outcome of CHD. Our aim was to identify factors that could predict the development of ECG markers of CHD, such as abnormal Q/QS patterns, ST segment depression and T wave abnormalities, in 70-year-old men, irrespective of clinical outcome. Methods Predictors for development of different ECG abnormalities were identified in a population-based study using stepwise logistic regression. Anthropometrical and metabolic factors, ECG abnormalities and vital signs from a health survey of men at age 50 were related to ECG abnormalities identified in the same cohort 20 years later. Results At the age of 70, 9% had developed a major abnormal Q/QS pattern, but 63% of these subjects had not been previously hospitalized due to MI, while 57% with symptomatic MI between age 50 and 70 had no major Q/QS pattern at age 70. T wave abnormalities (Odds ratio 3.11, 95% CI 1.18–8.17), high lipoprotein (a) levels, high body mass index (BMI) and smoking were identified as significant independent predictors for the development of abnormal major Q/QS patterns. T wave abnormalities and high fasting glucose levels were significant independent predictors for the development of ST segment depression without abnormal Q/QS pattern. Conclusion T wave abnormalities on resting ECG should be given special attention and correlated with clinical information. Risk factors for major Q/QS patterns need not be the same as traditional risk factors for clinically recognized CHD. High lipoprotein (a) levels may be a stronger risk factor for silent myocardial infarction (MI) compared to clinically recognized MI. PMID:16519804

Unravelling the complex MRI pattern in glutaric aciduria type I using statistical models-a cohort study in 180 patients.

PubMed

Garbade, Sven F; Greenberg, Cheryl R; Demirkol, Mübeccel; Gökçay, Gülden; Ribes, Antonia; Campistol, Jaume; Burlina, Alberto B; Burgard, Peter; Kölker, Stefan

2014-09-01

Glutaric aciduria type I (GA-I) is a cerebral organic aciduria caused by inherited deficiency of glutaryl-CoA dehydrogenase and is characterized biochemically by an accumulation of putatively neurotoxic dicarboxylic metabolites. The majority of untreated patients develops a complex movement disorder with predominant dystonia during age 3-36 months. Magnetic resonance imaging (MRI) studies have demonstrated striatal and extrastriatal abnormalities. The major aim of this study was to elucidate the complex neuroradiological pattern of patients with GA-I and to associate the MRI findings with the severity of predominant neurological symptoms. In 180 patients, detailed information about the neurological presentation and brain region-specific MRI abnormalities were obtained via a standardized questionnaire. Patients with a movement disorder had more often MRI abnormalities in putamen, caudate, cortex, ventricles and external CSF spaces than patients without or with minor neurological symptoms. Putaminal MRI changes and strongly dilated ventricles were identified as the most reliable predictors of a movement disorder. In contrast, abnormalities in globus pallidus were not clearly associated with a movement disorder. Caudate and putamen as well as cortex, ventricles and external CSF spaces clearly collocalized on a two-dimensional map demonstrating statistical similarity and suggesting the same underlying pathomechanism. This study demonstrates that complex statistical methods are useful to decipher the age-dependent and region-specific MRI patterns of rare neurometabolic diseases and that these methods are helpful to elucidate the clinical relevance of specific MRI findings.

ACOG Committee Opinion No. 651: Menstruation in Girls and Adolescents: Using the Menstrual Cycle as a Vital Sign.

PubMed

2015-12-01

Despite variations worldwide and within the U.S. population, median age at menarche has remained relatively stable-between 12 years and 13 years-across well-nourished populations in developed countries. Environmental factors, including socioeconomic conditions, nutrition, and access to preventive health care, may influence the timing and progression of puberty. A number of medical conditions can cause abnormal uterine bleeding, characterized by unpredictable timing and variable amount of flow. Clinicians should educate girls and their caretakers (eg, parents or guardians) about what to expect of a first menstrual period and the range for normal cycle length of subsequent menses. Identification of abnormal menstrual patterns in adolescence may improve early identification of potential health concerns for adulthood. It is important for clinicians to have an understanding of the menstrual patterns of adolescent girls, the ability to differentiate between normal and abnormal menstruation, and the skill to know how to evaluate the adolescent girl patient. By including an evaluation of the menstrual cycle as an additional vital sign, clinicians reinforce its importance in assessing overall health status for patients and caretakers.

Accurate means of detecting and characterizing abnormal patterns of ventricular activation by phase image analysis

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

Botvinick, E.H.; Frais, M.A.; Shosa, D.W.

1982-08-01

The ability of scintigraphic phase image analysis to characterize patterns of abnormal ventricular activation was investigated. The pattern of phase distribution and sequential phase changes over both right and left ventricular regions of interest were evaluated in 16 patients with normal electrical activation and wall motion and compared with those in 8 patients with an artificial pacemaker and 4 patients with sinus rhythm with the Wolff-Parkinson-White syndrome and delta waves. Normally, the site of earliest phase angle was seen at the base of the interventricular septum, with sequential change affecting the body of the septum and the cardiac apex andmore » then spreading laterally to involve the body of both ventricles. The site of earliest phase angle was located at the apex of the right ventricle in seven patients with a right ventricular endocardial pacemaker and on the lateral left ventricular wall in one patient with a left ventricular epicardial pacemaker. In each case the site corresponded exactly to the position of the pacing electrode as seen on posteroanterior and left lateral chest X-ray films, and sequential phase changes spread from the initial focus to affect both ventricles. In each of the patients with the Wolff-Parkinson-White syndrome, the site of earliest ventricular phase angle was located, and it corresponded exactly to the site of the bypass tract as determined by endocardial mapping. In this way, four bypass pathways, two posterior left paraseptal, one left lateral and one right lateral, were correctly localized scintigraphically. On the basis of the sequence of mechanical contraction, phase image analysis provides an accurate noninvasive method of detecting abnormal foci of ventricular activation.« less

Parkinson's disease: increased motor network activity in the absence of movement.

PubMed

Ko, Ji Hyun; Mure, Hideo; Tang, Chris C; Ma, Yilong; Dhawan, Vijay; Spetsieris, Phoebe; Eidelberg, David

2013-03-06

We used a network approach to assess systems-level abnormalities in motor activation in humans with Parkinson's disease (PD). This was done by measuring the expression of the normal movement-related activation pattern (NMRP), a previously validated activation network deployed by healthy subjects during motor performance. In this study, NMRP expression was prospectively quantified in (15)O-water PET scans from a PD patient cohort comprised of a longitudinal early-stage group (n = 12) scanned at baseline and at two or three follow-up visits two years apart, and a moderately advanced group scanned on and off treatment with either subthalamic nucleus deep brain stimulation (n = 14) or intravenous levodopa infusion (n = 14). For each subject and condition, we measured NMRP expression during both movement and rest. Resting expression of the abnormal PD-related metabolic covariance pattern was likewise determined in the same subjects. NMRP expression was abnormally elevated (p < 0.001) in PD patients scanned in the nonmovement rest state. By contrast, network activity measured during movement did not differ from normal (p = 0.34). In the longitudinal cohort, abnormal increases in resting NMRP expression were evident at the earliest clinical stages (p < 0.05), which progressed significantly over time (p = 0.003). Analogous network changes were present at baseline in the treatment cohort (p = 0.001). These abnormalities improved with subthalamic nucleus stimulation (p < 0.005) but not levodopa (p = 0.25). In both cohorts, the changes in NMRP expression that were observed did not correlate with concurrent PD-related metabolic covariance pattern measurements (p > 0.22). Thus, the resting state in PD is characterized by changes in the activity of normal as well as pathological brain networks.

Electroencephalographic features of convulsive epilepsy in Africa: A multicentre study of prevalence, pattern and associated factors

PubMed Central

Kariuki, Symon M.; White, Steven; Chengo, Eddie; Wagner, Ryan G.; Ae-Ngibise, Kenneth A.; Kakooza-Mwesige, Angelina; Masanja, Honorati; Ngugi, Anthony K.; Sander, Josemir W.; Neville, Brian G.; Newton, Charles R.

2016-01-01

Objective We investigated the prevalence and pattern of electroencephalographic (EEG) features of epilepsy and the associated factors in Africans with active convulsive epilepsy (ACE). Methods We characterized electroencephalographic features and determined associated factors in a sample of people with ACE in five African sites. Mixed-effects modified Poisson regression model was used to determine factors associated with abnormal EEGs. Results Recordings were performed on 1426 people of whom 751 (53%) had abnormal EEGs, being an adjusted prevalence of 2.7 (95% confidence interval (95% CI), 2.5–2.9) per 1000. 52% of the abnormal EEG had focal features (75% with temporal lobe involvement). The frequency and pattern of changes differed with site. Abnormal EEGs were associated with adverse perinatal events (risk ratio (RR) = 1.19 (95% CI, 1.07–1.33)), cognitive impairments (RR = 1.50 (95% CI, 1.30–1.73)), use of anti-epileptic drugs (RR = 1.25 (95% CI, 1.05–1.49)), focal seizures (RR = 1.09 (95% CI, 1.00–1.19)) and seizure frequency (RR = 1.18 (95% CI, 1.10–1.26) for daily seizures; RR = 1.22 (95% CI, 1.10–1.35) for weekly seizures and RR = 1.15 (95% CI, 1.03–1.28) for monthly seizures)). Conclusions EEG abnormalities are common in Africans with epilepsy and are associated with preventable risk factors. Significance EEG is helpful in identifying focal epilepsy in Africa, where timing of focal aetiologies is problematic and there is a lack of neuroimaging services. PMID:26337840

Is screening for abnormal ECG patterns justified in long-term follow-up of childhood cancer survivors treated with anthracyclines?

PubMed

Pourier, Milanthy S; Mavinkurve-Groothuis, Annelies M C; Loonen, Jacqueline; Bökkerink, Jos P M; Roeleveld, Nel; Beer, Gil; Bellersen, Louise; Kapusta, Livia

2017-03-01

ECG and echocardiography are noninvasive screening tools to detect subclinical cardiotoxicity in childhood cancer survivors (CCSs). Our aims were as follows: (1) assess the prevalence of abnormal ECG patterns, (2) determine the agreement between abnormal ECG patterns and echocardiographic abnormalities; and (3) determine whether ECG screening for subclinical cardiotoxicity in CCSs is justified. We retrospectively studied ECG and echocardiography in asymptomatic CCSs more than 5 years after anthracycline treatment. Exclusion criteria were abnormal ECG and/or echocardiogram at the start of therapy, incomplete follow-up data, clinical heart failure, cardiac medication, and congenital heart disease. ECG abnormalities were classified using the Minnesota Code. Level of agreement between ECG and echocardiography was calculated with Cohen kappa. We included 340 survivors with a mean follow-up of 14.5 years (range 5-32). ECG was abnormal in 73 survivors (21.5%), with ventricular conduction disorders, sinus bradycardia, and high-amplitude R waves being most common. Prolonged QTc (>0.45 msec) was found in two survivors, both with a cumulative anthracycline dose of 300 mg/m 2 or higher. Echocardiography showed abnormalities in 44 survivors (12.9%), mostly mild valvular abnormalities. The level of agreement between ECG and echocardiography was low (kappa 0.09). Male survivors more often had an abnormal ECG (corrected odds ratio: 3.00, 95% confidence interval: 1.68-5.37). Abnormal ECG patterns were present in 21% of asymptomatic long-term CCSs. Lack of agreement between abnormal ECG patterns and echocardiographic abnormalities may suggest that ECG is valuable in long-term follow-up of CCSs. However, it is not clear whether these abnormal ECG patterns will be clinically relevant. © 2016 Wiley Periodicals, Inc.

Abnormal Pulmonary Function in Adults with Sickle Cell Anemia

PubMed Central

Klings, Elizabeth S.; Wyszynski, Diego F.; Nolan, Vikki G.; Steinberg, Martin H.

2006-01-01

Rationale: Pulmonary complications of sickle cell anemia (Hb-SS) commonly cause morbidity, yet few large studies of pulmonary function tests (PFTs) in this population have been reported. Objectives: PFTs (spirometry, lung volumes, and diffusion capacity for carbon monoxide [DLCO]) from 310 adults with Hb-SS were analyzed to determine the pattern of pulmonary dysfunction and their association with other systemic complications of sickle cell disease. Methods: Raw PFT data were compared with predicted values. Each subject was subclassified into one of five groups: obstructive physiology, restrictive physiology, mixed obstructive/restrictive physiology, isolated low DLCO, or normal. The association between laboratory data of patients with decreased DLCO or restrictive physiology and those of normal subjects was assessed by multivariate linear regression. Measurements and Main Results: Normal PFTs were present in only 31 of 310 (10%) patients. Overall, adults with Hb-SS were characterized by decreased total lung capacities (70.2 ± 14.7% predicted) and DlCO (64.5 ± 19.9%). The most common PFT patterns were restrictive physiology (74%) and isolated low DlCO (13%). Decreased DLCO was associated with thrombocytosis (p = 0.05), with hepatic dysfunction (elevated alanine aminotransferase; p = 0.07), and a trend toward renal dysfunction (elevated blood urea nitrogen and creatinine; p = 0.05 and 0.07, respectively). Conclusions: Pulmonary function is abnormal in 90% of adult patients with Hb-SS. Common abnormalities include restrictive physiology and decreased DLCO. Decreased DLCO may indicate more severe sickle vasculopathy characterized by impaired hepatic and renal function. PMID:16556694

[Eating disorders].

PubMed

Miyake, Yoshie; Okamoto, Yuri; Jinnin, Ran; Shishida, Kazuhiro; Okamoto, Yasumasa

2015-02-01

Eating disorders are characterized by aberrant patterns of eating behavior, including such symptoms as extreme restriction of food intake or binge eating, and severe disturbances in the perception of body shape and weight, as well as a drive for thinness and obsessive fears of becoming fat. Eating disorder is an important cause for physical and psychosocial morbidity in young women. Patients with eating disorders have a deficit in the cognitive process and functional abnormalities in the brain system. Recently, brain-imaging techniques have been used to identify specific brain areas that function abnormally in patients with eating disorders. We have discussed the clinical and cognitive aspects of eating disorders and summarized neuroimaging studies of eating disorders.

The Shepherd's Crook Sign: A New Neuroimaging Pareidolia in Joubert Syndrome.

PubMed

Manley, Andrew T; Maertens, Paul M

2015-01-01

By pareidolically recognizing specific patterns indicative of particular diseases, neuroimagers reinforce their mnemonic strategies and improve their neuroimaging diagnostic skills. Joubert Syndrome (JS) is an autosomal recessive disorder characterized clinically by mental retardation, episodes of abnormal deep and rapid breathing, abnormal eye movements, and ataxia. Many neuroimaging signs characteristic of JS have been reported. In retrospective case study, two consanguineous neonates diagnosed with JS were evaluated with brain magnetic resonance imaging (MRI), computed tomography (CT), and neurosonography. Both cranial ultrasound and MRI of the brain showed the characteristic molar tooth sign. There was a shepherd's crook in the sagittal views of the posterior fossa where the shaft of the crook is made by the brainstem and the pons. The arc of the crook is made by the abnormal superior cerebellar peduncle and cerebellar hemisphere. By ultrasound, the shepherd's crook sign was seen through the posterior fontanelle only. CT imaging also showed the shepherd's crook sign. Neuroimaging diagnosis of JS, which already involves the pareidolical recognition of specific patterns indicative of the disease, can be improved by recognition of the shepherd's crook sign on MRI, CT, and cranial ultrasound. Copyright © 2014 by the American Society of Neuroimaging.

Analysis Of Laryngeal Biomechanics Of Deaf Speakers Utilizing High-Speed Cinematography

NASA Astrophysics Data System (ADS)

Metz, Dale E.; Whitehead, Robert L.

1982-02-01

Since the formalization of the myoelastic-aerodynamic theory of vocal fold vibration, it has been generally accepted that biomechanical and aerodynamic forces determine the nature of vocal fold vibration patterns, speaking fundamental frequency and vocal intensity. The speech of the deaf is frequently characterized by abnormal voice qualities and aberrant frequency and intensity variations suggesting mismanagement of the biomechanical and aerodynamic forces acting on the larynx. Unfortunately, efforts to remediate these abnormal laryngeal activities are frequently ineffective. It is reasonable to suggest that more effective remedial strategies could be developed if we had a better understanding of the underlying nature of the problems deaf persons experience when trying to control laryngeal functioning for speech purposes. Toward this end, we are employing high speed laryngeal filming procedures in conjunction with glottal impedance, respiratory kinematic and acous-tical measurement procedures to assess abnormal laryngeal functioning of deaf speakers. All data are collected simultaneously and are time-locked to facilitate analysis of specific laryngeal events. This unique combination of instrumentation has provided important insights regarding laryngeal functioning of the deaf. For example, we have observed that deaf speakers may assume abnormal glottal configurations during phonation that pro-hibit normal laryngeal functioning and disturb upper airway dynamics. Also, normal vibratory patterns are frequently disturbed. Instrumentation, data collection protocols, analysis procedures and selected findings will be discussed.

Identification of abnormal accident patterns at intersections

DOT National Transportation Integrated Search

1999-08-01

This report presents the findings and recommendations based on the Identification of Abnormal Accident Patterns at Intersections. This project used a statistically valid sampling method to determine whether a specific intersection has an abnormally h...

Neuroimaging in pedophilia.

PubMed

Wiebking, Christine; Northoff, Georg

2013-04-01

Paraphilia is a set of disorders characterized by abnormal sexual desires. Perhaps most discussed amongst them, pedophilia is a complex interaction of disturbances of the emotional, cognitive and sexual experience. Using new imaging techniques such as functional magnetic resonance imaging, neural correlates of emotional, sexual and cognitive abnormalities and interactions have been investigated. As described on the basis of current research, altered patterns of brain activity, especially in the frontal areas of the brain, are seen in pedophilia. Building on these results, the analysis of neural correlates of impaired psychological functions opens the opportunity to further explore sexual deviances, which may contribute ultimately to the development of tools for risk assessment, classification methods and new therapeutic approaches.

If the skull fits: magnetic resonance imaging and microcomputed tomography for combined analysis of brain and skull phenotypes in the mouse

PubMed Central

Blank, Marissa C.; Roman, Brian B.; Henkelman, R. Mark; Millen, Kathleen J.

2012-01-01

The mammalian brain and skull develop concurrently in a coordinated manner, consistently producing a brain and skull that fit tightly together. It is common that abnormalities in one are associated with related abnormalities in the other. However, this is not always the case. A complete characterization of the relationship between brain and skull phenotypes is necessary to understand the mechanisms that cause them to be coordinated or divergent and to provide perspective on the potential diagnostic or prognostic significance of brain and skull phenotypes. We demonstrate the combined use of magnetic resonance imaging and microcomputed tomography for analysis of brain and skull phenotypes in the mouse. Co-registration of brain and skull images allows comparison of the relationship between phenotypes in the brain and those in the skull. We observe a close fit between the brain and skull of two genetic mouse models that both show abnormal brain and skull phenotypes. Application of these three-dimensional image analyses in a broader range of mouse mutants will provide a map of the relationships between brain and skull phenotypes generally and allow characterization of patterns of similarities and differences. PMID:22947655

Dynamic Resting-State Functional Connectivity in Major Depression.

PubMed

Kaiser, Roselinde H; Whitfield-Gabrieli, Susan; Dillon, Daniel G; Goer, Franziska; Beltzer, Miranda; Minkel, Jared; Smoski, Moria; Dichter, Gabriel; Pizzagalli, Diego A

2016-06-01

Major depressive disorder (MDD) is characterized by abnormal resting-state functional connectivity (RSFC), especially in medial prefrontal cortical (MPFC) regions of the default network. However, prior research in MDD has not examined dynamic changes in functional connectivity as networks form, interact, and dissolve over time. We compared unmedicated individuals with MDD (n=100) to control participants (n=109) on dynamic RSFC (operationalized as SD in RSFC over a series of sliding windows) of an MPFC seed region during a resting-state functional magnetic resonance imaging scan. Among participants with MDD, we also investigated the relationship between symptom severity and RSFC. Secondary analyses probed the association between dynamic RSFC and rumination. Results showed that individuals with MDD were characterized by decreased dynamic (less variable) RSFC between MPFC and regions of parahippocampal gyrus within the default network, a pattern related to sustained positive connectivity between these regions across sliding windows. In contrast, the MDD group exhibited increased dynamic (more variable) RSFC between MPFC and regions of insula, and higher severity of depression was related to increased dynamic RSFC between MPFC and dorsolateral prefrontal cortex. These patterns of highly variable RSFC were related to greater frequency of strong positive and negative correlations in activity across sliding windows. Secondary analyses indicated that increased dynamic RSFC between MPFC and insula was related to higher levels of recent rumination. These findings provide initial evidence that depression, and ruminative thinking in depression, are related to abnormal patterns of fluctuating communication among brain systems involved in regulating attention and self-referential thinking.

Menstrual Abnormalities in School Going Girls – Are They Related to Dietary and Exercise Pattern?

PubMed Central

Vani K., Rupa; K.S., Veena; L., Subitha; Kumar V.R., Hemanth; A., Bupathy

2013-01-01

Context: Adolescence is the transitional phase of physical and mental development between childhood and adulthood and is characterized by immense hormonal changes.75% of girls experience some problems associated with menstruation. Aim: We tried to find out the prevalence of menstrual abnormalities in school going girls in Pondicherry and their association with dietary and exercise habits. Setting and Design: A cross-sectional questionnaire based study was conducted in adolescent girls who attained menarche in four secondary schools of Pondicherry, India. Material and Methods: All students who attained menarche and willing to participate in the study were invited to answer the questionnaire, which dealt with anthropometric data, socioeconomic data, menstrual history, and diet and exercise pattern. Statistical Analysis: Chi-square test and Fisher’s exact test was used to compare the dietary and exercise patterns among students having menstrual abnormalities and those who do not have menstrual abnormalities. Results: A total of 853 students participated in the study. Dysmenorrhea and premenstrual symptoms were the most frequent problems encountered. Premenstrual symptoms were significantly more common among girls who were overweight, in girls who were eating junk food regularly, in girls who were eating less food (dieting) in order to lose weight and in those who were not doing regular physical activity. Dysmenorrhea was significantly more common in the girls who were dieting to lose weight. Passage of clots was also significantly high in the girls who were dieting. Conclusion: Lifestyle modifications like regular physical activity, decreasing the intake of junk food and promoting healthy eating habits should be emphasised in school health education programs to improve their menstrual health. PMID:24392394

Morphometric abnormalities of the lateral ventricles in methamphetamine-dependent subjects☆

PubMed Central

Jeong, Hyeonseok S.; Lee, Sunho; Yoon, Sujung; Jung, Jiyoung J.; Cho, Han Byul; Kim, Binna N.; Ma, Jiyoung; Ko, Eun; Im, Jooyeon Jamie; Ban, Soonhyun; Renshaw, Perry F.; Lyoo, In Kyoon

2017-01-01

Background The presence of morphometric abnormalities of the lateral ventricles, which can reflect focal or diffuse atrophic changes of nearby brain structures, is not well characterized in methamphetamine dependence. The current study was aimed to examine the size and shape alterations of the lateral ventricles in methamphetamine-dependent subjects. Methods High-resolution brain structural images were obtained from 37 methamphetamine-dependent subjects and 25 demographically matched healthy individuals. Using a combined volumetric and surface-based morphometric approach, the structural variability of the lateral ventricles, with respect to extent and location, was examined. Results Methamphetamine-dependent subjects had an enlarged right lateral ventricle compared with healthy individuals. Morphometric analysis revealed a region-specific pattern of lateral ventricular expansion associated with methamphetamine dependence, which was mainly distributed in the areas adjacent to the ventral striatum, medial prefrontal cortex, and thalamus. Conclusions Patterns of shape decomposition in the lateral ventricles may have relevance to the structural vulnerability of the prefrontal-ventral striatal-thalamic circuit to methamphetamine-induced neurotoxicity. PMID:23769159

Electrophysiological signatures of atypical intrinsic brain connectivity networks in autism

NASA Astrophysics Data System (ADS)

Shou, Guofa; Mosconi, Matthew W.; Wang, Jun; Ethridge, Lauren E.; Sweeney, John A.; Ding, Lei

2017-08-01

Objective. Abnormal local and long-range brain connectivity have been widely reported in autism spectrum disorder (ASD), yet the nature of these abnormalities and their functional relevance at distinct cortical rhythms remains unknown. Investigations of intrinsic connectivity networks (ICNs) and their coherence across whole brain networks hold promise for determining whether patterns of functional connectivity abnormalities vary across frequencies and networks in ASD. In the present study, we aimed to probe atypical intrinsic brain connectivity networks in ASD from resting-state electroencephalography (EEG) data via characterizing the whole brain network. Approach. Connectivity within individual ICNs (measured by spectral power) and between ICNs (measured by coherence) were examined at four canonical frequency bands via a time-frequency independent component analysis on high-density EEG, which were recorded from 20 ASD and 20 typical developing (TD) subjects during an eyes-closed resting state. Main results. Among twelve identified electrophysiological ICNs, individuals with ASD showed hyper-connectivity in individual ICNs and hypo-connectivity between ICNs. Functional connectivity alterations in ASD were more severe in the frontal lobe and the default mode network (DMN) and at low frequency bands. These functional connectivity measures also showed abnormal age-related associations in ICNs related to frontal, temporal and motor regions in ASD. Significance. Our findings suggest that ASD is characterized by the opposite directions of abnormalities (i.e. hypo- and hyper-connectivity) in the hierarchical structure of the whole brain network, with more impairments in the frontal lobe and the DMN at low frequency bands, which are critical for top-down control of sensory systems, as well as for both cognition and social skills.

The Populus class III HD ZIP, popREVOLUTA, influences cambium initiation and patterning of woody stems.

PubMed

Robischon, Marcel; Du, Juan; Miura, Eriko; Groover, Andrew

2011-03-01

The secondary growth of a woody stem requires the formation of a vascular cambium at an appropriate position and proper patterning of the vascular tissues derived from the cambium. Class III homeodomain-leucine zipper (HD ZIP) transcription factors have been implicated in polarity determination and patterning in lateral organs and primary vascular tissues and in the initiation and function of shoot apical meristems. We report here the functional characterization of a Populus class III HD ZIP gene, popREVOLUTA (PRE), that demonstrates another role for class III HD ZIPs in regulating the development of cambia and secondary vascular tissues. PRE is orthologous to Arabidopsis (Arabidopsis thaliana) REVOLUTA and is expressed in both the shoot apical meristem and in the cambial zone and secondary vascular tissues. Transgenic Populus expressing a microRNA-resistant form of PRE presents unstable phenotypic abnormalities affecting both primary and secondary growth. Surprisingly, phenotypic changes include abnormal formation of cambia within cortical parenchyma that can produce secondary vascular tissues in reverse polarity. Genes misexpressed in PRE mutants include transcription factors and auxin-related genes previously implicated in class III HD ZIP functions during primary growth. Together, these results suggest that PRE plays a fundamental role in the initiation of the cambium and in regulating the patterning of secondary vascular tissues.

E2F4 is required for early eye patterning.

PubMed

Ruzhynsky, Vladimir A; Furimsky, Marosh; Park, David S; Wallace, Valerie A; Slack, Ruth S

2009-01-01

Increasingly, studies reveal novel functions for cell cycle proteins during development. Here, we investigated the role of E2F4 in eye development. E2F4-deficient mouse embryos exhibit severe early eye patterning defects, which are evident from embryonic day 11.5 and characterized by aberrant shape of the optic cup, coloboma as well as abnormal eye pigmentation. Loss of E2F4 is associated with proximal-distal patterning defects in the optic vesicle. These defects are characterized by the expansion of optic stalk marker gene expression to the optic cup and reduced expression of ventral optic cup markers. These defects are associated with a split of Shh expression domain at the ventral midline of the forebrain and expansion of the Shh activity into the ventral optic cup. Despite these patterning defects, early neuronal differentiation and Shh expression in the retina are not affected by E2F4 deletion. Overall, the results of our studies show a novel role of E2F4 in the early eye development. 2009 S. Karger AG, Basel.

Sexually dimorphic white matter geometry abnormalities in adolescent onset schizophrenia.

PubMed

Savadjiev, P; Whitford, T J; Hough, M E; Clemm von Hohenberg, C; Bouix, S; Westin, C-F; Shenton, M E; Crow, T J; James, A C; Kubicki, M

2014-05-01

The normal human brain is characterized by a pattern of gross anatomical asymmetry. This pattern, known as the "torque", is associated with a sexual dimorphism: The male brain tends to be more asymmetric than that of the female. This fact, along with well-known sex differences in brain development (faster in females) and onset of psychosis (earlier with worse outcome in males), has led to the theory that schizophrenia is a disorder in which sex-dependent abnormalities in the development of brain torque, the correlate of the capacity for language, cause alterations in interhemispheric connectivity, which are causally related to psychosis (Crow TJ, Paez P, Chance SE. 2007. Callosal misconnectivity and the sex difference in psychosis. Int Rev Psychiatry. 19(4):449-457.). To provide evidence toward this theory, we analyze the geometry of interhemispheric white matter connections in adolescent-onset schizophrenia, with a particular focus on sex, using a recently introduced framework for white matter geometry computation in diffusion tensor imaging data (Savadjiev P, Kindlmann GL, Bouix S, Shenton ME, Westin CF. 2010. Local white geometry from diffusion tensor gradients. Neuroimage. 49(4):3175-3186.). Our results reveal a pattern of sex-dependent white matter geometry abnormalities that conform to the predictions of Crow's torque theory and correlate with the severity of patients' symptoms. To the best of our knowledge, this is the first study to associate geometrical differences in white matter connectivity with torque in schizophrenia.

Clustering of Synoptic Pattern over the Korean Peninsula from Meteorological Models

NASA Astrophysics Data System (ADS)

Kim, Jinah; Heo, Kiyoung; Choi, Jungwoon; Jung, Sanghoon

2017-04-01

Numerical modeling data on meteorological and ocean science is one of example of big geographic data sources. The properties of the data including the volume, variety, and dynamic aspects pose new challenges for geographic visualization, and visual geoanalytics using big data analysis using machine learning method. A combination of algorithmic and visual approaches that make sense of large volumes of various types of spatiotemporal data are required to gain knowledge about complex phenomena. In the East coast of Korea, it is suffering from property damages and human causalities due to abnormal high waves (swell-like high-height waves). It is known to be caused by local meteorological conditions on the East Sea of Korean Peninsula in previous research and they proposed three kinds of pressure patterns that generate abnormal high waves. However, they cannot describe all kinds of pressure patterns that generate abnormal high waves. In our study, we propose unsupervised machine learning method for pattern clustering and applied it to classify a pattern which has occurred abnormal high waves using numerical meteorological model's reanalysis data from 2000 to 2015 and past historical records of accidents by abnormal high waves. About 25,000 patterns of total spatial distribution of sea surface pressure are clustered into 30 patterns and they are classified into seasonal sea level pressure patterns based on meteorological characteristics of Korean peninsula. Moreover, in order to determine the representative patterns which occurs abnormal high waves, we classified it again using historical accidents cases among the winter season pressure patterns. In this work, we clustered synoptic pattern over the Korean Peninsula in meteorological modeling reanalysis data and we could understand a seasonal variation through identifying the occurrence of clustered synoptic pattern. For the future work, we have to identify the relationship of wave modeling data for better understanding of abnormal high waves and we will develop pattern decision system to predict abnormal high waves in advances. This research was a part of the project titled "Development of Korea Operational Oceanographic System (KOOS), Phase 2" and "Investigation of Large Swell Waves and Rip currents and Development of The Disaster Response System," funded by the Ministry of Oceans & Fisheries Korea (Grant PM59691 and PM59240).

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

PubMed

Couldrey, Christine; Lee, Rita Sf

2010-03-07

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

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

PubMed Central

2010-01-01

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

Brugada Syndrome

MedlinePlus

... A telltale abnormality — called a type 1 Brugada ECG pattern — is detected by an electrocardiogram (ECG) test. Brugada syndrome is much more common in ... syndrome is an abnormal pattern on an electrocardiogram (ECG) called a type 1 Brugada ECG pattern. You ...

Cross-species assessments of motor and exploratory behavior related to bipolar disorder.

PubMed

Henry, Brook L; Minassian, Arpi; Young, Jared W; Paulus, Martin P; Geyer, Mark A; Perry, William

2010-07-01

Alterations in exploratory behavior are a fundamental feature of bipolar mania, typically characterized as motor hyperactivity and increased goal-directed behavior in response to environmental cues. In contrast, abnormal exploration associated with schizophrenia and depression can manifest as prominent withdrawal, limited motor activity, and inattention to the environment. While motor abnormalities are cited frequently as clinical manifestations of these disorders, relatively few empirical studies have quantified human exploratory behavior. This article reviews the literature characterizing motor and exploratory behavior associated with bipolar disorder and genetic and pharmacological animal models of the illness. Despite sophisticated assessment of exploratory behavior in rodents, objective quantification of human motor activity has been limited primarily to actigraphy studies with poor cross-species translational value. Furthermore, symptoms that reflect the cardinal features of bipolar disorder have proven difficult to establish in putative animal models of this illness. Recently, however, novel tools such as the human behavioral pattern monitor provide multivariate translational measures of motor and exploratory activity, enabling improved understanding of the neurobiology underlying psychiatric disorders.

Quantitative Folding Pattern Analysis of Early Primary Sulci in Human Fetuses with Brain Abnormalities.

PubMed

Im, K; Guimaraes, A; Kim, Y; Cottrill, E; Gagoski, B; Rollins, C; Ortinau, C; Yang, E; Grant, P E

2017-07-01

Aberrant gyral folding is a key feature in the diagnosis of many cerebral malformations. However, in fetal life, it is particularly challenging to confidently diagnose aberrant folding because of the rapid spatiotemporal changes of gyral development. Currently, there is no resource to measure how an individual fetal brain compares with normal spatiotemporal variations. In this study, we assessed the potential for automatic analysis of early sulcal patterns to detect individual fetal brains with cerebral abnormalities. Triplane MR images were aligned to create a motion-corrected volume for each individual fetal brain, and cortical plate surfaces were extracted. Sulcal basins were automatically identified on the cortical plate surface and compared with a combined set generated from 9 normal fetal brain templates. Sulcal pattern similarities to the templates were quantified by using multivariate geometric features and intersulcal relationships for 14 normal fetal brains and 5 fetal brains that were proved to be abnormal on postnatal MR imaging. Results were compared with the gyrification index. Significantly reduced sulcal pattern similarities to normal templates were found in all abnormal individual fetuses compared with normal fetuses (mean similarity [normal, abnormal], left: 0.818, 0.752; P < .001; right: 0.810, 0.753; P < .01). Altered location and depth patterns of sulcal basins were the primary distinguishing features. The gyrification index was not significantly different between the normal and abnormal groups. Automated analysis of interrelated patterning of early primary sulci could outperform the traditional gyrification index and has the potential to quantitatively detect individual fetuses with emerging abnormal sulcal patterns. © 2017 by American Journal of Neuroradiology.

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.

Mixed Pattern Matching-Based Traffic Abnormal Behavior Recognition

PubMed Central

Cui, Zhiming; Zhao, Pengpeng

2014-01-01

A motion trajectory is an intuitive representation form in time-space domain for a micromotion behavior of moving target. Trajectory analysis is an important approach to recognize abnormal behaviors of moving targets. Against the complexity of vehicle trajectories, this paper first proposed a trajectory pattern learning method based on dynamic time warping (DTW) and spectral clustering. It introduced the DTW distance to measure the distances between vehicle trajectories and determined the number of clusters automatically by a spectral clustering algorithm based on the distance matrix. Then, it clusters sample data points into different clusters. After the spatial patterns and direction patterns learned from the clusters, a recognition method for detecting vehicle abnormal behaviors based on mixed pattern matching was proposed. The experimental results show that the proposed technical scheme can recognize main types of traffic abnormal behaviors effectively and has good robustness. The real-world application verified its feasibility and the validity. PMID:24605045

Acute Kawasaki disease with emphasis on the echocardiographic profile: A single center experience

PubMed Central

Hamza, Hala S.; Zaher, Asmaa Z.; Agha, Hala M.

Background: Echocardiographic features of acute Kawasaki disease (KD) have not been well characterized in Egyptian children. This study aimed to provide insight into the pattern of cardiac involvement in Egyptian children with Kawasaki disease, focusing on echocardiographic coronary abnormalities and their associated risk predictors. Methods and Results: Medical records of 64 KD patients from 2012 to 2016 were retrospectively analyzed with recalculation of coronary artery z-scores during the first eight weeks after fever onset. All patients received intravenous immunoglobulin (IVIG) and 57.8% were treated within 10 days of illness onset. Coronary abnormalities were found in 53.1% of all patients, and in 43.2% of those who received IVIG within 10 days. Giant aneurysms (z-score>10) comprised 23.5% of all coronary abnormalities. Coronary thrombosis occurred in two patients (5%), both of whom developed myocardial infarction, and one succumbed to heart failure with eventual in-hospital death. Overall, 7% of patients had mitral regurgitation (n = 5), 1.5% had aortic regurgitation (n = 1), and 7.8% had pericardial effusion (n = 5). Among a number of laboratory and clinical predictors, platelet count had the strongest association with coronary abnormalities (Area under Receiver-operating characteristic (ROC) curve: 0.794; 95% confidence interval 0.678–0.910; P < 0.001). Conclusion: Coronary abnormalities occur in a substantial percentage of KD in Egypt, with associated evidence of severe inflammation. Further efforts are required to increase awareness of the disease and to emphasize the importance of early IVIG administration. Future studies should also be undertaken to characterize the long term progression profile of the disease as well as the possible genetic background of the disease in Egypt. PMID:29564348

Communication variations and aircrew performance

NASA Technical Reports Server (NTRS)

Kanki, Barbara G.; Folk, Valerie G.; Irwin, Cheryl M.

1991-01-01

The relationship between communication variations and aircrew performance (high-error vs low-error performances) was investigated by analyzing the coded verbal transcripts derived from the videotape records of 18 two-person air transport crews who participated in a high-fidelity, full-mission flight simulation. The flight scenario included a task which involved abnormal operations and required the coordinated efforts of all crew members. It was found that the best-performing crews were characterized by nearly identical patterns of communication, whereas the midrange and poorer performing crews showed a great deal of heterogeneity in their speech patterns. Although some specific speech sequences can be interpreted as being more or less facilitative to the crew-coordination process, predictability appears to be the key ingredient for enhancing crew performance. Crews communicating in highly standard (hence predictable) ways were better able to coordinate their task, whereas crews characterized by multiple, nonstandard communication profiles were less effective in their performance.

Characterization of esophageal pressure-flow abnormalities in patients with non-obstructive dysphagia and normal manometry findings.

PubMed

Chen, Chien-Lin; Yi, Chih-Hsun; Liu, Tso-Tsai; Hsu, Ching-Sheng; Omari, Taher I

2013-06-01

Patients with non-obstructive dysphagia (NOD) report symptoms of impaired esophageal bolus transit without evidence of bolus stasis. In such patients, manometric investigation may diagnose esophageal motility disorders; however, many have normal motor patterns. We hypothesized that patients with NOD would demonstrate evidence of high flow-resistance during bolus passage which in turn would relate to the reporting of bolus hold up perception. Esophageal pressure-impedance recordings of 5 mL liquid and viscous swallows from 18 NOD patients (11 male; 19-71 years) and 17 control subjects (9 male; 25-60 years) were analyzed. The relationship between intrabolus pressure and bolus flow timing in the esophagus was assessed using the pressure flow index (PFI). Bolus perception was assessed swallow by swallow using standardized descriptors. NOD patients were characterized by a higher PFI than controls. The PFI defined a pressure-flow abnormality in all patients who appeared normal based on the assessment esophageal motor patterns and bolus clearance. The PFI was higher for individual swallows during which subjects reported perception of bolus passage. Bolus flow-resistance is higher in NOD patients compared with controls as well as higher in relation to perception of bolus transit, suggesting the presence of an esophageal motility disorder despite normal findings on conventional analysis. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Magnetic resonance imaging spectrum of succinate dehydrogenase-related infantile leukoencephalopathy.

PubMed

Helman, Guy; Caldovic, Ljubica; Whitehead, Matthew T; Simons, Cas; Brockmann, Knut; Edvardson, Simon; Bai, Renkui; Moroni, Isabella; Taylor, J Michael; Van Haren, Keith; Taft, Ryan J; Vanderver, Adeline; van der Knaap, Marjo S

2016-03-01

Succinate dehydrogenase-deficient leukoencephalopathy is a complex II-related mitochondrial disorder for which the clinical phenotype, neuroimaging pattern, and genetic findings have not been comprehensively reviewed. Nineteen individuals with succinate dehydrogenase deficiency-related leukoencephalopathy were reviewed for neuroradiological, clinical, and genetic findings as part of institutional review board-approved studies at Children's National Health System (Washington, DC) and VU University Medical Center (Amsterdam, the Netherlands). All individuals had signal abnormalities in the central corticospinal tracts and spinal cord where imaging was available. Other typical findings were involvement of the cerebral hemispheric white matter with sparing of the U fibers, the corpus callosum with sparing of the outer blades, the basis pontis, middle cerebellar peduncles, and cerebellar white matter, and elevated succinate on magnetic resonance spectroscopy (MRS). The thalamus was involved in most studies, with a predilection for the anterior nucleus, pulvinar, and geniculate bodies. Clinically, infantile onset neurological regression with partial recovery and subsequent stabilization was typical. All individuals had mutations in SDHA, SDHB, or SDHAF1, or proven biochemical defect. Succinate dehydrogenase deficiency is a rare leukoencephalopathy, for which improved recognition by magnetic resonance imaging (MRI) in combination with advanced sequencing technologies allows noninvasive diagnostic confirmation. The MRI pattern is characterized by cerebral hemispheric white matter abnormalities with sparing of the U fibers, corpus callosum involvement with sparing of the outer blades, and involvement of corticospinal tracts, thalami, and spinal cord. In individuals with infantile regression and this pattern of MRI abnormalities, the differential diagnosis should include succinate dehydrogenase deficiency, in particular if MRS shows elevated succinate. © 2016 American Neurological Association.

Paradoxical ictal EEG lateralization in children with unilateral encephaloclastic lesions.

PubMed

Garzon, Eliana; Gupta, Ajay; Bingaman, William; Sakamoto, Americo C; Lüders, Hans

2009-09-01

Describe an ictal EEG pattern of paradoxical lateralization in children with unilateral encephaloclastic hemispheric lesion acquired early in life. Of 68 children who underwent hemispherectomy during 2003-2005, scalp video-EEG and brain MRI of six children with an ictal scalp EEG pattern discordant to the clinical and imaging data were reanalyzed. Medical charts were reviewed for clinical findings and seizure outcome. Age of seizure onset was 1 day-4 years. The destructive MRI lesion was an ischemic stroke in 2, a post-infectious encephalomalacia in 2, and a perinatal trauma and hemiconvulsive-hemiplegic syndrome in one patient each. Ictal EEG pattern was characterized by prominent ictal rhythms with either 3-7 Hz spike and wave complexes or beta frequency sharp waves (paroxysmal fast) over the unaffected (contralesional) hemisphere. Scalp video-EEG was discordant, however, other findings of motor deficits (hemiparesis; five severe, one mild), seizure semiology (4/6), interictal EEG abnormalities (3/6), and unilateral burden of MRI lesion guided the decision for hemispherectomy. After 12-39 months of post-surgery follow up, five of six patients were seizure free and one has brief staring spells. We describe a paradoxical lateralization of the EEG to the "good" hemisphere in children with unihemispheric encephaloclastic lesions. This EEG pattern is compatible with seizure free outcome after surgery, provided other clinical findings and tests are concordant with origin from the abnormal hemisphere.

Ametropia, retinal anatomy, and OCT abnormality patterns in glaucoma. 2. Impacts of optic nerve head parameters

NASA Astrophysics Data System (ADS)

Baniasadi, Neda; Wang, Mengyu; Wang, Hui; Jin, Qingying; Elze, Tobias

2017-12-01

Clinicians use retinal nerve fiber layer thickness (RNFLT) measured by optical coherence tomography (OCT) as an adjunct to glaucoma diagnosis. Ametropia is accompanied by changes to the optic nerve head (ONH), which may affect how OCT machines mark RNFLT measurements as abnormal. These changes in abnormality patterns may bias glaucoma diagnosis. Here, we investigate the relationship between OCT abnormality patterns and the following ONH-related and ametropia-associated parameters on 421 eyes of glaucoma patients: optic disc tilt and torsion, central retinal vessel trunk location (CRVTL), and nasal and temporal retinal curvature adjacent to ONH, quantified as nasal/temporal slopes of the inner limiting membrane. We applied multivariate logistic regression with abnormality marks as regressands to 40,401 locations of the peripapillary region and generated spatial maps of locations of false positive/negative abnormality marks independent of glaucoma severity. Effects of torsion and temporal slope were negligible. The effect of tilt could be explained by covariation with ametropia. For CRVTL/nasal slope, abnormality pattern shifts at 7.2%/23.5% of the peripapillary region were detected, respectively, independent of glaucoma severity and ametropia. Therefore, CRVTL and nasal curvature should be included in OCT RNFLT norms. Our spatial location maps may aid clinicians to improve diagnostic accuracy.

Ulnar neuropathy at or distal to the wrist: traumatic versus cumulative stress cases.

PubMed

Chiodo, Anthony; Chadd, Edmund

2007-04-01

To identify clinical and electromyographic characteristics of ulnar neuropathy at or below the wrist, comparing those caused by unitary trauma with those caused by suspected cumulative stress. Retrospective case series. University hospital electromyography laboratory. Patients with electrodiagnostic evidence of an ulnar neuropathy at or distal to the wrist over a 3-year period. Forty-seven hands from 42 patients (age range, 20-80y; mean, 52y) were identified and evaluated in this study. Record review of clinical history, physical examination, electromyography, and treatment. Etiology of injury, physical signs and symptoms, and electromyographic testing results. Ulnar neuropathy at or distal to the wrist is commonly mischaracterized because of other mononeuropathies in the upper extremity and because of peripheral polyneuropathy. Ulnar neuropathy because of cumulative stress presents typically with sensory symptoms (63%) and a normal examination (71%), whereas trauma cases present with motor with or without sensory symptoms (92%) with motor abnormalities (92%) confirmed on examination. Traumatic cases are characterized by electromyography by decreased sensory and motor-evoked amplitudes, prolonged motor distal latencies, and abnormal needle examination. The amplitude changes are noted comparing with laboratory norms and comparing side to side. No characteristic pattern of abnormalities on electromyography is noted in the cumulative stress cases. Patients with no motor symptoms, regardless of etiology, are more apt to have sensory distal latency prolongation, whereas those with motor symptoms have motor amplitude and needle examination abnormalities. Traumatic ulnar neuropathy at or distal to the wrist is characterized by motor symptoms and sensory and motor axonal loss by electromyography, whereas cumulative stress cases have sensory symptoms and electromyographic findings that are highly variable and noncharacteristic. Patients with no motor symptoms are more apt to show sensory distal latency abnormalities on electromyography, whereas those with motor symptoms show motor-evoked amplitude and needle electromyography abnormalities.

Cortex and amygdala morphology in psychopathy.

PubMed

Boccardi, Marina; Frisoni, Giovanni B; Hare, Robert D; Cavedo, Enrica; Najt, Pablo; Pievani, Michela; Rasser, Paul E; Laakso, Mikko P; Aronen, Hannu J; Repo-Tiihonen, Eila; Vaurio, Olli; Thompson, Paul M; Tiihonen, Jari

2011-08-30

Psychopathy is characterized by abnormal emotional processes, but only recent neuroimaging studies have investigated its cerebral correlates. The study aim was to map local differences of cortical and amygdalar morphology. Cortical pattern matching and radial distance mapping techniques were used to analyze the magnetic resonance images of 26 violent male offenders (age: 32±8) with psychopathy diagnosed using the Psychopathy Checklist-Revised (PCL-R) and no schizophrenia spectrum disorders, and in matched controls (age: 35± sp="0.12"/>11). The cortex displayed up to 20% reduction in the orbitofrontal and midline structures (corrected p<0.001 bilaterally). Up to 30% tissue reduction in the basolateral nucleus, and 10-30% enlargement effects in the central and lateral nuclei indicated abnormal structure of the amygdala (corrected p=0.05 on the right; and symmetrical pattern on the left). Psychopathy features specific morphology of the main cerebral structures involved in cognitive and emotional processing, consistent with clinical and functional data, and with a hypothesis of an alternative evolutionary brain development. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Abnormal fronto-striatal activation as a marker of threshold and subthreshold Bulimia Nervosa.

PubMed

Cyr, Marilyn; Yang, Xiao; Horga, Guillermo; Marsh, Rachel

2018-04-01

This study aimed to determine whether functional disturbances in fronto-striatal control circuits characterize adolescents with Bulimia Nervosa (BN) spectrum eating disorders regardless of clinical severity. FMRI was used to assess conflict-related brain activations during performance of a Simon task in two samples of adolescents with BN symptoms compared with healthy adolescents. The BN samples differed in the severity of their clinical presentation, illness duration and age. Multi-voxel pattern analyses (MVPAs) based on machine learning were used to determine whether patterns of fronto-striatal activation characterized adolescents with BN spectrum disorders regardless of clinical severity, and whether accurate classification of less symptomatic adolescents (subthreshold BN; SBN) could be achieved based on patterns of activation in adolescents who met DSM5 criteria for BN. MVPA classification analyses revealed that both BN and SBN adolescents could be accurately discriminated from healthy adolescents based on fronto-striatal activation. Notably, the patterns detected in more severely ill BN compared with healthy adolescents accurately discriminated less symptomatic SBN from healthy adolescents. Deficient activation of fronto-striatal circuits can characterize BN early in its course, when clinical presentations are less severe, perhaps pointing to circuit-based disturbances as useful biomarker or risk factor for the disorder, and a tool for understanding its developmental trajectory, as well as the development of early interventions. © 2018 Wiley Periodicals, Inc.

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.

Vocal fold contact patterns based on normal modes of vibration.

PubMed

Smith, Simeon L; Titze, Ingo R

2018-05-17

The fluid-structure interaction and energy transfer from respiratory airflow to self-sustained vocal fold oscillation continues to be a topic of interest in vocal fold research. Vocal fold vibration is driven by pressures on the vocal fold surface, which are determined by the shape of the glottis and the contact between vocal folds. Characterization of three-dimensional glottal shapes and contact patterns can lead to increased understanding of normal and abnormal physiology of the voice, as well as to development of improved vocal fold models, but a large inventory of shapes has not been directly studied previously. This study aimed to take an initial step toward characterizing vocal fold contact patterns systematically. Vocal fold motion and contact was modeled based on normal mode vibration, as it has been shown that vocal fold vibration can be almost entirely described by only the few lowest order vibrational modes. Symmetric and asymmetric combinations of the four lowest normal modes of vibration were superimposed on left and right vocal fold medial surfaces, for each of three prephonatory glottal configurations, according to a surface wave approach. Contact patterns were generated from the interaction of modal shapes at 16 normalized phases during the vibratory cycle. Eight major contact patterns were identified and characterized by the shape of the flow channel, with the following descriptors assigned: convergent, divergent, convergent-divergent, uniform, split, merged, island, and multichannel. Each of the contact patterns and its variation are described, and future work and applications are discussed. Copyright © 2018 Elsevier Ltd. All rights reserved.

Immune Abnormalities in Autism Spectrum Disorder-Could They Hold Promise for Causative Treatment?

PubMed

Gładysz, Dominika; Krzywdzińska, Amanda; Hozyasz, Kamil K

2018-01-06

Autism spectrum disorders (ASD) are characterized by impairments in language and communication development, social behavior, and the occurrence of stereotypic patterns of behavior and interests. Despite substantial speculation about causes of ASD, its exact etiology remains unknown. Recent studies highlight a link between immune dysfunction and behavioral traits. Various immune anomalies, including humoral and cellular immunity along with abnormalities at the molecular level, have been reported. There is evidence of altered immune function both in cerebrospinal fluid and peripheral blood. Several studies hypothesize a role for neuroinflammation in ASD and are supported by brain tissue and cerebrospinal fluid analysis, as well as evidence of microglial activation. It has been shown that immune abnormalities occur in a substantial number of individuals with ASD. Identifying subgroups with immune system dysregulation and linking specific cellular immunophenotypes to different symptoms would be key to defining a group of patients with immune abnormalities as a major etiology underlying behavioral symptoms. These determinations would provide the opportunity to investigate causative treatments for a defined patient group that may specifically benefit from such an approach. This review summarizes recent insights into immune system dysfunction in individuals with ASD and discusses the potential implications for future therapies.

Deep brain stimulation changes basal ganglia output nuclei firing pattern in the dystonic hamster.

PubMed

Leblois, Arthur; Reese, René; Labarre, David; Hamann, Melanie; Richter, Angelika; Boraud, Thomas; Meissner, Wassilios G

2010-05-01

Dystonia is a heterogeneous syndrome of movement disorders characterized by involuntary muscle contractions leading to abnormal movements and postures. While medical treatment is often ineffective, deep brain stimulation (DBS) of the internal pallidum improves dystonia. Here, we studied the impact of DBS in the entopeduncular nucleus (EP), the rodent equivalent of the human globus pallidus internus, on basal ganglia output in the dt(sz)-hamster, a well-characterized model of dystonia by extracellular recordings. Previous work has shown that EP-DBS improves dystonic symptoms in dt(sz)-hamsters. We report that EP-DBS changes firing pattern in the EP, most neurons switching to a less regular firing pattern during DBS. In contrast, EP-DBS did not change the average firing rate of EP neurons. EP neurons display multiphasic responses to each stimulation impulse, likely underlying the disruption of their firing rhythm. Finally, neurons in the substantia nigra pars reticulata display similar responses to EP-DBS, supporting the idea that EP-DBS affects basal ganglia output activity through the activation of common afferent fibers. Copyright 2010 Elsevier Inc. All rights reserved.

Dynamical complexity detection in geomagnetic activity indices using wavelet transforms and Tsallis entropy

NASA Astrophysics Data System (ADS)

Balasis, G.; Daglis, I. A.; Papadimitriou, C.; Kalimeri, M.; Anastasiadis, A.; Eftaxias, K.

2008-12-01

Dynamical complexity detection for output time series of complex systems is one of the foremost problems in physics, biology, engineering, and economic sciences. Especially in magnetospheric physics, accurate detection of the dissimilarity between normal and abnormal states (e.g. pre-storm activity and magnetic storms) can vastly improve space weather diagnosis and, consequently, the mitigation of space weather hazards. Herein, we examine the fractal spectral properties of the Dst data using a wavelet analysis technique. We show that distinct changes in associated scaling parameters occur (i.e., transition from anti- persistent to persistent behavior) as an intense magnetic storm approaches. We then analyze Dst time series by introducing the non-extensive Tsallis entropy, Sq, as an appropriate complexity measure. The Tsallis entropy sensitively shows the complexity dissimilarity among different "physiological" (normal) and "pathological" states (intense magnetic storms). The Tsallis entropy implies the emergence of two distinct patterns: (i) a pattern associated with the intense magnetic storms, which is characterized by a higher degree of organization, and (ii) a pattern associated with normal periods, which is characterized by a lower degree of organization.

Neonatal encephalopathy and the association to asphyxia in labor.

PubMed

Jonsson, Maria; Ågren, Johan; Nordén-Lindeberg, Solveig; Ohlin, Andreas; Hanson, Ulf

2014-12-01

In cases with moderate and severe neonatal encephalopathy, we aimed to determine the proportion that was attributable to asphyxia during labor and to investigate the association between cardiotocographic (CTG) patterns and neonatal outcome. In a study population of 71,189 births from 2 Swedish university hospitals, 80 cases of neonatal encephalopathy were identified. Cases were categorized by admission CTG patterns (normal or abnormal) and by the presence of asphyxia (cord pH, <7.00; base deficit, ≥12 mmol/L). Cases with normal admission CTG patterns and asphyxia at birth were considered to experience asphyxia related to labor. CTG patterns were assessed for the 2 hours preceding delivery. Admission CTG patterns were normal in 51 cases (64%) and abnormal in 29 cases (36%). The rate of cases attributable to asphyxia (ie, hypoxic ischemic encephalopathy) was 48 of 80 cases (60%), most of which evolved during labor (43/80 cases; 54%). Both severe neonatal encephalopathy and neonatal death were more frequent with an abnormal, rather than with a normal, admission CTG pattern (13 [45%] vs 11 [22%]; P = .03), and 6 [21%] vs 3 [6%]; P = .04), respectively. Comparison of cases with an abnormal and a normal admission CTG pattern also revealed more frequently observed decreased variability (12 [60%] and 8 [22%], respectively) and more late decelerations (8 [40%] and 1 [3%], respectively). Moderate and severe encephalopathy is attributable to asphyxia in 60% of cases, most of which evolve during labor. An abnormal admission CTG pattern indicates a poorer neonatal outcome and more often is associated with pathologic CTG patterns preceding delivery. Copyright © 2014 Elsevier Inc. All rights reserved.

Characterization of the of the Pathological and Biochemical Markers That Correlate to the Clinical Features of Autism. Subproject 2. Contribution of Significant Delay of Neuronal Development and Metabolic Shift of Neurons to Clinical Phenotype of Autism

DTIC Science & Technology

2013-04-01

skills, (e) problems with generalization of previously acquired skills, (f) rigidity and resistance to change, (g) social and communication ...their known role in social behavior, communication , and stereotypic behavior results in identification of a structural component of functional deficits...neurons. These abnormalities may contribute to social and communication deficits, and restricted repetitive and stereotyped patterns of behavior. 3

[How to characterize and treat sleep complaints in bipolar disorders?

PubMed

Geoffroy, P A; Micoulaud Franchi, J-A; Lopez, R; Poirot, I; Brion, A; Royant-Parola, S; Etain, B

2017-08-01

Sleep complaints are very common in bipolar disorders (BD) both during acute phases (manic and depressive episodes) and remission (about 80 % of patients with remitted BD have poor sleep quality). Sleep complaints during remission are of particular importance since they are associated with more mood relapses and worse outcomes. In this context, this review discusses the characterization and treatment of sleep complaints in BD. We examined the international scientific literature in June 2016 and performed a literature search with PubMed electronic database using the following headings: "bipolar disorder" and ("sleep" or "insomnia" or "hypersomnia" or "circadian" or "apnoea" or "apnea" or "restless legs"). Patients with BD suffer from sleep and circadian rhythm abnormalities during major depressive episodes (insomnia or hypersomnia, nightmares, nocturnal and/or early awakenings, non-restorative sleep) and manic episodes (insomnia, decreased need for sleep without fatigue), but also some of these abnormalities may persist during remission. These remission phases are characterized by a reduced quality and quantity of sleep, with a longer sleep duration, increased sleep latency, a lengthening of the wake time after sleep onset (WASO), a decrease of sleep efficiency, and greater variability in sleep/wake rhythms. Patients also present frequent sleep comorbidities: chronic insomnia, sleepiness, sleep phase delay syndrome, obstructive sleep apnea/hypopnea syndrome (OSAHS), and restless legs syndrome (RLS). These disorders are insufficiently diagnosed and treated whereas they are associated with mood relapses, treatment resistance, affect cognitive global functioning, reduce the quality of life, and contribute to weight gain or metabolic syndrome. Sleep and circadian rhythm abnormalities have been also associated with suicidal behaviors. Therefore, a clinical exploration with characterization of these abnormalities and disorders is essential. This exploration should be helped by questionnaires and documented on sleep diaries or even actimetric objective measures. Explorations such as ventilatory polygraphy, polysomnography or a more comprehensive assessment in a sleep laboratory may be required to complete the diagnostic assessment. Treatments obviously depend on the cause identified through assessment procedures. Treatment of chronic insomnia is primarily based on non-drug techniques (by restructuring behavior and sleep patterns), on psychotherapy (cognitive behavioral therapy for insomnia [CBT-I]; relaxation; interpersonal and social rhythm therapy [IPSRT]; etc.), and if necessary with hypnotics during less than four weeks. Specific treatments are needed in phase delay syndrome, OSAHS, or other more rare sleep disorders. BD are defined by several sleep and circadian rhythm abnormalities during all phases of the disorder. These abnormalities and disorders, especially during remitted phases, should be characterized and diagnosed to reduce mood relapses, treatment resistance and improve BD outcomes. Copyright © 2016 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

The importance of a normal breathing pattern for an effective abdominal-hollowing maneuver in healthy people: an experimental study.

PubMed

Ha, Sung-min; Kwon, Oh-yun; Kim, Su-jung; Choung, Sung-dae

2014-02-01

A normal breathing pattern while performing the abdominal-hollowing (AH) maneuver or spinal-stabilization exercise is essential for the success of rehabilitation programs and exercises. In previous studies, subjects were given standardized instructions to control the influence of respiration during the AH maneuver. However, the effect of breathing pattern on abdominal-muscle thickness during the AH maneuver has not been investigated. To compare abdominal-muscle thickness in subjects performing the AH maneuver under normal and abnormal breathing-pattern conditions and to investigate the effect of breathing pattern on the preferential contraction ratio (PCR) of the transverse abdominis. Comparative, repeated-measures experimental study. University research laboratory. 16 healthy subjects (8 male, 8 female) from a university population. A real-time ultrasound scanner was used to measure abdominal-muscle thickness during normal and abnormal breathing patterns. A paired t test was used to assess the effect of breathing pattern on abdominal-muscle thickness and PCR. Muscle thickness in the transverse abdominis and internal oblique muscles was significantly greater under the normal breathing pattern than under the abnormal pattern (P < .05). The PCR of the transverse abdominis was significantly higher under the normal breathing pattern compared with the abnormal pattern (P < .05). The results indicate that a normal breathing pattern is essential for performance of an effective AH maneuver. Thus, clinicians should ensure that patients adopt a normal breathing pattern before performing the AH maneuver and monitor transverse abdominis activation during the maneuver.

Cross-species assessments of Motor and Exploratory Behavior related to Bipolar Disorder

PubMed Central

Henry, Brook L.; Minassian, Arpi; Young, Jared W.; Paulus, Martin P.; Geyer, Mark A.; Perry, William

2010-01-01

Alterations in exploratory behavior are a fundamental feature of bipolar mania, typically characterized as motor hyperactivity and increased goal-directed behavior in response to environmental cues. In contrast, abnormal exploration associated with schizophrenia and depression can manifest as prominent withdrawal, limited motor activity, and inattention to the environment. While motor abnormalities are cited frequently as clinical manifestations of these disorders, relatively few empirical studies have quantified human exploratory behavior. This article reviews the literature characterizing motor and exploratory behavior associated with bipolar disorder and genetic and pharmacological animal models of the illness. Despite sophisticated assessment of exploratory behavior in rodents, objective quantification of human motor activity has been limited primarily to actigraphy studies with poor cross-species translational value. Furthermore, symptoms that reflect the cardinal features of bipolar disorder have proven difficult to establish in putative animal models of this illness. Recently, however, novel tools such as the Human Behavioral Pattern Monitor provide multivariate translational measures of motor and exploratory activity, enabling improved understanding of the neurobiology underlying psychiatric disorders. PMID:20398694

Increased sensorimotor network activity in DYT1 dystonia: a functional imaging study

PubMed Central

Argyelan, Miklos; Habeck, Christian; Ghilardi, M. Felice; Fitzpatrick, Toni; Dhawan, Vijay; Pourfar, Michael; Bressman, Susan B.; Eidelberg, David

2010-01-01

Neurophysiological studies have provided evidence of primary motor cortex hyperexcitability in primary dystonia, but several functional imaging studies suggest otherwise. To address this issue, we measured sensorimotor activation at both the regional and network levels in carriers of the DYT1 dystonia mutation and in control subjects. We used 15Oxygen-labelled water and positron emission tomography to scan nine manifesting DYT1 carriers, 10 non-manifesting DYT1 carriers and 12 age-matched controls while they performed a kinematically controlled motor task; they were also scanned in a non-motor audio-visual control condition. Within- and between-group contrasts were analysed with statistical parametric mapping. For network analysis, we first identified a normal motor-related activation pattern in a set of 39 motor and audio-visual scans acquired in an independent cohort of 18 healthy volunteer subjects. The expression of this pattern was prospectively quantified in the motor and control scans acquired in each of the gene carriers and controls. Network values for the three groups were compared with ANOVA and post hoc contrasts. Voxel-wise comparison of DYT1 carriers and controls revealed abnormally increased motor activation responses in the former group (P < 0.05, corrected; statistical parametric mapping), localized to the sensorimotor cortex, dorsal premotor cortex, supplementary motor area and the inferior parietal cortex. Network analysis of the normative derivation cohort revealed a significant normal motor-related activation pattern topography (P < 0.0001) characterized by covarying neural activity in the sensorimotor cortex, dorsal premotor cortex, supplementary motor area and cerebellum. In the study cohort, normal motor-related activation pattern expression measured during movement was abnormally elevated in the manifesting gene carriers (P < 0.001) but not in their non-manifesting counterparts. In contrast, in the non-motor control condition, abnormal increases in network activity were present in both groups of gene carriers (P < 0.001). In this condition, normal motor-related activation pattern expression in non-manifesting carriers was greater than in controls, but lower than in affected carriers. In the latter group, measures of normal motor-related activation pattern expression in the audio-visual condition correlated with independent dystonia clinical ratings (r = 0.70, P = 0.04). These findings confirm that overexcitability of the sensorimotor system is a robust feature of dystonia. The presence of elevated normal motor-related activation pattern expression in the non-motor condition suggests that abnormal integration of audio-visual input with sensorimotor network activity is an important trait feature of this disorder. Lastly, quantification of normal motor-related activation pattern expression in individual cases may have utility as an objective descriptor of therapeutic response in trials of new treatments for dystonia and related disorders. PMID:20207699

Mastocytosis: magnetic resonance imaging patterns of marrow disease.

PubMed

Avila, N A; Ling, A; Metcalfe, D D; Worobec, A S

1998-03-01

To report the bone marrow MRI findings of patients with mastocytosis and correlate them with clinical, pathologic, and radiographic features. Eighteen patients with mastocytosis had T1-weighted spin echo and short tau inversion recovery MRI of the pelvis at 0.5 T. In each patient the MR pattern of marrow disease was classified according to intensity and uniformity and was correlated with the clinical category of mastocytosis, bone marrow biopsy results, and radiographic findings. Two patients had normal MRI scans and normal bone marrow biopsies. One patient had a normal MRI scan and a marrow biopsy consistent with mastocytosis. Fifteen patients had abnormal MRI scans and abnormal marrow biopsies. There were several different MR patterns of marrow involvement; none was specifically associated with any given clinical category of mastocytosis. Fifteen of the 18 patients had radiographs of the pelvis; of those, 13 with abnormal MRI scans and abnormal marrow biopsies had the following radiographic findings: normal (nine); sclerosis (three); diffuse osteopenia (one). While radiographs are very insensitive for the detection of marrow abnormalities in mastocytosis, MRI is very sensitive and may display several different patterns of marrow involvement.

Breaking evolutionary and pleiotropic constraints in mammals: On sloths, manatees and homeotic mutations

PubMed Central

2011-01-01

Background Mammals as a rule have seven cervical vertebrae, except for sloths and manatees. Bateson proposed that the change in the number of cervical vertebrae in sloths is due to homeotic transformations. A recent hypothesis proposes that the number of cervical vertebrae in sloths is unchanged and that instead the derived pattern is due to abnormal primaxial/abaxial patterning. Results We test the detailed predictions derived from both hypotheses for the skeletal patterns in sloths and manatees for both hypotheses. We find strong support for Bateson's homeosis hypothesis. The observed vertebral and rib patterns cannot be explained by changes in primaxial/abaxial patterning. Vertebral patterns in sloths and manatees are similar to those in mice and humans with abnormal numbers of cervical vertebrae: incomplete and asymmetric homeotic transformations are common and associated with skeletal abnormalities. In sloths the homeotic vertebral shift involves a large part of the vertebral column. As such, similarity is greatest with mice mutant for genes upstream of Hox. Conclusions We found no skeletal abnormalities in specimens of sister taxa with a normal number of cervical vertebrae. However, we always found such abnormalities in conspecifics with an abnormal number, as in many of the investigated dugongs. These findings strongly support the hypothesis that the evolutionary constraints on changes of the number of cervical vertebrae in mammals is due to deleterious pleitropic effects. We hypothesize that in sloths and manatees low metabolic and activity rates severely reduce the usual stabilizing selection, allowing the breaking of the pleiotropic constraints. This probably also applies to dugongs, although to a lesser extent. PMID:21548920

Utility of Neurodiagnostic Studies in the Diagnosis of Autoimmune Encephalitis in Children.

PubMed

Albert, Dara V; Pluto, Charles P; Weber, Amanda; Vidaurre, Jorge; Barbar-Smiley, Fatima; Abdul Aziz, Rabheh; Driest, Kyla; Bout-Tabaku, Sharon; Ruess, Lynne; Rusin, Jerome A; Morgan-Followell, Bethanie

2016-02-01

Autoimmune encephalitis is currently a clinical diagnosis without widely accepted diagnostic criteria, often leading to a delay in diagnosis. The utility of magnetic resonance imaging (MRI) and electroencephalography (EEG) in this disease is unknown. The objective of this study was to identify disease-specific patterns of neurodiagnostic studies (MRI and EEG) for autoimmune encephalitis in children. We completed a retrospective chart review of encephalopathic patients seen at a large pediatric hospital over a four year interval. Clinical presentation, autoantibody status, and MRI and EEG findings were identified and compared. Individuals with autoantibodies were considered "definite" cases, whereas those without antibodies or those with only thyroperoxidase antibodies were characterized as "suspected." Eighteen patients met the inclusion criteria and autoantibodies were identified in nine of these. The patients with definite autoimmune encephalitis had MRI abnormalities within limbic structures, most notably the anteromedial temporal lobes (56%). Only individuals with suspected disease had nontemporal lobe cortical lesions. Sixteen patients had an EEG and 13 (81%) of these were abnormal. The most common findings were abnormal background rhythm (63%), generalized slowing (50%), focal slowing (43%), and focal epileptiform discharges (31%). Sleep spindle abnormalities occurred in 38% of patients. There were no specific differences in the EEG findings between the definite and suspected cases. Focal EEG findings only correlated with a focal lesion on MRI in a single definite case. Pediatric patients with definite autoimmune encephalitis have a narrow spectrum of MRI abnormalities. Conversely, EEG abnormalities are mostly nonspecific. All patients in our cohort had abnormalities on one or both of these neurodiagnostic studies. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Inflectional morphology in high-functioning autism: Evidence for speeded grammatical processing

PubMed Central

Walenski, Matthew; Mostofsky, Stewart H.; Ullman, Michael T.

2014-01-01

Autism is characterized by language and communication deficits. We investigated grammatical and lexical processes in high-functioning autism by contrasting the production of regular and irregular past-tense forms. Boys with autism and typically-developing control boys did not differ in accuracy or error rates. However, boys with autism were significantly faster than controls at producing rule-governed past-tenses (slip-slipped, plim-plimmed, bring-bringed), though not lexically-dependent past-tenses (bring-brought, squeeze-squeezed, splim-splam). This pattern mirrors previous findings from Tourette syndrome attributed to abnormalities of frontal/basal-ganglia circuits that underlie grammar. We suggest a similar abnormality underlying language in autism. Importantly, even when children with autism show apparently normal language (e.g., in accuracy or with diagnostic instruments), processes and/or brain structures subserving language may be atypical in the disorder. PMID:25342962

Molecular and phenotypic aspects of CHD7 mutation in CHARGE syndrome

PubMed Central

Zentner, Gabriel E.; Layman, Wanda S.; Martin, Donna M.; Scacheri, Peter C.

2010-01-01

CHARGE syndrome (Coloboma of the eye, Heart defects, Atresia of the choanae, Retardation of growth and/or development, Genital and/or urinary abnormalities, and Ear abnormalities (including deafness) is a genetic disorder characterized by a specific and a recognizable pattern of anomalies. De novo mutations in the gene encoding chromodomain helicase DNA binding protein 7 (CHD7) are the major cause of CHARGE syndrome. Here, we review the clinical features of 379 CHARGE patients who tested positive or negative for mutations in CHD7. We found that CHARGE individuals with CHD7 mutations more commonly have ocular colobomas, temporal bone anomalies (semicircular canal hypoplasia/dysplasia), and facial nerve paralysis compared with mutation negative individuals. We also highlight recent genetic and genomic studies that have provided functional insights into CHD7 and the pathogenesis of CHARGE syndrome. PMID:20186815

Ultrasound screening of periarticular soft tissue abnormality around metal-on-metal bearings.

PubMed

Nishii, Takashi; Sakai, Takashi; Takao, Masaki; Yoshikawa, Hideki; Sugano, Nobuhiko

2012-06-01

Although metal hypersensitivity or pseudotumors are concerns for metal-on-metal (MoM) bearings, detailed pathologies of patterns, severity, and incidence of periprosthetic soft tissue lesions are incompletely understood. We examined the potential of ultrasound for screening of periarticular soft tissue lesions around MoM bearings. Ultrasound examinations were conducted in 88 hips (79 patients) with MoM hip resurfacings or MoM total hip arthroplasties with a large femoral head. Four qualitative ultrasound patterns were shown, including normal pattern in 69 hips, joint-expansion pattern in 11 hips, cystic pattern in 5 hips, and mass pattern in 3 hips. Hips with the latter 3 abnormal patterns showed significantly higher frequency of clinical symptoms, without significant differences of sex, duration of implantation, head sizes, and cup abduction/anteversion angles, compared with hips with normal pattern. Ultrasound examination provides sensitive screening of soft tissue reactions around MoM bearings and may be useful in monitoring progression and defining treatment for periarticular soft tissue abnormalities. Copyright © 2012 Elsevier Inc. All rights reserved.

Near-infrared fundus autofluorescence in subclinical best vitelliform macular dystrophy.

PubMed

Parodi, Maurizio Battaglia; Iacono, Pierluigi; Del Turco, Claudia; Bandello, Francesco

2014-12-01

To describe fundus autofluorescence (FAF) on short-wavelength FAF and near-infrared FAF in the subclinical form of Best vitelliform macular dystrophy. Cross-sectional prospective study. Patients affected by the subclinical form of Best vitelliform macular dystrophy (positive testing for BEST1 gene mutation, fully preserved best-corrected visual acuity, normal fundus appearance) were recruited. Each patient underwent a complete ophthalmologic examination, including electro-oculogram (EOG), short-wavelength FAF, near-infrared FAF, spectral-domain OCT (SD OCT), and microperimetry. Main outcome measure was the identification of abnormal FAF patterns. Forty-six patients showing mutations in the BEST1 gene were examined. Forty patients presented a bilateral Best vitelliform macular dystrophy, 2 patients showed a unilateral Best vitelliform macular dystrophy, and 4 patients had a bilateral subclinical form. Patients with the unilateral form (2 eyes) and patients with the subclinical form (8 eyes) were analyzed. Three BEST1 sequence variants were identified: c.73C>T (p.Arg25Trp), c.28G>A (p.Ala10Thr), and c.652C>G (p.Arg218Gly). Short-wavelength FAF was normal in all eyes. Near-infrared FAF detected a pattern consisting of a central hypo-autofluorescence surrounded by a round area of hyper-autofluorescence. A bilateral reduced EOG response was detected in 1 patient. SD OCT revealed a thicker, well-defined, and more reflective interdigitation zone in 2 patients (4 eyes, 40%). Microperimetry of the central 10 degrees revealed a slight, diffuse reduction of retinal sensitivity. Mean retinal sensitivity within the central 2 and 4 degrees was lower and matched the hypo-autofluorescent area detected on near-infrared FAF. Additional relative scotomata were detected within the 10-degree area. No change in clinical, functional, or FAF pattern was found over the follow-up. Subclinical Best vitelliform macular dystrophy is characterized by the absence of biomicroscopic fundus abnormality and fully preserved visual acuity, but shows an abnormal near-infrared FAF pattern, with central hypo-autofluorescence. Copyright © 2014 Elsevier Inc. All rights reserved.

Characterization of ultrasonic vocalizations of Fragile X mice.

PubMed

Belagodu, Amogh P; Johnson, Aaron M; Galvez, Roberto

2016-09-01

Fragile X Syndrome (FXS) is the leading form of inherited intellectual disability. It is caused by the transcriptional silencing of FMR1, the gene which codes for the Fragile X Mental Retardation Protein (FMRP). Patients who have FXS exhibit numerous behavioral and cognitive impairments, such as attention-deficit/hyperactivity disorder, obsessive compulsive disorder, and autistic-like behaviors. In addition to these behavioral abnormalities, FXS patients have also been shown to exhibit various deficits in communication such as abnormal sentence structures, increased utterances, repetition of sounds and words, and reduced articulation. These deficits can dramatically hinder communication for FXS patients, exacerbating learning and cognition impairments while decreasing their quality of life. To examine the biological underpinnings of these communication abnormalities, studies have used a mouse model of the Fragile X Syndrome; however, these vocalization studies have resulted in inconsistent findings that often do not correlate with abnormalities observed in FXS patients. Interestingly, a detailed examination of frequency modulated vocalizations that are believed to be a better assessment of rodent communication has never been conducted. The following study used courtship separation to conduct a detailed examination of frequency modulated ultrasonic vocalizations (USV) in FXS mice. Our analyses of frequency modulated USVs demonstrated that adult FXS mice exhibited longer phrases and more motifs. Phrases are vocalizations consisting of multiple frequency modulated ultrasonic vocalizations, while motifs are repeated frequency modulated USV patterns. Fragile X mice had a higher proportion of "u" syllables in all USVs and phrases while their wildtype counterparts preferred isolated "h" syllables. Although the specific importance of these syllables towards communication deficits still needs to be evaluated, these findings in production of USVs are consistent with the repetitive and perseverative speech patterns observed in FXS patients. This study demonstrates that FXS mice can be used to study the underlying biological mechanism(s) mediating FXS vocalization abnormalities. Copyright © 2016 Elsevier B.V. All rights reserved.

High-Frequency EEG Variations in Children with Autism Spectrum Disorder during Human Faces Visualization

PubMed Central

Reategui, Camille; Costa, Bruna Karen de Sousa; da Fonseca, Caio Queiroz; da Silva, Luana; Morya, Edgard

2017-01-01

Autism spectrum disorder (ASD) is a neuropsychiatric disorder characterized by the impairment in the social reciprocity, interaction/language, and behavior, with stereotypes and signs of sensory function deficits. Electroencephalography (EEG) is a well-established and noninvasive tool for neurophysiological characterization and monitoring of the brain electrical activity, able to identify abnormalities related to frequency range, connectivity, and lateralization of brain functions. This research aims to evidence quantitative differences in the frequency spectrum pattern between EEG signals of children with and without ASD during visualization of human faces in three different expressions: neutral, happy, and angry. Quantitative clinical evaluations, neuropsychological evaluation, and EEG of children with and without ASD were analyzed paired by age and gender. The results showed stronger activation in higher frequencies (above 30 Hz) in frontal, central, parietal, and occipital regions in the ASD group. This pattern of activation may correlate with developmental characteristics in the children with ASD. PMID:29018811

Amplitude-integrated EEG in newborns with critical congenital heart disease predicts preoperative brain magnetic resonance imaging findings.

PubMed

Mulkey, Sarah B; Yap, Vivien L; Bai, Shasha; Ramakrishnaiah, Raghu H; Glasier, Charles M; Bornemeier, Renee A; Schmitz, Michael L; Bhutta, Adnan T

2015-06-01

The study aims are to evaluate cerebral background patterns using amplitude-integrated electroencephalography in newborns with critical congenital heart disease, determine if amplitude-integrated electroencephalography is predictive of preoperative brain injury, and assess the incidence of preoperative seizures. We hypothesize that amplitude-integrated electroencephalography will show abnormal background patterns in the early preoperative period in infants with congenital heart disease that have preoperative brain injury on magnetic resonance imaging. Twenty-four newborns with congenital heart disease requiring surgery at younger than 30 days of age were prospectively enrolled within the first 3 days of age at a tertiary care pediatric hospital. Infants had amplitude-integrated electroencephalography for 24 hours beginning close to birth and preoperative brain magnetic resonance imaging. The amplitude-integrated electroencephalographies were read to determine if the background pattern was normal, mildly abnormal, or severely abnormal. The presence of seizures and sleep-wake cycling were noted. The preoperative brain magnetic resonance imaging scans were used for brain injury and brain atrophy assessment. Fifteen of 24 infants had abnormal amplitude-integrated electroencephalography at 0.71 (0-2) (mean [range]) days of age. In five infants, the background pattern was severely abnormal. (burst suppression and/or continuous low voltage). Of the 15 infants with abnormal amplitude-integrated electroencephalography, 9 (60%) had brain injury. One infant with brain injury had a seizure on amplitude-integrated electroencephalography. A severely abnormal background pattern on amplitude-integrated electroencephalography was associated with brain atrophy (P = 0.03) and absent sleep-wake cycling (P = 0.022). Background cerebral activity is abnormal on amplitude-integrated electroencephalography following birth in newborns with congenital heart disease who have findings of brain injury and/or brain atrophy on preoperative brain magnetic resonance imaging. Copyright © 2015 Elsevier Inc. All rights reserved.

Correlation of pulmonary function and usual interstitial pneumonia computed tomography patterns in idiopathic pulmonary fibrosis.

PubMed

Arcadu, Antonella; Byrne, Suzanne C; Pirina, Pietro; Hartman, Thomas E; Bartholmai, Brian J; Moua, Teng

2017-08-01

Little is known about presenting 'inconsistent' or 'possible' usual interstitial pneumonia (UIP) computed tomography (CT) patterns advancing to 'consistent' UIP as disease progresses in idiopathic pulmonary fibrosis (IPF). We hypothesized that if 'consistent' UIP represented more advanced disease, such a pattern on presentation should also correlate with more severe pulmonary function test (PFT) abnormalities. Consecutive IPF patients (2005-2013) diagnosed by international criteria with baseline PFT and CT were included. Presenting CTs were assessed by three expert radiologists for consensus UIP pattern ('consistent', 'possible', and 'inconsistent'). Approximation of individual and combined interstitial abnormalities was also performed with correlation of interstitial abnormalities and UIP CT pattern made with PFT findings and survival. Three-hundred and fifty patients (70% male) were included with a mean age of 68.3 years. Mean percent predicted forced vital capacity (FVC%) and diffusion capacity (DLCO%) was 64% and 45.5% respectively. Older age and male gender correlated more with 'consistent' UIP CT pattern. FVC% was not associated with any UIP pattern but did correlate with total volume of radiologist assessed interstitial abnormalities. DLCO% was lower in those with 'consistent' UIP pattern. A 'consistent' UIP CT pattern was also not independently predictive of survival after correction for age, gender, FVC%, and DLCO%. PFT findings appear to correlate with extent of radiologic disease but not specific morphologic patterns. Whether such UIP patterns represent different stages of disease severity or radiologic progression is not supported by coinciding pulmonary function decline. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cocaine addiction is associated with abnormal prefrontal function, increased striatal connectivity and sensitivity to monetary incentives, and decreased connectivity outside the human reward circuit.

PubMed

Vaquero, Lucía; Cámara, Estela; Sampedro, Frederic; Pérez de Los Cobos, José; Batlle, Francesca; Fabregas, Josep Maria; Sales, Joan Artur; Cervantes, Mercè; Ferrer, Xavier; Lazcano, Gerardo; Rodríguez-Fornells, Antoni; Riba, Jordi

2017-05-01

Cocaine addiction has been associated with increased sensitivity of the human reward circuit to drug-related stimuli. However, the capacity of non-drug incentives to engage this network is poorly understood. Here, we characterized the functional sensitivity to monetary incentives and the structural integrity of the human reward circuit in abstinent cocaine-dependent (CD) patients and their matched controls. We assessed the BOLD response to monetary gains and losses in 30 CD patients and 30 healthy controls performing a lottery task in a magnetic resonance imaging scanner. We measured brain gray matter volume (GMV) using voxel-based morphometry and white matter microstructure using voxel-based fractional anisotropy (FA). Functional data showed that, after monetary incentives, CD patients exhibited higher activation in the ventral striatum than controls. Furthermore, we observed an inverted BOLD response pattern in the prefrontal cortex, with activity being highest after unexpected high gains and lowest after losses. Patients showed increased GMV in the caudate and the orbitofrontal cortex, increased white matter FA in the orbito-striatal pathway but decreased FA in antero-posterior association bundles. Abnormal activation in the prefrontal cortex correlated with GMV and FA increases in the orbitofrontal cortex. While functional abnormalities in the ventral striatum were inversely correlated with abstinence duration, structural alterations were not. In conclusion, results suggest abnormal incentive processing in CD patients with high salience for rewards and punishments in subcortical structures but diminished prefrontal control after adverse outcomes. They further suggest that hypertrophy and hyper-connectivity within the reward circuit, to the expense of connectivity outside this network, characterize cocaine addiction. © 2016 Society for the Study of Addiction.

Abnormal neuronal activity in Tourette syndrome and its modulation using deep brain stimulation

PubMed Central

Israelashvili, Michal; Loewenstern, Yocheved

2015-01-01

Tourette syndrome (TS) is a common childhood-onset disorder characterized by motor and vocal tics that are typically accompanied by a multitude of comorbid symptoms. Pharmacological treatment options are limited, which has led to the exploration of deep brain stimulation (DBS) as a possible treatment for severe cases. Multiple lines of evidence have linked TS with abnormalities in the motor and limbic cortico-basal ganglia (CBG) pathways. Neurophysiological data have only recently started to slowly accumulate from multiple sources: noninvasive imaging and electrophysiological techniques, invasive electrophysiological recordings in TS patients undergoing DBS implantation surgery, and animal models of the disorder. These converging sources point to system-level physiological changes throughout the CBG pathway, including both general altered baseline neuronal activity patterns and specific tic-related activity. DBS has been applied to different regions along the motor and limbic pathways, primarily to the globus pallidus internus, thalamic nuclei, and nucleus accumbens. In line with the findings that also draw on the more abundant application of DBS to Parkinson's disease, this stimulation is assumed to result in changes in the neuronal firing patterns and the passage of information through the stimulated nuclei. We present an overview of recent experimental findings on abnormal neuronal activity associated with TS and the changes in this activity following DBS. These findings are then discussed in the context of current models of CBG function in the normal state, during TS, and finally in the wider context of DBS in CBG-related disorders. PMID:25925326

Predicting depression based on dynamic regional connectivity: a windowed Granger causality analysis of MEG recordings.

PubMed

Lu, Qing; Bi, Kun; Liu, Chu; Luo, Guoping; Tang, Hao; Yao, Zhijian

2013-10-16

Abnormal inter-regional causalities can be mapped for the objective diagnosis of various diseases. These inter-regional connectivities are usually calculated over an entire scan and used to characterize the stationary strength of the connections. However, the connectivity within networks may undergo substantial changes during a scan. In this study, we developed an objective depression recognition approach using the dynamic regional interactions that occur in response to sad facial stimuli. The whole time-period magnetoencephalography (MEG) signals from the visual cortex, amygdala, anterior cingulate cortex (ACC) and inferior frontal gyrus (IFG) were separated into sequential time intervals. The Granger causality mapping method was used to identify the pairwise interaction pattern within each time interval. Feature selection was then undertaken within a minimum redundancy-maximum relevance (mRMR) framework. Typical classifiers were utilized to predict those patients who had depression. The overall performances of these classifiers were similar, and the highest classification accuracy rate was 87.5%. The best discriminative performance was obtained when the number of features was within a robust range. The discriminative network pattern obtained through support vector machine (SVM) analyses displayed abnormal causal connectivities that involved the amygdala during the early and late stages. These early and late connections in the amygdala appear to reveal a negative bias to coarse expression information processing and abnormal negative modulation in patients with depression, which may critically affect depression discrimination. © 2013 Elsevier B.V. All rights reserved.

Abnormal Superior Temporal Connectivity During Fear Perception in Schizophrenia

PubMed Central

Leitman, David I.; Loughead, James; Wolf, Daniel H.; Ruparel, Kosha; Kohler, Christian G.; Elliott, Mark A.; Bilker, Warren B.; Gur, Raquel E.; Gur, Ruben C.

2008-01-01

Patients with schizophrenia have difficulty in decoding facial affect. A study using event–related functional neuroimaging indicated that errors in fear detection in schizophrenia are associated with paradoxically higher activation in the amygdala and an associated network implicated in threat detection. Furthermore, this exaggerated activation to fearful faces correlated with severity of flat affect. These findings suggest that abnormal threat detection processing may reflect disruptions between nodes that comprise the affective appraisal circuit. Here we examined connectivity within this network by determining the pattern of intercorrelations among brain regions (regions of interest) significantly activated during fear identification in both healthy controls and patients using a novel procedure CORANOVA. This analysis tests differences in the interregional correlation strength between schizophrenia and healthy controls. Healthy subjects' task activation was principally characterized by robust correlations between medial structures like thalamus (THA) and amygdala (AMY) and middle frontal (MF), inferior frontal (IF), and prefrontal cortical (PFC) regions. In contrast, schizophrenia patients displayed no significant correlations between the medial regions and either MF or IF. Further, patients had significantly higher correlations between occipital lingual gyrus and superior temporal gyrus than healthy subjects. These between-group connectivity differences suggest that schizophrenia threat detection impairment may stem from abnormal stimulus integration. Such abnormal integration may disrupt the evaluation of threat within fronto-cortical regions. PMID:18550592

Combining differential expression, chromosomal and pathway analyses for the molecular characterization of renal cell carcinoma

PubMed Central

Furge, Kyle A; Dykema, Karl; Petillo, David; Westphal, Michael; Zhang, Zhongfa; Kort, Eric J; Teh, Bin Tean

2007-01-01

Using high-throughput gene-expression profiling technology, we can now gain a better understanding of the complex biology that is taking place in cancer cells. This complexity is largely dictated by the abnormal genetic makeup of the cancer cells. This abnormal genetic makeup can have profound effects on cellular activities such as cell growth, cell survival and other regulatory processes. Based on the pattern of gene expression, or molecular signatures of the tumours, we can distinguish or subclassify different types of cancers according to their cell of origin, behaviour, and the way they respond to therapeutic agents and radiation. These approaches will lead to better molecular subclassification of tumours, the basis of personalized medicine. We have, to date, done whole-genome microarray gene-expression profiling on several hundreds of kidney tumours. We adopt a combined bioinformatic approach, based on an integrative analysis of the gene-expression data. These data are used to identify both cytogenetic abnormalities and molecular pathways that are deregulated in renal cell carcinoma (RCC). For example, we have identified the deregulation of the VHL-hypoxia pathway in clear-cell RCC, as previously known, and the c-Myc pathway in aggressive papillary RCC. Besides the more common clear-cell, papillary and chromophobe RCCs, we are currently characterizing the molecular signatures of rarer forms of renal neoplasia such as carcinoma of the collecting ducts, mixed epithelial and stromal tumours, chromosome Xp11 translocations associated with papillary RCC, renal medullary carcinoma, mucinous tubular and spindle-cell carcinoma, and a group of unclassified tumours. Continued development and improvement in the field of molecular profiling will better characterize cancer and provide more accurate diagnosis, prognosis and prediction of drug response. PMID:18542781

Trichilemmal cyst nevus: a new complex organoid epidermal nevus.

PubMed

Tantcheva-Poor, Iliana; Reinhold, Katja; Krieg, Thomas; Happle, Rudolf

2007-11-01

A 31-year-old woman had an organoid nevus characterized by multiple trichilemmal cysts arranged in a bandlike pattern. The involved streaks followed Blaschko's lines and were covered, in addition, by multiple filiform hyperkeratoses and comedo-like plugs. Some histopathologic features of this complex nevus were reminiscent of those of well-established organoid nevi such as nevus comedonicus, porokeratotic eccrine nevus, or hair follicle nevus, but the presence of multiple large trichilemmal cysts was a conspicuously distinctive abnormality. Consequently, we propose for this new organoid nevus the names "trichilemmal cyst nevus" or "nevus trichilemmocysticus."

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

PubMed

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

2009-12-01

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

Waardenburg syndrome type I: Dental phenotypes and genetic analysis of an extended family.

PubMed

Sólia-Nasser, L; de Aquino, S-N; Paranaíba, L-M R; Gomes, A; Dos-Santos-Neto, P; Coletta, R-D; Cardoso, A-F; Frota, A-C; Martelli-Júnior, H

2016-05-01

The aim of this study was to describe the pattern of inheritance and the clinical features in a large family with Waardenburg syndrome type I (WS1), detailing the dental abnormalities and screening for PAX3 mutations. To characterize the pattern of inheritance and clinical features, 29 family members were evaluated by dermatologic, ophthalmologic, otorhinolaryngologic and orofacial examination. Molecular analysis of the PAX3 gene was performed. The pedigree of the family,including the last four generations, was constructed and revealed non-consanguineous marriages. Out of 29 descendants, 16 family members showed features of WS1, with 9 members showing two major criteria indicative of WS1. Five patients showed white forelock and iris hypopigmentation, and four showed dystopia canthorum and iris hypopigmentation. Two patients had hearing loss. Dental abnormalities were identified in three family members, including dental agenesis, conical teeth and taurodontism. Sequencing analysis failed to identify mutations in the PAX3 gene. These results confirm that WS1 was transmitted in this family in an autosomal dominant pattern with variable expressivity and high penetrance. The presence of dental manifestations, especially tooth agenesis and conical teeth which resulted in considerable aesthetic impact on affected individuals was a major clinical feature. This article reveals the presence of well-defined dental changes associated with WS1 and tries to establish a possible association between these two entities showing a new spectrum of WS1.

Results of Nailfold Capillaroscopy in Patients with Normal-Tension Glaucoma.

PubMed

Kosior-Jarecka, Ewa; Bartosińska, Joanna; Łukasik, Urszula; Wróbel-Dudzińska, Dominika; Krasowska, Dorota; Chodorowska, Grażyna; Żarnowski, Tomasz

2018-06-01

The aim of the study was to evaluate the results of nailfold videocapillaroscopic examination in patients with normal-tension glaucoma (NTG) in comparison to age-matched individuals without glaucoma and young healthy volunteers and to assess the relation between the results of this examination with clinical status in NTG group. The studied group consisted of 188 patients: 80 patients with NTG and 2 control groups (58 young healthy and 50 age-matched volunteers). The nailfold videocapillaroscopy (NVC) was performed in all participants. The results of every NVC were qualified as a normal or abnormal pattern. In the NTG group, ophthalmic examination was performed and medical history regarding glaucoma, chronic general disorders, and vascular risk factors was recorded. In the NTG group, an abnormal NVC pattern was more common than in young controls (p = 0.0008). Microbleedings were present more frequently in NTG patients (p = 0.0365). Enlargement of capillaries (p = 0.0006) and branching capillaries (p = 0.0221) were more frequent in the NTG group compared to age-matched controls. Maximal intraocular pressure was higher in NTG patients with abnormal NVC pattern than with normal NVC (p = 0.0000). Disc hemorrhages were more frequently observed in patients with abnormal NVC pattern (p = 0.0313). Presence of paracentral scotoma was associated with abnormal NVC pattern (p = 0.0054). Abnormalities in nailfold capillaroscopy are more frequent in NTG patients. The results of capillaroscopic examination differ in NTG patients according to the profile of ocular and general risk factor.

Immunoglobulin patterns in humans over 95 years of age.

PubMed Central

Radl, J; Sepers, J M; Skvaril, F; Morell, A; Hijmans, W

1975-01-01

Immunoglobulin patterns were investigated in seventy-three volunteers older than 95 years. An idiopathic paraproteinaemia was found in 19% of the cases. A restriction of heterogeneity and an imbalance in the kappa/lambda ratio of the immunoglobulins was seen in a number of other sera. Determinations of immunoglobulin levels in sera of individuals without paraproteinaemia showed an increase in IgA and IgG. The quantitations of the IgG subclasses demonstrated that an increase in the IgG1 and IgG3 subclasses is responsible for the elevated level of the IgG. The variation in the immunoglobulin levels increased significantly with age of IgM and for the three major IgG subclasses. No abnormalities were found in the urine or in the mixed saliva. These results indicate that selective changes in the extent of the antibody-immunoglobulin repertoire characterize the immunoglobulin pattern of ageing man. PMID:1212818

An Ethyl-Nitrosourea-Induced Point Mutation in Phex Causes Exon Skipping, X-Linked Hypophosphatemia, and Rickets

PubMed Central

Carpinelli, Marina R.; Wicks, Ian P.; Sims, Natalie A.; O’Donnell, Kristy; Hanzinikolas, Katherine; Burt, Rachel; Foote, Simon J.; Bahlo, Melanie; Alexander, Warren S.; Hilton, Douglas J.

2002-01-01

We describe the clinical, genetic, biochemical, and molecular characterization of a mouse that arose in the first generation (G1) of a random mutagenesis screen with the chemical mutagen ethyl-nitrosourea. The mouse was observed to have skeletal abnormalities inherited with an X-linked dominant pattern of inheritance. The causative mutation, named Skeletal abnormality 1 (Ska1), was shown to be a single base pair mutation in a splice donor site immediately following exon 8 of the Phex (phosphate-regulating gene with homologies to endopeptidases located on the X-chromosome) gene. This point mutation caused skipping of exon 8 from Phex mRNA, hypophosphatemia, and features of rickets. This experimentally induced phenotype mirrors the human condition X-linked hypophosphatemia; directly confirms the role of Phex in phosphate homeostasis, normal skeletal development, and rickets; and illustrates the power of mutagenesis in exploring animal models of human disease. PMID:12414538

An ethyl-nitrosourea-induced point mutation in phex causes exon skipping, x-linked hypophosphatemia, and rickets.

PubMed

Carpinelli, Marina R; Wicks, Ian P; Sims, Natalie A; O'Donnell, Kristy; Hanzinikolas, Katherine; Burt, Rachel; Foote, Simon J; Bahlo, Melanie; Alexander, Warren S; Hilton, Douglas J

2002-11-01

We describe the clinical, genetic, biochemical, and molecular characterization of a mouse that arose in the first generation (G(1)) of a random mutagenesis screen with the chemical mutagen ethyl-nitrosourea. The mouse was observed to have skeletal abnormalities inherited with an X-linked dominant pattern of inheritance. The causative mutation, named Skeletal abnormality 1 (Ska1), was shown to be a single base pair mutation in a splice donor site immediately following exon 8 of the Phex (phosphate-regulating gene with homologies to endopeptidases located on the X-chromosome) gene. This point mutation caused skipping of exon 8 from Phex mRNA, hypophosphatemia, and features of rickets. This experimentally induced phenotype mirrors the human condition X-linked hypophosphatemia; directly confirms the role of Phex in phosphate homeostasis, normal skeletal development, and rickets; and illustrates the power of mutagenesis in exploring animal models of human disease.

Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1

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

Verhaak, Roel GW; Hoadley, Katherine A; Purdom, Elizabeth

The Cancer Genome Atlas Network recently cataloged recurrent genomic abnormalities in glioblastoma multiforme (GBM). We describe a robust gene expression-based molecular classification of GBM into Proneural, Neural, Classical, and Mesenchymal subtypes and integrate multidimensional genomic data to establish patterns of somatic mutations and DNA copy number. Aberrations and gene expression of EGFR, NF1, and PDGFRA/IDH1 each define the Classical, Mesenchymal, and Proneural subtypes, respectively. Gene signatures of normal brain cell types show a strong relationship between subtypes and different neural lineages. Additionally, response to aggressive therapy differs by subtype, with the greatest benefit in the Classical subtype and no benefitmore » in the Proneural subtype. We provide a framework that unifies transcriptomic and genomic dimensions for GBM molecular stratification with important implications for future studies.« less

Prenatal Diagnosis of Persistent Hyperplastic Primary Vitreous: Report of 2 Cases and Review of the Literature.

PubMed

Esmer, Aytul Corbacioglu; Sivrikoz, Tugba Sarac; Gulec, Elif Yilmaz; Sezer, Salim; Kalelioglu, Ibrahim; Has, Recep; Yuksel, Atil

2016-10-01

Persistent hyperplastic primary vitreous is a spectrum of congenital ocular abnormalities characterized by leukocoria, microphthalmia, cataracts, extensive intravitreal hemorrhage, persistence of the hyaloid artery, glaucoma, and retinal detachment. It might be isolated or associated with congenital syndromes such as trisomy 13, Walker-Warburg syndrome, and Norrie disease. We present 2 cases of persistent hyperplastic primary vitreous diagnosed by prenatal sonography in the early third trimester. Bilateral hyperechoic lenses and retinal nonattachment were detected in the sonographic examination of the first case, whereas irregular echogenic bands between the lenses and posterior walls of the eyes were prominent in the second case. In both of the cases, ocular findings were accompanied by intracranial findings, including severe hydrocephalus, an abnormal gyral pattern, and cerebellar hypoplasia, suggesting the diagnosis of Walker-Warburg syndrome. We also present a review of the literature regarding the prenatal diagnosis of this malformation.

Computer-Aided Diagnosis of Splenic Enlargement Using Wave Pattern of Spleen in Abdominal CT Images: Initial Observations

NASA Astrophysics Data System (ADS)

Seong, Won; Cho, June-Sik; Noh, Seung-Moo; Park, Jong-Won

In general, the spleen accompanied by abnormal abdomen is hypertrophied. However, if the spleen size is originally small, it is hard to detect the splenic enlargement due to abnormal abdomen by simply measure the size. On the contrary, the spleen size of a person having a normal abdomen may be large by nature. Therefore, measuring the size of spleen is not a reliable diagnostic measure of its enlargement or the abdomen abnormality. This paper proposes an automatic method to diagnose the splenic enlargement due to abnormality, by examining the boundary pattern of spleen in abdominal CT images.

Genes commonly deleted in childhood B-cell precursor acute lymphoblastic leukemia: association with cytogenetics and clinical features

PubMed Central

Schwab, Claire J.; Chilton, Lucy; Morrison, Heather; Jones, Lisa; Al-Shehhi, Halima; Erhorn, Amy; Russell, Lisa J.; Moorman, Anthony V.; Harrison, Christine J.

2013-01-01

In childhood B-cell precursor acute lymphoblastic leukemia, cytogenetics is important in diagnosis and as an indicator of response to therapy, thus playing a key role in risk stratification of patients for treatment. Little is known of the relationship between different cytogenetic subtypes in B-cell precursor acute lymphoblastic leukemia and the recently reported copy number abnormalities affecting significant leukemia associated genes. In a consecutive series of 1427 childhood B-cell precursor acute lymphoblastic leukemia patients, we have determined the incidence and type of copy number abnormalities using multiplex ligation-dependent probe amplification. We have shown strong links between certain deletions and cytogenetic subtypes, including the novel association between RB1 deletions and intrachromosomal amplification of chromosome 21. In this study, we characterized the different copy number abnormalities and show heterogeneity of PAX5 and IKZF1 deletions and the recurrent nature of RB1 deletions. Whole gene losses are often indicative of larger deletions, visible by conventional cytogenetics. An increased number of copy number abnormalities is associated with NCI high risk, specifically deletions of IKZF1 and CDKN2A/B, which occur more frequently among these patients. IKZF1 deletions and rearrangements of CRLF2 among patients with undefined karyotypes may point to the poor risk BCR-ABL1-like group. In conclusion, this study has demonstrated in a large representative cohort of children with B-cell precursor acute lymphoblastic leukemia that the pattern of copy number abnormalities is highly variable according to the primary genetic abnormality. PMID:23508010

Walking deficits and centrophobism in an α-synuclein fly model of Parkinson's disease1

PubMed Central

Chen, A Y; Wilburn, P; Hao, X; Tully, T

2014-01-01

Parkinson's disease (PD) is a movement neurodegenerative disorder, characterized by bradykinesia, rigidity and tremor, constituting difficulties in walking and abnormal gait. Previous research shows that Drosophila expressing human α-synuclein A30P (A30P) develop deficits in geotaxis climbing; however, geotaxis climbing is a different movement modality from walking. Whether A30P flies would exhibit abnormal walking in a horizontal plane, a measure more relevant to PD, is not known. In this study, we characterized A30P fly walking using a high-speed camera and an automatic behavior tracking system. We found that old but not young A30P flies exhibited walking abnormalities, specifically decreased total moving distance, distance per movement, velocity, angular velocity and others, compared with old control flies. Those features match the definition of bradykinesia. Multivariate analysis further suggested a synergistic effect of aging and A30P, resulting in a distinct pattern of walking deficits, as seen in aged A30P flies. Psychiatric problems are common in PD patients with anxiety affecting 40–69% of patients. Central avoidance is one assessment of anxiety in various animal models. We found old but not young A30P flies exhibited increased centrophobism, suggesting possible elevated anxiety. Here, we report the first quantitative measures of walking qualities in a PD fly model and propose an alternative behavior paradigm for evaluating motor functions apart from climbing assay. PMID:25113870

Detecting subject-specific activations using fuzzy clustering

PubMed Central

Seghier, Mohamed L.; Friston, Karl J.; Price, Cathy J.

2007-01-01

Inter-subject variability in evoked brain responses is attracting attention because it may reflect important variability in structure–function relationships over subjects. This variability could be a signature of degenerate (many-to-one) structure–function mappings in normal subjects or reflect changes that are disclosed by brain damage. In this paper, we describe a non-iterative fuzzy clustering algorithm (FCP: fuzzy clustering with fixed prototypes) for characterizing inter-subject variability in between-subject or second-level analyses of fMRI data. The approach identifies the contribution of each subject to response profiles in voxels surviving a classical F-statistic criterion. The output identifies subjects who drive activation in specific cortical regions (local effects) or in voxels distributed across neural systems (global effects). The sensitivity of the approach was assessed in 38 normal subjects performing an overt naming task. FCP revealed that several subjects had either abnormally high or abnormally low responses. FCP may be particularly useful for characterizing outlier responses in rare patients or heterogeneous populations. In these cases, atypical activations may not be detected by standard tests, under parametric assumptions. The advantage of using FCP is that it searches all voxels systematically and can identify atypical activation patterns in a quantitative and unsupervised manner. PMID:17478103

Use of a Novel High-Resolution Magnetic Resonance Neurography Protocol to Detect Abnormal Dorsal Root Ganglia in Sjögren Patients With Neuropathic Pain

PubMed Central

Birnbaum, Julius; Duncan, Trisha; Owoyemi, Kristie; Wang, Kenneth C.; Carrino, John; Chhabra, Avneesh

2014-01-01

Abstract The diagnosis and treatment of patients with Sjögren syndrome (SS) with neuropathic pain pose several challenges. Patients with SS may experience unorthodox patterns of burning pain not conforming to a traditional “stocking-and-glove” distribution, which can affect the face, torso, and proximal extremities. This distribution of neuropathic pain may reflect mechanisms targeting the proximal-most element of the peripheral nervous system—the dorsal root ganglia (DRG). Skin biopsy can diagnose such a small-fiber neuropathy and is a surrogate marker of DRG neuronal cell loss. However, SS patients have been reported who have similar patterns of proximal neuropathic pain, despite having normal skin biopsy studies. In such cases, DRGs may be targeted by mechanisms not associated with neuronal cell loss. Therefore, alternative approaches are warranted to help characterize abnormal DRGs in SS patients with proximal neuropathic pain. We performed a systematic review of the literature to define the frequency and spectrum of SS peripheral neuropathies, and to better understand the attribution of SS neuropathic pain to peripheral neuropathies. We found that the frequency of SS neuropathic pain exceeded the prevalence of peripheral neuropathies, and that painful peripheral neuropathies occurred less frequently than neuropathies not always associated with pain. We developed a novel magnetic resonance neurography (MRN) protocol to evaluate DRG abnormalities. Ten SS patients with proximal neuropathic pain were evaluated by this MRN protocol, as well as by punch skin biopsies evaluating for intraepidermal nerve fiber density (IENFD) of unmyelinated nerves. Five patients had radiographic evidence of DRG abnormalities. Patients with MRN DRG abnormalities had increased IENFD of unmyelinated nerves compared to patients without MRN DRG abnormalities (30.2 [interquartile range, 4.4] fibers/mm vs. 11.0 [4.1] fibers/mm, respectively; p = 0.03). Two of these 5 SS patients whose neuropathic pain resolved with intravenous immunoglobulin (IVIg) therapy had improvement of MRN DRG abnormalities. We have developed a novel MRN protocol that can detect DRG abnormalities in SS patients with neuropathic pain who do not have markers of peripheral neuropathy. We found that SS patients with MRN DRG abnormalities had statistically significant, increased IENFD on skin biopsy studies, which may suggest a relationship between trophic mediators and neuropathic pain. Given that our literature review has demonstrated that many SS neuropathic pain patients do not have a neuropathy, our findings suggest an important niche for this MRN DRG technique in the evaluation of broader subsets of SS neuropathic pain patients who may not have underlying neuropathies. The improvement of MRN DRG abnormalities in patients with IVIg-induced remission of neuropathic pain suggests that our MRN protocol may be capturing reversible, immune-mediated mechanisms targeting the DRG. PMID:24797167

Thin-section computed tomography findings in 104 immunocompetent patients with adenovirus pneumonia.

PubMed

Park, Chan Kue; Kwon, Hoon; Park, Ji Young

2017-08-01

Background To date, there has been no computed tomography (CT) evaluation of adenovirus pneumonia in a large number of immunocompetent patients. Purpose To describe the thin-section CT findings of immunocompetent patients with adenovirus pneumonia. Material and Methods We prospectively enrolled 104 patients with adenovirus pneumonia from a military hospital. CT scans of each patient were retrospectively and independently assessed by two radiologists for the presence of abnormalities, laterality and zonal predominance of the parenchymal abnormalities, and dominant imaging patterns and their anatomic distributions. Results CT findings included consolidation (n = 92), ground-glass opacity (GGO; n = 82), septal thickening (n = 34), nodules (n = 46), bronchial wall thickening (n = 32), pleural effusion (n = 16), and lymphadenopathy (n = 3). Eighty-four patients (81%) exhibited unilateral parenchymal abnormalities and 57 (57%) exhibited lower lung zone abnormalities. The most frequently dominant CT pattern was consolidation with surrounding GGO (n = 50), with subpleural (70%) and peribronchovascular (94%) distributions. Consolidation-the second-most common pattern (n = 33)-also exhibited subpleural (79%) and peribronchovascular (97%) distributions. The dominant nodule pattern (n = 14) exhibited mixed (64%) and peribronchovascular (100%) distributions. A dominant GGO pattern was only observed in four patients; none had central distribution. Conclusion Although the manifestations of adenovirus pneumonia on CT are varied, we found the most frequent pattern was consolidation with or without surrounding GGO, with subpleural and peribronchovascular distributions. Parenchymal abnormalities were predominantly unilateral and located in the lower lung zone. If dominant consolidation findings are present in immunocompetent patients during the early stages, adenovirus pneumonia should be considered.

Identifying Neural Patterns of Functional Dyspepsia Using Multivariate Pattern Analysis: A Resting-State fMRI Study

PubMed Central

Liu, Peng; Qin, Wei; Wang, Jingjing; Zeng, Fang; Zhou, Guangyu; Wen, Haixia; von Deneen, Karen M.; Liang, Fanrong; Gong, Qiyong; Tian, Jie

2013-01-01

Background Previous imaging studies on functional dyspepsia (FD) have focused on abnormal brain functions during special tasks, while few studies concentrated on the resting-state abnormalities of FD patients, which might be potentially valuable to provide us with direct information about the neural basis of FD. The main purpose of the current study was thereby to characterize the distinct patterns of resting-state function between FD patients and healthy controls (HCs). Methodology/Principal Findings Thirty FD patients and thirty HCs were enrolled and experienced 5-mintue resting-state scanning. Based on the support vector machine (SVM), we applied multivariate pattern analysis (MVPA) to investigate the differences of resting-state function mapped by regional homogeneity (ReHo). A classifier was designed by using the principal component analysis and the linear SVM. Permutation test was then employed to identify the significant contribution to the final discrimination. The results displayed that the mean classifier accuracy was 86.67%, and highly discriminative brain regions mainly included the prefrontal cortex (PFC), orbitofrontal cortex (OFC), supplementary motor area (SMA), temporal pole (TP), insula, anterior/middle cingulate cortex (ACC/MCC), thalamus, hippocampus (HIPP)/parahippocamus (ParaHIPP) and cerebellum. Correlation analysis revealed significant correlations between ReHo values in certain regions of interest (ROI) and the FD symptom severity and/or duration, including the positive correlations between the dmPFC, pACC and the symptom severity; whereas, the positive correlations between the MCC, OFC, insula, TP and FD duration. Conclusions These findings indicated that significantly distinct patterns existed between FD patients and HCs during the resting-state, which could expand our understanding of the neural basis of FD. Meanwhile, our results possibly showed potential feasibility of functional magnetic resonance imaging diagnostic assay for FD. PMID:23874543

Characterization of sleep patterns and problems in healthcare workers in a tertiary care hospital.

PubMed

Buscemi, Dolores; Anvari, Rezza; Raj, Rishi; Nugent, Kenneth

2014-01-01

Restrictions in sleep can have important adverse effects on health and job performance. We collected information about sleep from US healthcare workers to determine whether they had sleep difficulties. We used an Internet-based survey to collect information on sleep patterns and sleep quality in healthcare workers at a tertiary care hospital. We classified these workers into short sleepers (<7 hours), normal sleepers (7-8 hours), and long sleepers (≥9 hours). We compared these three groups using simple descriptive statistics. We used logistic regression to identify factors associated with short sleep times. Of 3012 questionnaires distributed, 376 healthcare workers (12.5%) replied to this survey. The median age was 38 years, the median body mass index was 28 kg/m, and 76% were women. The median sleep duration on weekdays was 7 hours. Sixty-nine respondents (18.4%) were short sleepers, 269 of the respondents (71.5%) were normal sleepers, and 38 respondents (10.1%) were long sleepers. A total of 113 (30.1%) had sleep difficulties more than 50% of the time and 140 respondents (37.3%) were bothered by lack of energy from poor sleep. Short sleepers were less likely than other types of sleepers to have normal bedtimes and regular mealtimes. Eighty-four respondents (22.3%) went to bed between 2 AM and 2 PM. These workers were younger; slept less on the weekdays and weekends; and reported more difficulty with sleeping, feeling depressed, overconsumption of alcoholic beverages, and personal stressors. Most healthcare workers have healthy sleep patterns; however, many workers have poor sleep quality. Workers with "odd" bedtimes have abnormal sleep patterns and abnormal sleep quality; these workers need additional evaluation to understand the causes and consequences of their sleep patterns.

Spectrum of temporal bone abnormalities in patients with Waardenburg syndrome and SOX10 mutations.

PubMed

Elmaleh-Bergès, M; Baumann, C; Noël-Pétroff, N; Sekkal, A; Couloigner, V; Devriendt, K; Wilson, M; Marlin, S; Sebag, G; Pingault, V

2013-01-01

Waardenburg syndrome, characterized by deafness and pigmentation abnormalities, is clinically and genetically heterogeneous, consisting of 4 distinct subtypes and involving several genes. SOX10 mutations have been found both in types 2 and 4 Waardenburg syndrome and neurologic variants. The purpose of this study was to evaluate both the full spectrum and relative frequencies of inner ear malformations in these patients. Fifteen patients with Waardenburg syndrome and different SOX10 mutations were studied retrospectively. Imaging was performed between February 2000 and March 2010 for cochlear implant work-up, diagnosis of hearing loss, and/or evaluation of neurologic impairment. Eleven patients had both CT and MR imaging examinations, 3 had MR imaging only, and 1 had CT only. Temporal bone abnormalities were bilateral. The most frequent pattern associated agenesis or hypoplasia of ≥1 semicircular canal, an enlarged vestibule, and a cochlea with a reduced size and occasionally an abnormal shape, but with normal partition in the 13/15 cases that could be analyzed. Three patients lacked a cochlear nerve, bilaterally in 2 patients. In addition, associated abnormalities were found when adequate MR imaging sequences were available: agenesis of the olfactory bulbs (7/8), hypoplastic or absent lacrimal glands (11/14), hypoplastic parotid glands (12/14), and white matter signal anomalies (7/13). In the appropriate clinical context, bilateral agenesis or hypoplasia of the semicircular canals or both, associated with an enlarged vestibule and a cochlear deformity, strongly suggests a diagnosis of Waardenburg syndrome linked to a SOX10 mutation.

Peripheral neuropathy in genetically characterized patients with mitochondrial disorders: A study from south India.

PubMed

Bindu, Parayil Sankaran; Govindaraju, Chikanna; Sonam, Kothari; Nagappa, Madhu; Chiplunkar, Shwetha; Kumar, Rakesh; Gayathri, Narayanappa; Bharath, M M Srinivas; Arvinda, Hanumanthapura R; Sinha, Sanjib; Khan, Nahid Akthar; Govindaraj, Periyasamy; Nunia, Vandana; Paramasivam, Arumugam; Thangaraj, Kumarasamy; Taly, Arun B

2016-03-01

There are relatively few studies, which focus on peripheral neuropathy in large cohorts of genetically characterized patients with mitochondrial disorders. This study sought to analyze the pattern of peripheral neuropathy in a cohort of patients with mitochondrial disorders. The study subjects were derived from a cohort of 52 patients with a genetic diagnosis of mitochondrial disorders seen over a period of 8 years (2006-2013). All patients underwent nerve conduction studies and those patients with abnormalities suggestive of peripheral neuropathy were included in the study. Their phenotypic features, genotype, pattern of peripheral neuropathy and nerve conduction abnormalities were analyzed retrospectively. The study cohort included 18 patients (age range: 18 months-50 years, M:F- 1.2:1).The genotype included mitochondrial DNA point mutations (n=11), SURF1 mutations (n=4) and POLG1(n=3). Axonal neuropathy was noted in 12 patients (sensori-motor:n=4; sensory:n=4; motor:n=4) and demyelinating neuropathy in 6. Phenotype-genotype correlations revealed predominant axonal neuropathy in mtDNA point mutations and demyelinating neuropathy in SURF1. Patients with POLG related disorders had both sensory ataxic neuropathy and axonal neuropathy. A careful analysis of the family history, clinical presentation, biochemical, histochemical and structural analysis may help to bring out the mitochondrial etiology in patients with peripheral neuropathy and may facilitate targeted gene testing. Presence of demyelinating neuropathy in Leigh's syndrome may suggest underlying SURF1 mutations. Sensory ataxic neuropathy with other mitochondrial signatures should raise the possibility of POLG related disorder. Copyright © 2015. Published by Elsevier B.V.

Gait analysis in anorexia and bulimia nervosa.

PubMed

Cimolin, Veronica; Galli, Manuela; Vismara, Luca; Vimercati, Sara Laura; Precilios, Helmer; Cattani, Laila; Fabris De Souza, Shirley; Petroni, Maria Letizia; Capodaglio, Paolo

2013-09-13

Anorexia (AN) and Bulimia Nervosa (BN) are two common eating disorders, which appear to share some reduced motor capacities, such as a reduced balance. The presence and the extent of other motor disorders have not been investigated in a comprehensive way. The aim of this study was to quantify gait pattern in AN and BN individuals in order to ascertain possible differences from the normality range and provide novel data for developing some evidence-based rehabilitation strategies. Nineteen AN patients (age 30.16+9.73) and 20 BN patients (age 26.8+8.41) were assessed with quantitative 3D computerized Gait Analysis. Results were compared with a group of healthy controls (CG; 30.7+5.6). AN and BN patients were characterized by different gait strategies compared to CG. Spatio-temporal parameters indicated shorter step length, with AN showing the shortest values. AN walked slower than BN and CG. As for kinematics, AN and BN showed a nonphysiologic pattern at pelvis and hip level on the sagittal and frontal plane, with BN yielding the most abnormal values. Both AN and BN patients were characterized by high ankle plantar flexion capacity at toe-off when compared to CG. As for ankle kinetics, both AN and BN showed physiologic patterns. Stiffness at hip level was close to CG in both pathologic groups; at the ankle level, stiffness was significantly decreased in both groups, with AN displaying lower values. Both AN and BN were characterized by an altered gait pattern compared to CG. Biomechanical differences were evident mainly at pelvis and hip level. Loss of lean mass may lead to musculoskeletal adaptation, ultimately causing alterations in the gait pattern.

Urinary tract infection pattern in adult women followed from childhood.

PubMed

Gebäck, Carin; Hansson, Sverker; Martinell, Jeanette; Sandberg, Torsten; Jodal, Ulf

2016-07-01

The aim of this study was to describe the pattern of urinary tract infection (UTI) and bladder function in women who had experienced recurrent UTI in childhood, with and without consequent renal damage, and followed for three to four decades. A population-based cohort of women who had been followed from the first UTI in childhood and previously studied at a median age of 27 years was studied at a median age of 41 years. Renal damage was evaluated by (99m)Tc-dimercaptosuccinic acid scan. Clinical data were collected on the pattern of recurrent UTIs and bladder function. A total of 86 women were investigated, of whom 58 had suffered renal damage and 28 were without. Febrile UTI in adulthood had occurred in 22 patients, once in 15 women and twice or more in seven women. There was a change in the infection pattern over time, evident already in childhood, that was characterized by a decrease in UTI frequency and a shift from febrile to non-febrile infections. A significant association was found between renal damage and febrile UTI (p = 0.046), and between abnormal bladder function and recurrent non-febrile UTI (p = 0.002). There was no relationship between persisting vesicoureteral reflux (VUR) and proneness to either symptomatic UTI (p = 0.99) or febrile UTI in adulthood (p = 0.14). Among this study cohort there was a continuously decreasing rate of febrile UTI in adulthood. Persisting VUR was not related to UTI in adulthood. Abnormal bladder function was related to non-febrile UTI but not to febrile UTI.

Electrocardiographic features of sudden unexpected death in epilepsy.

PubMed

Chyou, Janice Y; Friedman, Daniel; Cerrone, Marina; Slater, William; Guo, Yu; Taupin, Daniel; O'Rourke, Sean; Priori, Silvia G; Devinsky, Orrin

2016-07-01

Sudden unexpected death in epilepsy (SUDEP) is the most common cause of epilepsy-related mortality. We hypothesized that electrocardiography (ECG) features may distinguish SUDEP cases from living subjects with epilepsy. Using a matched case-control design, we compared ECG studies of 12 consecutive cases of SUDEP over 10 years and 22 epilepsy controls matched for age, sex, epilepsy type (focal, generalized, or unknown/mixed type), concomitant antiepileptic, and psychotropic drug classes. Conduction intervals and prevalence of abnormal ventricular conduction diagnosis (QRS ≥110 msec), abnormal ventricular conduction pattern (QRS <110 msec, morphology of incomplete right or left bundle branch block or intraventricular conduction delay), early repolarization, and features of inherited cardiac channelopathies were assessed. Abnormal ventricular conduction diagnosis and pattern distinguished SUDEP cases from matched controls. Abnormal ventricular conduction diagnosis was present in two cases and no controls. Abnormal ventricular conduction pattern was more common in cases than controls (58% vs. 18%, p = 0.04). Early repolarization was similarly prevalent in cases and controls, but the overall prevalence exceeded that of published community-based cohorts. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

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.

Athlete's heart patterns in elite rugby players: effects of training specificities.

PubMed

Chevalier, Laurent; Kervio, Gaëlle; Corneloup, Luc; Vincent, Marie-Pierre; Baudot, Christophe; Rebeyrol, Jean-Louis; Merle, Francis; Gencel, Laurent; Carré, François

2013-02-01

Athlete's heart patterns have been widely described. However, to our knowledge, few studies have focused on professional rugby players, who train differently according to their field position. To describe electrocardiographic and echocardiographic patterns observed in elite rugby players according to their field position. One hundred and thirty-five professional rugby players at the end of the competitive season were included. According to a modified Pelliccia's classification, 68.1% of electrocardiograms were normal or had minor abnormalities, 27.2% were mildly abnormal and 3.7% were distinctly abnormal. Heart rate was higher in scrum first-row players (P<0.05). Absolute and indexed left ventricular end-diastolic internal diameters (LVIDd; absolute value 59.3±4.7 mm) exceeded 65 mm and 32 mm/m2 in 13% and 1.5% of players, respectively. Indexed LVIDd values were higher in back players (P<0.001). Left ventricular interventricular septum and posterior wall thicknesses (absolute values 9.4±1.7 mm and 9.2±1.6 mm, respectively) exceeded 13 mm in 3.7% of players. Concentric cardiac hypertrophy was noted in 3.7% of players. Except for one Wolff-Parkinson-White pattern, players with significant ECG or echocardiographic abnormalities showed no cardiovascular event or disease during follow-up. Thus, elite rugby players present similar heart patterns to elite athletes in other sports. Major electrocardiographic and echocardiographic abnormalities are quite rare. Eccentric cardiac remodelling is more frequent in back players. Copyright © 2013. Published by Elsevier Masson SAS.

Abnormal Patterns of Tongue-Palate Contact in the Speech of Individuals with Cleft Palate

ERIC Educational Resources Information Center

Gibbon, Fiona

2004-01-01

Individuals with cleft palate, even those with adequate velopharyngeal function, are at high risk for disordered lingual articulation. This article attempts to summarize current knowledge of abnormal tongue-palate contact patterns derived from electropalatographic (EPG) data in speakers with cleft palate. These data, which have been reported in 23…

Dynamic Analysis of the Abnormal Isometric Strength Movement Pattern between Shoulder and Elbow Joint in Patients with Hemiplegia.

PubMed

Liu, Yali; Hong, Yuezhen; Ji, Linhong

2018-01-01

Patients with hemiplegia usually have weak muscle selectivity and usually perform strength at a secondary joint (secondary strength) during performing a strength at one joint (primary strength). The abnormal strength pattern between shoulder and elbow joint has been analyzed by the maximum value while the performing process with strength changing from 0 to maximum then to 0 was a dynamic process. The objective of this study was to develop a method to dynamically analyze the strength changing process. Ten patients were asked to perform four group asks (maximum and 50% maximum voluntary strength in shoulder abduction, shoulder adduction, elbow flexion, and elbow extension). Strength and activities from seven muscles were measured. The changes of secondary strength had significant correlation with those of primary strength in all tasks ( R > 0.76, p < 0.01). The antagonistic muscles were moderately influenced by the primary strength ( R > 0.4, p < 0.01). Deltoid muscles, biceps brachii, triceps brachii, and brachioradialis had significant influences on the abnormal strength pattern (all p < 0.01). The dynamic method was proved to be efficient to analyze the different influences of muscles on the abnormal strength pattern. The muscles, deltoid muscles, biceps brachii, triceps brachii, and brachioradialis, much influenced the stereotyped movement pattern between shoulder and elbow joint.

Dynamic Analysis of the Abnormal Isometric Strength Movement Pattern between Shoulder and Elbow Joint in Patients with Hemiplegia

PubMed Central

2018-01-01

Patients with hemiplegia usually have weak muscle selectivity and usually perform strength at a secondary joint (secondary strength) during performing a strength at one joint (primary strength). The abnormal strength pattern between shoulder and elbow joint has been analyzed by the maximum value while the performing process with strength changing from 0 to maximum then to 0 was a dynamic process. The objective of this study was to develop a method to dynamically analyze the strength changing process. Ten patients were asked to perform four group asks (maximum and 50% maximum voluntary strength in shoulder abduction, shoulder adduction, elbow flexion, and elbow extension). Strength and activities from seven muscles were measured. The changes of secondary strength had significant correlation with those of primary strength in all tasks (R > 0.76, p < 0.01). The antagonistic muscles were moderately influenced by the primary strength (R > 0.4, p < 0.01). Deltoid muscles, biceps brachii, triceps brachii, and brachioradialis had significant influences on the abnormal strength pattern (all p < 0.01). The dynamic method was proved to be efficient to analyze the different influences of muscles on the abnormal strength pattern. The muscles, deltoid muscles, biceps brachii, triceps brachii, and brachioradialis, much influenced the stereotyped movement pattern between shoulder and elbow joint. PMID:29610654

Factors Regulating Vagal Sensory Development: Potential Role in Obesities of Developmental Origin

PubMed Central

Fox, Edward A.; Murphy, Michelle C.

2008-01-01

Contributors to increased obesity in children may include perinatal under- or overnutrition. Humans and rodents raised under these conditions develop obesity, which like obesities of other etiologies has been associated with increased meal size. Since vagal sensory innervation of the gastrointestinal (GI) tract transmits satiation signals that regulate meal size, one mechanism through which abnormal perinatal nutrition could increase meal size is by altering vagal development, possibly by causing changes in the expression of factors that control it. Therefore, we have begun to characterize development of vagal innervation of the GI tract and the expression patterns and functions of the genes involved in this process. Important events in development of mouse vagal GI innervation occurred between midgestation and the second postnatal week, suggesting they could be vulnerable to effects of abnormal nutrition preor postnatally. One gene investigated was brain- derived neurotrophic factor (BDNF), which regulates survival of a subpopulation of vagal sensory neurons. BDNF was expressed in some developing stomach wall tissues innervated by vagal afferents. At birth, mice deficient in BDNF exhibited a 50% reduction of putative intraganglionic laminar ending mechanoreceptor precursors, and a 50% increase in axons that had exited fiber bundles. Additionally, BDNF was required for patterning of individual axons and fiber bundles in the antrum and differentiation of intramuscular array mechanoreceptors in the forestomach. It will be important to determine whether abnormal perinatal environments alter development of vagal sensory innervation of the GI tract, involving effects on expression of BDNF, or other factors regulating vagal development. PMID:18234244

Preaxial Polydactyly in Sost/Sostdc1 Double Knockouts

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

Yee, C M; Collette, N M; Loots, G G

2011-07-29

In the United States, {approx}5% are born with congenital birth defects due to abnormal function of cellular processes and interactions. Sclerosteosis, a rare autosomal recessive disease, causes hyperostosis of the axial and appendicular skeleton, and patients present radial deviation, digit syndactyly, nail dysplasia, and overall high bone mineral density. Sclerosteosis is due to a loss of function of sclerostin (Sost). Sost is a Wnt (abbrev.) antagonist; when mutated, nonfunctional Sost results in hyperactive osteoblast activity which leads to abnormal high bone mass. Previous studies have shown that Sost overexpression in transgenic mice causes reduced bone mineral density and a varietymore » of limb phenotypes ranging from lost, fused, and split phalanges. Consistent with clinical manifestations of Sclerosteosis, Sost knockout mice exhibit increased generalized bone mineral density and syndactyly of the digits. Sostdc1 is a paralog of Sost that has also been described as an antagonist of Wnt signaling, in developing tooth buds. Unlike Sost knockouts, Sostdc1 null mice do not display any limb abnormalities. To determine if Sost and Sostdc1 have redundant functions during limb patterning, we examined Sost; Sostdc1 mice determined that they exhibit a novel preaxial polydactyly phenotype with a low penetrance. LacZ staining, skeletal preparations, and in situ hybridization experiments were used to help characterize this novel phenotype and understand how this phenotype develops. We find Sost and Sostdc1 to have complementary expression patterns during limb development, and the loss of their expression alters the transcription of several key limb regulators, such as Fgf8, Shh and Grem.« less

Esophageal motor disease and reflux patterns in patients with advanced pulmonary disease undergoing lung transplant evaluation.

PubMed

Seccombe, J; Mirza, F; Hachem, R; Gyawali, C P

2013-08-01

Advanced pulmonary disorders are linked to esophageal hypomotility and reflux disease. However, characterization of esophageal function using high resolution manometry (HRM) and ambulatory pH monitoring, segregation by pulmonary pathology, and comparison to traditional reflux disease are all limited in the literature. Over a 4 year period, 73 patients (55.2 ± 1.3 years, 44F) were identified who underwent esophageal function testing as part of lung transplant evaluation for advanced pulmonary disease (interstitial lung disease, ILD = 47, obstructive lung disease, OLD = 24, other = 2). Proportions of patients with motor dysfunction (≥ 80% failed sequences = severe hypomotility) and/or abnormal reflux parameters (acid exposure time, AET ≥ 4%) were determined, and compared to a cohort of 1081 patients (48.4 ± 0.4 years, 613F) referred for esophageal function testing prior to antireflux surgery (ARS). The proportion of esophageal body hypomotility was significantly higher within advanced pulmonary disease categories (35.6%), particularly ILD (44.7%), compared to ARS patients (12.1%, P < 0.0001). Abnormal AET was noted in 56.5%, and was similar between ILD and OLD, but less frequent than in the ARS group (P = 0.04). Post-transplant chronic rejection trended towards association with pretransplant elevated AET in OLD (P = 0.08) but not ILD. Mortality was not predicted by esophageal motor pattern or reflux evidence. Interstitial lung disease has a highly significant association with esophageal body hypomotility. Consequently, prevalence of abnormal esophageal acid exposure is high, but implications for post lung transplant chronic rejection remain unclear. © 2013 John Wiley & Sons Ltd.

A mutation in Ccdc39 causes neonatal hydrocephalus with abnormal motile cilia development in mice.

PubMed

Abdelhamed, Zakia; Vuong, Shawn M; Hill, Lauren; Shula, Crystal; Timms, Andrew; Beier, David; Campbell, Kenneth; Mangano, Francesco T; Stottmann, Rolf W; Goto, June

2018-01-09

Pediatric hydrocephalus is characterized by an abnormal accumulation of cerebrospinal fluid (CSF) and is one of the most common congenital brain abnormalities. However, little is known about the molecular and cellular mechanisms regulating CSF flow in the developing brain. Through whole-genome sequencing analysis, we report that a homozygous splice site mutation in coiled-coil domain containing 39 ( Ccdc39 ) is responsible for early postnatal hydrocephalus in the progressive hydrocephal us ( prh ) mouse mutant. Ccdc39 is selectively expressed in embryonic choroid plexus and ependymal cells on the medial wall of the forebrain ventricle, and the protein is localized to the axoneme of motile cilia. The Ccdc39 prh/prh ependymal cells develop shorter cilia with disorganized microtubules lacking the axonemal inner arm dynein. Using high-speed video microscopy, we show that an orchestrated ependymal ciliary beating pattern controls unidirectional CSF flow on the ventricular surface, which generates bulk CSF flow in the developing brain. Collectively, our data provide the first evidence for involvement of Ccdc39 in hydrocephalus and suggest that the proper development of medial wall ependymal cilia is crucial for normal mouse brain development. © 2018. Published by The Company of Biologists Ltd.

Electrocardiographic left ventricular strain pattern: everything old is new again.

PubMed

Schocken, Douglas D

2014-01-01

Electrocardiographic left ventricular hypertrophy (LVH) has many faces with countless features. Beyond the classic measures of LVH, including QRS voltage and duration, the left ventricular (LV) strain pattern is an element whereby characteristic R-ST depression is followed by a concave ST segment that ends in an asymmetrically inverted T wave. The LV strain pattern generally appears in states of increased systemic blood pressure and must be differentiated from similar but not identical ST-T waves indicating ischemia. The LV strain pattern has been found in population studies to be associated with poor prognosis and increased risk of adverse cardiovascular outcomes. Regression of LV strain pattern parallels decline in systemic BP during clinical trials of anti-hypertensive therapies but does not indicate or serve as a surrogate for decrease in LV mass. Newer techniques in data collection and processing may allow the process of strain to be studied in more detail to determine the ways in which electrical remodeling of the left ventricle as characterized by LVH with 'repolarization abnormalities' indicates how CV risk might be managed by using LV strain pattern as an electrocardiographic biomarker. Copyright © 2014 Elsevier Inc. All rights reserved.

Biochemical Characterization of Prions.

PubMed

Fiorini, Michele; Bongianni, Matilde; Monaco, Salvatore; Zanusso, Gianluigi

2017-01-01

Prion disease or transmissible spongiform encephalopathies are characterized by the presence of the abnormal form of the prion protein (PrP Sc ). The pathological and transmissible properties of PrP Sc are enciphered in its secondary and tertiary structures. Since it's well established that different strains of prions are linked to different conformations of PrP Sc , biochemical characterization of prions seems a preliminary but reliable approach to detect, analyze, and compare prion strains. Experimental biochemical procedures might be helpful in distinguishing PrP Sc physicochemical properties and include resistance to proteinase K (PK) digestion, insolubility in nonionic detergents, PK-resistance under denaturing conditions and sedimentation properties in sucrose gradients. This biochemical approach has been extensively applied in human prion disorders and subsequently expanded for PrP Sc characterization in animals. In particular, in sporadic Creutzfedlt-Jakob disease (sCJD) PrP Sc is characterized by two main glycotypes conventionally named Type 1 and Type 2, based on the apparent gel migration at 21 and 19kDa of the PrP Sc PK-resistant fragment. An additional PrP Sc type was identified in sCJD characterized by an unglycosylated dominant glycoform pattern and in 2010 a variably protease-sensitive prionopathy (VPSPr) was reported showing a PrP Sc with an electrophoretic ladder like pattern. Additionally, the presence of PrP Sc truncated fragments completes the electrophoretic characterization of different prion strains. By two-dimensional (2D) electrophoretic analysis additional PrP Sc pattern was identified, since this procedure provides information about the isoelectric point and the different peptides length related to PK cleavage, as well as to glycosylation extent or GPI anchor presence. We here provide and extensive review on PrP Sc biochemical analysis in human and animal prion disorders. Further, we show that PrP Sc glycotypes observed in CJD share similarities with PrP Sc in bovine spongiform encephalopathy forms (BSE). © 2017 Elsevier Inc. All rights reserved.

A common brain network links development, aging, and vulnerability to disease.

PubMed

Douaud, Gwenaëlle; Groves, Adrian R; Tamnes, Christian K; Westlye, Lars Tjelta; Duff, Eugene P; Engvig, Andreas; Walhovd, Kristine B; James, Anthony; Gass, Achim; Monsch, Andreas U; Matthews, Paul M; Fjell, Anders M; Smith, Stephen M; Johansen-Berg, Heidi

2014-12-09

Several theories link processes of development and aging in humans. In neuroscience, one model posits for instance that healthy age-related brain degeneration mirrors development, with the areas of the brain thought to develop later also degenerating earlier. However, intrinsic evidence for such a link between healthy aging and development in brain structure remains elusive. Here, we show that a data-driven analysis of brain structural variation across 484 healthy participants (8-85 y) reveals a largely--but not only--transmodal network whose lifespan pattern of age-related change intrinsically supports this model of mirroring development and aging. We further demonstrate that this network of brain regions, which develops relatively late during adolescence and shows accelerated degeneration in old age compared with the rest of the brain, characterizes areas of heightened vulnerability to unhealthy developmental and aging processes, as exemplified by schizophrenia and Alzheimer's disease, respectively. Specifically, this network, while derived solely from healthy subjects, spatially recapitulates the pattern of brain abnormalities observed in both schizophrenia and Alzheimer's disease. This network is further associated in our large-scale healthy population with intellectual ability and episodic memory, whose impairment contributes to key symptoms of schizophrenia and Alzheimer's disease. Taken together, our results suggest that the common spatial pattern of abnormalities observed in these two disorders, which emerge at opposite ends of the life spectrum, might be influenced by the timing of their separate and distinct pathological processes in disrupting healthy cerebral development and aging, respectively.

Early Brain Vulnerability in Wolfram Syndrome

PubMed Central

Hershey, Tamara; Lugar, Heather M.; Shimony, Joshua S.; Rutlin, Jerrel; Koller, Jonathan M.; Perantie, Dana C.; Paciorkowski, Alex R.; Eisenstein, Sarah A.; Permutt, M. Alan

2012-01-01

Wolfram Syndrome (WFS) is a rare autosomal recessive disease characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, diabetes insipidus, deafness, and neurological dysfunction leading to death in mid-adulthood. WFS is caused by mutations in the WFS1 gene, which lead to endoplasmic reticulum (ER) stress-mediated cell death. Case studies have found widespread brain atrophy in late stage WFS. However, it is not known when in the disease course these brain abnormalities arise, and whether there is differential vulnerability across brain regions and tissue classes. To address this limitation, we quantified regional brain abnormalities across multiple imaging modalities in a cohort of young patients in relatively early stages of WFS. Children and young adults with WFS were evaluated with neurological, cognitive and structural magnetic resonance imaging measures. Compared to normative data, the WFS group had intact cognition, significant anxiety and depression, and gait abnormalities. Compared to healthy and type 1 diabetic control groups, the WFS group had smaller intracranial volume and preferentially affected gray matter volume and white matter microstructural integrity in the brainstem, cerebellum and optic radiations. Abnormalities were detected in even the youngest patients with mildest symptoms, and some measures did not follow the typical age-dependent developmental trajectory. These results establish that WFS is associated with smaller intracranial volume with specific abnormalities in the brainstem and cerebellum, even at the earliest stage of clinical symptoms. This pattern of abnormalities suggests that WFS has a pronounced impact on early brain development in addition to later neurodegenerative effects, representing a significant new insight into the WFS disease process. Longitudinal studies will be critical for confirming and expanding our understanding of the impact of ER stress dysregulation on brain development. PMID:22792385

Mutations in KIAA0586 Cause Lethal Ciliopathies Ranging from a Hydrolethalus Phenotype to Short-Rib Polydactyly Syndrome

PubMed Central

Alby, Caroline; Piquand, Kevin; Huber, Céline; Megarbané, André; Ichkou, Amale; Legendre, Marine; Pelluard, Fanny; Encha-Ravazi, Ferechté; Abi-Tayeh, Georges; Bessières, Bettina; El Chehadeh-Djebbar, Salima; Laurent, Nicole; Faivre, Laurence; Sztriha, László; Zombor, Melinda; Szabó, Hajnalka; Failler, Marion; Garfa-Traore, Meriem; Bole, Christine; Nitschké, Patrick; Nizon, Mathilde; Elkhartoufi, Nadia; Clerget-Darpoux, Françoise; Munnich, Arnold; Lyonnet, Stanislas; Vekemans, Michel; Saunier, Sophie; Cormier-Daire, Valérie; Attié-Bitach, Tania; Thomas, Sophie

2015-01-01

KIAA0586, the human ortholog of chicken TALPID3, is a centrosomal protein that is essential for primary ciliogenesis. Its disruption in animal models causes defects attributed to abnormal hedgehog signaling; these defects include polydactyly and abnormal dorsoventral patterning of the neural tube. Here, we report homozygous mutations of KIAA0586 in four families affected by lethal ciliopathies ranging from a hydrolethalus phenotype to short-rib polydactyly. We show defective ciliogenesis, as well as abnormal response to SHH-signaling activation in cells derived from affected individuals, consistent with a role of KIAA0586 in primary cilia biogenesis. Whereas centriolar maturation seemed unaffected in mutant cells, we observed an abnormal extended pattern of CEP290, a centriolar satellite protein previously associated with ciliopathies. Our data show the crucial role of KIAA0586 in human primary ciliogenesis and subsequent abnormal hedgehog signaling through abnormal GLI3 processing. Our results thus establish that KIAA0586 mutations cause lethal ciliopathies. PMID:26166481

Polyethylene wear in Oxford unicompartmental knee replacement: a retrieval study of 47 bearings.

PubMed

Kendrick, B J L; Longino, D; Pandit, H; Svard, U; Gill, H S; Dodd, C A F; Murray, D W; Price, A J

2010-03-01

The Oxford Unicompartmental Knee replacement (UKR) was introduced as a design to reduce polyethylene wear. There has been one previous retrieval study involving this implant, which reported very low rates of wear in some specimens but abnormal patterns of wear in others. There has been no further investigation of these abnormal patterns. The bearings were retrieved from 47 patients who had received a medial Oxford UKR for anteromedial osteoarthritis of the knee. None had been studied previously. The mean time to revision was 8.4 years (sd 4.1), with 20 having been implanted for over ten years. The macroscopic pattern of polyethylene wear and the linear penetration were recorded for each bearing. The mean rate of linear penetration was 0.07 mm/year. The patterns of wear fell into three categories, each with a different rate of linear penetration; 1) no abnormal macroscopic wear and a normal articular surface, n = 16 (linear penetration rate = 0.01 mm/year); 2) abnormal macroscopic wear and normal articular surfaces with extra-articular impingement, n = 16 (linear penetration rate = 0.05 mm/year); 3) abnormal macroscopic wear and abnormal articular surfaces with intra-articular impingement +/- signs of non-congruous articulation, n = 15 (linear penetration rate = 0.12 mm/year). The differences in linear penetration rate were statistically significant (p < 0.001). These results show that very low rates of polyethylene wear are possible if the device functions normally. However, if the bearing displays suboptimal function (extra-articular, intra-articular impingement or incongruous articulation) the rates of wear increase significantly.

Mutations in the Human Laminin β2 (LAMB2) Gene and the Associated Phenotypic Spectrum

PubMed Central

Matejas, Verena; Hinkes, Bernward; Alkandari, Faisal; Al-Gazali, Lihadh; Annexstad, Ellen; Aytac, Mehmet B.; Barrow, Margaret; Bláhová, Kvĕta; Bockenhauer, Detlef; Cheong, Hae Il; Maruniak-Chudek, Iwona; Cochat, Pierre; Dötsch, Jörg; Gajjar, Priya; Hennekam, Raoul C.; Janssen, Françoise; Kagan, Mikhail; Kariminejad, Ariana; Kemper, Markus J.; Koenig, Jens; Kogan, Jillene; Kroes, Hester Y.; Kuwertz-Bröking, Eberhard; Lewanda, Amy F.; Medeira, Ana; Muscheites, Jutta; Niaudet, Patrick; Pierson, Michel; Saggar, Anand; Seaver, Laurie; Suri, Mohnish; Tsygin, Alexey; Wühl, Elke; Zurowska, Aleksandra; Uebe, Steffen; Hildebrandt, Friedhelm; Antignac, Corinne; Zenker, Martin

2010-01-01

Mutations of LAMB2 typically cause autosomal recessive Pierson syndrome, a disorder characterized by congenital nephrotic syndrome, ocular and neurologic abnormalities, but may occasionally be associated with milder or oligosymptomatic disease variants. LAMB2 encodes the basement membrane protein laminin β2 which is incorporated in specific heterotrimeric laminin isoforms and has an expression pattern corresponding to the pattern of organ manifestations in Pierson syndrome. Herein we review all previously reported and several novel LAMB2 mutations in relation to the associated phenotype in patients from 39 unrelated families. The majority of disease-causing LAMB2 mutations are truncating, consistent with the hypothesis that loss of laminin β2 function is the molecular basis of Pierson syndrome. While truncating mutations are distributed across the entire gene, missense mutations are clearly clustered in the N-terminal LN domain, which is important for intermolecular interactions. There is an association of missense mutations and small in frame deletions with a higher mean age at onset of renal disease and with absence of neurologic abnormalities, thus suggesting that at least some of these may represent hypomorphic alleles. Nevertheless, genotype alone does not appear to explain the full range of clinical variability, and therefore hitherto unidentified modifiers are likely to exist. PMID:20556798

Abnormal environmental light exposure in the intensive care environment.

PubMed

Fan, Emily P; Abbott, Sabra M; Reid, Kathryn J; Zee, Phyllis C; Maas, Matthew B

2017-08-01

We sought to characterize ambient light exposure in the intensive care unit (ICU) environment to identify patterns of light exposure relevant to circadian regulation. A light monitor was affixed to subjects' bed at eye level in a modern intensive care unit and continuously recorded illuminescence for at least 24h per subject. Blood was sampled hourly and measured for plasma melatonin. Subjects underwent hourly vital sign and bedside neurologic assessments. Care protocols and the ICU environment were not modified for the study. A total of 67,324 30-second epochs of light data were collected from 17 subjects. Light intensity peaked in the late morning, median 64.1 (interquartile range 19.7-138.7) lux. The 75th percentile of light intensity exceeded 100lx only between 9AM and noon, and never exceeded 150lx. There was no correlation between melatonin amplitude and daytime, nighttime or total light exposure (Spearman's correlation coefficients all <0.2 and p>0.5). Patients' environmental light exposure in the intensive care unit is consistently low and follows a diurnal pattern. No effect of nighttime light exposure was observed on melatonin secretion. Inadequate daytime light exposure in the ICU may contribute to abnormal circadian rhythms. Copyright © 2017 Elsevier Inc. All rights reserved.

Gender-specific effects of depression and suicidal ideation in prosocial behaviors.

PubMed

Cáceda, Ricardo; Moskovciak, Tori; Prendes-Alvarez, Stefania; Wojas, Justyna; Engel, Anzhelika; Wilker, Samantha H; Gamboa, Jorge L; Stowe, Zachary N

2014-01-01

Prosocial behaviors are essential to the ability to relate to others. Women typically display greater prosocial behavior than men. The impact of depression on prosocial behaviors and how gender interacts with those effects are not fully understood. We explored the role of gender in the potential effects of depression on prosocial behavior. We examined prosocial behaviors using a modified version of the Trust Game in a clinical population and community controls. Study participants were characterized on the severity of depression and anxiety, presence of suicidal ideation, history of childhood trauma, recent stressful life events, and impulsivity. We correlated behavioral outcomes with gender and clinical variables using analysis of variance and multiple regression analysis. The 89 participants comprised four study groups: depressed women, depressed men, healthy women and healthy men (n = 16-36). Depressed men exhibited reciprocity more frequently than healthy men. Depression induced an inversion of the gender-specific pattern of self-centered behavior. Suicidal ideation was associated with increased reciprocity behavior in both genders, and enhancement of the effect of depression on gender-specific self-centered behavior. Depression, particularly suicidal ideation, is associated with reversal of gender-specific patterns of prosocial behavior, suggesting abnormalities in sexual hormones regulation. This explanation is supported by known abnormalities in the hypothalamus-pituitary-adrenal and hypothalamus-pituitary-gonadal axes found in depression.

Analysis of the pattern of expression of the Fanconi anemia group C (Facc) gene during murine development

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

Krasnoshtein, F.; Buchwald, M.

1994-09-01

Fanconi anemia (FA) is an autosomal recessive disorder characterized by a variety of congenital and skeletal malformations, progressive pancytopanenia and predisposition to malignancies. FA cells display chromosomal instability and hypersensitivity to DNA-damaging agents. Both the human and the corresponding murine cDNAs have been cloned in our lab. Here we describe the expression of Facc during mouse development, using mRNA in situ hybridization. Our aim is to obtain clues on the possible function of the Facc gene product during development that may help elucidate basic defect(s) in FA. In addition, knowledge of the exact pattern of Facc expression will assist inmore » interpreting the phenotypes of mutant mice, currently being developed. In embryos the gene is diffusely expressed over the entire embryo, with higher hybridization levels in the mesenchyme and in both upper and lower extremities. Specific expression of Facc is seen in the perichondrium and marrow of long bones of hind limbs/hip; long bones of front limbs/shoulder region; developing digits of front and hind paws; and ribs. The signal is also detected in the following regions: cranial/frontal; facial/periorbital and maxillary/mandibular, hair follicles, diaphragm and lung. In addition, generalized Facc expression is seen during these embryonic stages. The pattern of Facc expression is consistent with the known skeletal abnormalities in FA patients, which include radial ray deformities, metacarpal hypoplasia, and abnormalities of lower limbs, ribs, head and face. The signal in the lung is consistent with the lung lobe absence and abnormal pulmonary drainage that have been detected in some FA patients. The sloped forehead and microcephaly in FA patients may have some association with the signal seen in the frontal region of the mouse cranium. Taken together, our results suggest that Facc is directly involved in the development of various embryonic tissues, particularly bone.« less

Abnormal small-world architecture of top–down control networks in obsessive–compulsive disorder

PubMed Central

Zhang, Tijiang; Wang, Jinhui; Yang, Yanchun; Wu, Qizhu; Li, Bin; Chen, Long; Yue, Qiang; Tang, Hehan; Yan, Chaogan; Lui, Su; Huang, Xiaoqi; Chan, Raymond C.K.; Zang, Yufeng; He, Yong; Gong, Qiyong

2011-01-01

Background Obsessive–compulsive disorder (OCD) is a common neuropsychiatric disorder that is characterized by recurrent intrusive thoughts, ideas or images and repetitive ritualistic behaviours. Although focal structural and functional abnormalities in specific brain regions have been widely studied in populations with OCD, changes in the functional relations among them remain poorly understood. This study examined OCD–related alterations in functional connectivity patterns in the brain’s top–down control network. Methods We applied resting-state functional magnetic resonance imaging to investigate the correlation patterns of intrinsic or spontaneous blood oxygen level–dependent signal fluctuations in 18 patients with OCD and 16 healthy controls. The brain control networks were first constructed by thresholding temporal correlation matrices of 39 brain regions associated with top–down control and then analyzed using graph theory-based approaches. Results Compared with healthy controls, the patients with OCD showed decreased functional connectivity in the posterior temporal regions and increased connectivity in various control regions such as the cingulate, precuneus, thalamus and cerebellum. Furthermore, the brain’s control networks in the healthy controls showed small-world architecture (high clustering coefficients and short path lengths), suggesting an optimal balance between modularized and distributed information processing. In contrast, the patients with OCD showed significantly higher local clustering, implying abnormal functional organization in the control network. Further analysis revealed that the changes in network properties occurred in regions of increased functional connectivity strength in patients with OCD. Limitations The patient group in the present study was heterogeneous in terms of symptom clusters, and most of the patients with OCD were medicated. Conclusion Our preliminary results suggest that the organizational patterns of intrinsic brain activity in the control networks are altered in patients with OCD and thus provide empirical evidence for aberrant functional connectivity in the large-scale brain systems in people with this disorder. PMID:20964957

Seizure and electroencephalographic changes in the newborn period induced by opiates and corrected by naloxone infusion.

PubMed

da Silva, O; Alexandrou, D; Knoppert, D; Young, G B

1999-03-01

To describe the association between opioid administration in the newborn period and neurologic abnormalities. Case reports of two infants who presented with seizure activity and abnormal electroencephalograms associated with opiate administration, and reversed by naloxone. The first was a preterm infant who developed a burst-suppression pattern on the electroencephalogram while receiving a continuous infusion of morphine and muscle paralysis. Naloxone injection during the electroencephalogram recording reversed the burst-suppression pattern. The second was a term infant receiving fentanyl infusion for pain control following surgery, who presented with motor seizure that was only partially controlled with barbiturates. An abnormal electroencephalogram recording during the opiate infusion improved with naloxone administration. Our observations indicate a potential for neurologic abnormalities, including induction of seizure activity and electroencephalogram abnormalities, suggesting caution when opiates are used for sedation and/or pain control in the newborn period.

Radionuclide bone scanning of osteosarcoma: falsely extended uptake patterns.

PubMed

Chew, F S; Hudson, T M

1982-07-01

The pathologic specimens of 18 osteosarcomas of long bones were examined to correlate histologic abnormalities with abnormalities seen on preoperative 99mTc pyrophosphate or methylene diphosphonate bone scans. Seven scans accurately represented the extent of the tumor. Eleven scans disclosed increased activity extending beyond the radiographic abnormalities. In eight of these, there was no occult tumor extension and in the other three, the scan activity did not accurately portray the skip metastases that were present. Therefore, these 11 scans demonstrated the falsely extended pattern of uptake beyond the true limits of the tumors. Pathologic slides were available for 10 of the 11 areas of bone that exhibited extended uptake. In two instances, there was no pathologic abnormality. In the other eight cases we found marrow hyperemia, medullary reactive bone, or periosteal new bone. This is the first description of these histologic abnormalities of medullary bone in areas of extended uptake on radionuclide bone scans.

Comprehensive genetic characterization of CLL: a study on 506 cases analysed with chromosome banding analysis, interphase FISH, IgV(H) status and immunophenotyping.

PubMed

Haferlach, C; Dicker, F; Schnittger, S; Kern, W; Haferlach, T

2007-12-01

In CLL data from chromosome banding analysis (CBA) have been scarce due to the low proliferative activity of CLL cells in vitro. We improved the cultivation technique using an immunostimulatory CpG-oligonucleotide DSP30 and IL-2. A total of 506 CLL samples were analysed with CBA and interphase FISH using probes for the detection of trisomy 12, IgH rearrangements and deletions of 6q21, 11q22.3 (ATM), 13q14 (D13S25 and D13S319) and 17p13 (TP53). A total of 500 of 506 (98.8%) cases were successfully stimulated for metaphase generation and are subject to this study. Aberrations were detected in 415 of 500 (83.0%) cases by CBA and in 392 of 500 (78.4%) cases by FISH. CBA detected 832 abnormalities and FISH only 502. Therefore, CBA offers important information in addition to FISH. (1) CLL is characterized mainly by genomic imbalances and reciprocal translocations are rare. (2) A subgroup with complex aberrant karyotype (16.4%) is identified which is associated with an unmutated IgV(H) status and CD38 expression (P=0.034 and 0.02, respectively). (3) Additional abnormalities are detectable providing new biological insights into different CLL subclasses revealing a much more heterogeneous pattern of cytogenetic abnormalities as assumed so far based on FISH data only. Therefore, prospective clinical trials should evaluate the prognostic impact of newly available CBA data.

EMQN best practice guidelines for the molecular genetic testing and reporting of fragile X syndrome and other fragile X-associated disorders

PubMed Central

Biancalana, Valérie; Glaeser, Dieter; McQuaid, Shirley; Steinbach, Peter

2015-01-01

Different mutations occurring in the unstable CGG repeat in 5' untranslated region of FMR1 gene are responsible for three fragile X-associated disorders. An expansion of over ∼200 CGG repeats when associated with abnormal methylation and inactivation of the promoter is the mutation termed ‘full mutation' and is responsible for fragile X syndrome (FXS), a neurodevelopmental disorder described as the most common cause of inherited intellectual impairment. The term ‘abnormal methylation' is used here to distinguish the DNA methylation induced by the expanded repeat from the ‘normal methylation' occurring on the inactive X chromosomes in females with normal, premutation, and full mutation alleles. All male and roughly half of the female full mutation carriers have FXS. Another anomaly termed ‘premutation' is characterized by the presence of 55 to ∼200 CGGs without abnormal methylation, and is the cause of two other diseases with incomplete penetrance. One is fragile X-associated primary ovarian insufficiency (FXPOI), which is characterized by a large spectrum of ovarian dysfunction phenotypes and possible early menopause as the end stage. The other is fragile X-associated tremor/ataxia syndrome (FXTAS), which is a late onset neurodegenerative disorder affecting males and females. Because of the particular pattern and transmission of the CGG repeat, appropriate molecular testing and reporting is very important for the optimal genetic counselling in the three fragile X-associated disorders. Here, we describe best practice guidelines for genetic analysis and reporting in FXS, FXPOI, and FXTAS, including carrier and prenatal testing. PMID:25227148

Walking deficits and centrophobism in an α-synuclein fly model of Parkinson's disease.

PubMed

Chen, A Y; Wilburn, P; Hao, X; Tully, T

2014-11-01

Parkinson's disease (PD) is a movement neurodegenerative disorder, characterized by bradykinesia, rigidity and tremor, constituting difficulties in walking and abnormal gait. Previous research shows that Drosophila expressing human α-synuclein A30P (A30P) develop deficits in geotaxis climbing; however, geotaxis climbing is a different movement modality from walking. Whether A30P flies would exhibit abnormal walking in a horizontal plane, a measure more relevant to PD, is not known. In this study, we characterized A30P fly walking using a high-speed camera and an automatic behavior tracking system. We found that old but not young A30P flies exhibited walking abnormalities, specifically decreased total moving distance, distance per movement, velocity, angular velocity and others, compared with old control flies. Those features match the definition of bradykinesia. Multivariate analysis further suggested a synergistic effect of aging and A30P, resulting in a distinct pattern of walking deficits, as seen in aged A30P flies. Psychiatric problems are common in PD patients with anxiety affecting 40-69% of patients. Central avoidance is one assessment of anxiety in various animal models. We found old but not young A30P flies exhibited increased centrophobism, suggesting possible elevated anxiety. Here, we report the first quantitative measures of walking qualities in a PD fly model and propose an alternative behavior paradigm for evaluating motor functions apart from climbing assay. © 2014 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.

Abnormal epithelial structure and chronic lung inflammation after repair of chlorine-induced airway injury

PubMed Central

Mo, Yiqun; Chen, Jing; Humphrey, David M.; Fodah, Ramy A.; Warawa, Jonathan M.

2014-01-01

Chlorine is a toxic gas used in a variety of industrial processes and is considered a chemical threat agent. High-level chlorine exposure causes acute lung injury, but the long-term effects of acute chlorine exposure are unclear. Here we characterized chronic pulmonary changes following acute chlorine exposure in mice. A/J mice were exposed to 240 parts per million-hour chlorine or sham-exposed to air. Chlorine inhalation caused sloughing of bronchial epithelium 1 day after chlorine exposure, which was repaired with restoration of a pseudostratified epithelium by day 7. The repaired epithelium contained an abnormal distribution of epithelial cells containing clusters of club or ciliated cells rather than the uniformly interspersed pattern of these cells in unexposed mice. Although the damaged epithelium in A/J mice was repaired rapidly, and minimal airway fibrosis was observed, chlorine-exposed mice developed pneumonitis characterized by infiltration of alveoli with neutrophils and prominent, large, foamy macrophages. Levels of CXCL1/KC, CXCL5/LPS-induced CXC chemokine, granulocyte colony-stimulating factor, and VEGF in bronchoalveolar (BAL) fluid from chlorine-exposed mice showed steadily increasing trends over time. BAL protein levels were increased on day 4 and remained elevated out to day 28. The number of bacteria cultured from lungs of chlorine-exposed mice 4 wk after exposure was not increased compared with sham-exposed mice, indicating that the observed pneumonitis was not driven by bacterial infection of the lung. The results indicate that acute chlorine exposure may cause chronic abnormalities in the lungs despite rapid repair of injured epithelium. PMID:25398987

Abnormal epithelial structure and chronic lung inflammation after repair of chlorine-induced airway injury.

PubMed

Mo, Yiqun; Chen, Jing; Humphrey, David M; Fodah, Ramy A; Warawa, Jonathan M; Hoyle, Gary W

2015-01-15

Chlorine is a toxic gas used in a variety of industrial processes and is considered a chemical threat agent. High-level chlorine exposure causes acute lung injury, but the long-term effects of acute chlorine exposure are unclear. Here we characterized chronic pulmonary changes following acute chlorine exposure in mice. A/J mice were exposed to 240 parts per million-hour chlorine or sham-exposed to air. Chlorine inhalation caused sloughing of bronchial epithelium 1 day after chlorine exposure, which was repaired with restoration of a pseudostratified epithelium by day 7. The repaired epithelium contained an abnormal distribution of epithelial cells containing clusters of club or ciliated cells rather than the uniformly interspersed pattern of these cells in unexposed mice. Although the damaged epithelium in A/J mice was repaired rapidly, and minimal airway fibrosis was observed, chlorine-exposed mice developed pneumonitis characterized by infiltration of alveoli with neutrophils and prominent, large, foamy macrophages. Levels of CXCL1/KC, CXCL5/LPS-induced CXC chemokine, granulocyte colony-stimulating factor, and VEGF in bronchoalveolar (BAL) fluid from chlorine-exposed mice showed steadily increasing trends over time. BAL protein levels were increased on day 4 and remained elevated out to day 28. The number of bacteria cultured from lungs of chlorine-exposed mice 4 wk after exposure was not increased compared with sham-exposed mice, indicating that the observed pneumonitis was not driven by bacterial infection of the lung. The results indicate that acute chlorine exposure may cause chronic abnormalities in the lungs despite rapid repair of injured epithelium. Copyright © 2015 the American Physiological Society.

Abnormal tuning of saccade-related cells in pontine reticular formation of strabismic monkeys.

PubMed

Walton, Mark M G; Mustari, Michael J

2015-08-01

Strabismus is a common disorder, characterized by a chronic misalignment of the eyes and numerous visual and oculomotor abnormalities. For example, saccades are often highly disconjugate. For humans with pattern strabismus, the horizontal and vertical disconjugacies vary with eye position. In monkeys, manipulations that disturb binocular vision during the first several weeks of life result in a chronic strabismus with characteristics that closely match those in human patients. Early onset strabismus is associated with altered binocular sensitivity of neurons in visual cortex. Here we test the hypothesis that brain stem circuits specific to saccadic eye movements are abnormal. We targeted the pontine paramedian reticular formation, a structure that directly projects to the ipsilateral abducens nucleus. In normal animals, neurons in this structure are characterized by a high-frequency burst of spikes associated with ipsiversive saccades. We recorded single-unit activity from 84 neurons from four monkeys (two normal, one exotrope, and one esotrope), while they made saccades to a visual target on a tangent screen. All 24 neurons recorded from the normal animals had preferred directions within 30° of pure horizontal. For the strabismic animals, the distribution of preferred directions was normal on one side of the brain, but highly variable on the other. In fact, 12/60 neurons recorded from the strabismic animals preferred vertical saccades. Many also had unusually weak or strong bursts. These data suggest that the loss of corresponding binocular vision during infancy impairs the development of normal tuning characteristics for saccade-related neurons in brain stem. Copyright © 2015 the American Physiological Society.

Hallermann-Streiff Syndrome

PubMed Central

Thomas, Jayakar; Ragavi, B Sindhu; Raneesha, PK; Ahmed, N Ashwak; Cynthia, S; Manoharan, D; Manoharan, R

2013-01-01

Hallermann-Streiff syndrome (HSS) is a rare disorder characterized by dyscephalia, with facial and dental abnormalities. We report a 12-year-old female child who presented with abnormal facial features, dental abnormalities and sparse scalp hair. PMID:24082185

[Chatergee syndrome and anesthesia. Apropos of a case].

PubMed

Le Marec, C; Belat, C; Caroff, P; Puidupin, M; Paris, A; Fourel, D; Dumas, P; Le Guern, G

1996-01-01

A combination of complete left bundle branch block (LBBB) and symmetrical negative T waves on the ECG characterizes the Chattergee syndrome. This pattern is infrequently and fortuitously detected in the absence of clinical symptoms. However, when appearing during general anaesthesia, it may lead to diagnostic difficulties to rule out a myocardial ischaemia. One case of this pattern was observed near the end of an otherwise non-complicated cholecystectomy in a ASA II 45 year old man, ECG abnormalities lasted for only a short time. Recovery and outcome were uneventful. Investigations were negative except for an early LBBB during the exercise test. Echocardiography and coronarography were normal. No therapy was given. In such perioperative cases, it is recommended to keep a very cautious attitude and to search for an incipient coronary disease which cannot be completely excluded in some cases.

Epicardial adipose tissue volume a diagnostic study for independent predicting disorder of circadian rhythm of blood pressure in patients with essential hypertension.

PubMed

Zhou, L; Deng, Y; Gong, J; Chen, X; Zhang, Q; Wang, J

2016-05-30

The aim of the study was to determine whether epicardial adipose tissue volume (EATV), a new cardiometabolic risk factor, is associated with circadian changes of blood pressure (BP) in patients with newly diagnosed essential hypertension. Ninety patients with newly diagnosed essential hypertension underwent ambulatory blood pressure monitoring for 24 h. EATV was measured using cardiac computed tomography. These patients were categorized into three groups according to their BP patterns (group 1, n=46, dipper hypertension, also called normal pattern; group 2, n=24, non-dipper hypertension; group 3, n=20, anti-dipper hypertension; group 2 and 3 are also called abnormal pattern). Data were collected retrospectively and compared between hypertensive patients with normal pattern and abnormal pattern. The normal pattern hypertensive patient had significant lower mean EATV and BP ((EATV, 91.3±29.4 cm3) than those of abnormal pattern patients including group 2 (EATV, 116.2±31.06cm3, <0.01) and group 3 (EATV, 124.8±28.5cm3, P<0.01). Mean systolic BP over 24 h (BPs24) and mean diastolic BP over 24 h (BPd24) of group 1 (BPs24, 135.7 ± 12.6 mmHg; BPd24, 83.6 ± 10.6 mmHg) were significantly lower than those of group 2 (BPs24, 150.1± 17.6 mmHg, P<0.01; BPd24, 93.2 ± 16.5 mmHg, P<0.01) and group 3 (BPs24, 154.1 ± 16.6mmHg, P<0.01; BPd24, 93.8 ± 17.5 mmHg; P<0.01). Bivariate correlation analysis showed that correlation coefficient of EATV with abnormal blood pressure mode was 0.500 (p<0.001), partial correlation coefficient after adjustment for waist circumference and body mass index was 0.469 (p<0.001). When multivariate backward logistic regression analysis was performed to assess the correlation of BP pattern with EAT volume, it showed that the prevalence of abnormal BP pattern (non-dipper and anti-dipper BP pattern) increased by 1.54 times after adjusting for age and gender per additional 10 cm3 of EAT volume. Receiver operating characteristic curve for EAT alone indicated that the cutoff value of 95.17cm3 had the best performance in predicting abnormal BP pattern with a sensitivity of 75.0% and a specificity of 72.7%. EATV was elevated in newly diagnosed and untreated patients with non-dipper hypertension and anti-dipper hypertension. EATV measured by cardiac computed tomography can be used to indicate the increased risk of circadian rhythm of blood pressure.

Self-regulation of brain oscillations as a treatment for aberrant brain connections in children with autism.

PubMed

Pineda, J A; Juavinett, A; Datko, M

2012-12-01

Autism is a highly varied developmental disorder typically characterized by deficits in reciprocal social interaction, difficulties with verbal and nonverbal communication, and restricted interests and repetitive behaviors. Although a wide range of behavioral, pharmacological, and alternative medicine strategies have been reported to ameliorate specific symptoms for some individuals, there is at present no cure for the condition. Nonetheless, among the many incompatible observations about aspects of the development, anatomy, and functionality of the autistic brain, it is widely agreed that it is characterized by widespread aberrant connectivity. Such disordered connectivity, be it increased, decreased, or otherwise compromised, may complicate healthy synchronization and communication among and within different neural circuits, thereby producing abnormal processing of sensory inputs necessary for normal social life. It is widely accepted that the innate properties of brain electrical activity produce pacemaker elements and linked networks that oscillate synchronously or asynchronously, likely reflecting a type of functional connectivity. Using phase coherence in multiple frequency EEG bands as a measure of functional connectivity, studies have shown evidence for both global hypoconnectivity and local hyperconnectivity in individuals with ASD. However, the nature of the brain's experience-dependent structural plasticity suggests that these abnormal patterns may be reversed with the proper type of treatment. Indeed, neurofeedback (NF) training, an intervention based on operant conditioning that results in self-regulation of brain electrical oscillations, has shown promise in addressing marked abnormalities in functional and structural connectivity. It is hypothesized that neurofeedback produces positive behavioral changes in ASD children by normalizing the aberrant connections within and between neural circuits. NF exploits the brain's plasticity to normalize aberrant connectivity patterns apparent in the autistic brain. By grounding this training in known anatomical (e.g., mirror neuron system) and functional markers (e.g., mu rhythms) of autism, NF training holds promise to support current treatments for this complex disorder. The proposed hypothesis specifically states that neurofeedback-induced alpha mu (8-12Hz) rhythm suppression or desynchronization, a marker of cortical activation, should induce neuroplastic changes and lead to normalization in relevant mirroring networks that have been associated with higher-order social cognition. Copyright © 2012 Elsevier Ltd. All rights reserved.

Repeatability and Reliability Characterization of Phonocardiograph Systems Using Wavelet and Backpropagation Neural Network

NASA Astrophysics Data System (ADS)

Sumarna; Astono, J.; Purwanto, A.; Agustika, D. K.

2018-04-01

Phonocardiograph (PCG) system consisting of an electronic stethoscope, mic condenser, mic preamp, and the battery has been developed. PCG system is used to detect heart abnormalities. Although PCG is not popular because of many things that affect its performance, in this research we try to reduce the factors that affecting its consistency To find out whether the system is repeatable and reliable the system have to be characterized first. This research aims to see whether the PCG system can provide the same results for measurements of the same patient. Characterization of the system is done by analyzing whether the PCG system can recognize the S1 and S2 part of the same person. From the recording result, S1 and S2 then transformed by using Discrete Wavelet Transform of Haar mother wavelet of level 1 and extracted the feature by using data range of approximation coefficients. The result was analyzed by using pattern recognition system of backpropagation neural network. Partially obtained data used as training data and partly used as test data. From the results of the pattern recognition system, it can be concluded that the system accuracy in recognizing S1 reach 87.5% and S2 only hit 67%.

Characteristic cardiac phenotypes are detected by cardiovascular magnetic resonance in patients with different clinical phenotypes and genotypes of mitochondrial myopathy.

PubMed

Florian, Anca; Ludwig, Anna; Stubbe-Dräger, Bianca; Boentert, Matthias; Young, Peter; Waltenberger, Johannes; Rösch, Sabine; Sechtem, Udo; Yilmaz, Ali

2015-05-22

Mitochondrial myopathies (MM) are a heterogeneous group of inherited conditions resulting from a primary defect in the mitochondrial respiratory chain with consecutively impaired cellular energy metabolism. Small sized studies using mainly electrocardiography (ECG) and echocardiography have revealed cardiac abnormalities ranging from conduction abnormalities and arrhythmias to hypertrophic or dilated cardiomyopathy in these patients. Recently, characteristic patterns of cardiac involvement were documented by cardiovascular magnetic resonance (CMR) in patients with chronic progressive external ophthalmoplegia (CPEO)/Kearns-Sayre syndrome (KSS) and with mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS). The present study aimed to characterize the prevalence and pattern of cardiac abnormalities and to test the additional diagnostic value of CMR in this patient population. The hypothesis that different neuromuscular MM syndromes present with different cardiac disease phenotypes was evaluated. Sixty-four MM patients (50 ± 15 years, 44% male) and 25 matched controls (52 ± 14 years, 36% male) prospectively underwent cardiac evaluations including CMR (comprising cine- and late-gadolinium-enhancement (LGE) imaging). Based on the neuromuscular phenotype and genotype, the patients were grouped: (a) CPEO/KSS (N = 33); (b) MELAS/-like (N = 11); c) myoclonic epilepsy with ragged-red fibers (MERRF) (N = 3) and d) other non-specific MM forms (N = 17). Among the 64 MM patients, 34 (53%) had at least one abnormal CMR finding: 18 (28%) demonstrated an impaired left ventricular ejection-fraction (LV-EF <60%), 14 (22%) had unexplained LV hypertrophy and 21 (33%) were LGE-positive. Compared to controls, MM patients showed significantly higher maximal wall thickness (10 ± 3 vs. 8 ± 2 mm, p = 0.005) and concentricity (LV mass to end-diastolic volume: 0.84 ± 0.27 vs. 0.67 ± 0.11, p < 0.0001) with frequent presence of non-ischemic LGE (30% vs. 0%, p = 0.001). CPEO/KSS showed a predominantly intramural pattern of LGE mostly confined to the basal LV inferolateral wall (8/10; 80%) in addition to a tendency toward concentric remodelling. MELAS/-like patients showed the highest frequency of cardiac disease (in 10/11 (91%)), a mostly concentric LV hypertrophy (6/9; 67%) with or without LV systolic dysfunction and a predominantly focal, patchy LGE equally distributed among LV segments (8/11; 73%). Patients with MERRF and non-specific MM had no particular findings. Pathological CMR findings indicating cardiac involvement were detected significantly more often than pathological ECG results or elevated cardiac serum biomarkers (34 (53%) vs. 18 (28%) vs. 21 (33%); p = 0.008). Cardiac involvement is a frequent finding in MM patients - and particularly present in KSS/CPEO as well as MELAS/-like patients. Despite a high variability in clinical presentation, CPEO/KSS patients typically show an intramural pattern of LGE in the basal inferolateral wall whereas MELAS patients are characterized by overt concentric hypertrophy and a rather unique, focally accentuated and diffusely distributed LGE.

Vertebral metastases from neuroendocrine tumours: How to avoid false positives on 68Ga-DOTA-TOC PET using CT pattern analysis?

PubMed

Gauthé, Mathieu; Testart Dardel, Nathalie; Ruiz Santiago, Fernando; Ohnona, Jessica; Nataf, Valérie; Montravers, Françoise; Talbot, Jean-Noël

2018-03-12

To develop criteria to improve discrimination between vertebral metastases from neuroendocrine tumours (NETs) and benign bone lesions on PET combined with CT using DOTA-D-Phe 1 -Tyr 3 -octreotide labelled with gallium-68 ( 68 Ga-DOTA-TOC). In 535 NET patients, 68 Ga-DOTA-TOC PET/CT examinations were reviewed retrospectively for vertebral CT lesions and/or PET foci. For each vertebral PET abnormality, appearance on CT, biological volume (BV), standardized uptake value (SUV max ) and ratios to those of reference organs were determined. All vertebral abnormalities were characterized as a metastasis, a typical vertebral haemangioma (VH) or other benign lesion. In 79 patients (14.8 %), we found 107 metastases, 34 VHs and 31 other benign lesions in the spine. The optimal cut-off values to differentiate metastases from benign lesions were BV ≥0.72 cm 3 , SUVmax ≥2, SUVmax ratio to a reference vertebra ≥2.1, to liver ≥0.28 and to spleen ≥0.14. They corresponded to lesion-based 68 Ga-DOTA-TOC PET/CT sensitivity of 87 %, 98 %, 97 %, 99 % and 94 %, and specificity of 55 %, 100 %, 90 %, 97 %, 100 %, respectively. The high sensitivity of 68 Ga-DOTA-TOC-PET/CT in detecting NET vertebral metastases was confirmed; this study showed that specificity could be improved by combining CT features and quantifying 68 Ga-DOTA-TOC uptake. • Bone metastases in neuroendocrine tumours correlate with prognosis. • Benign bone lesions may mimic metastases on 68 Ga-DOTA-TOC PET/CT imaging. • The specific polka-dot CT pattern may be missing in some vertebral haemangiomas. • Lesion atypical for haemangiomas can be better characterized by quantifying 68 Ga-DOTA-TOC uptake.

Targeted molecular investigation in patients within the clinical spectrum of Auriculocondylar syndrome.

PubMed

Romanelli Tavares, Vanessa L; Zechi-Ceide, Roseli M; Bertola, Debora R; Gordon, Christopher T; Ferreira, Simone G; Hsia, Gabriella S P; Yamamoto, Guilherme L; Ezquina, Suzana A M; Kokitsu-Nakata, Nancy M; Vendramini-Pittoli, Siulan; Freitas, Renato S; Souza, Josiane; Raposo-Amaral, Cesar A; Zatz, Mayana; Amiel, Jeanne; Guion-Almeida, Maria L; Passos-Bueno, Maria Rita

2017-04-01

Auriculocondylar syndrome, mainly characterized by micrognathia, small mandibular condyle, and question mark ears, is a rare disease segregating in an autosomal dominant pattern in the majority of the families reported in the literature. So far, pathogenic variants in PLCB4, GNAI3, and EDN1 have been associated with this syndrome. It is caused by a developmental abnormality of the first and second pharyngeal arches and it is associated with great inter- and intra-familial clinical variability, with some patients not presenting the typical phenotype of the syndrome. Moreover, only a few patients of each molecular subtype of Auriculocondylar syndrome have been reported and sequenced. Therefore, the spectrum of clinical and genetic variability is still not defined. In order to address these questions, we searched for alterations in PLCB4, GNAI3, and EDN1 in patients with typical Auriculocondylar syndrome (n = 3), Pierre Robin sequence-plus (n = 3), micrognathia with additional craniofacial malformations (n = 4), or non-specific auricular dysplasia (n = 1), which could represent subtypes of Auriculocondylar syndrome. We found novel pathogenic variants in PLCB4 only in two of three index patients with typical Auriculocondylar syndrome. We also performed a detailed comparative analysis of the patients presented in this study with those previously published, which showed that the pattern of auricular abnormality and full cheeks were associated with molecularly characterized individuals with Auriculocondylar syndrome. Finally, our data contribute to a better definition of a set of parameters for clinical classification that may be used as a guidance for geneticists ordering molecular testing for Auriculocondylar syndrome. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Unsupervised segmentation of lungs from chest radiographs

NASA Astrophysics Data System (ADS)

Ghosh, Payel; Antani, Sameer K.; Long, L. Rodney; Thoma, George R.

2012-03-01

This paper describes our preliminary investigations for deriving and characterizing coarse-level textural regions present in the lung field on chest radiographs using unsupervised grow-cut (UGC), a cellular automaton based unsupervised segmentation technique. The segmentation has been performed on a publicly available data set of chest radiographs. The algorithm is useful for this application because it automatically converges to a natural segmentation of the image from random seed points using low-level image features such as pixel intensity values and texture features. Our goal is to develop a portable screening system for early detection of lung diseases for use in remote areas in developing countries. This involves developing automated algorithms for screening x-rays as normal/abnormal with a high degree of sensitivity, and identifying lung disease patterns on chest x-rays. Automatically deriving and quantitatively characterizing abnormal regions present in the lung field is the first step toward this goal. Therefore, region-based features such as geometrical and pixel-value measurements were derived from the segmented lung fields. In the future, feature selection and classification will be performed to identify pathological conditions such as pulmonary tuberculosis on chest radiographs. Shape-based features will also be incorporated to account for occlusions of the lung field and by other anatomical structures such as the heart and diaphragm.

Autosomal Recessive Hypotrichosis with Woolly Hair Caused by a Mutation in the Keratin 25 Gene Expressed in Hair Follicles.

PubMed

Zernov, Nikolay V; Skoblov, Mikhail Y; Marakhonov, Andrey V; Shimomura, Yutaka; Vasilyeva, Tatyana A; Konovalov, Fedor A; Abrukova, Anna V; Zinchenko, Rena A

2016-06-01

Hypotrichosis is an abnormal condition characterized by decreased hair density and various defects in hair structure and growth patterns. In particular, in woolly hair, hypotrichosis is characterized by a tightly curled structure and abnormal growth. In this study, we present a detailed comparative examination of individuals affected by autosomal-recessive hypotrichosis (ARH), which distinguishes two types of ARH. Earlier, we demonstrated that exon 4 deletion in the lipase H gene caused an ARH (hypotrichosis 7; MIM: 604379) in populations of the Volga-Ural region of Russia. Screening for this mutation in all affected individuals revealed its presence only in the group with the hypotrichosis 7 phenotype. Other patients formed a separate group of woolly hair-associated ARH, with a homozygous missense mutation c.712G>T (p.Val238Leu) in a highly conserved position of type I keratin KRT25 (K25). Haplotype analysis indicated a founder effect. An expression study in the HaCaT cell line demonstrated a deleterious effect of the p.Val238Leu mutation on the formation of keratin intermediate filaments. Hence, we have identified a previously unreported missense mutation in the KRT25 gene causing ARH with woolly hair. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Lung perfusion characteristics in pulmonary arterial hypertension (PAH) and peripheral forms of chronic thromboembolic pulmonary hypertension (pCTEPH): Dual-energy CT experience in 31 patients.

PubMed

Giordano, Jessica; Khung, Suonita; Duhamel, Alain; Hossein-Foucher, Claude; Bellèvre, Dimitri; Lamblin, Nicolas; Remy, Jacques; Remy-Jardin, Martine

2017-04-01

To compare lung perfusion in PAH and pCTEPH on dual-energy CT (DECT) examinations. Thirty-one patients with PAH (group 1; n = 19) and pCTEPH (group 2; n = 12) underwent a dual-energy chest CTA with reconstruction of diagnostic and perfusion images. Perfusion alterations were analysed at a segmental level. V/Q scintigraphy was available in 22 patients (group 1: 13/19; group 2: 9/12). CT perfusion was abnormal in 52.6 % of group 1 patients and in 100 % of group 2 patients (p = 0.0051). The patterns of perfusion alteration significantly differed between the two groups (p < 0.0001): (1) in group 1, 96.6 % of segments with abnormal perfusion showed patchy defects; (2) in group 2, the most frequent abnormalities consisted of patchy (58.5 %) and PE-type (37.5 %) defects. Paired comparison of CT perfusion and scintigraphy showed concordant findings in 76.9 % of group 1 (10/13) and 100 % of group 2 (9/9) patients, with a predominant or an exclusive patchy pattern in group 1 and a mixed pattern of abnormalities in group 2. Lung perfusion alterations at DECT are less frequent and more homogeneous in PAH than in pCTEPH, with a high level of concordant findings with V/Q scintigraphy. • Depiction of chronic pulmonary embolism exclusively located on peripheral arteries is difficult. • The main differential diagnosis of pCTEPH is PAH. • The pattern of DECT perfusion changes can help differentiate PAH and pCETPH. • In PAH, almost all segments with abnormal perfusion showed patchy defects. • In pCTEPH, patchy and PE-type defects were the most frequent abnormalities.

Syndromic intellectual disability: a new phenotype caused by an aromatic amino acid decarboxylase gene (DDC) variant.

PubMed

Graziano, Claudio; Wischmeijer, Anita; Pippucci, Tommaso; Fusco, Carlo; Diquigiovanni, Chiara; Nõukas, Margit; Sauk, Martin; Kurg, Ants; Rivieri, Francesca; Blau, Nenad; Hoffmann, Georg F; Chaubey, Alka; Schwartz, Charles E; Romeo, Giovanni; Bonora, Elena; Garavelli, Livia; Seri, Marco

2015-04-01

The causative variant in a consanguineous family in which the three patients (two siblings and a cousin) presented with intellectual disability, Marfanoid habitus, craniofacial dysmorphisms, chronic diarrhea and progressive kyphoscoliosis, has been identified through whole exome sequencing (WES) analysis. WES study identified a homozygous DDC variant in the patients, c.1123C>T, resulting in p.Arg375Cys missense substitution. Mutations in DDC cause a recessive metabolic disorder (aromatic amino acid decarboxylase, AADC, deficiency, OMIM #608643) characterized by hypotonia, oculogyric crises, excessive sweating, temperature instability, dystonia, severe neurologic dysfunction in infancy, and specific abnormalities of neurotransmitters and their metabolites in the cerebrospinal fluid (CSF). In our family, analysis of neurotransmitters and their metabolites in patient's CSF shows a pattern compatible with AADC deficiency, although the clinical signs are different from the classic form. Our work expands the phenotypic spectrum associated with DDC variants, which therefore can cause an additional novel syndrome without typical movement abnormalities. Copyright © 2015 Elsevier B.V. All rights reserved.

Identification of abnormal motor cortex activation patterns in children with cerebral palsy by functional near-infrared spectroscopy

NASA Astrophysics Data System (ADS)

Khan, Bilal; Tian, Fenghua; Behbehani, Khosrow; Romero, Mario I.; Delgado, Mauricio R.; Clegg, Nancy J.; Smith, Linsley; Reid, Dahlia; Liu, Hanli; Alexandrakis, George

2010-05-01

We demonstrate the utility of functional near-infrared spectroscopy (fNIRS) as a tool for physicians to study cortical plasticity in children with cerebral palsy (CP). Motor cortex activation patterns were studied in five healthy children and five children with CP (8.4+/-2.3 years old in both groups) performing a finger-tapping protocol. Spatial (distance from center and area difference) and temporal (duration and time-to-peak) image metrics are proposed as potential biomarkers for differentiating abnormal cortical activation in children with CP from healthy pediatric controls. In addition, a similarity image-analysis concept is presented that unveils areas that have similar activation patterns as that of the maximum activation area, but are not discernible by visual inspection of standard activation images. Metrics derived from the images presenting areas of similarity are shown to be sensitive identifiers of abnormal activation patterns in children with CP. Importantly, the proposed similarity concept and related metrics may be applicable to other studies for the identification of cortical activation patterns by fNIRS.

Abnormal Image Detection in Endoscopy Videos Using a Filter Bank and Local Binary Patterns

PubMed Central

Nawarathna, Ruwan; Oh, JungHwan; Muthukudage, Jayantha; Tavanapong, Wallapak; Wong, Johnny; de Groen, Piet C.; Tang, Shou Jiang

2014-01-01

Finding mucosal abnormalities (e.g., erythema, blood, ulcer, erosion, and polyp) is one of the most essential tasks during endoscopy video review. Since these abnormalities typically appear in a small number of frames (around 5% of the total frame number), automated detection of frames with an abnormality can save physician’s time significantly. In this paper, we propose a new multi-texture analysis method that effectively discerns images showing mucosal abnormalities from the ones without any abnormality since most abnormalities in endoscopy images have textures that are clearly distinguishable from normal textures using an advanced image texture analysis method. The method uses a “texton histogram” of an image block as features. The histogram captures the distribution of different “textons” representing various textures in an endoscopy image. The textons are representative response vectors of an application of a combination of Leung and Malik (LM) filter bank (i.e., a set of image filters) and a set of Local Binary Patterns on the image. Our experimental results indicate that the proposed method achieves 92% recall and 91.8% specificity on wireless capsule endoscopy (WCE) images and 91% recall and 90.8% specificity on colonoscopy images. PMID:25132723

[Clinical and molecular study in a family with cleidocranial dysplasia].

PubMed

Callea, Michele; Fattori, Fabiana; Bertini, Enrico S; Yavuz, Izzet; Bellacchio, Emanuele; Avendaño, Andrea; Araque, Dianora; Lacruz-Rengel, María A; Da Silva, Gloria; Cammarata-Scalisi, Francisco

2017-12-01

Cleidocranial dysplasia is an uncommon bone dysplasia with an autosomal dominant inheritance pattern characterized by short stature, large fontanels, midface hypoplasia, absence or hypoplasia of clavicles and orodental alterations. This is Estudio clínico y molecular en una familia con displasia cleidocraneal Clinical and molecular study in a family with cleidocranial dysplasia produced by mutations in the RUNX2 gene located at 6p21.1. We report two male adolescents (cousins), with cleidocranial dysplasia who presented a heterozygous missense mutation (c.674G> A, p.R225Q) in the RUNX2 gene, characterized by severe phenotype, such as absent clavicles, but with variation in the delayed fontanel closure, dental abnormalities (anomalies in shape and number) and scoliosis, thus demonstrating intrafamilial variation in these patients with the same genotype. Sociedad Argentina de Pediatría.

Abnormal regional cerebral blood flow in childhood autism.

PubMed

Ohnishi, T; Matsuda, H; Hashimoto, T; Kunihiro, T; Nishikawa, M; Uema, T; Sasaki, M

2000-09-01

Neuroimaging studies of autism have shown abnormalities in the limbic system and cerebellar circuits and additional sites. These findings are not, however, specific or consistent enough to build up a coherent theory of the origin and nature of the brain abnormality in autistic patients. Twenty-three children with infantile autism and 26 non-autistic controls matched for IQ and age were examined using brain-perfusion single photon emission computed tomography with technetium-99m ethyl cysteinate dimer. In autistic subjects, we assessed the relationship between regional cerebral blood flow (rCBF) and symptom profiles. Images were anatomically normalized, and voxel-by-voxel analyses were performed. Decreases in rCBF in autistic patients compared with the control group were identified in the bilateral insula, superior temporal gyri and left prefrontal cortices. Analysis of the correlations between syndrome scores and rCBF revealed that each syndrome was associated with a specific pattern of perfusion in the limbic system and the medial prefrontal cortex. The results confirmed the associations of (i) impairments in communication and social interaction that are thought to be related to deficits in the theory of mind (ToM) with altered perfusion in the medial prefrontal cortex and anterior cingulate gyrus, and (ii) the obsessive desire for sameness with altered perfusion in the right medial temporal lobe. The perfusion abnormalities seem to be related to the cognitive dysfunction observed in autism, such as deficits in ToM, abnormal responses to sensory stimuli, and the obsessive desire for sameness. The perfusion patterns suggest possible locations of abnormalities of brain function underlying abnormal behaviour patterns in autistic individuals.

Comprehensive classification test of scapular dyskinesis: A reliability study.

PubMed

Huang, Tsun-Shun; Huang, Han-Yi; Wang, Tyng-Guey; Tsai, Yung-Shen; Lin, Jiu-Jenq

2015-06-01

Assessment of scapular dyskinesis (SD) is of clinical interest, as SD is believed to be related to shoulder pathology. However, no clinical assessment with sufficient reliability to identify SD and provide treatment strategies is available. The purpose of this study was to investigate the reliability of the comprehensive SD classification method. Cross-sectional reliability study. Sixty subjects with unilateral shoulder pain were evaluated by two independent physiotherapists with a visual-based palpation method. SD was classified as single abnormal scapular pattern [inferior angle (pattern I), medial border (pattern II), superior border of scapula prominence or abnormal scapulohumeral rhythm (pattern III)], a mixture of the above abnormal scapular patterns, or normal pattern (pattern IV). The assessment of SD was evaluated as subjects performed bilateral arm raising/lowering movements with a weighted load in the scapular plane. Percentage of agreement and kappa coefficients were calculated to determine reliability. Agreement between the 2 independent physiotherapists was 83% (50/60, 6 subjects as pattern III and 44 subjects as pattern IV) in the raising phase and 68% (41/60, 5 subjects as pattern I, 12 subjects as pattern II, 12 subjects as pattern IV, 12 subjects as mixed patterns I and II) in the lowering phase. The kappa coefficients were 0.49-0.64. We concluded that the visual-based palpation classification method for SD had moderate to substantial inter-rater reliability. The appearance of different types of SD was more pronounced in the lowering phase than in the raising phase of arm movements. Copyright © 2014 Elsevier Ltd. All rights reserved.

Histopathological pattern of abnormal uterine bleeding in endometrial biopsies.

PubMed

Vaidya, S; Lakhey, M; Vaidya, S; Sharma, P K; Hirachand, S; Lama, S; KC, S

2013-03-01

Abnormal uterine bleeding is a common presenting complaint in gyanecology out patient department. Histopathological evaluation of the endometrial samples plays a significant role in the diagnosis of abnormal uterine bleeding. This study was carried out to determine the histopathological pattern of the endometrium in women of various age groups presenting with abnormal uterine bleeding. Endometrial biopsies and curettings of patients presenting with abnormal uterine bleeding was retrospectively studied. A total of 403 endometrial biopsies and curettings were analyzed. The age of the patients ranged from 18 to 70 years. Normal cyclical endometrium was seen in 165 (40.94%) cases, followed by 54 (13.40%) cases of disordered proliferative endometrium and 44 (10.92%) cases of hyperplasia. Malignancy was seen in 10 (2.48%) cases. Hyperplasia and malignancy were more common in the perimenopausal and postmenopausal age groups. Histopathological examination of endometrial biopsies and curettings in patients presenting with abnormal uterine bleeding showed a wide spectrum of changes ranging from normal endometrium to malignancy. Endometrial evaluation is specially recommended in women of perimenopausal and postmenopausal age groups presenting with AUB, to rule out a possibility of any preneoplastic condition or malignancy.

Mutations in KIAA0586 Cause Lethal Ciliopathies Ranging from a Hydrolethalus Phenotype to Short-Rib Polydactyly Syndrome.

PubMed

Alby, Caroline; Piquand, Kevin; Huber, Céline; Megarbané, André; Ichkou, Amale; Legendre, Marine; Pelluard, Fanny; Encha-Ravazi, Ferechté; Abi-Tayeh, Georges; Bessières, Bettina; El Chehadeh-Djebbar, Salima; Laurent, Nicole; Faivre, Laurence; Sztriha, László; Zombor, Melinda; Szabó, Hajnalka; Failler, Marion; Garfa-Traore, Meriem; Bole, Christine; Nitschké, Patrick; Nizon, Mathilde; Elkhartoufi, Nadia; Clerget-Darpoux, Françoise; Munnich, Arnold; Lyonnet, Stanislas; Vekemans, Michel; Saunier, Sophie; Cormier-Daire, Valérie; Attié-Bitach, Tania; Thomas, Sophie

2015-08-06

KIAA0586, the human ortholog of chicken TALPID3, is a centrosomal protein that is essential for primary ciliogenesis. Its disruption in animal models causes defects attributed to abnormal hedgehog signaling; these defects include polydactyly and abnormal dorsoventral patterning of the neural tube. Here, we report homozygous mutations of KIAA0586 in four families affected by lethal ciliopathies ranging from a hydrolethalus phenotype to short-rib polydactyly. We show defective ciliogenesis, as well as abnormal response to SHH-signaling activation in cells derived from affected individuals, consistent with a role of KIAA0586 in primary cilia biogenesis. Whereas centriolar maturation seemed unaffected in mutant cells, we observed an abnormal extended pattern of CEP290, a centriolar satellite protein previously associated with ciliopathies. Our data show the crucial role of KIAA0586 in human primary ciliogenesis and subsequent abnormal hedgehog signaling through abnormal GLI3 processing. Our results thus establish that KIAA0586 mutations cause lethal ciliopathies. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Organizing pneumonia pattern in the follow-up CT of Legionella-infected patients.

PubMed

Haroon, Attiya; Higa, Futoshi; Hibiya, Kenji; Haranaga, Shusaku; Yara, Satomi; Tateyama, Masao; Fujita, Jiro

2011-08-01

The main aim of this study was to describe the appearance of the CT pattern of organizing pneumonia in Legionella-infected patients. Serial CT scans obtained from five sporadic cases of Legionella pneumophila pneumonia were retrospectively reviewed. The mean time of follow-up was 14 days. Chest CT was analyzed with regard to frequency and appearance of CT patterns of pulmonary abnormalities. Consolidation and ground-glass opacities, with or without an air bronchogram, were the most common abnormalities detected in CT scans during follow-up patients with L. pneumophila pneumonia. Two patterns were observed: subpleural and peribronchovascular. The subpleural pattern was seen in four patients and the peribronchovascular pattern in one. Interlobular septal thickening was seen in one patient. Pleural effusion was seen in one patient. The CT pattern of organizing pneumonia, a subpleural pattern, was frequently observed after treatment of L. pneumophila pneumonia.

Stress Cardiac MRI in Women With Myocardial Infarction and Nonobstructive Coronary Artery Disease.

PubMed

Mauricio, Rina; Srichai, Monvadi B; Axel, Leon; Hochman, Judith S; Reynolds, Harmony R

2016-10-01

In a prospective study, cardiac MRI (CMR) and intravascular ultrasound were performed in women with myocardial infarction (MI) and nonobstructive coronary artery disease (MINOCA). Forty participants underwent adenosine-stress CMR (sCMR). Abnormal perfusion may co-localize with ischemic late gadolinium enhancement (LGE) and T2-weighted signal hyperintensity (T2+), suggesting microvascular dysfunction contributed to MI. Qualitative perfusion analysis was performed by 2 independent readers. Abnormal myocardial perfusion reserve index (MPRI) was defined as global average ≤1.84. Abnormal rest perfusion was present in 10 patients (25%) and stress perfusion abnormalities in 25 (63%). Abnormal stress perfusion was not associated with LGE but tended to occur with T2+. Among patients with abnormal perfusion and LGE, the LGE pattern was ischemic in half. The locations of abnormal perfusion and LGE matched in 75%, T2+ in 100%. Abnormal stress perfusion was not associated with plaque disruption and matched in location in 63%. MPRI was abnormal in 10 patients (25%) and was not associated with LGE, T2+ or plaque disruption. Abnormal perfusion on sCMR is common among women with MINOCA. Abnormal perfusion usually co-localized with LGE and/or T2+ when present. Variability in LGE pattern leads to uncertainty about whether the finding of abnormal perfusion was cause or consequence of the tissue state leading to LGE. Low MPRI, possibly indicating diffuse microvascular disease, was observed with and without LGE and T2+. Multiple mechanisms may lead to abnormal perfusion on sCMR. Microvascular dysfunction may contribute to the pathogenesis of and coexist with other causes of MINOCA. © 2016 Wiley Periodicals, Inc.

Dynamic Changes in Amygdala Activation and Functional Connectivity in Children and Adolescents with Anxiety Disorders

PubMed Central

Swartz, Johnna R.; Phan, K. Luan; Angstadt, Mike; Fitzgerald, Kate D.; Monk, Christopher S.

2015-01-01

Anxiety disorders are associated with abnormalities in amygdala function and prefrontal cortex-amygdala connectivity. The majority of fMRI studies have examined mean group differences in amygdala activation or connectivity in children and adolescents with anxiety disorders relative to controls, but emerging evidence suggests that abnormalities in amygdala function are dependent on the timing of the task and may vary across the course of a scanning session. The goal of the present study was to extend our knowledge of the dynamics of amygdala dysfunction by examining whether changes in amygdala activation and connectivity over scanning differ in pediatric anxiety disorder patients relative to typically developing controls during an emotion processing task. Examining changes in activation over time allows for a comparison of how brain function differs during initial exposure to novel stimuli versus more prolonged exposure. Participants included 34 anxiety disorder patients and 19 controls 7 to 19 years old. Participants performed an emotional face matching task during fMRI scanning and the task was divided into thirds in order to examine change in activation over time. Results demonstrated that patients exhibited an abnormal pattern of amygdala activation characterized by an initially heightened amygdala response relative to controls at the beginning of scanning, followed by significant decreases in activation over time. In addition, controls evidenced greater prefrontal cortex-amygdala connectivity during the beginning of scanning relative to patients. These results indicate that differences in emotion processing between the groups vary from initial exposure to novel stimuli relative to more prolonged exposure. Implications are discussed regarding how this pattern of neural activation may relate to altered early-occurring or anticipatory emotion-regulation strategies and maladaptive later-occurring strategies in children and adolescents with anxiety disorders. PMID:25422963

p14(ARF) nuclear overexpression in aggressive B-cell lymphomas is a sensor of malfunction of the common tumor suppressor pathways.

PubMed

Sánchez-Aguilera, Abel; Sánchez-Beato, Margarita; García, Juan F; Prieto, Ignacio; Pollan, Marina; Piris, Miguel A

2002-02-15

p14(ARF), the alternative product from the human INK4a/ARF locus, antagonizes Hdm2 and mediates p53 activation in response to oncogenic stimuli. An immunohistochemical study of p14(ARF) expression in 74 samples of aggressive B-cell lymphomas was performed, demonstrating an array of different abnormalities. A distinct nucleolar expression pattern was detected in nontumoral tissue and a subset of lymphomas (50/74). In contrast, a group of cases (8/74) showed absence of p14(ARF) expression, dependent either on promoter hypermethylation or gene loss. Additionally, 16 out of 74 cases displayed an abnormal nuclear p14(ARF) overexpression not confined to the nucleoli, as confirmed by confocal microscopy, and that was associated with high levels of p53 and Hdm2. A genetic study of these cases failed to show any alteration in the p14(ARF) gene, but revealed the presence of p53 mutations in over 50% of these cases. An increased growth fraction and a more aggressive clinical course, with a shortened survival time, also characterized the group of tumors with p14(ARF) nuclear overexpression. Moreover, this p14(ARF) expression pattern was more frequent in tumors displaying accumulated alterations in the p53, p16(INK4a), and p27(KIP1) tumor supressors. These observations, together with the consideration of the central role of p14(ARF) in cell cycle control, suggest that p14(ARF) abnormal nuclear overexpression is a sensor of malfunction of the major cell cycle regulatory pathways, and consequently a marker of a high tumor aggressivity.

Engrailed-2 (En2) deletion produces multiple neurodevelopmental defects in monoamine systems, forebrain structures and neurogenesis and behavior

PubMed Central

Genestine, Matthieu; Lin, Lulu; Durens, Madel; Yan, Yan; Jiang, Yiqin; Prem, Smrithi; Bailoor, Kunal; Kelly, Brian; Sonsalla, Patricia K.; Matteson, Paul G.; Silverman, Jill; Crawley, Jacqueline N.; Millonig, James H.; DiCicco-Bloom, Emanuel

2015-01-01

Many genes involved in brain development have been associated with human neurodevelopmental disorders, but underlying pathophysiological mechanisms remain undefined. Human genetic and mouse behavioral analyses suggest that ENGRAILED-2 (EN2) contributes to neurodevelopmental disorders, especially autism spectrum disorder. In mouse, En2 exhibits dynamic spatiotemporal expression in embryonic mid-hindbrain regions where monoamine neurons emerge. Considering their importance in neuropsychiatric disorders, we characterized monoamine systems in relation to forebrain neurogenesis in En2-knockout (En2-KO) mice. Transmitter levels of serotonin, dopamine and norepinephrine (NE) were dysregulated from Postnatal day 7 (P7) to P21 in En2-KO, though NE exhibited the greatest abnormalities. While NE levels were reduced ∼35% in forebrain, they were increased 40–75% in hindbrain and cerebellum, and these patterns paralleled changes in locus coeruleus (LC) fiber innervation, respectively. Although En2 promoter was active in Embryonic day 14.5–15.5 LC neurons, expression diminished thereafter and gene deletion did not alter brainstem NE neuron numbers. Significantly, in parallel with reduced NE levels, En2-KO forebrain regions exhibited reduced growth, particularly hippocampus, where P21 dentate gyrus granule neurons were decreased 16%, suggesting abnormal neurogenesis. Indeed, hippocampal neurogenic regions showed increased cell death (+77%) and unexpectedly, increased proliferation. Excess proliferation was restricted to early Sox2/Tbr2 progenitors whereas increased apoptosis occurred in differentiating (Dcx) neuroblasts, accompanied by reduced newborn neuron survival. Abnormal neurogenesis may reflect NE deficits because intra-hippocampal injections of β-adrenergic agonists reversed cell death. These studies suggest that disruption of hindbrain patterning genes can alter monoamine system development and thereby produce forebrain defects that are relevant to human neurodevelopmental disorders. PMID:26220976

Assessment of Microvascular Abnormalities by Nailfold Capillaroscopy in Juvenile Dermatomyositis After Medium- to Long-Term Followup.

PubMed

Barth, Zoltan; Witczak, Birgit N; Flatø, Berit; Koller, Akos; Sjaastad, Ivar; Sanner, Helga

2018-05-01

In juvenile dermatomyositis (DM), microvascular abnormalities, measured by nailfold capillaroscopy (NFC), are common early in the disease course. We aimed to compare the presence of NFC abnormalities in patients with medium- to long-term juvenile DM with that of controls, and to explore associations between NFC abnormalities and disease activity and other disease characteristics. Fifty-eight juvenile DM patients with a median disease duration of 16.8 (range 2-38) years were clinically examined and compared with matched controls. By NFC, we assessed nailfold capillary density (NCD), giant capillaries, scleroderma, and neovascular pattern (defined as scleroderma active or late pattern). NFC was analyzed with researchers blinded to patient/control identity and disease characteristics. We measured disease activity and damage by validated tools, and patients were categorized as having active or inactive disease according to the Paediatric Rheumatology International Trials Organisation criteria. Compared to controls, patients had decreased NCD (mean ± SD 6.4 ± 2.1/mm versus 7.6 ± 0.8/mm; P = 0.001) and showed more abnormality in all other NFC parameters; 36% of patients versus 4% of controls had NCD <6/mm (P < 0.001). Giant capillaries, scleroderma, and neovascular pattern were found in 9%, 84%, and 41% of patients, respectively. Patients with active disease (n = 30) presented more frequently with neovascular pattern than patients with inactive disease (n = 28) (P = 0.041). Decreased NCD and neovascular pattern were associated with higher levels of disease activity and impaired muscle function. After medium- to long-term followup, juvenile DM patients had decreased NCD and, often, neovascular pattern; both were associated with higher levels of disease activity and impaired muscle function. This suggests that NFC can be a biomarker for disease activity in longstanding juvenile DM too. © 2017, American College of Rheumatology.

Linked functional network abnormalities during intrinsic and extrinsic activity in schizophrenia as revealed by a data-fusion approach.

PubMed

Hashimoto, Ryu-Ichiro; Itahashi, Takashi; Okada, Rieko; Hasegawa, Sayaka; Tani, Masayuki; Kato, Nobumasa; Mimura, Masaru

2018-01-01

Abnormalities in functional brain networks in schizophrenia have been studied by examining intrinsic and extrinsic brain activity under various experimental paradigms. However, the identified patterns of abnormal functional connectivity (FC) vary depending on the adopted paradigms. Thus, it is unclear whether and how these patterns are inter-related. In order to assess relationships between abnormal patterns of FC during intrinsic activity and those during extrinsic activity, we adopted a data-fusion approach and applied partial least square (PLS) analyses to FC datasets from 25 patients with chronic schizophrenia and 25 age- and sex-matched normal controls. For the input to the PLS analyses, we generated a pair of FC maps during the resting state (REST) and the auditory deviance response (ADR) from each participant using the common seed region in the left middle temporal gyrus, which is a focus of activity associated with auditory verbal hallucinations (AVHs). PLS correlation (PLS-C) analysis revealed that patients with schizophrenia have significantly lower loadings of a component containing positive FCs in default-mode network regions during REST and a component containing positive FCs in the auditory and attention-related networks during ADR. Specifically, loadings of the REST component were significantly correlated with the severities of positive symptoms and AVH in patients with schizophrenia. The co-occurrence of such altered FC patterns during REST and ADR was replicated using PLS regression, wherein FC patterns during REST are modeled to predict patterns during ADR. These findings provide an integrative understanding of altered FCs during intrinsic and extrinsic activity underlying core schizophrenia symptoms.

Describing temporal variation in reticuloruminal pH using continuous monitoring data.

PubMed

Denwood, M J; Kleen, J L; Jensen, D B; Jonsson, N N

2018-01-01

Reticuloruminal pH has been linked to subclinical disease in dairy cattle, leading to considerable interest in identifying pH observations below a given threshold. The relatively recent availability of continuously monitored data from pH boluses gives new opportunities for characterizing the normal patterns of pH over time and distinguishing these from abnormal patterns using more sensitive and specific methods than simple thresholds. We fitted a series of statistical models to continuously monitored data from 93 animals on 13 farms to characterize normal variation within and between animals. We used a subset of the data to relate deviations from the normal pattern to the productivity of 24 dairy cows from a single herd. Our findings show substantial variation in pH characteristics between animals, although animals within the same farm tended to show more consistent patterns. There was strong evidence for a predictable diurnal variation in all animals, and up to 70% of the observed variation in pH could be explained using a simple statistical model. For the 24 animals with available production information, there was also a strong association between productivity (as measured by both milk yield and dry matter intake) and deviations from the expected diurnal pattern of pH 2 d before the productivity observation. In contrast, there was no association between productivity and the occurrence of observations below a threshold pH. We conclude that statistical models can be used to account for a substantial proportion of the observed variability in pH and that future work with continuously monitored pH data should focus on deviations from a predictable pattern rather than the frequency of observations below an arbitrary pH threshold. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Environmental factors influencing the risk of autism

PubMed Central

Karimi, Padideh; Kamali, Elahe; Mousavi, Seyyed Mohammad; Karahmadi, Mojgan

2017-01-01

Autism is a developmental disability with age of onset in childhood (under 3 years old), which is characterized by definite impairments in social interactions, abnormalities in speech, and stereotyped pattern of behaviors. Due to the progress of autism in recent decades, a wide range of studies have been done to identify the etiological factors of autism. It has been found that genetic and environmental factors are both involved in autism pathogenesis. Hence, in this review article, a set of environmental factors involved in the occurrence of autism has been collected, and finally, some practical recommendations for reduction of the risk of this devastating disease in children are represented. PMID:28413424

ANIMAL MODELS OF DYSTONIA: LESSONS FROM A MUTANT RAT

PubMed Central

LeDoux, Mark S.

2010-01-01

Dystonia is a motor sign characterized by involuntary muscle contractions which produce abnormal postures. Genetic factors contribute significantly to primary dystonia. In comparison, secondary dystonia can be caused by a wide variety of metabolic, structural, infectious, toxic and inflammatory insults to the nervous system. Although classically ascribed to dysfunction of the basal ganglia, studies of diverse animal models have pointed out that dystonia is a network disorder with important contributions from abnormal olivocerebellar signaling. In particular, work with the dystonic (dt) rat has engendered dramatic paradigm shifts in dystonia research. The dt rat manifests generalized dystonia caused by deficiency of the neuronally-restricted protein caytaxin. Electrophysiological and biochemical studies have shown that defects at the climbing fiber-Purkinje cell synapse in the dt rat lead to abnormal bursting firing patterns in the cerebellar nuclei, which increases linearly with postnatal age. In a general sense, the dt rat has shown the scientific and clinical communities that dystonia can arise from dysfunctional cerebellar cortex. Furthermore, work with the dt rat has provided evidence that dystonia (1) is a neurodevelopmental network disorder and (2) can be driven by abnormal cerebellar output. In large part, work with other animal models has expanded upon studies in the dt rat and shown that primary dystonia is a multi-nodal network disorder associated with defective sensorimotor integration. In addition, experiments in genetically-engineered models have been used to examine the underlying cellular pathologies that drive primary dystonia. PMID:21081162

Quantifying cortical development in typically developing toddlers and young children, 1-6 years of age.

PubMed

Remer, Justin; Croteau-Chonka, Elise; Dean, Douglas C; D'Arpino, Sara; Dirks, Holly; Whiley, Dannielle; Deoni, Sean C L

2017-06-01

Cortical maturation, including age-related changes in thickness, volume, surface area, and folding (gyrification), play a central role in developing brain function and plasticity. Further, abnormal cortical maturation is a suspected substrate in various behavioral, intellectual, and psychiatric disorders. However, in order to characterize the altered development associated with these disorders, appreciation of the normative patterns of cortical development in neurotypical children between 1 and 6 years of age, a period of peak brain development during which many behavioral and developmental disorders emerge, is necessary. To this end, we examined measures of cortical thickness, surface area, mean curvature, and gray matter volume across 34 bilateral regions in a cohort of 140 healthy children devoid of major risk factors for abnormal development. From these data, we observed linear, logarithmic, and quadratic patterns of change with age depending on brain region. Cortical thinning, ranging from 10% to 20%, was observed throughout most of the brain, with the exception of posterior brain structures, which showed initial cortical thinning from 1 to 5 years, followed by thickening. Cortical surface area expansion ranged from 20% to 108%, and cortical curvature varied by 1-20% across the investigated age range. Right-left hemisphere asymmetry was observed across development for each of the 4 cortical measures. Our results present new insight into the normative patterns of cortical development across an important but under studied developmental window, and provide a valuable reference to which trajectories observed in neurodevelopmental disorders may be compared. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Desynchronization boost by non-uniform coordinated reset stimulation in ensembles of pulse-coupled neurons

PubMed Central

Lücken, Leonhard; Yanchuk, Serhiy; Popovych, Oleksandr V.; Tass, Peter A.

2013-01-01

Several brain diseases are characterized by abnormal neuronal synchronization. Desynchronization of abnormal neural synchrony is theoretically compelling because of the complex dynamical mechanisms involved. We here present a novel type of coordinated reset (CR) stimulation. CR means to deliver phase resetting stimuli at different neuronal sub-populations sequentially, i.e., at times equidistantly distributed in a stimulation cycle. This uniform timing pattern seems to be intuitive and actually applies to the neural network models used for the study of CR so far. CR resets the population to an unstable cluster state from where it passes through a desynchronized transient, eventually resynchronizing if left unperturbed. In contrast, we show that the optimal stimulation times are non-uniform. Using the model of weakly pulse-coupled neurons with phase response curves, we provide an approach that enables to determine optimal stimulation timing patterns that substantially maximize the desynchronized transient time following the application of CR stimulation. This approach includes an optimization search for clusters in a low-dimensional pulse coupled map. As a consequence, model-specific non-uniformly spaced cluster states cause considerably longer desynchronization transients. Intriguingly, such a desynchronization boost with non-uniform CR stimulation can already be achieved by only slight modifications of the uniform CR timing pattern. Our results suggest that the non-uniformness of the stimulation times can be a medically valuable parameter in the calibration procedure for CR stimulation, where the latter has successfully been used in clinical and pre-clinical studies for the treatment of Parkinson's disease and tinnitus. PMID:23750134

Waardenburg syndrome type I: Dental phenotypes and genetic analysis of an extended family

PubMed Central

de Aquino, Sibele-Nascimento; Paranaíba, Lívia-Maris-R.; Gomes, Andreia; dos-Santos-Neto, Pedro; Coletta, Ricardo-D.; Cardoso, Aline-Francoise; Frota, Ana-Cláudia; Martelli-Júnior, Hercílio

2016-01-01

Background The aim of this study was to describe the pattern of inheritance and the clinical features in a large family with Waardenburg syndrome type I (WS1), detailing the dental abnormalities and screening for PAX3 mutations. Material and Methods To characterize the pattern of inheritance and clinical features, 29 family members were evaluated by dermatologic, ophthalmologic, otorhinolaryngologic and orofacial examination. Molecular analysis of the PAX3 gene was performed. Results The pedigree of the family,including the last four generations, was constructed and revealed non-consanguineous marriages. Out of 29 descendants, 16 family members showed features of WS1, with 9 members showing two major criteria indicative of WS1. Five patients showed white forelock and iris hypopigmentation, and four showed dystopia canthorum and iris hypopigmentation. Two patients had hearing loss. Dental abnormalities were identified in three family members, including dental agenesis, conical teeth and taurodontism. Sequencing analysis failed to identify mutations in the PAX3 gene. Conclusions These results confirm that WS1 was transmitted in this family in an autosomal dominant pattern with variable expressivity and high penetrance. The presence of dental manifestations, especially tooth agenesis and conical teeth which resulted in considerable aesthetic impact on affected individuals was a major clinical feature. Clinical relevance: This article reveals the presence of well-defined dental changes associated with WS1 and tries to establish a possible association between these two entities showing a new spectrum of WS1. Key words:Waardenburg syndrome, hearing loss, oral manifestations, mutation. PMID:27031059

Sleep disorder among medical students: relationship to their academic performance.

PubMed

Abdulghani, Hamza M; Alrowais, Norah A; Bin-Saad, Norah S; Al-Subaie, Nourah M; Haji, Alhan M A; Alhaqwi, Ali I

2012-01-01

Medical students are exposed to a significant level of pressure due to academic demands. Their sleep pattern is characterized by insufficient sleep duration, delayed sleep onset, and occurrence of napping episodes during the day. To examine the prevalence of sleep disorder among medical students and investigate any relationship between sleep disorder and academic performance. This is a cross-sectional self-administered questionnaire-based study. The participants were medical students of the first, second, and third academic years. The Epworth Sleepiness Scale (ESS) was also included to identify sleep disorder and grade point average was recorded for academic performance. There were 491 responses with a response rate of 55%. The ESS score demonstrated that 36.6% of participants were considered to have abnormal sleep habits, with a statistically significant increase in female students (p = 0.000). Sleeping between 6-10 h per day was associated with normal ESS scores (p = 0.019) as well as the academic grades ≥ 3.75. Abnormal ESS scores were associated with lower academic achievement (p = 0.002). A high prevalence of sleep disorder was found in this group of students, specifically female students. Analysis of the relationship between sleep disorder and academic performance indicates a significant relationship between abnormal ESS scores, total sleeping hours, and academic performance.

Evaluation of afferent pain pathways in adrenomyeloneuropathic patients.

PubMed

Yagüe, Sara; Veciana, Misericordia; Casasnovas, Carlos; Ruiz, Montserrat; Pedro, Jordi; Valls-Solé, Josep; Pujol, Aurora

2018-03-01

Patients with adrenomyeloneuropathy may have dysfunctions of visual, auditory, motor and somatosensory pathways. We thought on examining the nociceptive pathways by means of laser evoked potentials (LEPs), to obtain additional information on the pathophysiology of this condition. In 13 adrenomyeloneuropathic patients we examined LEPs to leg, arm and face stimulation. Normative data were obtained from 10 healthy subjects examined in the same experimental conditions. We also examined brainstem auditory evoked potentials (BAEPs), pattern reversal full-field visual evoked potentials (VEPs), motor evoked potentials (MEPs) and somatosensory evoked potentials (SEPs). Upper and lower limb MEPs and SEPs, as well as BAEPs, were abnormal in all patients, while VEPs were abnormal in 3 of them (23.1%). LEPs revealed abnormalities to stimulation of the face in 4 patients (30.7%), the forearm in 4 patients (30.7%) and the leg in 10 patients (76.9%). The pathologic process of adrenomyeloneuropathy is characterized by a preferential involvement of auditory, motor and somatosensory tracts and less severely of the visual and nociceptive pathways. This non-inflammatory distal axonopathy preferably damages large myelinated spinal tracts but there is also partial involvement of small myelinated fibres. LEPs studies can provide relevant information about afferent pain pathways involvement in adrenomyeloneuropathic patients. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Distinct neuronal patterns of positive and negative moral processing in psychopathy.

PubMed

Fede, Samantha J; Borg, Jana Schaich; Nyalakanti, Prashanth K; Harenski, Carla L; Cope, Lora M; Sinnott-Armstrong, Walter; Koenigs, Mike; Calhoun, Vince D; Kiehl, Kent A

2016-12-01

Psychopathy is a disorder characterized by severe and frequent moral violations in multiple domains of life. Numerous studies have shown psychopathy-related limbic brain abnormalities during moral processing; however, these studies only examined negatively valenced moral stimuli. Here, we aimed to replicate prior psychopathy research on negative moral judgments and to extend this work by examining psychopathy-related abnormalities in the processing of controversial moral stimuli and positive moral processing. Incarcerated adult males (N = 245) completed a functional magnetic resonance imaging protocol on a mobile imaging system stationed at the prison. Psychopathy was assessed using the Hare Psychopathy Checklist-Revised (PCL-R). Participants were then shown words describing three types of moral stimuli: wrong (e.g., stealing), not wrong (e.g., charity), and controversial (e.g., euthanasia). Participants rated each stimulus as either wrong or not wrong. PCL-R total scores were correlated with not wrong behavioral responses to wrong moral stimuli, and were inversely related to hemodynamic activity in the anterior cingulate cortex in the contrast of wrong > not wrong. In the controversial > noncontroversial comparison, psychopathy was inversely associated with activity in the temporal parietal junction and dorsolateral prefrontal cortex. These results indicate that psychopathy-related abnormalities are observed during the processing of complex, negative, and positive moral stimuli.

EEG - A Valuable Biomarker of Brain Injury in Preterm Infants.

PubMed

Pavlidis, Elena; Lloyd, Rhodri O; Boylan, Geraldine B

2017-01-01

This review focuses on the role of electroencephalography (EEG) in monitoring abnormalities of preterm brain function. EEG features of the most common developmental brain injuries in preterm infants, including intraventricular haemorrhage, periventricular leukomalacia, and perinatal asphyxia, are described. We outline the most common EEG biomarkers associated with these injuries, namely seizures, positive rolandic sharp waves, EEG suppression/increased interburst intervals, mechanical delta brush activity, and other deformed EEG waveforms, asymmetries, and asynchronies. The increasing survival rate of preterm infants, in particular those that are very and extremely preterm, has led to a growing demand for a specific and shared characterization of the patterns related to adverse outcome in this unique population. This review includes abundant high-quality images of the EEG patterns seen in premature infants and will provide a valuable resource for everyone working in developmental neuroscience. © 2017 S. Karger AG, Basel.

Chronic traumatic encephalopathy: a spectrum of neuropathological changes following repetitive brain trauma in athletes and military personnel

PubMed Central

2014-01-01

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that occurs in association with repetitive traumatic brain injury experienced in sport and military service. In most instances, the clinical symptoms of the disease begin after a long period of latency ranging from several years to several decades. The initial symptoms are typically insidious, consisting of irritability, impulsivity, aggression, depression, short-term memory loss and heightened suicidality. The symptoms progress slowly over decades to include cognitive deficits and dementia. The pathology of CTE is characterized by the accumulation of phosphorylated tau protein in neurons and astrocytes in a pattern that is unique from other tauopathies, including Alzheimer’s disease. The hyperphosphorylated tau abnormalities begin focally, as perivascular neurofibrillary tangles and neurites at the depths of the cerebral sulci, and then spread to involve superficial layers of adjacent cortex before becoming a widespread degeneration affecting medial temporal lobe structures, diencephalon and brainstem. Most instances of CTE (>85% of cases) show abnormal accumulations of phosphorylated 43 kDa TAR DNA binding protein that are partially colocalized with phosphorylated tau protein. As CTE is characterized pathologically by frontal and temporal lobe atrophy, by abnormal deposits of phosphorylated tau and by 43 kDa TAR DNA binding protein and is associated clinically with behavioral and personality changes, as well as cognitive impairments, CTE is increasingly categorized as an acquired frontotemporal lobar degeneration. Currently, some of the greatest challenges are that CTE cannot be diagnosed during life and the incidence and prevalence of the disorder remain uncertain. Furthermore, the contribution of age, gender, genetics, stress, alcohol and substance abuse to the development of CTE remains to be determined. PMID:24423082

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

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

Anti-kindling Induced by Two-Stage Coordinated Reset Stimulation with Weak Onset Intensity

PubMed Central

Zeitler, Magteld; Tass, Peter A.

2016-01-01

Abnormal neuronal synchrony plays an important role in a number of brain diseases. To specifically counteract abnormal neuronal synchrony by desynchronization, Coordinated Reset (CR) stimulation, a spatiotemporally patterned stimulation technique, was designed with computational means. In neuronal networks with spike timing–dependent plasticity CR stimulation causes a decrease of synaptic weights and finally anti-kindling, i.e., unlearning of abnormally strong synaptic connectivity and abnormal neuronal synchrony. Long-lasting desynchronizing aftereffects of CR stimulation have been verified in pre-clinical and clinical proof of concept studies. In general, for different neuromodulation approaches, both invasive and non-invasive, it is desirable to enable effective stimulation at reduced stimulation intensities, thereby avoiding side effects. For the first time, we here present a two-stage CR stimulation protocol, where two qualitatively different types of CR stimulation are delivered one after another, and the first stage comes at a particularly weak stimulation intensity. Numerical simulations show that a two-stage CR stimulation can induce the same degree of anti-kindling as a single-stage CR stimulation with intermediate stimulation intensity. This stimulation approach might be clinically beneficial in patients suffering from brain diseases characterized by abnormal neuronal synchrony where a first treatment stage should be performed at particularly weak stimulation intensities in order to avoid side effects. This might, e.g., be relevant in the context of acoustic CR stimulation in tinnitus patients with hyperacusis or in the case of electrical deep brain CR stimulation with sub-optimally positioned leads or side effects caused by stimulation of the target itself. We discuss how to apply our method in first in man and proof of concept studies. PMID:27242500

Histology, composition, and quality traits of chicken Pectoralis major muscle affected by wooden breast abnormality.

PubMed

Soglia, F; Mudalal, S; Babini, E; Di Nunzio, M; Mazzoni, M; Sirri, F; Cavani, C; Petracci, M

2016-03-01

Only a few years ago, the poultry industry began to face a recent abnormality in breast meat, known as wooden breast, which frequently overlaps with white striping. This study aimed to assess the impact of wooden breast abnormality on quality traits of meat. For this purpose, 32 normal (NRM), 32 wooden (WB), and 32 wooden and white-striped (WB/WS) Pectoralis major muscles were selected from the same flock of heavy broilers (males, Ross 708, weighing around 3.7 kg) in the deboning area of a commercial processing plant at 3 h postmortem and used to assess histology, proximate (moisture, protein, fat, ash, and collagen) and mineral composition (Mg, K, P, Na and Ca), sarcoplasmic and myofibrillar protein patterns, and technological traits of breast meat. Compared to the normal group, WB/WS fillets showed more severe histological lesions characterized by fiber degeneration, fibrosis, and lipidosis, coupled with a significantly harder texture. With regard to proximate and mineral composition, abnormal samples exhibited significantly (P < 0.001) higher moisture, fat, and collagen contents coupled with lower (P < 0.001) amounts of protein and ash. Furthermore, increased calcium (131 vs. 84 mg kg(-1); P < 0.05) and sodium (741 vs. 393 mg kg(-1); P < 0.001) levels were found in WB/WS meat samples. The SDS-PAGE analysis revealed a significantly lower amount of calcium-ATPase (SERCA, 114 kDa), responsible for the translocation of Ca ions across the membrane, in normal breasts compared to abnormal ones. As for meat quality traits, fillets affected by wooden abnormality exhibited significantly (P < 0.001) higher ultimate pH and lower water-holding/water-binding capacity. In particular, compared to normal, abnormal samples showed reduced marinade uptake coupled with increased drip loss and cooking losses as well. In conclusion, this study revealed that meat affected by wooden breast or both wooden breast and white striping abnormalities exhibit poorer nutritional value, harder texture, and impaired water-holding capacity. © 2015 Poultry Science Association Inc.

Psychological stress exposure to aged mice causes abnormal feeding patterns with changes in the bout number.

PubMed

Yamada, Chihiro; Mogami, Sachiko; Hattori, Tomohisa

2017-11-09

Stress responses are affected by aging. However, studies on stress-related changes in feeding patterns with aging subject are minimal. We investigated feeding patterns induced by two psychological stress models, revealing characteristics of stress-induced feeding patterns as "meal" and "bout" (defined as the minimum feeding behavior parameters) in aged mice. Feeding behaviors of C57BL/6J mice were monitored for 24 h by an automatic monitoring device. Novelty stress reduced the meal amount over the 24 h in both young and aged mice, but as a result of a time course study it was persistent in aged mice. In addition, the decreased bout number was more pronounced in aged mice than in young mice. The 24-h meal and bout parameters did not change in either the young or aged mice following water avoidance stress (WAS). However, the meal amount and bout number increased in aged mice for 0-6 h after WAS exposure but remained unchanged in young mice. Our findings suggest that changes in bout number may lead to abnormal stress-related feeding patterns and may be one tool for evaluating eating abnormality in aged mice.

The relative efficacy of connectivity guided and symptom based EEG biofeedback for autistic disorders.

PubMed

Coben, Robert; Myers, Thomas E

2010-03-01

Autism is a neurodevelopmental disorder characterized by deficits in communication, social interaction, and a limited range of interests with repetitive stereotypical behavior. Various abnormalities have been documented in the brains of individuals with autism, both anatomically and functionally. The connectivity theory of autism is a recently developed theory of the neurobiological cause of autisic symptoms. Different patterns of hyper- and hypo-connectivity have been identified with the use of quantitative electroencephalogray (QEEG), which may be amenable to neurofeedback. In this study, we compared the results of two published controlled studies examining the efficacy of neurofeedback in the treatment of autism. Specifically, we examined whether a symptom based approach or an assessment/connectivity guided based approach was more effective. Although both methods demonstrated significant improvement in symptoms of autism, connectivity guided neurofeedback demonstrated greater reduction on various subscales of the Autism Treatment Evaluation Checklist (ATEC). Furthermore, when individuals were matched for severity of symptoms, the amount of change per session was significantly higher in the Coben and Padolsky (J Neurother 11:5-23, 2007) study for all five measures of the ATEC. Our findings suggest that an approach guided by QEEG based connectivity assessment may be more efficacious in the treatment of autism. This permits the targeting and amelioration of abnormal connectivity patterns in the brains of people who are autistic.

Characterization of distinct classes of differential gene expression in osteoblast cultures from non-syndromic craniosynostosis bone.

PubMed

Rojas-Peña, Monica L; Olivares-Navarrete, Rene; Hyzy, Sharon; Arafat, Dalia; Schwartz, Zvi; Boyan, Barbara D; Williams, Joseph; Gibson, Greg

2014-01-01

Craniosynostosis, the premature fusion of one or more skull sutures, occurs in approximately 1 in 2500 infants, with the majority of cases non-syndromic and of unknown etiology. Two common reasons proposed for premature suture fusion are abnormal compression forces on the skull and rare genetic abnormalities. Our goal was to evaluate whether different sub-classes of disease can be identified based on total gene expression profiles. RNA-Seq data were obtained from 31 human osteoblast cultures derived from bone biopsy samples collected between 2009 and 2011, representing 23 craniosynostosis fusions and 8 normal cranial bones or long bones. No differentiation between regions of the skull was detected, but variance component analysis of gene expression patterns nevertheless supports transcriptome-based classification of craniosynostosis. Cluster analysis showed 4 distinct groups of samples; 1 predominantly normal and 3 craniosynostosis subtypes. Similar constellations of sub-types were also observed upon re-analysis of a similar dataset of 199 calvarial osteoblast cultures. Annotation of gene function of differentially expressed transcripts strongly implicates physiological differences with respect to cell cycle and cell death, stromal cell differentiation, extracellular matrix (ECM) components, and ribosomal activity. Based on these results, we propose non-syndromic craniosynostosis cases can be classified by differences in their gene expression patterns and that these may provide targets for future clinical intervention.

Characterization of Distinct Classes of Differential Gene Expression in Osteoblast Cultures from Non-Syndromic Craniosynostosis Bone

PubMed Central

Rojas-Peña, Monica L.; Olivares-Navarrete, Rene; Hyzy, Sharon; Arafat, Dalia; Schwartz, Zvi; Boyan, Barbara D.; Williams, Joseph; Gibson, Greg

2014-01-01

Craniosynostosis, the premature fusion of one or more skull sutures, occurs in approximately 1 in 2500 infants, with the majority of cases non-syndromic and of unknown etiology. Two common reasons proposed for premature suture fusion are abnormal compression forces on the skull and rare genetic abnormalities. Our goal was to evaluate whether different sub-classes of disease can be identified based on total gene expression profiles. RNA-Seq data were obtained from 31 human osteoblast cultures derived from bone biopsy samples collected between 2009 and 2011, representing 23 craniosynostosis fusions and 8 normal cranial bones or long bones. No differentiation between regions of the skull was detected, but variance component analysis of gene expression patterns nevertheless supports transcriptome-based classification of craniosynostosis. Cluster analysis showed 4 distinct groups of samples; 1 predominantly normal and 3 craniosynostosis subtypes. Similar constellations of sub-types were also observed upon re-analysis of a similar dataset of 199 calvarial osteoblast cultures. Annotation of gene function of differentially expressed transcripts strongly implicates physiological differences with respect to cell cycle and cell death, stromal cell differentiation, extracellular matrix (ECM) components, and ribosomal activity. Based on these results, we propose non-syndromic craniosynostosis cases can be classified by differences in their gene expression patterns and that these may provide targets for future clinical intervention. PMID:25184005

Peripheral neuropathy in Tangier disease: A literature review and assessment.

PubMed

Mercan, Metin; Yayla, Vildan; Altinay, Serdar; Seyhan, Serhat

2018-06-01

Tangier disease (TD) (OMIM#205400) is a rare cause of inherited metabolic neuropathies characterized by marked deficiency of high-density lipoproteins and accumulation of cholesterol esters in various tissue resulting from reverse cholesterol transport deficiency. We report a case of a patient with TD with multifocal demyelinating neuropathy with conduction block who presents with winging scapula, tongue, and asymmetric extremity weakness. We also present a review of all studies published from 1960 to 2017 regarding peripheral neuropathy in TD. Our search identified 54 patients with TD with peripheral neuropathy. Syringomyelia-like neuropathy subtype (52.4%) was more frequent than multifocal sensorial and motor neuropathy subtype (26.2%), focal neuropathy subtype (19.1%), and distal symmetric polyneuropathy subtype (2.4%). Splenomegaly was the most common (40.7%) clinical manifestation in these patients. The pattern of electrodiagnostic abnormalities are: (1) demyelinating abnormalities were more predominant in the upper extremities than in the lower extremities and (2) slowing of motor nerve conduction was more prominent in the intermediate segment than in distal nerve segments. The sural-sparing pattern was present in 34.6% and conduction block was present in 11.5% of the patients. Our literature review and our case showed the clinical spectrum of TD neuropathy is quite wide and that it should be considered in the differential diagnosis of non-uniform demyelinating neuropathies. © 2018 Peripheral Nerve Society.

Age-Related Evolution Patterns in Online Handwriting

PubMed Central

2016-01-01

Characterizing age from handwriting (HW) has important applications, as it is key to distinguishing normal HW evolution with age from abnormal HW change, potentially triggered by neurodegenerative decline. We propose, in this work, an original approach for online HW style characterization based on a two-level clustering scheme. The first level generates writer-independent word clusters from raw spatial-dynamic HW information. At the second level, each writer's words are converted into a Bag of Prototype Words that is augmented by an interword stability measure. This two-level HW style representation is input to an unsupervised learning technique, aiming at uncovering HW style categories and their correlation with age. To assess the effectiveness of our approach, we propose information theoretic measures to quantify the gain on age information from each clustering layer. We have carried out extensive experiments on a large public online HW database, augmented by HW samples acquired at Broca Hospital in Paris from people mostly between 60 and 85 years old. Unlike previous works claiming that there is only one pattern of HW change with age, our study reveals three major aging HW styles, one specific to aged people and the two others shared by other age groups. PMID:27752277

[Marshmallow for investigating functional disturbances of the esophageal body].

PubMed

Keren, S; Argaman, E

1992-09-01

Manometric studies using water boluses do not always demonstrate disturbances in esophageal motility. We tested the use of a marshmallow bolus to induce abnormal manometric patterns in patients with dysphagia in whom manometric studies using water boluses were normal or nearly so. The study group included 12 normal volunteers and 22 patients with dysphagia and nearly normal manometric studies. Pressure was recorded along the esophageal body using 10 "wet" swallows followed by 10 "solid" swallows of marshmallow. In normal subjects there were fewer abnormal contractions after solid swallows than after wet swallows. In 15 patients solid swallows induced abnormal motility patterns which were not observed after wet swallows. The probability of inducing abnormal contractions in patients after solid swallows is significantly greater than after wet swallows (p < 0.0001). Solid swallowing is therefore useful in evaluating functional disturbances of the esophagus in patients with dysphagia.

Complex patterns of abnormal heartbeats

NASA Technical Reports Server (NTRS)

Schulte-Frohlinde, Verena; Ashkenazy, Yosef; Goldberger, Ary L.; Ivanov, Plamen Ch; Costa, Madalena; Morley-Davies, Adrian; Stanley, H. Eugene; Glass, Leon

2002-01-01

Individuals having frequent abnormal heartbeats interspersed with normal heartbeats may be at an increased risk of sudden cardiac death. However, mechanistic understanding of such cardiac arrhythmias is limited. We present a visual and qualitative method to display statistical properties of abnormal heartbeats. We introduce dynamical "heartprints" which reveal characteristic patterns in long clinical records encompassing approximately 10(5) heartbeats and may provide information about underlying mechanisms. We test if these dynamics can be reproduced by model simulations in which abnormal heartbeats are generated (i) randomly, (ii) at a fixed time interval following a preceding normal heartbeat, or (iii) by an independent oscillator that may or may not interact with the normal heartbeat. We compare the results of these three models and test their limitations to comprehensively simulate the statistical features of selected clinical records. This work introduces methods that can be used to test mathematical models of arrhythmogenesis and to develop a new understanding of underlying electrophysiologic mechanisms of cardiac arrhythmia.

Unsupervised Pattern Classifier for Abnormality-Scaling of Vibration Features for Helicopter Gearbox Fault Diagnosis

NASA Technical Reports Server (NTRS)

Jammu, Vinay B.; Danai, Kourosh; Lewicki, David G.

1996-01-01

A new unsupervised pattern classifier is introduced for on-line detection of abnormality in features of vibration that are used for fault diagnosis of helicopter gearboxes. This classifier compares vibration features with their respective normal values and assigns them a value in (0, 1) to reflect their degree of abnormality. Therefore, the salient feature of this classifier is that it does not require feature values associated with faulty cases to identify abnormality. In order to cope with noise and changes in the operating conditions, an adaptation algorithm is incorporated that continually updates the normal values of the features. The proposed classifier is tested using experimental vibration features obtained from an OH-58A main rotor gearbox. The overall performance of this classifier is then evaluated by integrating the abnormality-scaled features for detection of faults. The fault detection results indicate that the performance of this classifier is comparable to the leading unsupervised neural networks: Kohonen's Feature Mapping and Adaptive Resonance Theory (AR72). This is significant considering that the independence of this classifier from fault-related features makes it uniquely suited to abnormality-scaling of vibration features for fault diagnosis.

Proteogenomic characterization of human colon and rectal cancer

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

Zhang, Bing; Wang, Jing; Wang, Xiaojing

2014-09-18

We analyzed proteomes of colon and rectal tumors previously characterized by the Cancer Genome Atlas (TCGA) and performed integrated proteogenomic analyses. Protein sequence variants encoded by somatic genomic variations displayed reduced expression compared to protein variants encoded by germline variations. mRNA transcript abundance did not reliably predict protein expression differences between tumors. Proteomics identified five protein expression subtypes, two of which were associated with the TCGA "MSI/CIMP" transcriptional subtype, but had distinct mutation and methylation patterns and associated with different clinical outcomes. Although CNAs showed strong cis- and trans-effects on mRNA expression, relatively few of these extend to the proteinmore » level. Thus, proteomics data enabled prioritization of candidate driver genes. Our analyses identified HNF4A, a novel candidate driver gene in tumors with chromosome 20q amplifications. Integrated proteogenomic analysis provides functional context to interpret genomic abnormalities and affords novel insights into cancer biology.« less

Recognizing patterns of visual field loss using unsupervised machine learning

NASA Astrophysics Data System (ADS)

Yousefi, Siamak; Goldbaum, Michael H.; Zangwill, Linda M.; Medeiros, Felipe A.; Bowd, Christopher

2014-03-01

Glaucoma is a potentially blinding optic neuropathy that results in a decrease in visual sensitivity. Visual field abnormalities (decreased visual sensitivity on psychophysical tests) are the primary means of glaucoma diagnosis. One form of visual field testing is Frequency Doubling Technology (FDT) that tests sensitivity at 52 points within the visual field. Like other psychophysical tests used in clinical practice, FDT results yield specific patterns of defect indicative of the disease. We used Gaussian Mixture Model with Expectation Maximization (GEM), (EM is used to estimate the model parameters) to automatically separate FDT data into clusters of normal and abnormal eyes. Principal component analysis (PCA) was used to decompose each cluster into different axes (patterns). FDT measurements were obtained from 1,190 eyes with normal FDT results and 786 eyes with abnormal (i.e., glaucomatous) FDT results, recruited from a university-based, longitudinal, multi-center, clinical study on glaucoma. The GEM input was the 52-point FDT threshold sensitivities for all eyes. The optimal GEM model separated the FDT fields into 3 clusters. Cluster 1 contained 94% normal fields (94% specificity) and clusters 2 and 3 combined, contained 77% abnormal fields (77% sensitivity). For clusters 1, 2 and 3 the optimal number of PCA-identified axes were 2, 2 and 5, respectively. GEM with PCA successfully separated FDT fields from healthy and glaucoma eyes and identified familiar glaucomatous patterns of loss.

Electrophysiological abnormalities associated with extensive myelinated retinal nerve fibers.

PubMed

Tay, Su Ann; Sanjay, Srinivasan

2012-07-01

An observational case report of electrophysiological abnormalities in a patient with anisomyopic amblyopia as a result of unilateral extensive myelinated retinal nerve fibers (MNFs) is illustrated. The electrophysiological readings revealed an abnormal pattern electroretinogram (PERG) but normal full-field electroretinogram readings in the affected eye. The visual-evoked potential was also undetectable in that eye. Our findings suggest that extensive MNFs can be associated with electrophysiological abnormalities, in particular the PERG, which can aid in diagnosing the cause of impaired vision when associated with amblyopia.

Morphological abnormalities in the cladoceran Ilyocryptus spinifer (Apipucos Reservoir, Pernambuco State, Brazil).

PubMed

Elmoor-Loureiro, L M

2004-02-01

In a sample taken from Apipucos Reservoir (Recife, PE, Brazil) for taxonomic study, a high percentage (40%) was found of cladoceran Ilyocryptus spinifer individuals with morphological abnormalities on their postabdomen. There was not a fixed pattern of the malformations, which varied in gravity, and could affect the postanal spines or terminal claws. The postabdominal abnormalities are described and compared to the ones described in the literature. The hypothesis of the morphological abnormalities being induced by an occasional environmental toxicant is discussed.

Morphometric of blastomeres in Salmo salar.

PubMed

Effer, Brian R; Sánchez, Rubén R; Ubilla, Andrea M; Figueroa, Elías V; Valdebenito, Iván I

2014-11-01

For Salmo salar, there is a lack of information on the morphology of the first blastomeres formed during embryonic development and which could be used as a diagnostic tool for the first stages of development. The purpose of this investigation, therefore, was to characterize morphometrically the first blastomeres of S. salar. From a pool of eggs incubated at 7.5°C, 100 microphotographs of blastodiscs were extracted and analyzed at different incubation periods: 12, 14, 16, 20 or 24 h. Blastodiscs were characterized morphologically after 16, 20 or 24 h incubation, and classified into symmetric or asymmetric groups according to their morphology. The ratio of length (L) versus width (W) of each blastomere was determined, to establish its symmetry. In addition, 20 microphotographs of blastodiscs of normal appearance were analysed morphologically (control blastodisc: CB) for comparison (20 or 24 h). Results show that the first cleavage ends after 16 h of development. Seven categories were established during blastomere characterization: 47% normal (G1); 27% with dispersed margins (G2); 10% unequal (G3); 9% 'pie-shaped' (G4); 3% amorphous (G5); 2% three equal blastomeres and one different one (G6); and 2% with eccentric cleavage (G7). Although the incidence of abnormal cleavage in S. salar is uncertain, there is a potential for some asymmetries to be corrected during embryogenesis to generate viable individuals. More studies are necessary to correlate these abnormal cleavage patterns with indicators of quality in the later stages of embryogenesis in this species, to establish a quality assessment tool for gametes and/or embryos in salmonid species.

Involvement of the VEP1 gene in vascular strand development in Arabidopsis thaliana.

PubMed

Jun, Ji Hyung; Ha, Chan Man; Nam, Hong Gil

2002-03-01

A dominant mutant line characterized by abnormal leaf venation pattern was isolated from a transgenic Arabidopsis plant pool that was generated with Agrobacterium culture harboring an Arabidopsis antisense cDNA library. In the mutant line, the phenotype was due to antisense suppression of a gene we named VEP1 (Vein Patterning). The predicted amino acid sequence of the gene contained a motif related to the mammalian death domain that is found in the apoptotic machinery. Reduced expression of the VEP1 gene resulted in the reduced complexity of the venation pattern of the cotyledons and foliar leaves, which was mainly due to the reduced number of the minor veins and their incomplete connection. The analysis of mutant embryos indicated that the phenotype was originated, at least in part, from a defect in the procambium patterning. In the mutant, the stem and root were thinner than those in wild type. This phenotype was associated with reduced vascular development. The promoter activity of the VEP1 gene was detected preferentially in the vascular regions. We propose that the death domain-containing protein VEP1 functions as a positive element required for vascular strand development in Arabidopsis thaliana.

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

A Genetic Algorithm for Learning Significant Phrase Patterns in Radiology Reports

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

Patton, Robert M; Potok, Thomas E; Beckerman, Barbara G

2009-01-01

Radiologists disagree with each other over the characteristics and features of what constitutes a normal mammogram and the terminology to use in the associated radiology report. Recently, the focus has been on classifying abnormal or suspicious reports, but even this process needs further layers of clustering and gradation, so that individual lesions can be more effectively classified. Using a genetic algorithm, the approach described here successfully learns phrase patterns for two distinct classes of radiology reports (normal and abnormal). These patterns can then be used as a basis for automatically analyzing, categorizing, clustering, or retrieving relevant radiology reports for themore » user.« less

Language comprehension in nonspeaking children with severe cerebral palsy: Neuroanatomical substrate?

PubMed

Geytenbeek, Joke J; Oostrom, Kim J; Harlaar, Laurike; Becher, Jules G; Knol, Dirk L; Barkhof, Frederik; Pinto, Pedro S; Vermeulen, R Jeroen

2015-09-01

To identify relations between brain abnormalities and spoken language comprehension, MRI characteristics of 80 nonspeaking children with severe CP were examined. MRI scans were analysed for patterns of brain abnormalities and scored for specific MRI measures: white matter (WM) areas; size of lateral ventricles, WM abnormality/reduction, cysts, subarachnoid space, corpus callosum thinning and grey matter (GM) areas; cortical GM abnormalities, thalamus, putamen, globus pallidus and nucleus caudatus and cerebellar abnormalities. Language comprehension was assessed with a new validated instrument (C-BiLLT). MRI scans of 35 children were classified as a basal ganglia necrosis (BGN) pattern, with damage to central GM areas; in 60% of these children damage to WM areas was also found. MRI scans of 13 children were classified as periventricular leukomalacia (PVL) with little concomitant damage to central GM areas, 13 as malformations and 19 as miscellaneous. Language comprehension was best in children with BGN, followed by malformations and miscellaneous, and was poorest in PVL. Linear regression modelling per pattern group (malformations excluded), with MRI measures as independent variables, revealed that corpus callosum thinning in BGN and parieto-occipital WM reduction in PVL were the most important explanatory factors for poor language comprehension. No MRI measures explained outcomes in language comprehension in the miscellaneous group. Comprehension of spoken language differs between MRI patterns of severe CP. In children with BGN and PVL differences in language comprehension performance is attributed to damage in the WM areas. Language comprehension was most affected in children with WM lesions in the subcortical and then periventricular areas, most characteristic for children with PVL. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Colitis induced by sodium polystyrene sulfonate in sorbitol: A report of six cases.

PubMed

Jacob, Sheba S K; Parameswaran, Ashok; Parameswaran, Sarojini Ashok; Dhus, Ubal

2016-03-01

Drug-related injury has been noted in virtually all organ systems, and recognition of the patterns of injury associated with medication enables modification of treatment and reduces the morbidity associated with the side effects of drugs. With the large number of new drugs being developed, documentation of the morphology of the changes seen as an adverse effect becomes important to characterize the pattern of injury. The pathologist is often the first to identify these abnormalities and correlate them with a particular drug. Kayexalate or sodium polystyrene sulfonate (SPS), a linear polymer derived from polystyrene containing sulfonic acid and sulfonate functional groups is used to treat hyperkalemia. It is usually administered with an osmotic laxative sorbitol orally or as retention enema. This combination has been implicated in causing damage to different parts of the gastrointestinal (GI) tract especially the colon and causes an established pattern of injury, recognizable by the presence of characteristic crystals, is presented to create a greater awareness of the Kayexalate colitis. This entity should be included in the differential diagnosis of lower GI mucosal injury in a setting of uremia and hyperkalemia.

Bioelectrical Signals and Ion Channels in the Modeling of Multicellular Patterns and Cancer Biophysics.

PubMed

Cervera, Javier; Alcaraz, Antonio; Mafe, Salvador

2016-02-04

Bioelectrical signals and ion channels are central to spatial patterns in cell ensembles, a problem of fundamental interest in positional information and cancer processes. We propose a model for electrically connected cells based on simple biological concepts: i) the membrane potential of a single cell characterizes its electrical state; ii) the long-range electrical coupling of the multicellular ensemble is realized by a network of gap junction channels between neighboring cells; and iii) the spatial distribution of an external biochemical agent can modify the conductances of the ion channels in a cell membrane and the multicellular electrical state. We focus on electrical effects in small multicellular ensembles, ignoring slow diffusional processes. The spatio-temporal patterns obtained for the local map of cell electric potentials illustrate the normalization of regions with abnormal cell electrical states. The effects of intercellular coupling and blocking of specific channels on the electrical patterns are described. These patterns can regulate the electrically-induced redistribution of charged nanoparticles over small regions of a model tissue. The inclusion of bioelectrical signals provides new insights for the modeling of cancer biophysics because collective multicellular states show electrical coupling mechanisms that are not readily deduced from biochemical descriptions at the individual cell level.

Bioelectrical Signals and Ion Channels in the Modeling of Multicellular Patterns and Cancer Biophysics

PubMed Central

Cervera, Javier; Alcaraz, Antonio; Mafe, Salvador

2016-01-01

Bioelectrical signals and ion channels are central to spatial patterns in cell ensembles, a problem of fundamental interest in positional information and cancer processes. We propose a model for electrically connected cells based on simple biological concepts: i) the membrane potential of a single cell characterizes its electrical state; ii) the long-range electrical coupling of the multicellular ensemble is realized by a network of gap junction channels between neighboring cells; and iii) the spatial distribution of an external biochemical agent can modify the conductances of the ion channels in a cell membrane and the multicellular electrical state. We focus on electrical effects in small multicellular ensembles, ignoring slow diffusional processes. The spatio-temporal patterns obtained for the local map of cell electric potentials illustrate the normalization of regions with abnormal cell electrical states. The effects of intercellular coupling and blocking of specific channels on the electrical patterns are described. These patterns can regulate the electrically-induced redistribution of charged nanoparticles over small regions of a model tissue. The inclusion of bioelectrical signals provides new insights for the modeling of cancer biophysics because collective multicellular states show electrical coupling mechanisms that are not readily deduced from biochemical descriptions at the individual cell level. PMID:26841954

Bioelectrical Signals and Ion Channels in the Modeling of Multicellular Patterns and Cancer Biophysics

NASA Astrophysics Data System (ADS)

Cervera, Javier; Alcaraz, Antonio; Mafe, Salvador

2016-02-01

Bioelectrical signals and ion channels are central to spatial patterns in cell ensembles, a problem of fundamental interest in positional information and cancer processes. We propose a model for electrically connected cells based on simple biological concepts: i) the membrane potential of a single cell characterizes its electrical state; ii) the long-range electrical coupling of the multicellular ensemble is realized by a network of gap junction channels between neighboring cells; and iii) the spatial distribution of an external biochemical agent can modify the conductances of the ion channels in a cell membrane and the multicellular electrical state. We focus on electrical effects in small multicellular ensembles, ignoring slow diffusional processes. The spatio-temporal patterns obtained for the local map of cell electric potentials illustrate the normalization of regions with abnormal cell electrical states. The effects of intercellular coupling and blocking of specific channels on the electrical patterns are described. These patterns can regulate the electrically-induced redistribution of charged nanoparticles over small regions of a model tissue. The inclusion of bioelectrical signals provides new insights for the modeling of cancer biophysics because collective multicellular states show electrical coupling mechanisms that are not readily deduced from biochemical descriptions at the individual cell level.

Nailfold capillaroscopy in systemic sclerosis: data from the EULAR scleroderma trials and research (EUSTAR) database.

PubMed

Ingegnoli, Francesca; Ardoino, Ilaria; Boracchi, Patrizia; Cutolo, Maurizio

2013-09-01

The aims of this study were to obtain cross-sectional data on capillaroscopy in an international multi-center cohort of Systemic Sclerosis (SSc) and to investigate the frequency of the capillaroscopic patterns and their disease-phenotype associations. Data collected between June 2004 and October 2011 in the EULAR Scleroderma Trials and Research (EUSTAR) registry were examined. Patients' profiles based on clinical and laboratory data were obtained by cluster analysis and the association between profiles and capillaroscopy was investigated by multinomial logistic regression. 62 of the 110 EUSTAR centers entered data on capillaroscopy in the EUSTAR database. 376 of the 2754 patients (13.65%) were classified as scleroderma pattern absent, but non-specific capillary abnormalities were noted in 55.48% of the cases. Four major patients' profiles were identified characterized by a progressive severity for skin involvement, as well as an increased number of systemic manifestations. The "early" and "active" scleroderma patterns were generally observed in patients with mild/moderate skin involvement and a low number of disease manifestations, while the "late" scleroderma pattern was found more frequently in the more severe forms of the disease. These data indicate the importance of capillaroscopy in SSc management and that capillaroscopic patterns are directly related to the extent of organ involvement. Copyright © 2013 Elsevier Inc. All rights reserved.

Female-patterned alopecia in teenage brothers with unusual histologic features.

PubMed

Carlson, J Andrew; Malysz, Jozef; Schwartz, Joseph

2006-11-01

Patterned hair loss, follicular miniaturization, and increased telogen hair counts characterize androgenic alopecia (AGA). Follicular inflammation in AGA has been associated with treatment resistance and progressive hair loss. Brothers, 15 and 18 years old, presented with frontal and mid-scalp hair loss with an intact frontal hairline noted over a 1-year period. The elder reported past use of androgenic steroids. Laboratory assessment for metabolic and hormonal abnormalities was unrevealing, and hair pull test was negative. Scalp biopsies revealed decreased terminal hairs, marked diameter variation of anagen hairs, decreased terminal to vellus hair ratios (3.7:1/3.4:1, older/younger), and increased telogen counts (23%/21%). Infrabulbar and peri-isthmic (follicular bulge region) lymphocytic infiltrates were present. Hair loss has progressed, unabated by daily topical 0.5% clobetasol (for 6 months), daily 5% minoxidil (1 year), and latter, daily oral finasteride (2 years - older brother only). Based on patterned hair loss and miniaturized hairs, these brothers have AGA. The female pattern of hair loss (diffuse hair loss affecting the central scalp with preservation of frontal hair line) coupled with follicular isthmic lymphocytic inflammation represents an unusual presentation, possibly a treatment resistant, inflammatory variant of AGA. The differential diagnosis includes exogenous androgen-mediated hair loss, cicatricial pattern hair loss, or the superimposition of alopecia areata.

A possible cause of the AO polarity reversal from winter to summer in 2010 and its relation to hemispheric extreme summer weather

NASA Astrophysics Data System (ADS)

Otomi, Y.; Tachibana, Y.; Nakamura, T.

2012-12-01

In 2010, the Northern Hemisphere, in particular Russia, Europe and Japan, experienced an abnormally hot summer characterized by record-breaking warm temperatures and associated with a strongly positive Arctic Oscillation (AO). In contrast, in winter 2009/2010, the continent suffered from anomalously cold weather associated with a record-breaking negative AO. The winter-to-summer of the AO index during 2009/2010 evolved as follows: a strongly negative wintertime AO index continued until May, after which it abruptly changed, becoming strongly positive in July and continuing so until the beginning of August. The abrupt change of the AO index from strongly negative to strongly positive in 2010 thus corresponded to the change from the abnormally cold winter of 2009/2010 to the abnormally hot summer of 2010, which shows that the AO index is a good indicator of abnormal weather on a planetary-scale, and that extra-seasonal prediction of the AO is a key to long-term forecasting. In this study, we therefore aimed to examine the cause of the 2010 change in the AO index from strongly negative to strongly positive. We suggest that an oceanic memory of the strongly negative wintertime AO may have influenced the strongly positive summertime AO. The winter sea surface temperatures (SST) in the North Atlantic Ocean showed a tripolar anomaly pattern which is warm SST anomalies over the tropics and high latitudes and cold SST anomalies over the midlatitudes. The strongly negative wintertime AO would cause the warm SST anomaly in this region. The warm SST anomalies continued into summer 2010 because of the large oceanic heat capacity. In May and June, the heat flux anomaly changed from downward to upward in the tropics, and in July and August, the center of the upward anomaly moved westward. The area of the upward heat flux anomaly coincided with the area of the warm SST anomaly from May to August. The numerical model experiment showed that the tripolar SST pattern resulted in an anomalous height and wind pattern that caused a blocking high over Europe. The observed wave activity flux also seems to emanate from Europe. This midlatitude atmospheric response implies that strengthening of the positive geopotential anomalies over Europe was associated with the Atlantic tripolar SST anomaly. The positive geopotential anomaly in the area of the polar jet stream caused eastward propagation of Rossby waves, and the exceeding amplification of Rossby waves might have led to the formation of blocking anticyclones. As a consequence of these interactions, the positive AO pressure pattern can continue for a long time. Thus, a possible cause of the AO polarity reversal might be the "memory" of the negative winter AO in the North Atlantic Ocean, suggesting an interseasonal linkage of the AO in which the oceanic memory of a wintertime negative AO induces a positive AO in the following summer. Understanding of this interseasonal linkage may aid in the long-term prediction of such abnormal summer events. If this reversal pattern recurs, it might be possible to predict the summertime AO from the wintertime AO. Main parts of this study were published in Climatic Dynamics by Otomi et al, (2012).

Brief report: circadian melatonin, thyroid-stimulating hormone, prolactin, and cortisol levels in serum of young adults with autism.

PubMed

Nir, I; Meir, D; Zilber, N; Knobler, H; Hadjez, J; Lerner, Y

1995-12-01

An abnormal circadian pattern of melatonin was found in a group of young adults with an extreme autism syndrome. Although not out of phase, the serum melatonin levels differed from normal in amplitude and mesor. Marginal changes in diurnal rhythms of serum TSH and possibly prolactin were also recorded. Subjects with seizures tended to have an abnormal pattern of melatonin correlated with EEG changes. In others, a parallel was evidenced between thyroid function and impairment in verbal communication. There appears to be a tendency for various types of neuroendocrinological abnormalities in autistics, and melatonin, as well as possibly TSH and perhaps prolactin, could serve as biochemical variables of the biological parameters of the disease.

Diagnosis & Treatment of Dystonia

PubMed Central

Jinnah, H. A.

2014-01-01

Synopsis The dystonias are a group of disorders characterized by excessive involuntary muscle contractions leading to abnormal postures and/or repetitive movements. There are many different clinical manifestations and many different causes. A careful assessment of the clinical manifestations is helpful for identifying syndromic patterns that focus diagnostic testing on potential causes. If a cause can be identified, specific etiology-based treatments may be available. However, in the majority of cases, a specific cause cannot be identified, and treatments are based on symptoms. Treatment options include counseling and education, oral medications, botulinum toxin injections, and several surgical procedures. A substantial reduction in symptoms and improved quality of life can be achieved in the majority of patients by combining these various options. PMID:25432724

Atypical pattern of discriminating sound features in adults with Asperger syndrome as reflected by the mismatch negativity.

PubMed

Kujala, T; Aho, E; Lepistö, T; Jansson-Verkasalo, E; Nieminen-von Wendt, T; von Wendt, L; Näätänen, R

2007-04-01

Asperger syndrome, which belongs to the autistic spectrum of disorders, is characterized by deficits of social interaction and abnormal perception, like hypo- or hypersensitivity in reacting to sounds and discriminating certain sound features. We determined auditory feature discrimination in adults with Asperger syndrome with the mismatch negativity (MMN), a neural response which is an index of cortical change detection. We recorded MMN for five different sound features (duration, frequency, intensity, location, and gap). Our results suggest hypersensitive auditory change detection in Asperger syndrome, as reflected in the enhanced MMN for deviant sounds with a gap or shorter duration, and speeded MMN elicitation for frequency changes.

Clinical analysis of a large kindred with the pallister ulnar-mammary syndrome

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

Bamshad, M.; Root, S.; Carey, J.C.

1996-11-11

The ulnar-mammary syndrome (UMS) is an autosomal dominant disorder characterized by posterior limb deficiencies or duplications, apocrine/mammary gland hypoplasia and/or dysfunction, abnormal dentition, delayed puberty in males, and genital anomalies. We present the clinical descriptions of 33 members of a six generation kindred with UMS. The number of affected individuals in this family is more than the sum of all previously reported cases of UMS. The clinical expression of UMS is highly variable. While most patients have limb deficiencies, the range of abnormalities extends from hypoplasia of the terminal phalanx of the 5th digit to complete absence of the ulnamore » and 3rd, 4th, and 5th digits. Moreover, affected individuals may have posterior digital duplications with or without contralateral limb deficiencies. Apocrine gland abnormalities range from diminished axillary perspiration with normal breast development and lactation, to complete absence of the breasts and no axillary perspiration. Dental abnormalities include misplaced or absent teeth. Affected males consistently undergo delayed puberty, and both sexes have diminished to absent axillary hair. Imperforate hymen were seen in some affected women. A gene for UMS was mapped to chromosome area 12q23-q24.1. A mutation in the gene causing UMS can interfere with limb patterning in the proximal/distal, anterior/posterior, and dorsal/ventral axes. This mutation disturbs development of the posterior elements of forearm, wrist, and hand while growth and development of the anterior elements remain normal. 24 refs., 4 figs., 1 tab.« less

Epigenetics in Medullary Thyroid Cancer: From Pathogenesis to Targeted Therapy.

PubMed

Vitale, Giovanni; Dicitore, Alessandra; Messina, Erika; Sciammarella, Concetta; Faggiano, Antongiulio; Colao, Annamaria

2016-01-01

Medullary thyroid carcinoma (MTC) originates from the parafollicular C cells of the thyroid gland. Mutations of the RET proto-oncogene are implicated in the pathogenesis of MTC. Germline activating mutations of this gene have been reported in about 88-98% of familial MTCs, while somatic mutations of RET gene have been detected in about 23-70% of sporadic forms. Although these genetic events are well characterized, much less is known about the role of epigenetic abnormalities in MTC. The present review reports a detailed description of epigenetic abnormalities (DNA methylation, histone modifications and miRNA profile), probably involved in the pathogenesis and progression of MTC. A systematic review was performed using Pubmed and Google patents databases. We report the current understanding of epigenetic patterns in MTC and discuss the potential use of current knowledge in designing novel therapeutic strategies through epigenetic drugs, focusing on recent patents in this field. Taking into account the reversibility of epigenetic alterations and the recent development in this field, epigenetic therapy may emerge for clinical use in the near future for patients with advanced MTC.

Role of Genetic Factors in the Pathogenesis of Radial Deficiencies in Humans

PubMed Central

Elmakky, Amira; Stanghellini, Ilaria; Landi, Antonio; Percesepe, Antonio

2015-01-01

Radial deficiencies (RDs), defined as under/abnormal development or absence of any of the structures of the forearm, radial carpal bones and thumb, occur with a live birth incidence ranging from 1 out of 30,000 to 1 out 6,000 newborns and represent about one third/one fourth of all the congenital upper limb anomalies. About half of radial disorders have a mendelian cause and pattern of inheritance, whereas the remaining half appears sporadic with no known gene involved. In sporadic forms certain anomalies, such as thumb or radial hypoplasia, may occur either alone or in association with systemic conditions, like vertebral abnormalities or renal defects. All the cases with a mendelian inheritance are syndromic forms, which include cardiac defects (in Holt-Oram syndrome), bone marrow failure (in Fanconi anemia), platelet deficiency (in thrombocytopenia-absent-radius syndrome), ocular motility impairment (in Okihiro syndrome). The genetics of radial deficiencies is complex, characterized by genetic heterogeneity and high inter- and intra-familial clinical variability: this review will analyze the etiopathogenesis and the genotype/phenotype correlations of the main radial deficiency disorders in humans. PMID:26962299

Mutational analysis of the glycosylphosphatidylinositol (GPI) anchor pathway demonstrates that GPI-anchored proteins are required for cell wall biogenesis and normal hyphal growth in Neurospora crassa.

PubMed

Bowman, Shaun M; Piwowar, Amy; Al Dabbous, Mash'el; Vierula, John; Free, Stephen J

2006-03-01

Using mutational and proteomic approaches, we have demonstrated the importance of the glycosylphosphatidylinositol (GPI) anchor pathway for cell wall synthesis and integrity and for the overall morphology of the filamentous fungus Neurospora crassa. Mutants affected in the gpig-1, gpip-1, gpip-2, gpip-3, and gpit-1 genes, which encode components of the N. crassa GPI anchor biosynthetic pathway, have been characterized. GPI anchor mutants exhibit colonial morphologies, significantly reduced rates of growth, altered hyphal growth patterns, considerable cellular lysis, and an abnormal "cell-within-a-cell" phenotype. The mutants are deficient in the production of GPI-anchored proteins, verifying the requirement of each altered gene for the process of GPI-anchoring. The mutant cell walls are abnormally weak, contain reduced amounts of protein, and have an altered carbohydrate composition. The mutant cell walls lack a number of GPI-anchored proteins, putatively involved in cell wall biogenesis and remodeling. From these studies, we conclude that the GPI anchor pathway is critical for proper cell wall structure and function in N. crassa.

Smoldering Multiple Myeloma

PubMed Central

Gao, Minjie; Yang, Guang; Kong, Yuanyuan; Wu, Xiaosong; Shi, Jumei

2015-01-01

Smoldering multiple myeloma (SMM) is an asymptomatic precursor stage of multiple myeloma (MM) characterized by clonal bone marrow plasma cells (BMPC) ≥ 10% and/or M protein level ≥ 30 g/L in the absence of end organ damage. It represents an intermediate stage between monoclonal gammopathy of undetermined significance (MGUS) and symptomatic MM. The risk of progression to symptomatic MM is not uniform, and several parameters have been reported to predict the risk of progression. These include the level of M protein and the percentage of BMPC, the proportion of immunophenotypically aberrant plasma cells, and the presence of immunoparesis, free light-chain (FLC) ratio, peripheral blood plasma cells (PBPC), pattern of serum M protein evolution, abnormal magnetic resonance imaging (MRI), cytogenetic abnormalities, IgA isotype, and Bence Jones proteinuria. So far treatment is still not recommended for SMM, because several trials suggested that patients with SMM do not benefit from early treatment. However, the Mateos et al. trial showed a survival benefit after early treatment with lenalidomide plus dexamethasone in patients with high-risk SMM. This trial has prompted a reevaluation of early treatment in an asymptomatic patient population. PMID:26000300

Analysis of maternal-zygotic ugdh mutants reveals divergent roles for HSPGs in vertebrate embryogenesis and provides new insight into the initiation of left-right asymmetry.

PubMed

Superina, Simone; Borovina, Antonia; Ciruna, Brian

2014-03-15

Growth factors and morphogens regulate embryonic patterning, cell fate specification, cell migration, and morphogenesis. The activity and behavior of these signaling molecules are regulated in the extracellular space through interactions with proteoglycans (Bernfield et al., 1999; Perrimon and Bernfield 2000; Lander and Selleck 2000; Selleck 2000). Proteoglycans are high molecular-weight proteins consisting of a core protein with covalently linked glycosaminoglycan (GAG) side chains, which are thought to mediate ligand interaction. Drosophila mutant embryos deficient for UDP-glucose dehydrogenase activity (Ugdh, required for GAG synthesis) exhibit abnormal Fgf, Wnt and TGFß signaling and die during gastrulation, indicating a broad and critical role for proteoglycans during early embryonic development (Lin et al., 1999; Lin and Perrimon 2000) (Hacker et al., 1997). Mouse Ugdh mutants also die at gastrulation, however, only Fgf signaling appears disrupted (Garcia-Garcia and Anderson, 2003). These findings suggested a possible divergence in the requirement for proteoglycans during Drosophila and mouse embryogenesis, and that mammals may have evolved alternative means of regulating Wnt and TGFß activity. To further examine the function of proteoglycans in vertebrate development, we have characterized zebrafish mutants devoid of both maternal and zygotic Ugdh/Jekyll activity (MZjekyll). We demonstrate that MZjekyll mutant embryos display abnormal Fgf, Shh, and Wnt signaling activities, with concomitant defects in central nervous system patterning, cardiac ventricular fate specification and axial morphogenesis. Furthermore, we uncover a novel role for proteoglycans in left-right pattern formation. Our findings resolve longstanding questions into the evolutionary conservation of Ugdh function and provide new mechanistic insights into the initiation of left-right asymmetry. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

The pattern and diagnostic criteria of sensory neuronopathy: a case–control study

PubMed Central

Camdessanché, Jean-Philippe; Jousserand, Guillemette; Ferraud, Karine; Vial, Christophe; Petiot, Philippe; Honnorat, Jérôme

2009-01-01

Acquired sensory neuronopathies encompass a group of paraneoplastic, dysimmune, toxic or idiopathic disorders characterized by degeneration of peripheral sensory neurons in dorsal root ganglia. As dorsal root ganglia cannot easily be explored, the clinical diagnosis of these disorders may be difficult. The question as to whether there exists a common clinical pattern of sensory neuronopathies, allowing the establishment of validated and easy-to-use diagnostic criteria, has not yet been addressed. In this study, logistic regression was used to construct diagnostic criteria on a retrospective study population of 78 patients with sensory neuronopathies and 56 with other sensory neuropathies. For this, sensory neuronopathy was provisionally considered as unambiguous in 44 patients with paraneoplastic disorder or cisplatin treatment and likely in 34 with a dysimmune or idiopathic setting who may theoretically have another form of neuropathy. To test the homogeneity of the sensory neuronopathy population, likely candidates were compared with unambiguous cases and then the whole population was compared with the other sensory neuropathies population. Criteria accuracy was checked on 37 prospective patients referred for diagnosis of sensory neuropathy. In the study population, sensory neuronopathy showed a common clinical and electrophysiological pattern that was independent of the underlying cause, including unusual forms with only patchy sensory loss, mild electrical motor nerve abnormalities and predominant small fibre or isolated lower limb involvement. Logistic regression allowed the construction of a set of criteria that gave fair results with the following combination: ataxia in the lower or upper limbs + asymmetrical distribution + sensory loss not restricted to the lower limbs + at least one sensory action potential absent or three sensory action potentials <30% of the lower limit of normal in the upper limbs + less than two nerves with abnormal motor nerve conduction study in the lower limbs. PMID:19506068

Lactate and the Lactate-to-Pyruvate Molar Ratio Cannot Be Used as Independent Biomarkers for Monitoring Brain Energetic Metabolism: A Microdialysis Study in Patients with Traumatic Brain Injuries

PubMed Central

Sahuquillo, Juan; Merino, Maria-Angels; Sánchez-Guerrero, Angela; Arikan, Fuat; Vidal-Jorge, Marian; Martínez-Valverde, Tamara; Rey, Anna; Riveiro, Marilyn; Poca, Maria-Antonia

2014-01-01

Background For decades, lactate has been considered an excellent biomarker for oxygen limitation and therefore of organ ischemia. The aim of the present study was to evaluate the frequency of increased brain lactate levels and the LP ratio (LPR) in a cohort of patients with severe or moderate traumatic brain injury (TBI) subjected to brain microdialysis monitoring to analyze the agreement between these two biomarkers and to indicate brain energy metabolism dysfunction. Methods Forty-six patients with an admission Glasgow coma scale score of ≤13 after resuscitation admitted to a dedicated 10-bed Neurotraumatology Intensive Care Unit were included, and 5305 verified samples of good microdialysis data were analyzed. Results Lactate levels were above 2.5 mmol/L in 56.9% of the samples. The relationships between lactate and the LPR could not be adequately modeled by any linear or non-linear model. Neither Cohen’s kappa nor Gwet’s statistic showed an acceptable agreement between both biomarkers to classify the samples in regard to normal or abnormal metabolism. The dataset was divided into four patterns defined by the lactate concentrations and the LPR. A potential interpretation for these patterns is suggested and discussed. Pattern 4 (low pyruvate levels) was found in 10.7% of the samples and was characterized by a significantly low concentration of brain glucose compared with the other groups. Conclusions Our study shows that metabolic abnormalities are frequent in the macroscopically normal brain in patients with traumatic brain injuries and a very poor agreement between lactate and the LPR when classifying metabolism. The concentration of lactate in the dialysates must be interpreted while taking into consideration the LPR to distinguish between anaerobic metabolism and aerobic hyperglycolysis. PMID:25025772

Resting ECG findings in elite football players.

PubMed

Bohm, Philipp; Ditzel, Roman; Ditzel, Heribert; Urhausen, Axel; Meyer, Tim

2013-01-01

The purpose of the study was to evaluate ECG abnormalities in a large sample of elite football players. Data from 566 elite male football players (57 of them of African origin) above 16 years of age were screened retrospectively (age: 20.9 ± 5.3 years; BMI: 22.9 ± 1.7 kg · m(-2), training history: 13.8 ± 4.7 years). The resting ECGs were analysed and classified according to the most current ECG categorisation of the European Society of Cardiology (ESC) (2010) and a classification of Pelliccia et al. (2000) in order to assess the impact of the new ESC-approach. According to the classification of Pelliccia, 52.5% showed mildly abnormal ECG patterns and 12% were classified as distinctly abnormal ECG patterns. According to the classification of the ESC, 33.7% showed 'uncommon ECG patterns'. Short-QT interval was the most frequent ECG pattern in this group (41.9%), followed by a shortened PR-interval (19.9%). When assessed with a QTc cut-off-point of 340 ms (instead of 360 ms), only 22.2% would have had 'uncommon ECG patterns'. Resting ECG changes amongst elite football players are common. Adjustment of the ESC criteria by adapting proposed time limits for the ECG (e.g. QTc, PR) should further reduce the rate of false-positive results.

UPTAKE OF STRONTIUM-85 IN NON-MALIGNANT VERTEBRAL LESIONS IN MAN

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

Bauer, G.C.H.; Scoccianti, P.

1961-01-01

By means of external scintillation counting, it was possible to demonstrate abnormally high spinal uptake of intravenously injected Sr/sup 85/ in various diseases of the vertebral column. A total dose of 50 mu c carrier-free Sr/sup 85/ was injected 7 to 14 days before recording spinal radioactivity with a collimated scintillation detector. An abnormal activity pattern was defined as a deviation from the normal pattern of twice the standard deviation of the normal mean value. Abnormal spinal patterns were detected in vertebral fractures, ankylosing spondylitis, tuberculous spondylitis, nonspecific discitis, and in a case with a lytic lesion of unknown origin.more » The value of 14 days was found more reliable than that at 7 days since by this time Sr/sup 85/ levels in soft tissues had fallen to low values. In 1 case, erroneous results were obtained from spinal counting due to a kidney stone which produced high activity in the spinal region. (H.H.D.)« less

[Velopharyngeal closure pattern and speech performance among submucous cleft palate patients].

PubMed

Heng, Yin; Chunli, Guo; Bing, Shi; Yang, Li; Jingtao, Li

2017-06-01

To characterize the velopharyngeal closure patterns and speech performance among submucous cleft palate patients. Patients with submucous cleft palate visiting the Department of Cleft Lip and Palate Surgery, West China Hospital of Stomatology, Sichuan University between 2008 and 2016 were reviewed. Outcomes of subjective speech evaluation including velopharyngeal function, consonant articulation, and objective nasopharyngeal endoscopy including the mobility of soft palate, pharyngeal walls were retrospectively analyzed. A total of 353 cases were retrieved in this study, among which 138 (39.09%) demonstrated velopharyngeal competence, 176 (49.86%) velopharyngeal incompetence, and 39 (11.05%) marginal velopharyngeal incompetence. A total of 268 cases were subjected to nasopharyngeal endoscopy examination, where 167 (62.31%) demonstrated circular closure pattern, 89 (33.21%) coronal pattern, and 12 (4.48%) sagittal pattern. Passavant's ridge existed in 45.51% (76/167) patients with circular closure and 13.48% (12/89) patients with coronal closure. Among the 353 patients included in this study, 137 (38.81%) presented normal articulation, 124 (35.13%) consonant elimination, 51 (14.45%) compensatory articulation, 36 (10.20%) consonant weakening, 25 (7.08%) consonant replacement, and 36 (10.20%) multiple articulation errors. Circular closure was the most prevalent velopharyngeal closure pattern among patients with submucous cleft palate, and high-pressure consonant deletion was the most common articulation abnormality. Articulation error occurred more frequently among patients with a low velopharyngeal closure rate.

Lung functions among patients with pulmonary tuberculosis in Dar es Salaam - a cross-sectional study.

PubMed

Manji, Mohamed; Shayo, Grace; Mamuya, Simon; Mpembeni, Rose; Jusabani, Ahmed; Mugusi, Ferdinand

2016-04-23

Approximately 40-60 % of patients remain sufferers of sequela of obstructive, restrictive or mixed patterns of lung disease despite treatment for pulmonary tuberculosis (PTB). The prevalence of these abnormalities in Tanzania remains unknown. A descriptive cross-sectional study was carried out among 501 patients with PTB who had completed at least 20 weeks of treatment. These underwent spirometry and their lung functions were classified as normal or abnormal (obstructive, restrictive or mixed). Logistic regression models were used to explore factors associated with abnormal lung functions. Abnormal lung functions were present in 371 (74 %) patients. There were 210 (42 %) patients with obstructive, 65 (13 %) patients with restrictive and 96 (19 %) patients with mixed patterns respectively. Significant factors associated with abnormal lung functions included recurrent PTB (Adj OR 2.8, CI 1.274 - 6.106), Human Immunodeficiency Virus (HIV) negative status (Adj OR 1.7, CI 1.055 - 2.583), age more than 40 years (Adj OR 1.7, CI 1.080 - 2.804) and male sex (Adj OR 1.7, CI 1.123 - 2.614). The prevalence of abnormal lung functions is high and it is associated with male sex, age older than 40 years, recurrent PTB and HIV negative status.

Electrophysiological abnormalities associated with extensive myelinated retinal nerve fibers

PubMed Central

Tay, Su Ann; Sanjay, Srinivasan

2012-01-01

An observational case report of electrophysiological abnormalities in a patient with anisomyopic amblyopia as a result of unilateral extensive myelinated retinal nerve fibers (MNFs) is illustrated. The electrophysiological readings revealed an abnormal pattern electroretinogram (PERG) but normal full-field electroretinogram readings in the affected eye. The visual-evoked potential was also undetectable in that eye. Our findings suggest that extensive MNFs can be associated with electrophysiological abnormalities, in particular the PERG, which can aid in diagnosing the cause of impaired vision when associated with amblyopia. PMID:22824610

Microphthalmia, anophthalmia, and coloboma and associated ocular and systemic features: understanding the spectrum.

PubMed

Skalicky, Simon E; White, Andrew J R; Grigg, John R; Martin, Frank; Smith, Jeremy; Jones, Michael; Donaldson, Craig; Smith, James E H; Flaherty, Maree; Jamieson, Robyn V

2013-12-01

Microphthalmia, anophthalmia, and coloboma form an interrelated spectrum of congenital eye abnormalities. To document the ocular and systemic findings and inheritance patterns in patients with microphthalmia, anophthalmia, and coloboma disease to gain insight into the underlying developmental etiologies. This retrospective consecutive case series was conducted at a tertiary referral center. Included in the study were 141 patients with microphthalmia, anophthalmia, and coloboma disease without a recognized syndromic etiology who attended the Westmead Children's Hospital, Sydney, from 1981-2012. Cases were grouped on the basis of the presence or absence of an optic fissure closure defect (OFCD); those with OFCD were further subdivided into microphthalmic and nonmicrophthalmic cases. Anophthalmic cases were considered as a separate group. Associated ocular and systemic abnormalities and inheritance patterns were assessed. Of 141 cases, 61 (43%) were microphthalmic non-OFCD (NOFCD), 34 (24%) microphthalmic OFCD, 32 (23%) nonmicrophthalmic coloboma (OFCD), 9 (6%) anophthalmic, and 5 (4%) were unclassified. Sixty-three (45%) had bilateral disease. Eighty-four patients (60%) had an associated ocular abnormality; of these, cataract (P < .001) and posterior segment anomalies (P < .001) were most common in the NOFCD group. Forty-eight (34%) had an associated systemic abnormality, most commonly neurological, musculoskeletal and facial, urological and genital, or cardiac. Neurological abnormalities were most common in the anophthalmic group (P = .003), while urological abnormalities were particularly seen in the OFCD groups (P = .009). Familial cases were identified in both the OFCD and NOFCD groups, with a likely autosomal dominant inheritance pattern in 9 of 10 families. This series indicated that the OFCD/NOFCD distinction may be useful in guiding evaluation for ocular and systemic associations, as well as the direction and analysis of genetic investigation.

Nailfold capillary abnormalities in erectile dysfunction of systemic sclerosis: a EUSTAR group analysis.

PubMed

Keck, Andrea D; Foocharoen, Chingching; Rosato, Edoardo; Smith, Vanessa; Allanore, Yannick; Distler, Oliver; Stamenkovic, Bojana; Pereira Da Silva, José Antonio; Hadj Khelifa, Sondess; Denisov, Lev N; Hachulla, Eric; García de la Peña Lefebvre, Paloma; Sibilia, Jean; Airò, Paolo; Caramaschi, Paola; Müller-Ladner, Ulf; Wiland, Piotr; Walker, Ulrich A

2014-04-01

The objective of this study was to analyse an association between nailfold capillary abnormalities and the presence and severity of erectile dysfunction (ED) in men with SSc. A cross-sectional analysis of the prospective European League Against Rheumatism (EULAR) Scleroderma Trial and Research database was performed. Men with SSc were included if they had undergone nailfold capillaroscopy and simultaneous ED assessment with the 5-item International Index for Erectile Function (IIEF-5). Eighty-six men met the inclusion criteria. Eight men (9.3%) had not had sexual intercourse and could not be assigned an IIEF-5 score. Sixty-nine of the 78 men (88.5%) with an IIEF-5 score had nailfold capillary abnormalities, of whom 54 (78.3%) suffered from ED. Nine men (11.5%) had no nailfold capillary abnormalities, of whom six (66.7%) had ED (P = 0.44). ED was more frequent in older men (P = 0.002) and in men with diffuse disease (P = 0.06). Men with abnormal capillaroscopy had a higher median EULAR disease activity than men without (P = 0.02), a lower diffusing capacity of the lung (P = 0.001) and a higher modified Rodnan skin score (P = 0.04), but mean IIEF-5 scores did not differ [15.7 (S.D. 6.2) vs 15.7 (S.D. 6.3)]. IIEF-5 scores did not differ between men with early (n = 12), active (n = 27) or late (n = 27) patterns (IIEF-5 scores of 17.9, 16.3 and 14.7, respectively). There were no differences in the prevalence of early, active and late capillaroscopy patterns between men with or without ED. Neither the presence or absence of abnormal capillaroscopy findings nor the subdivision into early, active and late patterns is associated with coexistent ED in SSc.

Altered Regional Cerebral Blood Flow in Idiopathic Hypersomnia.

PubMed

Boucetta, Soufiane; Montplaisir, Jacques; Zadra, Antonio; Lachapelle, Francis; Soucy, Jean-Paul; Gravel, Paul; Dang-Vu, Thien Thanh

2017-10-01

Idiopathic hypersomnia is characterized by excessive daytime sleepiness, despite normal or long sleep time. Its pathophysiological mechanisms remain unclear. This pilot study aims at characterizing the neural correlates of idiopathic hypersomnia using single photon emission computed tomography. Thirteen participants with idiopathic hypersomnia and 16 healthy controls were scanned during resting wakefulness using a high-resolution single photon emission computed tomography scanner with 99mTc-ethyl cysteinate dimer to assess cerebral blood flow. The main analysis compared regional cerebral blood flow distribution between the two groups. Exploratory correlations between regional cerebral blood flow and clinical characteristics evaluated the functional correlates of those brain perfusion patterns. Significance was set at p < .05 after correction for multiple comparisons. Participants with idiopathic hypersomnia showed regional cerebral blood flow decreases in medial prefrontal cortex and posterior cingulate cortex and putamen, as well as increases in amygdala and temporo-occipital cortices. Lower regional cerebral blood flow in the medial prefrontal cortex was associated with higher daytime sleepiness. These preliminary findings suggest that idiopathic hypersomnia is characterized by functional alterations in brain areas involved in the modulation of vigilance states, which may contribute to the daytime symptoms of this condition. The distribution of regional cerebral blood flow changes was reminiscent of the patterns associated with normal non-rapid-eye-movement sleep, suggesting the possible presence of incomplete sleep-wake transitions. These abnormalities were strikingly distinct from those induced by acute sleep deprivation, suggesting that the patterns seen here might reflect a trait associated with idiopathic hypersomnia rather than a non-specific state of sleepiness. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Epigenome Aberrations: Emerging Driving Factors of the Clear Cell Renal Cell Carcinoma

PubMed Central

Mehdi, Ali; Riazalhosseini, Yasser

2017-01-01

Clear cell renal cell carcinoma (ccRCC), the most common form of Kidney cancer, is characterized by frequent mutations of the von Hippel-Lindau (VHL) tumor suppressor gene in ~85% of sporadic cases. Loss of pVHL function affects multiple cellular processes, among which the activation of hypoxia inducible factor (HIF) pathway is the best-known function. Constitutive activation of HIF signaling in turn activates hundreds of genes involved in numerous oncogenic pathways, which contribute to the development or progression of ccRCC. Although VHL mutations are considered as drivers of ccRCC, they are not sufficient to cause the disease. Recent genome-wide sequencing studies of ccRCC have revealed that mutations of genes coding for epigenome modifiers and chromatin remodelers, including PBRM1, SETD2 and BAP1, are the most common somatic genetic abnormalities after VHL mutations in these tumors. Moreover, recent research has shed light on the extent of abnormal epigenome alterations in ccRCC tumors, including aberrant DNA methylation patterns, abnormal histone modifications and deregulated expression of non-coding RNAs. In this review, we discuss the epigenetic modifiers that are commonly mutated in ccRCC, and our growing knowledge of the cellular processes that are impacted by them. Furthermore, we explore new avenues for developing therapeutic approaches based on our knowledge of epigenome aberrations of ccRCC. PMID:28812986

Epigenome Aberrations: Emerging Driving Factors of the Clear Cell Renal Cell Carcinoma.

PubMed

Mehdi, Ali; Riazalhosseini, Yasser

2017-08-16

Clear cell renal cell carcinoma (ccRCC), the most common form of Kidney cancer, is characterized by frequent mutations of the von Hippel-Lindau ( VHL ) tumor suppressor gene in ~85% of sporadic cases. Loss of pVHL function affects multiple cellular processes, among which the activation of hypoxia inducible factor (HIF) pathway is the best-known function. Constitutive activation of HIF signaling in turn activates hundreds of genes involved in numerous oncogenic pathways, which contribute to the development or progression of ccRCC. Although VHL mutations are considered as drivers of ccRCC, they are not sufficient to cause the disease. Recent genome-wide sequencing studies of ccRCC have revealed that mutations of genes coding for epigenome modifiers and chromatin remodelers, including PBRM1 , SETD2 and BAP1 , are the most common somatic genetic abnormalities after VHL mutations in these tumors. Moreover, recent research has shed light on the extent of abnormal epigenome alterations in ccRCC tumors, including aberrant DNA methylation patterns, abnormal histone modifications and deregulated expression of non-coding RNAs. In this review, we discuss the epigenetic modifiers that are commonly mutated in ccRCC, and our growing knowledge of the cellular processes that are impacted by them. Furthermore, we explore new avenues for developing therapeutic approaches based on our knowledge of epigenome aberrations of ccRCC.

NLRP7 affects trophoblast lineage differentiation, binds to overexpressed YY1 and alters CpG methylation

USDA-ARS?s Scientific Manuscript database

Maternal-effect mutations in NLRP7 cause rare biparentally inherited hydatidiform moles (BiHMs), abnormal pregnancies containing hypertrophic vesicular trophoblast but no embryo. BiHM trophoblasts display abnormal DNA methylation patterns affecting maternally methylated germline differentially methy...

Separation of sulfated urinary glycosaminoglycans by high-resolution electrophoresis for isotyping of mucopolysaccharidoses in Malaysia.

PubMed

Nor, Azimah; Zabedah, Md Yunus; Norsiah, Md Desa; Ngu, Lock Hock; Suhaila, Abd Rahman

2010-06-01

Mucopolysaccharidoses (MPS) are a group of inherited disorders caused by the deficiency of specific lysosomal enzymes involved in glycosaminoglycans (GAGs) degradation. Currently, there are 11 enzyme deficiencies resulting in seven distinct MPS clinical syndromes and their subtypes. Different MPS syndromes cannot be clearly distinguished clinically due to overlapping signs and symptoms. Measurement of GAGs content in urine and separation of GAGs using high-resolution electrophoresis (HRE) are very useful initial screening tests for isotyping of MPS before specific enzyme diagnostics. In this study, we measured total urinary GAGs by a method using dimethylmethylene blue (DMB), and followed by isolation and separation of GAGs using high resolution electrophoresis (HRE) technique. Of 760 urine samples analyzed, 40 have abnormal GAGs HRE patterns. Thirty-five of these 40 cases have elevated urinary GAGs levels as well. These abnormal HRE patterns could be classified into 4 patterns: Pattern A (elevated DS and HS; suggestive of MPS I, II or VII; 16 cases), Pattern B (elevated HS and CS; suggestive of MPS III; 17 cases), and Pattern C (elevated KS and CS; suggestive of MPS IV, 5 cases), and Pattern D (elevated DS; suggestive of MPS VI; 2 cases). Based on the GAGs HRE pattern and a few discriminating clinical signs, we performed selective enzymatic investigation in 16 cases. In all except one case with MPS VII, the enzymatic diagnosis correlated well with the provisional MPS type as suggested by the abnormal HRE pattern. Our results showed that GAGs HRE is a useful, inexpensive and practical first-line screening test when MPS is suspected clinically, and it provides an important guide to further enzymatic studies on a selective basis.

Abnormal early dynamic individual patterns of functional networks in low gamma band for depression recognition.

PubMed

Bi, Kun; Chattun, Mahammad Ridwan; Liu, Xiaoxue; Wang, Qiang; Tian, Shui; Zhang, Siqi; Lu, Qing; Yao, Zhijian

2018-06-13

The functional networks are associated with emotional processing in depression. The mapping of dynamic spatio-temporal brain networks is used to explore individual performance during early negative emotional processing. However, the dysfunctions of functional networks in low gamma band and their discriminative potentialities during early period of emotional face processing remain to be explored. Functional brain networks were constructed from the MEG recordings of 54 depressed patients and 54 controls in low gamma band (30-48 Hz). Dynamic connectivity regression (DCR) algorithm analyzed the individual change points of time series in response to emotional stimuli and constructed individualized spatio-temporal patterns. The nodal characteristics of patterns were calculated and fed into support vector machine (SVM). Performance of the classification algorithm in low gamma band was validated by dynamic topological characteristics of individual patterns in comparison to alpha and beta band. The best discrimination accuracy of individual spatio-temporal patterns was 91.01% in low gamma band. Individual temporal patterns had better results compared to group-averaged temporal patterns in all bands. The most important discriminative networks included affective network (AN) and fronto-parietal network (FPN) in low gamma band. The sample size is relatively small. High gamma band was not considered. The abnormal dynamic functional networks in low gamma band during early emotion processing enabled depression recognition. The individual information processing is crucial in the discovery of abnormal spatio-temporal patterns in depression during early negative emotional processing. Individual spatio-temporal patterns may reflect the real dynamic function of subjects while group-averaged data may neglect some individual information. Copyright © 2018. Published by Elsevier B.V.

Joint imaging in polymyalgia rheumatica

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

O'Duffy, J.D.; Wahner, H.W.; Hunder, G.G.

1976-08-01

Technetium pertechnetate joint scintigrams were abnormal in 24 of 25 patients with polymyalgia rheumatica, in all 16 with rheumatoid arthritis, in 4 of 13 with nonarticular rheumatism, but in none of 26 control patients. Abnormal uptake in polymyalgia patients was commonest in shoulders and was less likely to be symmetric than in patients with rheumatoid arthritis, in whom distal joint abnormalities predominated. The pattern of abnormal uptake in polymyalgia rheumatica was not different in those with biopsy-proved giant cell arteritis. Correlation between symptoms and abnormal scintigrams was 72%, and abnormal uptake was present in 81% of joints of patients havingmore » physical abnormalities. Biopsy showed lymphocytic synovitis in the knee of one patient. After treatment the number of abnormal joints declined. These findings suggest that synovitis is common in polymyalgia rheumatica, and that it may account for some or most of the symptoms in this condition.« less

Tinnitus Perception and Distress Is Related to Abnormal Spontaneous Brain Activity as Measured by Magnetoencephalography

PubMed Central

Weisz, Nathan; Moratti, Stephan; Meinzer, Marcus; Dohrmann, Katalin; Elbert, Thomas

2005-01-01

Background The neurophysiological mechanisms underlying tinnitus perception are not well understood. Surprisingly, there have been no group studies comparing abnormalities in ongoing, spontaneous neuronal activity in individuals with and without tinnitus perception. Methods and Findings Here, we show that the spontaneous neuronal activity of a group of individuals with tinnitus (n = 17) is characterised by a marked reduction in alpha (8–12 Hz) power together with an enhancement in delta (1.5–4 Hz) as compared to a normal hearing control group (n = 16). This pattern was especially pronounced for temporal regions. Moreover, correlations with tinnitus-related distress revealed strong associations with this abnormal spontaneous activity pattern, particularly in right temporal and left frontal areas. Overall, effects were stronger for the alpha than for the delta frequency band. A data stream of 5 min, recorded with a whole-head neuromagnetometer under a resting condition, was sufficient to extract the marked differences. Conclusions Despite some limitations, there are arguments that the regional pattern of abnormal spontaneous activity we found could reflect a tinnitus-related cortical network. This finding, which suggests that a neurofeedback approach could reduce the adverse effects of this disturbing condition, could have important implications for the treatment of tinnitus. PMID:15971936

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

PubMed

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

2013-09-12

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

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

PubMed Central

2013-01-01

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

Differential diagnosis of bilateral parietal abnormalities in I-123 IMP SPECT imaging

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

Kuwabara, Y.; Ichiya, Y.; Otsuka, M.

1990-12-01

This report discusses the clinical significance of bilateral parietal abnormalities on I-123 IMP SPECT imaging in 158 patients with cerebral disorders. This pattern was seen in 15 out of 21 patients with Alzheimer's disease; it was also seen in 4 out of 5 patients with Parkinson's disease with dementia, in 3 out of 17 patients with vascular dementia, in 1 out of 36 patients with cerebral infarction without dementia, in 1 out of 2 patients with hypoglycemia, and in 1 out of 2 patients with CO intoxication. Detection of bilateral parietal abnormalities is a useful finding in the diagnosis ofmore » Alzheimer's disease, but one should keep in mind that other cerebral disorders may also show a similar pattern with I-123 IMP SPECT imaging.« less

ECG findings in comparison to cardiovascular MR imaging in viral myocarditis.

PubMed

Deluigi, Claudia C; Ong, Peter; Hill, Stephan; Wagner, Anja; Kispert, Eva; Klingel, Karin; Kandolf, Reinhard; Sechtem, Udo; Mahrholdt, Heiko

2013-04-30

We sought (1) to assess prevalence and type of ECG abnormalities in patients with biopsy proven myocarditis and signs of myocardial damage indicated by LGE, and (2) to evaluate whether ECG abnormalities are related to the pattern of myocardial damage. Prevalence and type of ECG abnormalities in patients presenting biopsy proven myocarditis, as well as any relation between ECG abnormalities and the in vivo pattern of myocardial damage are unknown. Eighty-four consecutive patients fulfilled the following criteria: (1) newly diagnosed biopsy proven viral myocarditis, and (2) non-ischemic LGE, and (3) standard 12-lead-ECG upon admission. Sixty-five patients with biopsy proven myocarditis had abnormal ECGs upon admission (77%). In this group, ST-abnormalities were detected most frequently (69%), followed by bundle-branch-block in 26%, and Q-waves in 8%. Atrial fibrillation was present in 6%, and AV-Block in two patients. In patients with septal LGE ST-abnormalities were more frequently located in anterolateral leads compared to patients with lateral LGE, in whom ST-abnormalities were most frequently observed in inferolateral leads. Bundle-branch-block occurred more often in patients with septal LGE (11/17). Four of five patients with Q-waves had severe and almost transmural LGE in the lateral wall. ECG abnormalities can be found in most patients with biopsy proven viral myocarditis at initial presentation. However, similar to suspected acute myocardial infarction, a normal ECG does not rule out myocarditis. ECG findings are related to the amount and area of damage as indicated by LGE, which confirms the important clinical role of ECG. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

stem fasciated, a Recessive Mutation in Sunflower (Helianthus annuus), Alters Plant Morphology and Auxin Level

PubMed Central

FAMBRINI, MARCO; BONSIGNORI, ELISA; RAPPARINI, FRANCESCA; CIONINI, GIULIANO; MICHELOTTI, VANIA; BERTINI, DANIELE; BARALDI, RITA; PUGLIESI, CLAUDIO

2006-01-01

• Background and Aims Plant lateral organs such as leaves arise from a group of initial cells within the flanks of the shoot apical meristem (SAM). Alterations in the initiation of lateral organs are often associated with changes in the dimension and arrangement of the SAM as well as with abnormal hormonal homeostasis. A mutation named stem fasciated (stf) that affects various aspects of plant development, including SAM shape and auxin level, was characterized in sunflower (Helianthus annuus). • Methods F1, F2 and F3 generations were obtained through reciprocal crosses between stf and normal plants. For the genetic analysis, a χ2 test was used. Phenotypic observations were made in field-grown and potted plants. A histological analysis of SAM, hypocotyl, epicotyl, stem and root apical meristem was also conducted. To evaluate the level of endogenous indole-3-acetic acid (IAA), a capillary gas chromatography–mass spectrometry–selected ion monitoring analysis was performed. • Key Results stf is controlled by a single nuclear recessive gene. stf plants are characterized by a dramatically increased number of leaves and vascular bundles in the stem, as well as by a shortened plastochron and an altered phyllotaxis pattern. By histological analysis, it was demonstrated that the stf phenotype is related to an enlarged vegetative SAM. Microscopy analysis of the mutant's apex also revealed an abnormal enlargement of nuclei in both central and peripheral zones and a disorganized distribution of cells in the L2 layer of the central zone. The stf mutant showed a high endogenous free IAA level, whereas auxin perception appeared normal. • Conclusions The observed phenotype and the high level of auxin detected in stf plants suggest that the STF gene is necessary for the proper initiation of primordia and for the establishment of a phyllotactic pattern through control of both SAM arrangement and hormonal homeostasis. PMID:16845141

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

PubMed

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

2006-05-01

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

Hypsarrhythmia assessment exhibits poor interrater reliability: a threat to clinical trial validity.

PubMed

Hussain, Shaun A; Kwong, Grace; Millichap, John J; Mytinger, John R; Ryan, Nicole; Matsumoto, Joyce H; Wu, Joyce Y; Lerner, Jason T; Sankar, Raman

2015-01-01

Hypsarrhythmia is the classic interictal electroencephalographic pattern associated with infantile spasms, and characterized by high voltage, disorganization, and multifocal independent epileptiform discharges. Given this seemingly simple definition, one might expect excellent interrater reliability (IRR) in the identification of this pattern. Alternatively, it may be argued that assessments of voltage and disorganization are fairly subjective, and thus quite challenging in borderline cases. We sought to test the IRR of hypsarrhythmia assessment in a systematic fashion. Six blinded pediatric electroencephalographers from four centers reviewed 22 electroencephalography (EEG) samples from patients with infantile spasms. Each sample was 5 min in duration and included only wakefulness. Raters determined if each EEG was abnormal and if hypsarrhythmia was present/absent, and characterized relevant features: voltage, organization, epileptiform discharges, slowing, interictal attenuations, symmetry, and synchrony. In addition, raters indicated their level of confidence for each assessment. Multirater kappa statistics (κ) were calculated for the assessment of hypsarrhythmia and each feature. Although IRR was favorable in determining whether a study was normal or abnormal (κ=0.89), reliability was unfavorable for assessment of hypsarrhythmia (κ=0.40), modified hypsarrhythmia (κ=0.47), high voltage (κ=0.37), disorganization (κ=0.22), multifocal epileptiform discharges (κ=0.68), interictal voltage attenuations (κ=0.21), slowing (κ=0.20), asymmetry (κ=0.26), and asynchrony (κ=0.08). Despite generally unsatisfactory interrater agreement, raters consistently reported high confidence in assessments. This study contradicts the view that hypsarrhythmia assessment is straightforward. Even small variability in the identification of hypsarrhythmia has potentially deleterious consequences for clinical care, as its presence or absence impacts decisions to pursue high-risk and high-cost therapies. These inconsistencies may similarly confound studies in which abolition of hypsarrhythmia is an outcome measure. There is a great need for practical, reliable, and unbiased measures of hypsarrhythmia. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Common therapeutic mechanisms of pallidal deep brain stimulation for hypo- and hyperkinetic movement disorders

PubMed Central

Iriki, Atsushi; Isoda, Masaki

2015-01-01

Abnormalities in cortico-basal ganglia (CBG) networks can cause a variety of movement disorders ranging from hypokinetic disorders, such as Parkinson's disease (PD), to hyperkinetic conditions, such as Tourette syndrome (TS). Each condition is characterized by distinct patterns of abnormal neural discharge (dysrhythmia) at both the local single-neuron level and the global network level. Despite divergent etiologies, behavioral phenotypes, and neurophysiological profiles, high-frequency deep brain stimulation (HF-DBS) in the basal ganglia has been shown to be effective for both hypo- and hyperkinetic disorders. The aim of this review is to compare and contrast the electrophysiological hallmarks of PD and TS phenotypes in nonhuman primates and discuss why the same treatment (HF-DBS targeted to the globus pallidus internus, GPi-DBS) is capable of ameliorating both symptom profiles. Recent studies have shown that therapeutic GPi-DBS entrains the spiking of neurons located in the vicinity of the stimulating electrode, resulting in strong stimulus-locked modulations in firing probability with minimal changes in the population-scale firing rate. This stimulus effect normalizes/suppresses the pathological firing patterns and dysrhythmia that underlie specific phenotypes in both the PD and TS models. We propose that the elimination of pathological states via stimulus-driven entrainment and suppression, while maintaining thalamocortical network excitability within a normal physiological range, provides a common therapeutic mechanism through which HF-DBS permits information transfer for purposive motor behavior through the CBG while ameliorating conditions with widely different symptom profiles. PMID:26180116

Using Fuzzy Clustering for Real-time Space Flight Safety

NASA Technical Reports Server (NTRS)

Lee, Charles; Haskell, Richard E.; Hanna, Darrin; Alena, Richard L.

2004-01-01

To ensure space flight safety, it is necessary to monitor myriad sensor readings on the ground and in flight. Since a space shuttle has many sensors, monitoring data and drawing conclusions from information contained within the data in real time is challenging. The nature of the information can be critical to the success of the mission and safety of the crew and therefore, must be processed with minimal data-processing time. Data analysis algorithms could be used to synthesize sensor readings and compare data associated with normal operation with the data obtained that contain fault patterns to draw conclusions. Detecting abnormal operation during early stages in the transition from safe to unsafe operation requires a large amount of historical data that can be categorized into different classes (non-risk, risk). Even though the 40 years of shuttle flight program has accumulated volumes of historical data, these data don t comprehensively represent all possible fault patterns since fault patterns are usually unknown before the fault occurs. This paper presents a method that uses a similarity measure between fuzzy clusters to detect possible faults in real time. A clustering technique based on a fuzzy equivalence relation is used to characterize temporal data. Data collected during an initial time period are separated into clusters. These clusters are characterized by their centroids. Clusters formed during subsequent time periods are either merged with an existing cluster or added to the cluster list. The resulting list of cluster centroids, called a cluster group, characterizes the behavior of a particular set of temporal data. The degree to which new clusters formed in a subsequent time period are similar to the cluster group is characterized by a similarity measure, q. This method is applied to downlink data from Columbia flights. The results show that this technique can detect an unexpected fault that has not been present in the training data set.

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.

Role of "Sural Sparing" Pattern (Absent/Abnormal Median and Ulnar with Present Sural SNAP) Compared to Absent/Abnormal Median or Ulnar with Normal Sural SNAP in Acute Inflammatory Demyelinating Polyneuropathy.

PubMed

Surpur, Spurthi Sunil; Govindarajan, Raghav

2017-01-01

Sural sparing defined as absent/abnormal median sensory nerve action potential (SNAP) amplitude or absent/abnormal ulnar SNAP amplitude with a normal sural SNAP amplitude is thought to be a marker for inflammatory demyelinating polyneuropathies. If sural sparing pattern specifically defined as absent/abnormal median and ulnar SNAP amplitude with normal sural SNAP amplitude (AMUNS) is sensitive and specific when compared with either absent/abnormal median and normal sural (AMNS) or absent/abnormal ulnar and normal sural (AUNS) for acute inflammatory demyelinating polyneuropathy (AIDP), chronic inflammatory demyelinating polyneuropathy (CIDP), select non-diabetic axonopathies (AXPs), and diabetic neuropathies (DNs). Retrospective analysis from 2001 to 2010 on all newly diagnosed AIDP, CIDP, select non-diabetic AXP, and DN. There were 20 AIDP and 23 CIDP. Twenty AXP and 50 DN patients between 2009 and 2010 were included as controls. AMUNS was seen in 65% of AIDP, 39% CIDP compared with 10% of AXP and 6% for DN with sensitivity of 51%, specificity of 92%, whereas the specificity of AMNS/AUNS was 73% and its sensitivity was 58%. If a patient has AMUNS they are >12 times more likely to have AIDP ( p  < 0.001). Sural sparing is highly specific but not sensitive when compared with either AMNS or AUNS in AIDP but does not add to sensitivity or specificity in CIDP.

Histological Pattern Of Endometrial Samples In Postmenopausal Women With Abnormal Uterine Bleeding.

PubMed

Deeba, Farhat; Shaista; Khan, Bushra

2016-01-01

Abnormal uterine bleeding is one of the most common clinical problems in gynaecological practice and is an indicator of various underlying disorders. An endometrial biopsy should be done in all women over 35 years with AUB to rule out endometrial cancer or pre-malignant lesion and to initiate treatment. However, wide range of histological patterns on endometrial biopsy offer a diagnostic challenge to practicing pathologists. The objective of this study was to determine histological patterns of endometrium in postmenopausal women with abnormal uterine bleeding. This cross-sectional study was conducted in the department of obstetrics and gynaecology, Benazir Bhutto Shaheed women and children teaching hospital, Abbottabad from 15/11/2014 to 14/05/2015. This study involved 110 postmenopausal women presenting with abnormal uterine bleeding. A written informed consent was obtained from every patient. The mean age of the patients was 61.60±6.17 years and the mean duration of AUB was 5.20±2.80 years. Most of the patients were para 6 (28.2%) and para 5 (28.2%) followed by para 4 (18.2%) and para 3 (17.3%) while only 8.2% were para 1. The most common histological pattern observed was complex hyperplasia without atypia (30.9%) followed by atrophic endometrium (24.5%), simple hyperplasia (23.6%), malignancy (12.7%), complex hyperplasia with atypia (4.5%) and benign endometrial polyp (3.6%). When stratified the data, there was no significant difference of histological patterns across various age groups (p=.673), duration of AUB (p=.064) and parity (p=.242). The most common histological pattern observed in postmenopausal women with AUB was complex hyperplasia without atypia (30.9%) followed by atrophic endometrium (24.5%), simple hyperplasia (23.6%), malignancy (12.7%), complex hyperplasia with atypia (4.5%) and benign endometrial polyp (3.6%).

In vivo quantification of intraventricular flow during left ventricular assist device support

NASA Astrophysics Data System (ADS)

Vu, Vi; Wong, Kin; Del Alamo, Juan; Aguilo, Pablo M. L.; May-Newman, Karen; Department of Bioengineering, San Diego State University Collaboration; Department of Mechanical; Aerospace Engineering, University of California San Diego Collaboration; Mechanical Assist Device Program, Sharp Memorial Hospital Collaboration

2014-11-01

Left ventricular assist devices (LVADs) are mechanical pumps that are surgically connected to the left ventricle (LV) and aorta to increase aortic flow and end-organ perfusion. Clinical studies have demonstrated that LVADs improve patient health and quality of life and significantly reduce the mortality of cardiac failure. However, In the presence of left ventricular assisted devices (LVAD), abnormal flow patterns and stagnation regions are often linked to thrombosis. The aim of our study is to evaluate the flow patterns in the left ventricle of the LVAD-assisted heart, with a focus on alterations in vortex development and blood stasis. To this aim, we applied color Doppler echocardiography to measure 2D, time resolved velocity fields in patients before and after implantation of LVADs. In agreement with our previous in vitro studies (Wong et al., Journal of Biomechanics 47, 2014), LVAD implantation resulted in decreased flow velocities and increased blood residence time near the outflow tract. The variation of residence time changes with LVAD operational speed was characterized for each patient.

Different nerve ultrasound patterns in charcot-marie-tooth types and hereditary neuropathy with liability to pressure palsies.

PubMed

Padua, Luca; Coraci, Daniele; Lucchetta, Marta; Paolasso, Ilaria; Pazzaglia, Costanza; Granata, Giuseppe; Cacciavillani, Mario; Luigetti, Marco; Manganelli, Fiore; Pisciotta, Chiara; Piscosquito, Giuseppe; Pareyson, Davide; Briani, Chiara

2018-01-01

Nerve ultrasound in Charcot-Marie-Tooth (CMT) disease has focused mostly on the upper limbs. We performed an evaluation of a large cohort of CMT patients in which we sonographically characterized nerve abnormalities in different disease types, ages, and nerves. Seventy patients affected by different CMT types and hereditary neuropathy with liability to pressure palsies (HNPP) were evaluated, assessing median, ulnar, fibular, tibial, and sural nerves bilaterally. Data were correlated with age. Nerve dimensions were correlated with CMT type, age, and nerve site. Nerves were larger in demyelinating than in axonal neuropathies. Nerve involvement was symmetric. CMT1 patients had larger nerves than did patients with other CMT types. Patients with HNPP showed enlargement at entrapment sites. Our study confirms the general symmetry of ultrasound nerve patterns in CMT. When compared with ultrasound studies of nerves of the upper limbs, evaluation of the lower limbs did not provide additional information. Muscle Nerve 57: E18-E23, 2018. © 2017 Wiley Periodicals, Inc.

Female impulsive aggression: a sleep research perspective.

PubMed

Lindberg, Nina; Tani, Pekka; Putkonen, Hanna; Sailas, Eila; Takala, Pirjo; Eronen, Markku; Virkkunen, Matti

2009-01-01

The rate of violent crimes among girls and women appears to be increasing. One in every five female prisoners has been reported to have antisocial personality disorder. However, it has been quite unclear whether the impulsive, aggressive behaviour among women is affected by the same biological mechanisms as among men. Psychiatric sleep research has attempted to identify diagnostically sensitive and specific sleep patterns associated with particular disorders. Most psychiatric disorders are typically characterized by a severe sleep disturbance associated with decreased amounts of slow wave sleep (SWS), the physiologically significant, refreshing part of sleep. Among men with antisocial behaviour with severe aggression, on the contrary, increased SWS has been reported, reflecting either specific brain pathology or a delay in the normal development of human sleep patterns. In our preliminary study among medication-free, detoxified female homicidal offenders with antisocial personality disorder, the same profound abnormality in sleep architecture was found. From the perspective of sleep research, the biological correlates of severe impulsive aggression seem to share similar features in both sexes.

On the Application of Pattern Recognition and AI Technique to the Cytoscreening of Vaginal Smears by Computer

NASA Astrophysics Data System (ADS)

Bow, Sing T.; Wang, Xia-Fang

1989-05-01

In this paper the concepts of pattern recognition, image processing and artificial intelligence are applied to the development of an intelligent cytoscreening system to differentiate the abnormal cytological objects from the normal ones in vaginal smears. To achieve this goal,work listed below are involved: 1. Enhancement of the microscopic images of the smears; 2. Elevation of the qualitative differentiation under the microscope by cytologists to a quantitative differentiation plateau on the epithelial cells, ciliated cells, vacuolated cells, foreign-body-giant cells, plasma cells, lymph cells, white blood cells, red blood cells, etc. These knowledges are to be inputted into our intelligent cyto-screening system to ameliorate machine differentiation; 3. Selection of a set of effective features to characterize the cytological objects onto various regions of the multiclustered by computer algorithms; and 4. Systematical summarization of the knowledge that a gynecologist has and the way he/she follows when dealing with a case.

Postnatal colonization with human "infant-type" Bifidobacterium species alters behavior of adult gnotobiotic mice.

PubMed

Luk, Berkley; Veeraragavan, Surabi; Engevik, Melinda; Balderas, Miriam; Major, Angela; Runge, Jessica; Luna, Ruth Ann; Versalovic, James

2018-01-01

Accumulating studies have defined a role for the intestinal microbiota in modulation of host behavior. Research using gnotobiotic mice emphasizes that early microbial colonization with a complex microbiota (conventionalization) can rescue some of the behavioral abnormalities observed in mice that grow to adulthood completely devoid of bacteria (germ-free mice). However, the human infant and adult microbiomes vary greatly, and effects of the neonatal microbiome on neurodevelopment are currently not well understood. Microbe-mediated modulation of neural circuit patterning in the brain during neurodevelopment may have significant long-term implications that we are only beginning to appreciate. Modulation of the host central nervous system by the early-life microbiota is predicted to have pervasive and lasting effects on brain function and behavior. We sought to replicate this early microbe-host interaction by colonizing gnotobiotic mice at the neonatal stage with a simplified model of the human infant gut microbiota. This model consortium consisted of four "infant-type" Bifidobacterium species known to be commensal members of the human infant microbiota present in high abundance during postnatal development. Germ-free mice and mice neonatally-colonized with a complex, conventional murine microbiota were used for comparison. Motor and non-motor behaviors of the mice were tested at 6-7 weeks of age, and colonization patterns were characterized by 16S ribosomal RNA gene sequencing. Adult germ-free mice were observed to have abnormal memory, sociability, anxiety-like behaviors, and motor performance. Conventionalization at the neonatal stage rescued these behavioral abnormalities, and mice colonized with Bifidobacterium spp. also exhibited important behavioral differences relative to the germ-free controls. The ability of Bifidobacterium spp. to improve the recognition memory of both male and female germ-free mice was a prominent finding. Together, these data demonstrate that the early-life gut microbiome, and human "infant-type" Bifidobacterium species, affect adult behavior in a strongly sex-dependent manner, and can selectively recapitulate the results observed when mice are colonized with a complex microbiota.

Behavioural and neural basis of anomalous motor learning in children with autism.

PubMed

Marko, Mollie K; Crocetti, Deana; Hulst, Thomas; Donchin, Opher; Shadmehr, Reza; Mostofsky, Stewart H

2015-03-01

Autism spectrum disorder is a developmental disorder characterized by deficits in social and communication skills and repetitive and stereotyped interests and behaviours. Although not part of the diagnostic criteria, individuals with autism experience a host of motor impairments, potentially due to abnormalities in how they learn motor control throughout development. Here, we used behavioural techniques to quantify motor learning in autism spectrum disorder, and structural brain imaging to investigate the neural basis of that learning in the cerebellum. Twenty children with autism spectrum disorder and 20 typically developing control subjects, aged 8-12, made reaching movements while holding the handle of a robotic manipulandum. In random trials the reach was perturbed, resulting in errors that were sensed through vision and proprioception. The brain learned from these errors and altered the motor commands on the subsequent reach. We measured learning from error as a function of the sensory modality of that error, and found that children with autism spectrum disorder outperformed typically developing children when learning from errors that were sensed through proprioception, but underperformed typically developing children when learning from errors that were sensed through vision. Previous work had shown that this learning depends on the integrity of a region in the anterior cerebellum. Here we found that the anterior cerebellum, extending into lobule VI, and parts of lobule VIII were smaller than normal in children with autism spectrum disorder, with a volume that was predicted by the pattern of learning from visual and proprioceptive errors. We suggest that the abnormal patterns of motor learning in children with autism spectrum disorder, showing an increased sensitivity to proprioceptive error and a decreased sensitivity to visual error, may be associated with abnormalities in the cerebellum. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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.

Defining the nature of the cerebral abnormalities in the premature infant: a qualitative magnetic resonance imaging study.

PubMed

Inder, Terrie E; Wells, Scott J; Mogridge, Nina B; Spencer, Carole; Volpe, Joseph J

2003-08-01

The aim of this study was to define qualitatively the nature and extent of white and gray matter abnormalities in a longitudinal population-based study of infants with very low birth weight. Perinatal factors were then related to the presence and severity of magnetic resonance imaging (MRI) abnormalities. From November 1998 to December 2000, 100 consecutive premature infants admitted to the neonatal intensive care unit at Christchurch Women's Hospital were recruited (98% eligible) after informed parental consent to undergo an MRI scan at term equivalent. The scans were analyzed by a single neuroradiologist experienced in pediatric MRI, with a second independent scoring of the MRI using a combination of criteria for white matter (cysts, signal abnormality, loss of volume, ventriculomegaly, corpus callosal thinning, myelination) and gray matter (gray matter signal abnormality, gyration, subarachnoid space). Results were analyzed against individual item scores as well as the presence of moderate-severe white matter score, total gray matter score, and total brain score. The mean gestational age was 27.9+/-2.4 weeks (range, 23-32 weeks), and mean birth weight was 1063+/-292 g. The greatest univariate predictors for moderate-severe white matter abnormality were lower gestational age (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.1-1.7; P<.01), maternal fever (OR, 2.2; 95% CI, 1.1-4.6; P<.04), proven sepsis in the infant at delivery (OR, 1.8; 95% CI, 1.1-3.6; P=0.03), inotropic support (OR, 2.7; 95% CI, 1.5-4.5; P<.001), patent ductus arteriosus (OR, 2.2; 95% CI, 1.2-3.8; P=.01), grade III/IV intraventricular hemorrhage (P=.015), and the occurrence of a pneumothorax (P=.05). There was a significant protective effect of intrauterine growth restriction (OR, 0.51; 95% CI, 0.23-0.99; P=.04). Gray matter abnormality was highly related to the presence and severity of white matter abnormality. A unique pattern of cerebral abnormality consisting of significant diffuse white matter atrophy, ventriculomegaly, immature gyral development, and enlarged subarachnoid space was found in 10 of 11 infants with birth gestation <26 weeks. Given the later outcome of these infants, this pattern may have very high risk for later global neurodevelopmental disability. This MRI study confirms a high incidence of cerebral white matter abnormality at term in an unselected population of premature infants, which is predominantly a result of noncystic injury in the extremely immature infant. We confirm that the major perinatal risk factors for white matter abnormality are related to perinatal infection, particularly maternal fever and infant sepsis, and hypotension with inotrope use. We have defined a distinct pattern of diffuse white and gray matter abnormality in the extremely immature infant.

Patterns of Growth and Decline in Lung Function in Persistent Childhood Asthma.

PubMed

McGeachie, M J; Yates, K P; Zhou, X; Guo, F; Sternberg, A L; Van Natta, M L; Wise, R A; Szefler, S J; Sharma, S; Kho, A T; Cho, M H; Croteau-Chonka, D C; Castaldi, P J; Jain, G; Sanyal, A; Zhan, Y; Lajoie, B R; Dekker, J; Stamatoyannopoulos, J; Covar, R A; Zeiger, R S; Adkinson, N F; Williams, P V; Kelly, H W; Grasemann, H; Vonk, J M; Koppelman, G H; Postma, D S; Raby, B A; Houston, I; Lu, Q; Fuhlbrigge, A L; Tantisira, K G; Silverman, E K; Tonascia, J; Weiss, S T; Strunk, R C

2016-05-12

Tracking longitudinal measurements of growth and decline in lung function in patients with persistent childhood asthma may reveal links between asthma and subsequent chronic airflow obstruction. We classified children with asthma according to four characteristic patterns of lung-function growth and decline on the basis of graphs showing forced expiratory volume in 1 second (FEV1), representing spirometric measurements performed from childhood into adulthood. Risk factors associated with abnormal patterns were also examined. To define normal values, we used FEV1 values from participants in the National Health and Nutrition Examination Survey who did not have asthma. Of the 684 study participants, 170 (25%) had a normal pattern of lung-function growth without early decline, and 514 (75%) had abnormal patterns: 176 (26%) had reduced growth and an early decline, 160 (23%) had reduced growth only, and 178 (26%) had normal growth and an early decline. Lower baseline values for FEV1, smaller bronchodilator response, airway hyperresponsiveness at baseline, and male sex were associated with reduced growth (P<0.001 for all comparisons). At the last spirometric measurement (mean [±SD] age, 26.0±1.8 years), 73 participants (11%) met Global Initiative for Chronic Obstructive Lung Disease spirometric criteria for lung-function impairment that was consistent with chronic obstructive pulmonary disease (COPD); these participants were more likely to have a reduced pattern of growth than a normal pattern (18% vs. 3%, P<0.001). Childhood impairment of lung function and male sex were the most significant predictors of abnormal longitudinal patterns of lung-function growth and decline. Children with persistent asthma and reduced growth of lung function are at increased risk for fixed airflow obstruction and possibly COPD in early adulthood. (Funded by the Parker B. Francis Foundation and others; ClinicalTrials.gov number, NCT00000575.).

Detection of abnormal living patterns for elderly living alone using support vector data description.

PubMed

Shin, Jae Hyuk; Lee, Boreom; Park, Kwang Suk

2011-05-01

In this study, we developed an automated behavior analysis system using infrared (IR) motion sensors to assist the independent living of the elderly who live alone and to improve the efficiency of their healthcare. An IR motion-sensor-based activity-monitoring system was installed in the houses of the elderly subjects to collect motion signals and three different feature values, activity level, mobility level, and nonresponse interval (NRI). These factors were calculated from the measured motion signals. The support vector data description (SVDD) method was used to classify normal behavior patterns and to detect abnormal behavioral patterns based on the aforementioned three feature values. The simulation data and real data were used to verify the proposed method in the individual analysis. A robust scheme is presented in this paper for optimally selecting the values of different parameters especially that of the scale parameter of the Gaussian kernel function involving in the training of the SVDD window length, T of the circadian rhythmic approach with the aim of applying the SVDD to the daily behavior patterns calculated over 24 h. Accuracies by positive predictive value (PPV) were 95.8% and 90.5% for the simulation and real data, respectively. The results suggest that the monitoring system utilizing the IR motion sensors and abnormal-behavior-pattern detection with SVDD are effective methods for home healthcare of elderly people living alone.

The pattern of abnormalities on sperm analysis: A study of 1186 infertile male in Yasmin IVF clinic Jakarta

NASA Astrophysics Data System (ADS)

Aulia, S. N.; Lestari, S. W.; Pratama, G.; Harzief, A. K.; Sumapraja, K.; Hestiantoro, A.; Wiweko, B.

2017-08-01

A declined in semen quality resulted an increase of male infertility has been reported. The pattern of abnormalities differs from one country to another. Conflicting results from different studies may be influenced by many factor. The aims are to evaluate the pattern of semen analysis of male partners of infertile couples and identify the current status of the contribution of male factor towards the infertility in our environment. The study is a descriptive analysis of the semen analysis of male partners in infertile couples, who were present at Yasmin IVF Clinic, infertility clinic of a Tertiary Care University Teaching Hospital between 1st January 2012 and 31st December 2015. A total of 1186 consenting male partners of infertile couple were recruited into the study. According to 2010 WHO normal reference values for semen parameters, 795 (67%) of patients were normozoospermia which had normal semen parameters and 391 (33%) patients had abnormal semen parameters. Oligozospermia was evident in 155 (39.5%) patients, being the most common disorder observed. It is followed by azoospermia (24.4%), oligoasthenozospermia (17.8%), asthenozospermia (5.9%), oligoasthenotera-tozospermia (5,7%), teratozospermia (2.6%), asthenoteratozospermia (2.8%), cryptozoospermia (0.8%), necrozospermia (0.3%), and oligoteratozospermia (0.3%). Abnormal semen quality remains a significant contribution to the overall infertility with oligozospermia being the most common semen quality abnormality. This condition is an indication for the need to focus on the prevention and management of male infertility. In addition, further studies are needed to address possible etiologies and treatment in order to improve fertility rates.

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

PubMed

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

2014-01-01

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

Advanced brain aging: relationship with epidemiologic and genetic risk factors, and overlap with Alzheimer disease atrophy patterns.

PubMed

Habes, M; Janowitz, D; Erus, G; Toledo, J B; Resnick, S M; Doshi, J; Van der Auwera, S; Wittfeld, K; Hegenscheid, K; Hosten, N; Biffar, R; Homuth, G; Völzke, H; Grabe, H J; Hoffmann, W; Davatzikos, C

2016-04-05

We systematically compared structural imaging patterns of advanced brain aging (ABA) in the general-population, herein defined as significant deviation from typical BA to those found in Alzheimer disease (AD). The hypothesis that ABA would show different patterns of structural change compared with those found in AD was tested via advanced pattern analysis methods. In particular, magnetic resonance images of 2705 participants from the Study of Health in Pomerania (aged 20-90 years) were analyzed using an index that captures aging atrophy patterns (Spatial Pattern of Atrophy for Recognition of BA (SPARE-BA)), and an index previously shown to capture atrophy patterns found in clinical AD (Spatial Patterns of Abnormality for Recognition of Early Alzheimer's Disease (SPARE-AD)). We studied the association between these indices and risk factors, including an AD polygenic risk score. Finally, we compared the ABA-associated atrophy with typical AD-like patterns. We observed that SPARE-BA had significant association with: smoking (P<0.05), anti-hypertensive (P<0.05), anti-diabetic drug use (men P<0.05, women P=0.06) and waist circumference for the male cohort (P<0.05), after adjusting for age. Subjects with ABA had spatially extensive gray matter loss in the frontal, parietal and temporal lobes (false-discovery-rate-corrected q<0.001). ABA patterns of atrophy were partially overlapping with, but notably deviating from those typically found in AD. Subjects with ABA had higher SPARE-AD values; largely due to the partial spatial overlap of associated patterns in temporal regions. The AD polygenic risk score was significantly associated with SPARE-AD but not with SPARE-BA. Our findings suggest that ABA is likely characterized by pathophysiologic mechanisms that are distinct from, or only partially overlapping with those of AD.

Impaired cognitive discrimination and discoordination of coupled theta-gamma oscillations in Fmr1 knockout mice

PubMed Central

Radwan, Basma; Dvorak, Dino; Fenton, André

2016-01-01

Fragile X syndrome (FXS) patients do not make the fragile X mental retardation protein (FMRP). Absence of FMRP causes dysregulated translation, abnormal synaptic plasticity and the most common form of inherited intellectual disability. But FMRP loss has minimal effects on memory itself, making it difficult to understand why absence of FMRP impairs memory discrimination and increases risk of autistic symptoms in patients, such as exaggerated responses to environmental changes. While Fmr1 knockout (KO) and wild-type (WT) mice perform cognitive discrimination tasks, we find abnormal patterns of coupling between theta and gamma oscillations in perisomatic and dendritic hippocampal CA1 local field potentials of the KO. Perisomatic CA1 theta-gamma phase-amplitude coupling (PAC) decreases with familiarity in both the WT and KO, but activating an invisible shock zone, subsequently changing its location, or turning it off, changes the pattern of oscillatory events in the LFPs recorded along the somato-dendritic axis of CA1. The cognition-dependent changes of this pattern of neural activity are relatively constrained in WT mice compared to KO mice, which exhibit abnormally weak changes during the cognitive challenge caused by changing the location of the shock zone and exaggerated patterns of change when the shock zone is turned off. Such pathophysiology might explain how dysregulated translation leads to intellectual disability in FXS. These findings demonstrate major functional abnormalities after the loss of FMRP in the dynamics of neural oscillations and that these impairments would be difficult to detect by steady-state measurements with the subject at rest or in steady conditions. PMID:26792400

Thalamus surface shape deformity in obsessive-compulsive disorder and schizophrenia.

PubMed

Kang, Do-Hyung; Kim, Sun Hyung; Kim, Chi-Won; Choi, Jung-Seok; Jang, Joon Hwan; Jung, Myung Hun; Lee, Jong-Min; Kim, Sun I; Kwon, Jun Soo

2008-04-16

The authors performed a three-dimensional shape deformation analysis to clarify the various patterns of specific thalamic nuclei abnormality using three age-matched and sex-matched groups of 22 patients with obsessive-compulsive disorder (OCD), 22 patients with schizophrenia and 22 control participants. Compared with the healthy volunteers, the anterior, lateral outward surface deformities of the thalamus were significant in OCD patients, whereas the posterior, medial outward deformities of the thalamus were prominent in schizophrenia patients. In terms of thalamic asymmetry, both OCD and schizophrenia patients exhibited the loss of a leftward pattern of asymmetry on the posterior, medial surface of the thalamus. Different patterns of shape abnormality of specific thalamic nuclei may be related to the different phenomenology of OCD and schizophrenia.

Technical Pitfall in 68Ga-Prostate Specific Membrane Antigen Imaging: Altered Biodistribution Caused by Free 68Ga-Citrate Due to Radiolysis Showing Increased Vascular Activity.

PubMed

Hod, Nir; Anconina, Reut; Levin, Daniel; Ezroh Kazap, Dina; Lantsberg, Sophie

2018-06-01

As with any new molecular imaging modality, accurate characterization of abnormalities on Ga-PSMA PET/CT imaging can be accomplished only if one is aware of the normal distribution pattern, physiological variants, and potential sources of false imaging findings. Altered biodistribution can have a significant impact on scan interpretation. Presented here is a rare case in which radiopharmaceutical radiolysis occurred causing excessive free Ga-citrate showing as an increased vascular activity. As Ga-PSMA PET/CT imaging is a relatively new imaging technique, it is important to be aware of such a potential technical pitfall in clinical practice in order to prevent scan misinterpretation.

Laugier-Hunziker syndrome: a case of asymptomatic mucosal and acral hyperpigmentation.

PubMed

Cusick, Elizabeth H; Marghoob, Ashfaq A; Braun, Ralph P

2017-04-01

Laugier-Hunziker syndrome (LHS) is a rare condition characterized by acquired hyperpigmentation involving the lips, oral mucosa, acral surfaces, nails and perineum. While patients with LHS may manifest pigmentation in all of the aforementioned areas, most present with pigmentation localized to only a few of these anatomical sites. We herein report a patient exhibiting the characteristic pigment distribution pattern associated with LHS. Since LHS is a diagnosis based on exclusion, we discuss the differential diagnosis of mucocutaneous hyperpigmentation. Due to the benign nature of the disease, it is critical to differentiate this disorder from conditions with similar mucocutaneous pigmentary changes with somatic abnormalities that require medical management. We also explore potential mechanisms that may explain the pathogenesis of LHS.

Venous sinus occlusive disease: MR findings

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

Yuh, W.T.C.; Simonson, T.M.; Tali, E.T.

1994-02-01

To study MR patterns of venous sinus occlusive disease and to relate them to the underlying pathophysiology by comparing the appearance and pathophysiologic features of venous sinus occlusive disease with those of arterial ischemic disease. The clinical data and MR examinations of 26 patients with venous sinus occlusive disease were retrospectively reviewed with special attention to mass effect, hemorrhage, and T2-weighted image abnormalities as well as to abnormal parenchymal, venous, or arterial enhancement after intravenous gadopentetate dimeglumine administration. Follow-up studies when available were evaluated for atrophy, infraction, chronic mass effect, and hemorrhage. Mass effect was present in 25 of 26more » patients. Eleven of the 26 had mass effect without abnormal signal on T2-weighted images. Fifteen patients had abnormal signal on T2-weighted images, but this was much less extensive than the degree of brain swelling in all cases. No patient showed abnormal parenchymal or arterial enhancement. Abnormal venous enhancement was seen in 10 of 13 patients who had contrast-enhanced studies. Intraparenchymal hemorrhage was seen in nine patients with high signal on T2-weighted images predominantly peripheral to the hematoma in eight. Three overall MR patterns were observed in acute sinus thrombosis: (1) mass effect without associated abnormal signal on T2-weighted images, (2) mass effect with associated abnormal signal on T2-weighted images and/or ventricular dilatation that may be reversible, and (3) intraparenchymal hematoma with surrounding edema. MR findings of venus sinus occlusive disease are different from those of arterial ischemia and may reflect different underlying pathophysiology. In venous sinus occlusive disease, the breakdown of the blood-brain barrier (vasogenic edema and abnormal parenchymal enhancement) does not always occur, and brain swelling can persist up to 2 years with or without abnormal signal on T2-weighted images. 34 refs., 5 figs.« less

Bone stress: a radionuclide imaging perspective. [/sup 99m/Tc-pyrophosphate

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

Roub, L.W.; Gumerman, L.W.; Hanley, E.N. Jr.

Thirty-five college athletes with lower leg pain underwent radiography and radionuclide studies to rule out a stress fracture. Their asymptomatic extremities and 13 pain-free athletes served as controls. Four main patterns were observed: (a) sharply marginated scintigraphic abnormalities and positive radiographs; (b) sharply marginated scintigraphic abnormalities and negatives radiographs; (c) ill-defined scintigraphic abnormalities and negative radiographs; and (d) negative radionuclide images and negative radiographs. Since the patients with the first two patterns were otherwise identical medically, the authors feel that this scintigraphic appearance is characterisic of bone stress in the appropriate clinical setting, regardless of the radiographic findings. A schemamore » is proposed to explain the occurrence of positive radionuclide images and negative radiographs in the same patient, using a broad conceptual approach to the problem of bone stress.« less

Visual Network Asymmetry and Default Mode Network Function in ADHD: An fMRI Study

PubMed Central

Hale, T. Sigi; Kane, Andrea M.; Kaminsky, Olivia; Tung, Kelly L.; Wiley, Joshua F.; McGough, James J.; Loo, Sandra K.; Kaplan, Jonas T.

2014-01-01

Background: A growing body of research has identified abnormal visual information processing in attention-deficit hyperactivity disorder (ADHD). In particular, slow processing speed and increased reliance on visuo-perceptual strategies have become evident. Objective: The current study used recently developed fMRI methods to replicate and further examine abnormal rightward biased visual information processing in ADHD and to further characterize the nature of this effect; we tested its association with several large-scale distributed network systems. Method: We examined fMRI BOLD response during letter and location judgment tasks, and directly assessed visual network asymmetry and its association with large-scale networks using both a voxelwise and an averaged signal approach. Results: Initial within-group analyses revealed a pattern of left-lateralized visual cortical activity in controls but right-lateralized visual cortical activity in ADHD children. Direct analyses of visual network asymmetry confirmed atypical rightward bias in ADHD children compared to controls. This ADHD characteristic was atypically associated with reduced activation across several extra-visual networks, including the default mode network (DMN). We also found atypical associations between DMN activation and ADHD subjects’ inattentive symptoms and task performance. Conclusion: The current study demonstrated rightward VNA in ADHD during a simple letter discrimination task. This result adds an important novel consideration to the growing literature identifying abnormal visual processing in ADHD. We postulate that this characteristic reflects greater perceptual engagement of task-extraneous content, and that it may be a basic feature of less efficient top-down task-directed control over visual processing. We additionally argue that abnormal DMN function may contribute to this characteristic. PMID:25076915

Evidence of Selection against Complex Mitotic-Origin Aneuploidy during Preimplantation Development

PubMed Central

McCoy, Rajiv C.; Demko, Zachary P.; Ryan, Allison; Banjevic, Milena; Hill, Matthew; Sigurjonsson, Styrmir; Rabinowitz, Matthew; Petrov, Dmitri A.

2015-01-01

Whole-chromosome imbalances affect over half of early human embryos and are the leading cause of pregnancy loss. While these errors frequently arise in oocyte meiosis, many such whole-chromosome abnormalities affecting cleavage-stage embryos are the result of chromosome missegregation occurring during the initial mitotic cell divisions. The first wave of zygotic genome activation at the 4–8 cell stage results in the arrest of a large proportion of embryos, the vast majority of which contain whole-chromosome abnormalities. Thus, the full spectrum of meiotic and mitotic errors can only be detected by sampling after the initial cell divisions, but prior to this selective filter. Here, we apply 24-chromosome preimplantation genetic screening (PGS) to 28,052 single-cell day-3 blastomere biopsies and 18,387 multi-cell day-5 trophectoderm biopsies from 6,366 in vitro fertilization (IVF) cycles. We precisely characterize the rates and patterns of whole-chromosome abnormalities at each developmental stage and distinguish errors of meiotic and mitotic origin without embryo disaggregation, based on informative chromosomal signatures. We show that mitotic errors frequently involve multiple chromosome losses that are not biased toward maternal or paternal homologs. This outcome is characteristic of spindle abnormalities and chaotic cell division detected in previous studies. In contrast to meiotic errors, our data also show that mitotic errors are not significantly associated with maternal age. PGS patients referred due to previous IVF failure had elevated rates of mitotic error, while patients referred due to recurrent pregnancy loss had elevated rates of meiotic error, controlling for maternal age. These results support the conclusion that mitotic error is the predominant mechanism contributing to pregnancy losses occurring prior to blastocyst formation. This high-resolution view of the full spectrum of whole-chromosome abnormalities affecting early embryos provides insight into the cytogenetic mechanisms underlying their formation and the consequences for human fertility. PMID:26491874

Large-scale brain networks are distinctly affected in right and left mesial temporal lobe epilepsy.

PubMed

de Campos, Brunno Machado; Coan, Ana Carolina; Lin Yasuda, Clarissa; Casseb, Raphael Fernandes; Cendes, Fernando

2016-09-01

Mesial temporal lobe epilepsy (MTLE) with hippocampus sclerosis (HS) is associated with functional and structural alterations extending beyond the temporal regions and abnormal pattern of brain resting state networks (RSNs) connectivity. We hypothesized that the interaction of large-scale RSNs is differently affected in patients with right- and left-MTLE with HS compared to controls. We aimed to determine and characterize these alterations through the analysis of 12 RSNs, functionally parceled in 70 regions of interest (ROIs), from resting-state functional-MRIs of 99 subjects (52 controls, 26 right- and 21 left-MTLE patients with HS). Image preprocessing and statistical analysis were performed using UF(2) C-toolbox, which provided ROI-wise results for intranetwork and internetwork connectivity. Intranetwork abnormalities were observed in the dorsal default mode network (DMN) in both groups of patients and in the posterior salience network in right-MTLE. Both groups showed abnormal correlation between the dorsal-DMN and the posterior salience, as well as between the dorsal-DMN and the executive-control network. Patients with left-MTLE also showed reduced correlation between the dorsal-DMN and visuospatial network and increased correlation between bilateral thalamus and the posterior salience network. The ipsilateral hippocampus stood out as a central area of abnormalities. Alterations on left-MTLE expressed a low cluster coefficient, whereas the altered connections on right-MTLE showed low cluster coefficient in the DMN but high in the posterior salience regions. Both right- and left-MTLE patients with HS have widespread abnormal interactions of large-scale brain networks; however, all parameters evaluated indicate that left-MTLE has a more intricate bihemispheric dysfunction compared to right-MTLE. Hum Brain Mapp 37:3137-3152, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Computerized scheme for detection of diffuse lung diseases on CR chest images

NASA Astrophysics Data System (ADS)

Pereira, Roberto R., Jr.; Shiraishi, Junji; Li, Feng; Li, Qiang; Doi, Kunio

2008-03-01

We have developed a new computer-aided diagnostic (CAD) scheme for detection of diffuse lung disease in computed radiographic (CR) chest images. One hundred ninety-four chest images (56 normals and 138 abnormals with diffuse lung diseases) were used. The 138 abnormal cases were classified into three levels of severity (34 mild, 60 moderate, and 44 severe) by an experienced chest radiologist with use of five different patterns, i.e., reticular, reticulonodular, nodular, air-space opacity, and emphysema. In our computerized scheme, the first moment of the power spectrum, the root-mean-square variation, and the average pixel value were determined for each region of interest (ROI), which was selected automatically in the lung fields. The average pixel value and its dependence on the location of the ROI were employed for identifying abnormal patterns due to air-space opacity or emphysema. A rule-based method was used for determining three levels of abnormality for each ROI (0: normal, 1: mild, 2: moderate, and 3: severe). The distinction between normal lungs and abnormal lungs with diffuse lung disease was determined based on the fractional number of abnormal ROIs by taking into account the severity of abnormalities. Preliminary results indicated that the area under the ROC curve was 0.889 for the 44 severe cases, 0.825 for the 104 severe and moderate cases, and 0.794 for all cases. We have identified a number of problems and reasons causing false positives on normal cases, and also false negatives on abnormal cases. In addition, we have discussed potential approaches for improvement of our CAD scheme. In conclusion, the CAD scheme for detection of diffuse lung diseases based on texture features extracted from CR chest images has the potential to assist radiologists in their interpretation of diffuse lung diseases.

Proteogenomic characterization of human colon and rectal cancer

PubMed Central

Zhang, Bing; Wang, Jing; Wang, Xiaojing; Zhu, Jing; Liu, Qi; Shi, Zhiao; Chambers, Matthew C.; Zimmerman, Lisa J.; Shaddox, Kent F.; Kim, Sangtae; Davies, Sherri R.; Wang, Sean; Wang, Pei; Kinsinger, Christopher R.; Rivers, Robert C.; Rodriguez, Henry; Townsend, R. Reid; Ellis, Matthew J.C.; Carr, Steven A.; Tabb, David L.; Coffey, Robert J.; Slebos, Robbert J.C.; Liebler, Daniel C.

2014-01-01

Summary We analyzed proteomes of colon and rectal tumors previously characterized by the Cancer Genome Atlas (TCGA) and performed integrated proteogenomic analyses. Somatic variants displayed reduced protein abundance compared to germline variants. mRNA transcript abundance did not reliably predict protein abundance differences between tumors. Proteomics identified five proteomic subtypes in the TCGA cohort, two of which overlapped with the TCGA “MSI/CIMP” transcriptomic subtype, but had distinct mutation, methylation, and protein expression patterns associated with different clinical outcomes. Although copy number alterations showed strong cis- and trans-effects on mRNA abundance, relatively few of these extend to the protein level. Thus, proteomics data enabled prioritization of candidate driver genes. The chromosome 20q amplicon was associated with the largest global changes at both mRNA and protein levels; proteomics data highlighted potential 20q candidates including HNF4A, TOMM34 and SRC. Integrated proteogenomic analysis provides functional context to interpret genomic abnormalities and affords a new paradigm for understanding cancer biology. PMID:25043054

When the threat comes from inside the body: a neuroscience based learning perspective of the etiology of panic disorder.

PubMed

Hamm, Alfons O; Richter, Jan; Pané-Farré, Christiane A

2014-01-01

Unexpected, recurrent panic attacks and anxious apprehension are two distinct emotional phenomena that constitute the core symptoms for diagnosing panic disorder. Taking a neuroscience perspective the current review paper presents both epidemiological and experimental psychophysiological evidence suggesting that panic attacks can be conceptualized as an unconditioned circa defense response pattern to intense internal threat stimuli, characterized by strong autonomic surge and escape behavior and abnormal plastic changes of the brain. Anxious apprehension develops after the experience of such severe panic attacks as conditioned responses to mild body symptoms. Theoretically these conditioned fear responses can be considered as post-encounter defense characterized by increased selective attention, increased threat appraisal and defensive freezing and startle potentiation evidencing altered brain circuits evoked by mild body symptoms. Agoraphobic avoidance starts very early during the defensive cascade and can be conceived as motivated behavior driven by the incentive to be in a safe context that is under control of the individual.

Lung volume reduction of pulmonary emphysema: the radiologist task.

PubMed

Milanese, Gianluca; Silva, Mario; Sverzellati, Nicola

2016-03-01

Several lung volume reduction (LVR) techniques have been increasingly evaluated in patients with advanced pulmonary emphysema, especially in the last decade. Radiologist plays a pivotal role in the characterization of parenchymal damage and, thus, assessment of eligibility criteria. This review aims to discuss the most common LVR techniques, namely LVR surgery, endobronchial valves, and coils LVR, with emphasis on the role of computed tomography (CT). Several trials have recently highlighted the importance of regional quantification of emphysema by computerized CT-based segmentation of hyperlucent parenchyma, which is strongly recommended for candidates to any LVR treatment. In particular, emphysema distribution pattern and fissures integrity are evaluated to tailor the choice of the most appropriate LVR technique. Furthermore, a number of CT measures have been tested for the personalization of treatment, according to imaging detected heterogeneity of parenchymal disease. CT characterization of heterogeneous parenchymal abnormalities provides criteria for selection of the preferable treatment in each patient and improves outcome of LVR as reflected by better quality of life, higher exercise tolerance, and lower mortality.

Default mode network abnormalities in posttraumatic stress disorder: A novel network-restricted topology approach.

PubMed

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

2018-08-01

Disruption in the default mode network (DMN) has been implicated in numerous neuropsychiatric disorders, including posttraumatic stress disorder (PTSD). However, studies have largely been limited to seed-based methods and involved inconsistent definitions of the DMN. Recent advances in neuroimaging and graph theory now permit the systematic exploration of intrinsic brain networks. In this study, we used resting-state functional magnetic resonance imaging (fMRI), diffusion MRI, and graph theoretical analyses to systematically examine the DMN connectivity and its relationship with PTSD symptom severity in a cohort of 65 combat-exposed US Veterans. We employed metrics that index overall connectivity strength, network integration (global efficiency), and network segregation (clustering coefficient). Then, we conducted a modularity and network-based statistical analysis to identify DMN regions of particular importance in PTSD. Finally, structural connectivity analyses were used to probe whether white matter abnormalities are associated with the identified functional DMN changes. We found decreased DMN functional connectivity strength to be associated with increased PTSD symptom severity. Further topological characterization suggests decreased functional integration and increased segregation in subjects with severe PTSD. Modularity analyses suggest a spared connectivity in the posterior DMN community (posterior cingulate, precuneus, angular gyrus) despite overall DMN weakened connections with increasing PTSD severity. Edge-wise network-based statistical analyses revealed a prefrontal dysconnectivity. Analysis of the diffusion networks revealed no alterations in overall strength or prefrontal structural connectivity. DMN abnormalities in patients with severe PTSD symptoms are characterized by decreased overall interconnections. On a finer scale, we found a pattern of prefrontal dysconnectivity, but increased cohesiveness in the posterior DMN community and relative sparing of connectivity in this region. The DMN measures established in this study may serve as a biomarker of disease severity and could have potential utility in developing circuit-based therapeutics. Published by Elsevier Inc.

The Use of Biologic Therapies in Uveitis.

PubMed

Schwartzman, Sergio; Schwartzman, Monica

2015-12-01

Therapy for autoimmune ophthalmic disease is currently evolving. The improved understanding of the abnormal immune response in the various forms of uveitis has resulted in targeted therapy. The aberrations of the immune system have been characterized by atypical cell populations, cytokine expression, and cell-cell interactions. Different patterns of cytokine expression have now been delineated in the abnormal uveal tract with exaggerated and/or abnormal expression of TNF, IL-1, IL-2, IL-6, and IL-17. The development of therapies for other conditions in which these cytokines play an important role has resulted in the availability of biological agents that have been adopted for use in the therapy for uveitis. Adalimumab and infliximab have been the best studied anti-TNF agents and indeed have now been recommended by an expert panel as first-line treatment of ocular manifestations of Behçet's disease and second-line treatment for other forms of uveitis (Levy-Clarke et al. (Ophthalmology, 2013). Other anti-TNF agents have been studied as well. Daclizumab, a monoclonal antibody directed against the IL-2 receptor, has also demonstrated utility in treating uveitis as have some of the anti-IL1 agents. Gevokizumab has been granted orphan drug designation for the treatment of resistant forms of uveitis. Therapies affecting IL-6, including tocilizumab are being studied, and available medications that block antigen presenting cell and T cell interaction such as abatacept have been reported to be effective in uveitis. Interferons as well as rituximab have also been evaluated in small studies. Although these biologic therapies have provided a larger armamentarium to treat uveitis, challenges remain. Uveitis is not a single illness; rather, it is a manifestation of many potential systemic diseases that may have very specific individual therapeutic targets. Identifying and characterizing these underlying diseases is not always achieved, and more importantly, the most effective therapies for each entity have not been defined.

A novel syndrome of hypohidrosis and intellectual disability is linked to COG6 deficiency.

PubMed

Shaheen, Ranad; Ansari, Shinu; Alshammari, Muneera J; Alkhalidi, Hisham; Alrukban, Hadeel; Eyaid, Wafaa; Alkuraya, Fowzan S

2013-07-01

Numerous syndromic forms of intellectual disability have been described including those with abnormal sweating pattern. To describe the clinical and molecular analysis of a large multiplex consanguineous Saudi family with an unusual constellation of severe intellectual disability, hypohidrosis, abnormal teeth, and acquired microcephaly. Clinical evaluation, autozygosity mapping, exome sequencing, and expression analysis. Autozygosity mapping revealed a single critical locus corresponding to chr13:39 338 062-40 857 430. Exome sequencing uncovered a deep intronic (NM_020751.2:c.1167-24A>G) variant in COG6 that largely replaces the consensus acceptor site, resulting in pronounced reduction of the normal transcript and consequent deficiency of COG6 protein. Patient cells also exhibited pronounced deficiency of STX6, consistent with the established stabilising effect of COG6 on STX6. Four additional patients representing two families of the same tribal origin as the original family were found to have the same mutation, confirming a founder effect. Remarkably, none of the patients displayed any detectable abnormality in the glycosylation pattern of transferrin, which contradicts a previously published report of a patient whose abnormal glycosylation pattern was presumed to be caused by a missense variant in COG6. Our data implicate COG6 in the pathogenesis of a novel hypohidrotic disorder in humans that is distinct from congenital disorders of glycosylation.

Retinal architecture and mfERG: Optic nerve head component response characteristics in MS.

PubMed

Schnurman, Zane S; Frohman, Teresa C; Beh, Shin C; Conger, Darrel; Conger, Amy; Saidha, Shiv; Galetta, Steven; Calabresi, Peter A; Green, Ari J; Balcer, Laura J; Frohman, Elliot M

2014-05-27

To describe a novel neurophysiologic signature of the retinal ganglion cell and to elucidate its relationship to abnormalities in validated structural and functional measures of the visual system. We used multifocal electroretinogram-generated optic nerve head component (ONHC) responses from normal subjects (n = 18), patients with multiple sclerosis (MS) (n = 18), and those with glaucoma (n = 3). We then characterized the relationship between ONHC response abnormalities and performance on low-contrast visual acuity, multifocal visual-evoked potential-induced cortical responses, and average and quadrant retinal nerve fiber layer (RNFL) thicknesses, as measured by spectral-domain optical coherence tomography. Compared with the eyes of normal subjects, the eyes of patients with MS exhibited an increased number of abnormal or absent ONHC responses (p < 0.0001). For every 7-letter reduction in low-contrast letter acuity, there were corresponding 4.6 abnormal ONHC responses at 2.5% contrast (p < 0.0001) and 6.6 abnormalities at the 1.25% contrast level (p < 0.0001). Regarding average RNFL thickness, for each 10-μm thickness reduction, we correspondingly observed 6.8 abnormal ONHC responses (p = 0.0002). The most robust association was between RNFL thinning in the temporal quadrant and ONHC response abnormalities (p < 0.0001). Further characterization of ONHC abnormalities (those that are reversible and irreversible) may contribute to the development of novel neurotherapeutic strategies aimed at achieving neuroprotective, and perhaps even neurorestorative, effects in disorders that target the CNS in general, and MS in particular. © 2014 American Academy of Neurology.

HLA-C expression pattern is spatially different between psoriasis and eczema skin lesions.

PubMed

Carlén, Lina; Sakuraba, Kazuko; Ståhle, Mona; Sánchez, Fabio

2007-02-01

Interactions between genetic and environmental factors underlie the immune dysregulation and keratinocyte abnormalities that characterize psoriasis. Among known psoriasis susceptibility loci (PSORS), PSORS1 on chromosome 6 has the strongest association to disease. Altered expression of some PSORS1 candidate genes has been reported but little is known about HLA-C expression in psoriasis. This study compared expression of major histocompatibility complex class Ia and HLA-C in psoriasis, allergic contact eczema, and normal skin. Although HLA-C was abundant in protein extracts from both eczema and psoriasis, a consistent and intriguing difference in the expression pattern was observed; strong immunoreactivity in the basal cell layer, polarized towards the basement membrane in psoriasis, whereas in eczema lesions HLA-C immunostaining was present mostly in suprabasal cells. Inflammatory cells in the dermis were strongly stained in both diseases. Normal skin epithelium showed less intense but similar HLA-C staining as eczema lesions. HLA class Ia expression overall resembled that of HLA-C in all samples. The distinct HLA-C expression patterns in psoriasis and eczema suggest a functional role in the specific psoriasis immune response and not only a general feature of inflammation.

[Disturbed respiratory cycle accompanying hypoxic-ischemic encephalopathy].

PubMed

Saito, Yoshiaki; Masuko, Kaori; Kaneko, Kaori; Saito, Kazuyo; Chikumaru, Yuri; Iwamoto, Hiroko; Matsui, Akira; Kimura, Seiji

2005-09-01

We report the case of a 2-year-old boy who experienced total asphyxia at 4 months of age, and suffered abnormalities at specific phases of the respiratory cycle. The patient was bedridden due to severe tetraplegia and showed little response to external stimuli. He has been tube-fed since the initial asphyxia and a tracheotomy was performed after recurrent hypoxic episodes as a result of the respiratory dysfunction. Upon examination, his respiratory pattern was characterized by arrest during the inspiratory phase with a possible over-riding secondary inspiration. The respiratory pause at the inspiratory phase was markedly prolonged during an episode of pulmonary infection, resulting in recurrent cyanosis that necessitated artificial ventilation. The "second" inspiration typically occurred during the mid- or late-inspiratory phases, with this pattern often shown to be variable after epileptic seizures. The characteristic breathing of this patient suggested that difficulty in forming a normal respiratory cycle, other than during periods of hypoventilation or apnoea, could be a significant respiratory dysfunction following asphyxiation. Strategies for the management of such patients should be carefully designed after close observation of breathing patterns within the respiratory cycle, and with consideration for the influence of epileptic seizures and other inputs from somatic afferents.

Recording In Vivo Human Colonic Motility: What Have We Learnt Over the Past 100 Years?

PubMed

Dinning, Phil G

To understand the abnormalities that underpin functional gut disorders we must first gain insight into the normal patterns of gut motility. While detailed information continually builds on the motor patterns (and mechanisms that control them) of the human esophagus and anorectum, our knowledge of normal and abnormal motility in the more inaccessible regions of the gut remains poor. This particularly true of the human colon. Investigation of in vivo colonic motor patterns is achieved through measures of transit (radiology, scintigraphy and, more recently, "smart pills") or by direct real-time recording of colonic contractility (intraluminal manometry). This short review will provide an overview of findings from the past and present and attempt to piece together the complex nature of colonic motor patterns. In doing so it will build a profile of human colonic motility and determine the likely mechanisms that control this motility.

[Assessment of blood flow in the middle cerebral artery and the umbilical artery in fetuses with umbilical venous pulsations].

PubMed

Borowski, Dariusz; Czuba, Bartosz; Kaczmarek, Piotr; Włoch, Agata; Pawłowicz, Paweł; Wyrwas, Dorota; Wielgos, Mirosław; Sodowski, Krzysztof; Szaflik, Krzysztof

2006-03-01

Umbilical venous pulsation is an important sign of hemodynamic compromise, especially during fetal heart failure and asphyxia. The aim of this study was to determine of the blow flow in the middle cerebral artery and the umbilical artery in fetuses with umbilical venous pulsations. The investigation included 18 fetuses with signs of the intrauterine growth restriction and umbilical venous pulsations after 28th weeks of gestation. We evaluated cerebral-placental ratio (CPR) and pulsation index (PI) in the middle cerebral artery (MCA) and the umbilical artery (UA). We observed brain sparring effect in all cases of analyzing fetuses. There were 77,8% of abnormal flow pattern in umbilical artery. 13 fetuses had a single pulsation pattern in umbilical vein and another 5 had double pulsation pattern. The coexistence of umbilical vein pulsation and abnormal flow pattern in umbilical artery is closely related to increased perinatal mortality.

Identification of Abnormal System Noise Temperature Patterns in Deep Space Network Antennas Using Neural Network Trained Fuzzy Logic

NASA Technical Reports Server (NTRS)

Lu, Thomas; Pham, Timothy; Liao, Jason

2011-01-01

This paper presents the development of a fuzzy logic function trained by an artificial neural network to classify the system noise temperature (SNT) of antennas in the NASA Deep Space Network (DSN). The SNT data were classified into normal, marginal, and abnormal classes. The irregular SNT pattern was further correlated with link margin and weather data. A reasonably good correlation is detected among high SNT, low link margin and the effect of bad weather; however we also saw some unexpected non-correlations which merit further study in the future.

Multimodal image analysis of clinical influences on preterm brain development

PubMed Central

Ball, Gareth; Aljabar, Paul; Nongena, Phumza; Kennea, Nigel; Gonzalez‐Cinca, Nuria; Falconer, Shona; Chew, Andrew T.M.; Harper, Nicholas; Wurie, Julia; Rutherford, Mary A.; Edwards, A. David

2017-01-01

Objective Premature birth is associated with numerous complex abnormalities of white and gray matter and a high incidence of long‐term neurocognitive impairment. An integrated understanding of these abnormalities and their association with clinical events is lacking. The aim of this study was to identify specific patterns of abnormal cerebral development and their antenatal and postnatal antecedents. Methods In a prospective cohort of 449 infants (226 male), we performed a multivariate and data‐driven analysis combining multiple imaging modalities. Using canonical correlation analysis, we sought separable multimodal imaging markers associated with specific clinical and environmental factors and correlated to neurodevelopmental outcome at 2 years. Results We found five independent patterns of neuroanatomical variation that related to clinical factors including age, prematurity, sex, intrauterine complications, and postnatal adversity. We also confirmed the association between imaging markers of neuroanatomical abnormality and poor cognitive and motor outcomes at 2 years. Interpretation This data‐driven approach defined novel and clinically relevant imaging markers of cerebral maldevelopment, which offer new insights into the nature of preterm brain injury. Ann Neurol 2017;82:233–246 PMID:28719076

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.

Association between abnormal nocturnal blood pressure profile and dementia in Parkinson's disease.

PubMed

Tanaka, Ryota; Shimo, Yasushi; Yamashiro, Kazuo; Ogawa, Takashi; Nishioka, Kenya; Oyama, Genko; Umemura, Atsushi; Hattori, Nobutaka

2018-01-01

Circadian blood pressure alterations are frequently observed in Parkinson's disease, but the association between these changes and dementia in the condition remains unclear. Here, we assess the relationship between abnormal nocturnal blood pressure profiles and dementia in Parkinson's disease. We enrolled 137 patients with Parkinson's disease, who underwent 24 h ambulatory blood pressure monitoring, following cognitive and clinical assessment. Twenty-seven patients (19.7%) were diagnosed with dementia in this cohort. We observed significant associations of dementia with age, male gender, Hoehn-Yahr (H-Y) stage, diabetes mellitus, history of stroke, presence of cerebrovascular lesions on MRI, and orthostatic hypotension. Univariate logistic regression analysis showed that among the patterns of nocturnal blood pressure profiles, the riser pattern was significantly associated with dementia (OR 11.6, 95%CI: 2.14-215.0, P < 0.01), and this trend was observed after adjusting for all confounding factors except orthostatic hypotension (OR 19.2, 95%CI: 1.12-1960.3, P = 0.04). However, coexistence of a riser pattern and orthostatic hypotension was related to a higher prevalence of dementia (45.2%) than was a riser pattern alone (9.5%). Furthermore, coexistence of a riser pattern and orthostatic hypotension was significantly more associated with dementia than was a riser pattern alone, even after adjusting for confounders (OR 1625.1, 95%CI: 21.9-1343909.5, P < 0.01). Our results suggest a relationship between a riser pattern coexisting with orthostatic hypotension and dementia in Parkinson's disease. Further prospective studies are warranted to investigate whether abnormal nocturnal blood pressure profiles predict dementia in Parkinson's disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

Redox/methylation mediated abnormal DNA methylation as regulators of ambient fine particulate matter-induced neurodevelopment related impairment in human neuronal cells

NASA Astrophysics Data System (ADS)

Wei, Hongying; Liang, Fan; Meng, Ge; Nie, Zhiqing; Zhou, Ren; Cheng, Wei; Wu, Xiaomeng; Feng, Yan; Wang, Yan

2016-09-01

Fine particulate matter (PM2.5) has been implicated as a risk factor for neurodevelopmental disorders including autism in children. However, the underlying biological mechanism remains unclear. DNA methylation is suggested to be a fundamental mechanism for the neuronal responses to environmental cues. We prepared whole particle of PM2.5 (PM2.5), water-soluble extracts (Pw), organic extracts (Po) and carbon core component (Pc) and characterized their chemical constitutes. We found that PM2.5 induced significant redox imbalance, decreased the levels of intercellular methyl donor S-adenosylmethionine and caused global DNA hypomethylation. Furthermore, PM2.5 exposure triggered gene-specific promoter DNA hypo- or hypermethylation and abnormal mRNA expression of autism candidate genes. PM2.5-induced DNA hypermethylation in promoter regions of synapse related genes were associated with the decreases in their mRNA and protein expression. The inhibiting effects of antioxidative reagents, a methylation-supporting agent and a DNA methyltransferase inhibitor demonstrated the involvement of redox/methylation mechanism in PM2.5-induced abnormal DNA methylation patterns and synaptic protein expression. The biological effects above generally followed a sequence of PM2.5 ≥ Pwo > Po > Pw > Pc. Our results implicated a novel epigenetic mechanism for the neurodevelopmental toxicity of particulate air pollution, and that eliminating the chemical components could mitigate the neurotoxicity of PM2.5.

Redox/methylation mediated abnormal DNA methylation as regulators of ambient fine particulate matter-induced neurodevelopment related impairment in human neuronal cells.

PubMed

Wei, Hongying; Liang, Fan; Meng, Ge; Nie, Zhiqing; Zhou, Ren; Cheng, Wei; Wu, Xiaomeng; Feng, Yan; Wang, Yan

2016-09-14

Fine particulate matter (PM2.5) has been implicated as a risk factor for neurodevelopmental disorders including autism in children. However, the underlying biological mechanism remains unclear. DNA methylation is suggested to be a fundamental mechanism for the neuronal responses to environmental cues. We prepared whole particle of PM2.5 (PM2.5), water-soluble extracts (Pw), organic extracts (Po) and carbon core component (Pc) and characterized their chemical constitutes. We found that PM2.5 induced significant redox imbalance, decreased the levels of intercellular methyl donor S-adenosylmethionine and caused global DNA hypomethylation. Furthermore, PM2.5 exposure triggered gene-specific promoter DNA hypo- or hypermethylation and abnormal mRNA expression of autism candidate genes. PM2.5-induced DNA hypermethylation in promoter regions of synapse related genes were associated with the decreases in their mRNA and protein expression. The inhibiting effects of antioxidative reagents, a methylation-supporting agent and a DNA methyltransferase inhibitor demonstrated the involvement of redox/methylation mechanism in PM2.5-induced abnormal DNA methylation patterns and synaptic protein expression. The biological effects above generally followed a sequence of PM2.5 ≥ Pwo > Po > Pw > Pc. Our results implicated a novel epigenetic mechanism for the neurodevelopmental toxicity of particulate air pollution, and that eliminating the chemical components could mitigate the neurotoxicity of PM2.5.

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

Hyperhomocysteinemia and MTHFR polymorphisms as antenatal risk factors of white matter abnormalities in two cohorts of late preterm and full term newborns.

PubMed

Marseglia, Lucia M; Nicotera, Antonio; Salpietro, Vincenzo; Giaimo, Elisa; Cardile, Giovanna; Bonsignore, Maria; Alibrandi, Angela; Caccamo, Daniela; Manti, Sara; D'Angelo, Gabriella; Mamì, Carmelo; Di Rosa, Gabriella

2015-01-01

Higher total homocysteine (tHcy) levels, and C677T and A1298C methylenetetrahydrofolate (MTHFR) polymorphisms, have been reported in preterm or full term newborns with neonatal encephalopathy following perinatal hypoxic-ischemic insult. This study investigated the causal role of tHcy and MTHFR polymorphisms together with other acquired risk factors on the occurrence of brain white matter abnormalities (WMA) detected by cranial ultrasound scans (cUS) in a population of late preterm and full term infants. A total of 171 newborns (81 M, 47.4%), 45 (26.3%) born <37 wks, and 126 (73.7%) born ≥37 wks were recruited in the study. cUS detected predominant WMA pattern in 36/171 newborns (21.1%) mainly characterized by abnormal periventricular white matter signal and mild-to-moderate periventricular white matter volume loss with ventricular dilatation (6/36, 16.6%). WMA resulted in being depending on tHcy levels (P < 0.014), lower GA (P < 0.000), lower Apgar score at 1 minutes (P < 0.000) and 5 minutes (P < 0.000), and 1298AC and 677CT/1298AC genotypes (P < 0.000 and P < 0.000). In conclusion, both acquired and genetic predisposing antenatal factors were significantly associated with adverse neonatal outcome and WMA. The role of A1298C polymorphism may be taken into account for prenatal assessment and treatment counseling.

Abnormalities in the structural covariance of emotion regulation networks in major depressive disorder.

PubMed

Wu, Huawang; Sun, Hui; Wang, Chao; Yu, Lin; Li, Yilan; Peng, Hongjun; Lu, Xiaobing; Hu, Qingmao; Ning, Yuping; Jiang, Tianzi; Xu, Jinping; Wang, Jiaojian

2017-01-01

Major depressive disorder (MDD) is a common psychiatric disorder that is characterized by cognitive deficits and affective symptoms. To date, an increasing number of neuroimaging studies have focused on emotion regulation and have consistently shown that emotion dysregulation is one of the central features and underlying mechanisms of MDD. Although gray matter morphological abnormalities in regions within emotion regulation networks have been identified in MDD, the interactions and relationships between these gray matter structures remain largely unknown. Thus, in this study, we adopted a structural covariance method based on gray matter volume to investigate the brain morphological abnormalities within the emotion regulation networks in a large cohort of 65 MDD patients and 65 age- and gender-matched healthy controls. A permutation test with p < 0.05 was used to identify the significant changes in covariance connectivity strengths between MDD patients and healthy controls. The structural covariance analysis revealed an increased correlation strength of gray matter volume between the left angular gyrus and the left amygdala and between the right angular gyrus and the right amygdala, as well as a decreased correlation strength of the gray matter volume between the right angular gyrus and the posterior cingulate cortex in MDD. Our findings support the notion that emotion dysregulation is an underlying mechanism of MDD by revealing disrupted structural covariance patterns in the emotion regulation network. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Redox/methylation mediated abnormal DNA methylation as regulators of ambient fine particulate matter-induced neurodevelopment related impairment in human neuronal cells

PubMed Central

Wei, Hongying; Liang, Fan; Meng, Ge; Nie, Zhiqing; Zhou, Ren; Cheng, Wei; Wu, Xiaomeng; Feng, Yan; Wang, Yan

2016-01-01

Fine particulate matter (PM2.5) has been implicated as a risk factor for neurodevelopmental disorders including autism in children. However, the underlying biological mechanism remains unclear. DNA methylation is suggested to be a fundamental mechanism for the neuronal responses to environmental cues. We prepared whole particle of PM2.5 (PM2.5), water-soluble extracts (Pw), organic extracts (Po) and carbon core component (Pc) and characterized their chemical constitutes. We found that PM2.5 induced significant redox imbalance, decreased the levels of intercellular methyl donor S-adenosylmethionine and caused global DNA hypomethylation. Furthermore, PM2.5 exposure triggered gene-specific promoter DNA hypo- or hypermethylation and abnormal mRNA expression of autism candidate genes. PM2.5-induced DNA hypermethylation in promoter regions of synapse related genes were associated with the decreases in their mRNA and protein expression. The inhibiting effects of antioxidative reagents, a methylation-supporting agent and a DNA methyltransferase inhibitor demonstrated the involvement of redox/methylation mechanism in PM2.5-induced abnormal DNA methylation patterns and synaptic protein expression. The biological effects above generally followed a sequence of PM2.5 ≥ Pwo > Po > Pw > Pc. Our results implicated a novel epigenetic mechanism for the neurodevelopmental toxicity of particulate air pollution, and that eliminating the chemical components could mitigate the neurotoxicity of PM2.5. PMID:27624276

Fundus autofluorescence and optical coherence tomography in relation to visual function in Usher syndrome type 1 and 2.

PubMed

Fakin, Ana; Jarc-Vidmar, Martina; Glavač, Damjan; Bonnet, Crystel; Petit, Christine; Hawlina, Marko

2012-12-15

Purpose of this study was to characterize retinal disease in Usher syndrome using fundus autofluorescence and optical coherence tomography. Study included 54 patients (26 male, 28 female) aged 7-70 years. There were 18 (33%) USH1 and 36 (67%) USH2 patients. 49/52 (94%) patients were found to carry at least one mutation in Usher genes. Ophthalmological examination included assessment of Snellen visual acuity, color vision with Ishihara tables, Goldmann visual fields (targets II/1-4 and V/4), microperimetry, fundus autofluorescence imaging and optical coherence tomography. Average age at disease onset (nyctalopia) was significantly lower in USH1 than USH2 patients (average 9 vs. 17 years, respectively; p<0.01); however no significant differences were found regarding type of autofluorescence patterns, frequency of foveal lesions and CME, rate of disease progression and age at legal blindness. All representative eyes had abnormal fundus autofluorescence of either hyperautofluorescent ring (55%), hyperautofluorescent foveal patch (35%) or foveal atrophy (10%). Disease duration of more than 30 years was associated with a high incidence of abnormal central fundus autofluorescence (patch or atrophy) and visual acuity loss. Copyright © 2012 Elsevier Ltd. All rights reserved.

Positive effects of neurofeedback on autism symptoms correlate with brain activation during imitation and observation.

PubMed

Datko, Michael; Pineda, Jaime A; Müller, Ralph-Axel

2018-03-01

Autism has been characterized by atypical task-related brain activation and functional connections, coinciding with deficits in sociocommunicative abilities. However, evidence of the brain's experience-dependent plasticity suggests that abnormal activity patterns may be reversed with treatment. In particular, neurofeedback training (NFT), an intervention based on operant conditioning resulting in self-regulation of brain electrical oscillations, has shown increasing promise in addressing abnormalities in brain function and behavior. We examined the effects of ≥ 20 h of sensorimotor mu-rhythm-based NFT in children with high-functioning autism spectrum disorders (ASD) and a matched control group of typically developing children (ages 8-17). During a functional magnetic resonance imaging imitation and observation task, the ASD group showed increased activation in regions of the human mirror neuron system following the NFT, as part of a significant interaction between group (ASD vs. controls) and training (pre- vs. post-training). These changes were positively correlated with behavioral improvements in the ASD participants, indicating that mu-rhythm NFT may be beneficial to individuals with ASD. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

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

PubMed

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

2012-08-01

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

Axonal degeneration in Alzheimer’s disease: When signaling abnormalities meet the axonal transport system

PubMed Central

Kanaan, Nicholas M.; Pigino, Gustavo F.; Brady, Scott T.; Lazarov, Orly; Binder, Lester I.; Morfini, Gerardo A.

2012-01-01

Alzheimer’s disease (AD) is characterized by progressive, age-dependent degeneration of neurons in the central nervous system. A large body of evidence indicates that neurons affected in AD follow a dying-back pattern of degeneration, where abnormalities in synaptic function and axonal connectivity long precede somatic cell death. Mechanisms underlying dying-back degeneration of neurons in AD remain elusive but several have been proposed, including deficits in fast axonal transport (FAT). Accordingly, genetic evidence linked alterations in FAT to dying-back degeneration of neurons, and FAT defects have been widely documented in various AD models. In light of these findings, we discuss experimental evidence linking several AD-related pathogenic polypeptides to aberrant activation of signaling pathways involved in the phosphoregulation of microtubule-based motor proteins. While each pathway appears to affect FAT in a unique manner, in the context of AD, many of these pathways might work synergistically to compromise the delivery of molecular components critical for the maintenance and function of synapses and axons. Therapeutic approaches aimed at preventing FAT deficits by normalizing the activity of specific protein kinases may help prevent degeneration of vulnerable neurons in AD. PMID:22721767

Duane retraction syndrome: causes, effects and management strategies

PubMed Central

Kekunnaya, Ramesh; Negalur, Mithila

2017-01-01

Duane retraction syndrome (DRS) is a congenital eye movement anomaly characterized by variable horizontal duction deficits, with narrowing of the palpebral fissure and globe retraction on attempted adduction, occasionally accompanied by upshoot or down-shoot. The etiopathogenesis of this condition can be explained by a spectrum of mechanical, innervational, neurologic and genetic abnormalities occurring independently or which influence each other giving rise to patterns of clinical presentations along with a complex set of ocular and systemic anomalies. Huber type I DRS is the most common form of DRS with an earlier presentation, while Huber type II is the least common presentation. Usually, patients with unilateral type I Duane syndrome have esotropia more frequently than exotropia, those with type II have exotropia and those with type III have esotropia and exotropia occurring equally common. Cases of bilateral DRS may have variable presentation depending upon the type of presentation in each eye. As regards its management, DRS classification based on primary position deviation as esotropic, exotropic or orthotropic is more relevant than Huber’s classification before planning surgery. Surgical approach to these patients is challenging and must be individualized based on the amount of ocular deviation, abnormal head position, associated globe retraction and overshoots. PMID:29133973

Papillorenal syndrome after Beta-interferon treatment in pregnancy.

PubMed

Gucev, Zoran S; Kirovski, Ilija; Jancevska, Aleksandra; Popjordanova, Nada; Tasic, Velibor

2009-01-01

Papillo-Renal Syndrome (PRS, or Renal-Coloboma Syndrome) is an autosomal dominant disorder, characterized by colobomatous eye defects, abnormal vascular pattern of the optic disk, renal hypoplasia, vesicoureteral reflux, high-frequency hearing loss, and sometimes central nervous system (CNS) abnormalities. The syndrome is associated with mutations in the PAX2 gene. This 11-year-old girl's mother was treated with beta-interferon (IFNbeta-1a) for multiple sclerosis (MS) during the pregnancy. The child failed to thrive in infancy and early childhood. The multicystic renal dystrophy, hypoplastic right kidney, and vesico-ureteral reflux (II-III grade) were diagnosed by ultrasound and radionucleotide renal scan. Subsequently, a morning glory anomaly and coloboma of the optic disc was discovered. Renal failure progressively followed. MRI of the head revealed a cyst of the right optic nerve. Genetic analysis revealed a mutation of the PAX2 gene (619 insG). The multicystic renal dystrophy and a cyst of the optic nerve in association with PRS syndrome have only rarely been described. The fact that this PRS patient stemmed from a pregnancy under beta-interferon treatment raises the question whether IFNbeta-1a treatment during pregnancy has influenced the manifestation or the severity of the PAX2 mutant phenotype in this child.

Mutational Analysis of the Glycosylphosphatidylinositol (GPI) Anchor Pathway Demonstrates that GPI-Anchored Proteins Are Required for Cell Wall Biogenesis and Normal Hyphal Growth in Neurospora crassa

PubMed Central

Bowman, Shaun M.; Piwowar, Amy; Al Dabbous, Mash'el; Vierula, John; Free, Stephen J.

2006-01-01

Using mutational and proteomic approaches, we have demonstrated the importance of the glycosylphosphatidylinositol (GPI) anchor pathway for cell wall synthesis and integrity and for the overall morphology of the filamentous fungus Neurospora crassa. Mutants affected in the gpig-1, gpip-1, gpip-2, gpip-3, and gpit-1 genes, which encode components of the N. crassa GPI anchor biosynthetic pathway, have been characterized. GPI anchor mutants exhibit colonial morphologies, significantly reduced rates of growth, altered hyphal growth patterns, considerable cellular lysis, and an abnormal “cell-within-a-cell” phenotype. The mutants are deficient in the production of GPI-anchored proteins, verifying the requirement of each altered gene for the process of GPI-anchoring. The mutant cell walls are abnormally weak, contain reduced amounts of protein, and have an altered carbohydrate composition. The mutant cell walls lack a number of GPI-anchored proteins, putatively involved in cell wall biogenesis and remodeling. From these studies, we conclude that the GPI anchor pathway is critical for proper cell wall structure and function in N. crassa. PMID:16524913

Implementation of a data packet generator using pattern matching for wearable ECG monitoring systems.

PubMed

Noh, Yun Hong; Jeong, Do Un

2014-07-15

In this paper, a packet generator using a pattern matching algorithm for real-time abnormal heartbeat detection is proposed. The packet generator creates a very small data packet which conveys sufficient crucial information for health condition analysis. The data packet envelopes real time ECG signals and transmits them to a smartphone via Bluetooth. An Android application was developed specifically to decode the packet and extract ECG information for health condition analysis. Several graphical presentations are displayed and shown on the smartphone. We evaluate the performance of abnormal heartbeat detection accuracy using the MIT/BIH Arrhythmia Database and real time experiments. The experimental result confirm our finding that abnormal heart beat detection is practically possible. We also performed data compression ratio and signal restoration performance evaluations to establish the usefulness of the proposed packet generator and the results were excellent.

Genome-wide characterization of JASMONATE-ZIM DOMAIN transcription repressors in wheat (Triticum aestivum L.).

PubMed

Wang, Yukun; Qiao, Linyi; Bai, Jianfang; Wang, Peng; Duan, Wenjing; Yuan, Shaohua; Yuan, Guoliang; Zhang, Fengting; Zhang, Liping; Zhao, Changping

2017-02-13

The JASMONATE-ZIM DOMAIN (JAZ) repressor family proteins are jasmonate co-receptors and transcriptional repressor in jasmonic acid (JA) signaling pathway, and they play important roles in regulating the growth and development of plants. Recently, more and more researches on JAZ gene family are reported in many plants. Although the genome sequencing of common wheat (Triticum aestivum L.) and its relatives is complete, our knowledge about this gene family remains vacant. Fourteen JAZ genes were identified in the wheat genome. Structural analysis revealed that the TaJAZ proteins in wheat were as conserved as those in other plants, but had structural characteristics. By phylogenetic analysis, all JAZ proteins from wheat and other plants were clustered into 11 sub-groups (G1-G11), and TaJAZ proteins shared a high degree of similarity with some JAZ proteins from Aegliops tauschii, Brachypodium distachyon and Oryza sativa. The Ka/Ks ratios of TaJAZ genes ranged from 0.0016 to 0.6973, suggesting that the TaJAZ family had undergone purifying selection in wheat. Gene expression patterns obtained by quantitative real-time PCR (qRT-PCR) revealed differential temporal and spatial regulation of TaJAZ genes under multifarious abiotic stress treatments of high salinity, drought, cold and phytohormone. Among these, TaJAZ7, 8 and 12 were specifically expressed in the anther tissues of the thermosensitive genic male sterile (TGMS) wheat line BS366 and normal control wheat line Jing411. Compared with the gene expression patterns in the normal wheat line Jing411, TaJAZ7, 8 and 12 had different expression patterns in abnormally dehiscent anthers of BS366 at the heading stage 6, suggesting that specific up- or down-regulation of these genes might be associated with the abnormal anther dehiscence in TGMS wheat line. This study analyzed the size and composition of the JAZ gene family in wheat, and investigated stress responsive and differential tissue-specific expression profiles of each TaJAZ gene in TGMS wheat line BS366. In addition, we isolated 3 TaJAZ genes that would be more likely to be involved in the regulation of abnormal anther dehiscence in TGMS wheat line. In conclusion, the results of this study contributed some novel and detailed information about JAZ gene family in wheat, and also provided 3 potential candidate genes for improving the TGMS wheat line.

Operational Based Vision Assessment Cone Contrast Test: Description and Operation

DTIC Science & Technology

2016-06-01

designed to detect abnormalities and characterize the contrast sensitivity of the color mechanisms of the human visual system. The OBVA CCT will...than 1, the individual is determined to have an abnormal L-M mechanism. The L-M sensitivity of mildly abnormal individuals (anomalous trichromats...response pads. This hardware is integrated with custom software that generates the stimuli, collects responses, and analyzes the results as outlined in

Patterns of repeated anal cytology results among HIV-positive and HIV-negative men who have sex with men.

PubMed

Robbins, Hilary A; Wiley, Dorothy J; Ho, Ken; Plankey, Michael; Reddy, Susheel; Joste, Nancy; Darragh, Teresa M; Breen, Elizabeth C; Young, Stephen; D'Souza, Gypsyamber

2018-06-01

Men who have sex with men (MSM) are at increased risk for anal cancer. In cervical cancer screening, patterns of repeated cytology results are used to identify low- and high-risk women, but little is known about these patterns for anal cytology among MSM. We analyzed Multicenter AIDS Cohort Study (MACS) data for MSM who were offered anal cytology testing annually (HIV-positive) or every 2 years (HIV-negative) for 4 years. Following an initial negative (normal) cytology, the frequency of a second negative cytology was lower among HIV-positive MSM with CD4 ≥ 500 (74%) or CD4 < 500 (68%) than HIV-negative MSM (83%) (p < 0.001). After an initial abnormal cytology, the frequency of a second abnormal cytology was highest among HIV-positive MSM with CD4 < 500 (70%) compared to CD4 ≥ 500 (53%) or HIV-negative MSM (46%) (p = 0.003). Among HIV-positive MSM with at least three results, 37% had 3 consecutive negative results; 3 consecutive abnormal results were more frequent among CD4 < 500 (22%) than CD4 ≥ 500 (10%) (p = 0.008). More than one-third of HIV-positive MSM have consistently negative anal cytology over three years. Following abnormal anal cytology, a repeated cytology is commonly negative in HIV-negative or immunocompetent HIV-positive men, while persistent cytological abnormality is more likely among HIV-positive men with CD4 < 500. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Sleep abnormalities in children with Dravet syndrome.

PubMed

Dhamija, Radhika; Erickson, Maia K; St Louis, Erik K; Wirrell, Elaine; Kotagal, Suresh

2014-05-01

Mutations in the voltage-gated sodium channel SCN1A gene are responsible for the majority of Dravet syndrome cases. There is evidence that the Nav1.1 channel coded by the SCN1A gene is involved in sleep regulation. We evaluated sleep abnormalities in children with Dravet syndrome using nocturnal polysomnography. We identified six children at our institution with genetically confirmed Dravet syndrome who had also undergone formal sleep consultation with nocturnal polysomnography. Indications for polysomnography were parental concern of daytime fatigue or sleepiness, hyperactivity, inattention, disruptive behavior, nighttime awakenings, or nocturnal seizures. Sleep studies were scored according to guidelines of the American Academy of Sleep Medicine and non-rapid eye movement cyclic alternating pattern was visually identified and scored according to established methods. The mean age of the subjects at the time of polysomnography was 6 years. Standard polysomnography did not show any consistent abnormalities in the obstructive or central apnea index, arousal index, sleep efficiency, or architecture. Cyclic alternating pattern analysis on five patients showed an increased mean rate of 50.3% (vs 31% to 34% in neurological normal children) with a mild increase in A1 subtype of 89.4% (vs 84.5%). A2/A3 subtype (5.3% vs 7.3%) and B phase duration (22.4 vs 24.7 seconds) were similar to previously reported findings in neurologically normal children. Despite parental concerns for sleep disturbance in patients with Dravet syndrome, we could not identify abnormalities in sleep macroarchitecture. Non-rapid eye movement sleep microarchitecture was, however, abnormal, with increased A1 subtype, somewhat resembling a tracé alternant pattern of neonates and possibly suggestive of cortical synaptic immaturity in Dravet syndrome. Larger studies are needed to replicate these results. Copyright © 2014 Elsevier Inc. All rights reserved.

Patterns of glaucomatous visual field loss in sita fields automatically identified using independent component analysis.

PubMed

Goldbaum, Michael H; Jang, Gil-Jin; Bowd, Chris; Hao, Jiucang; Zangwill, Linda M; Liebmann, Jeffrey; Girkin, Christopher; Jung, Tzyy-Ping; Weinreb, Robert N; Sample, Pamela A

2009-12-01

To determine if the patterns uncovered with variational Bayesian-independent component analysis-mixture model (VIM) applied to a large set of normal and glaucomatous fields obtained with the Swedish Interactive Thresholding Algorithm (SITA) are distinct, recognizable, and useful for modeling the severity of the field loss. SITA fields were obtained with the Humphrey Visual Field Analyzer (Carl Zeiss Meditec, Inc, Dublin, California) on 1,146 normal eyes and 939 glaucoma eyes from subjects followed by the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. VIM modifies independent component analysis (ICA) to develop separate sets of ICA axes in the cluster of normal fields and the 2 clusters of abnormal fields. Of 360 models, the model with the best separation of normal and glaucomatous fields was chosen for creating the maximally independent axes. Grayscale displays of fields generated by VIM on each axis were compared. SITA fields most closely associated with each axis and displayed in grayscale were evaluated for consistency of pattern at all severities. The best VIM model had 3 clusters. Cluster 1 (1,193) was mostly normal (1,089, 95% specificity) and had 2 axes. Cluster 2 (596) contained mildly abnormal fields (513) and 2 axes; cluster 3 (323) held mostly moderately to severely abnormal fields (322) and 5 axes. Sensitivity for clusters 2 and 3 combined was 88.9%. The VIM-generated field patterns differed from each other and resembled glaucomatous defects (eg, nasal step, arcuate, temporal wedge). SITA fields assigned to an axis resembled each other and the VIM-generated patterns for that axis. Pattern severity increased in the positive direction of each axis by expansion or deepening of the axis pattern. VIM worked well on SITA fields, separating them into distinctly different yet recognizable patterns of glaucomatous field defects. The axis and pattern properties make VIM a good candidate as a preliminary process for detecting progression.

Patterns of magnetic resonance imaging abnormalities in symptomatic patients with Krabbe disease correspond to phenotype.

PubMed

Abdelhalim, Ahmed N; Alberico, Ronald A; Barczykowski, Amy L; Duffner, Patricia K

2014-02-01

Initial magnetic resonance imaging studies of individuals with Krabbe disease were analyzed to determine whether the pattern of abnormalities corresponded to the phenotype. This was a retrospective, nonblinded study. Families/patients diagnosed with Krabbe disease submitted medical records and magnetic resonance imaging discs for central review. Institutional review board approval/informed consents were obtained. Sixty-four magnetic resonance imaging scans were reviewed by two neuroradiologists and a child neurologist according to phenotype: early infantile (onset 0-6 months) = 39 patients; late infantile (onset 7-12 months) = 10 patients; later onset (onset 13 months-10 years) = 11 patients; adolescent (onset 11-20 years) = one patient; and adult (21 years or greater) = three patients. Local interpretations were compared with central review. Magnetic resonance imaging abnormalities differed among phenotypes. Early infantile patients had a predominance of increased intensity in the dentate/cerebellar white matter as well as changes in the deep cerebral white matter. Later onset patients did not demonstrate involvement in the dentate/cerebellar white matter but had extensive involvement of the deep cerebral white matter, parieto-occipital region, and posterior corpus callosum. Late infantile patients exhibited a mixed pattern; 40% had dentate/cerebellar white matter involvement while all had involvement of the deep cerebral white matter. Adolescent/adult patients demonstrated isolated corticospinal tract involvement. Local and central reviews primarily differed in interpretation of the early infantile phenotype. Analysis of magnetic resonance imaging in a large cohort of symptomatic patients with Krabbe disease demonstrated imaging abnormalities correspond to specific phenotypes. Knowledge of these patterns along with typical clinical signs/symptoms should promote earlier diagnosis and facilitate treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

Temporal and quantitative associations of electronic fetal heart rate monitoring patterns and neonatal outcomes†.

PubMed

Ogunyemi, Dotun; Jovanovski, Andrew; Friedman, Perry; Sweatman, Brittany; Madan, Ichchha

2018-04-06

The objective of this study is to evaluate the associations of electronic fetal heart rate monitoring (EFM) patterns and adverse neonatal outcomes Study design: From 2013 to 2016; 12,067 term, singleton deliveries in labor ≥2 h with abnormal EFM defined as absent accelerations, variable, late or prolonged decelerations, tachycardia, bradycardia, or minimal variability were analyzed as any documentation during labor, in first hour and last hour of labor. Outcomes were composite neonatal adverse outcomes, neonatal intensive care unit (NICU) admission, neonatal hypoxia, neonatal hypoglycemia, umbilical artery pH, and base excess. Independent associations were ascertained using regression analysis. Significant independent associations occurred between any abnormal EFM during the last hour and five adverse neonatal outcomes; between abnormal EFM at any time and one adverse neonatal outcome while there was none with the first hour of labor. In the last hour, accelerations had significant negative associations with three adverse neonatal outcomes, while prolonged decelerations, late decelerations, tachycardia, and bradycardia had significant positive associations with three adverse neonatal outcomes. Throughout labor, increasing accelerations events were significantly negatively correlated with all adverse neonatal outcomes, while increasing frequency of late, variable, and prolonged decelerations were positively associated with five adverse neonatal outcomes. Hierarchical analysis showed that bradycardia/tachycardia contributed only 0.8%, while all EFM periodic changes contributed 1%; the addition of the frequencies of abnormal EFM events contributed 0.6% to the variance in umbilical artery pH and base excess. Terminal EFM patterns are independently associated with neonatal outcomes. Accelerations are protective of adverse neonatal outcomes. Increasing frequency of EFM patterns overtime contributes to neonatal outcome.

Impaired cognitive discrimination and discoordination of coupled theta-gamma oscillations in Fmr1 knockout mice.

PubMed

Radwan, Basma; Dvorak, Dino; Fenton, André A

2016-04-01

Fragile X syndrome (FXS) patients do not make the fragile X mental retardation protein (FMRP). The absence of FMRP causes dysregulated translation, abnormal synaptic plasticity and the most common form of inherited intellectual disability. But FMRP loss has minimal effects on memory itself, making it difficult to understand why the absence of FMRP impairs memory discrimination and increases risk of autistic symptoms in patients, such as exaggerated responses to environmental changes. While Fmr1 knockout (KO) and wild-type (WT) mice perform cognitive discrimination tasks, we find abnormal patterns of coupling between theta and gamma oscillations in perisomatic and dendritic hippocampal CA1 local field potentials of the KO. Perisomatic CA1 theta-gamma phase-amplitude coupling (PAC) decreases with familiarity in both the WT and KO, but activating an invisible shock zone, subsequently changing its location, or turning it off, changes the pattern of oscillatory events in the LFPs recorded along the somato-dendritic axis of CA1. The cognition-dependent changes of this pattern of neural activity are relatively constrained in WT mice compared to KO mice, which exhibit abnormally weak changes during the cognitive challenge caused by changing the location of the shock zone and exaggerated patterns of change when the shock zone is turned off. Such pathophysiology might explain how dysregulated translation leads to intellectual disability in FXS. These findings demonstrate major functional abnormalities after the loss of FMRP in the dynamics of neural oscillations and that these impairments would be difficult to detect by steady-state measurements with the subject at rest or in steady conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

Significance of abnormalities in developmental trajectory and asymmetry of cortical serotonin synthesis in autism.

PubMed

Chandana, Sreenivasa R; Behen, Michael E; Juhász, Csaba; Muzik, Otto; Rothermel, Robert D; Mangner, Thomas J; Chakraborty, Pulak K; Chugani, Harry T; Chugani, Diane C

2005-01-01

The role of serotonin in prenatal and postnatal brain development is well documented in the animal literature. In earlier studies using positron emission tomography (PET) with the tracer alpha[(11)C]methyl-l-tryptophan (AMT), we reported global and focal abnormalities of serotonin synthesis in children with autism. In the present study, we measured brain serotonin synthesis in a large group of autistic children (n = 117) with AMT PET and related these neuroimaging data to handedness and language function. Cortical AMT uptake abnormalities were objectively derived from small homotopic cortical regions using a predefined cutoff asymmetry threshold (>2 S.D. of normal asymmetry). Autistic children demonstrated several patterns of abnormal cortical involvement, including right cortical, left cortical, and absence of abnormal asymmetry. Global brain values for serotonin synthesis capacity (unidirectional uptake rate constant, K-complex) values were plotted as a function of age. K-complex values of autistic children with asymmetry or no asymmetry in cortical AMT uptake followed different developmental patterns, compared to that of a control group of non-autistic children. The autism groups, defined by presence or absence and side of cortical asymmetry, differed on a measure of language as well as handedness. Autistic children with left cortical AMT decreases showed a higher prevalence of severe language impairment, whereas those with right cortical decreases showed a higher prevalence of left and mixed handedness. Global as well as focal abnormally asymmetric development in the serotonergic system could lead to miswiring of the neural circuits specifying hemispheric specialization.

Refeeding syndrome or refeeding hypophosphatemia: a systematic review of cases.

PubMed

Skipper, Annalynn

2012-02-01

Nutrition support clinicians refer to the abnormalities in laboratory data and changes in clinical signs and symptoms that follow refeeding of starved or malnourished patients as refeeding syndrome. Theoretical descriptions of refeeding syndrome include a complex and extensive list of changes, such as hypophosphatemia, hypomagnesemia, hypokalemia, hyponatremia, hypocalcemia, hyperglycemia, and vitamin deficiency--all of which are accompanied by clinical signs and symptoms. In practice, clinicians see asymptomatic refeeding hypophosphatemia more often than a full-blown syndrome with multiple laboratory and clinical abnormalities. Confusion results because there is no widely accepted or uniformly applied set of defining characteristics for diagnosing refeeding syndrome. To gain insight into the clinical characteristics of refeeding syndrome described in the literature, a systematic review of reported cases and case series was conducted. Since 2000, 20 authors described 27 cases that contained sufficient data for review. Hypophosphatemia occurred in 26 patients (96%). While 19 patients (71%) experienced at least 1 other laboratory abnormality, only 14 (51%) exhibited a consistent pattern of abnormally low phosphorus and magnesium levels. Seven patients had hypocalcemia (26%), and hyponatremia was reported in 3 patients (11%). There were no reports of hyperglycemia. Mean data reported in case series containing data from 63 patients showed that hypophosphatemia was a consistent finding but that other abnormalities were not consistently identified. Findings suggest that refeeding hypophosphatemia is not accompanied by a consistent pattern of biochemical or clinical abnormalities among case reports or case series of patients reported to have refeeding syndrome.

Muscle imaging findings in GNE myopathy.

PubMed

Tasca, Giorgio; Ricci, Enzo; Monforte, Mauro; Laschena, Francesco; Ottaviani, Pierfrancesco; Rodolico, Carmelo; Barca, Emanuele; Silvestri, Gabriella; Iannaccone, Elisabetta; Mirabella, Massimiliano; Broccolini, Aldobrando

2012-07-01

GNE myopathy (MIM 600737) is an autosomal recessive muscle disease caused by mutations in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene. Besides the typical phenotype, characterized by the initial involvement of the distal leg muscles that eventually spreads proximally with sparing of the quadriceps, uncommon presentations with a non-canonical clinical phenotype, unusual muscle biopsy findings or both are increasingly recognized. The aim of our study was to characterize the imaging pattern of pelvic and lower limb muscles in GNE myopathy, thus providing additional diagnostic clues useful in the identification of patients with atypical features. We retrospectively evaluated muscle MRI and CT scans of a cohort of 13 patients heterogeneous for GNE mutations and degree of clinical severity. We found that severe involvement of the biceps femoris short head and, to a lesser extent, of the gluteus minimus, tibialis anterior, extensor hallucis and digitorum longus, soleus and gastrocnemius medialis was consistently present even in patients with early or atypical disease. The vastus lateralis, not the entire quadriceps, was the only muscle spared in advanced stages, while the rectus femoris, vastus intermedius and medialis showed variable signs of fatty replacement. Younger patients showed hyperintensities on T2-weighted sequences in muscles with a normal or, more often, abnormal T1-weighted signal. Our results define a pattern of muscle involvement that appears peculiar to GNE myopathy. Although these findings need to be further validated in a larger cohort, we believe that the recognition of this pattern may be instrumental in the initial clinical assessment of patients with possible GNE myopathy.

Proteomics Analysis of Human Skeletal Muscle Reveals Novel Abnormalities in Obesity and Type 2 Diabetes

PubMed Central

Hwang, Hyonson; Bowen, Benjamin P.; Lefort, Natalie; Flynn, Charles R.; De Filippis, Elena A.; Roberts, Christine; Smoke, Christopher C.; Meyer, Christian; Højlund, Kurt; Yi, Zhengping; Mandarino, Lawrence J.

2010-01-01

OBJECTIVE Insulin resistance in skeletal muscle is an early phenomenon in the pathogenesis of type 2 diabetes. Studies of insulin resistance usually are highly focused. However, approaches that give a more global picture of abnormalities in insulin resistance are useful in pointing out new directions for research. In previous studies, gene expression analyses show a coordinated pattern of reduction in nuclear-encoded mitochondrial gene expression in insulin resistance. However, changes in mRNA levels may not predict changes in protein abundance. An approach to identify global protein abundance changes involving the use of proteomics was used here. RESEARCH DESIGN AND METHODS Muscle biopsies were obtained basally from lean, obese, and type 2 diabetic volunteers (n = 8 each); glucose clamps were used to assess insulin sensitivity. Muscle protein was subjected to mass spectrometry–based quantification using normalized spectral abundance factors. RESULTS Of 1,218 proteins assigned, 400 were present in at least half of all subjects. Of these, 92 were altered by a factor of 2 in insulin resistance, and of those, 15 were significantly increased or decreased by ANOVA (P < 0.05). Analysis of protein sets revealed patterns of decreased abundance in mitochondrial proteins and altered abundance of proteins involved with cytoskeletal structure (desmin and alpha actinin-2 both decreased), chaperone function (TCP-1 subunits increased), and proteasome subunits (increased). CONCLUSIONS The results confirm the reduction in mitochondrial proteins in insulin-resistant muscle and suggest that changes in muscle structure, protein degradation, and folding also characterize insulin resistance. PMID:19833877

Neuroacanthocytosis associated with a defect of the 4.1R membrane protein

PubMed Central

Orlacchio, Antonio; Calabresi, Paolo; Rum, Adriana; Tarzia, Anna; Salvati, Anna Maria; Kawarai, Toshitaka; Stefani, Alessandro; Pisani, Antonio; Bernardi, Giorgio; Cianciulli, Paolo; Caprari, Patrizia

2007-01-01

Background Neuroacanthocytosis (NA) denotes a heterogeneous group of diseases that are characterized by nervous system abnormalities in association with acanthocytosis in the patients' blood. The 4.1R protein of the erythrocyte membrane is critical for the membrane-associated cytoskeleton structure and in central neurons it regulates the stabilization of AMPA receptors on the neuronal surface at the postsynaptic density. We report clinical, biochemical, and genetic features in four patients from four unrelated families with NA in order to explain the cause of morphological abnormalities and the relationship with neurodegenerative processes. Case presentation All patients were characterised by atypical NA with a novel alteration of the erythrocyte membrane: a 4.1R protein deficiency. The 4.1R protein content was significantly lower in patients (3.40 ± 0.42) than in controls (4.41 ± 0.40, P < 0.0001), reflecting weakened interactions of the cytoskeleton with the membrane. In patients IV:1 (RM23), IV:3 (RM15), and IV:6 (RM16) the 4.1 deficiency seemed to affect the horizontal interactions of spectrin and an impairment of the dimer self-association into tetramers was detected. In patient IV:1 (RM16) the 4.1 deficiency seemed to affect the skeletal attachment to membrane and the protein band 3 was partially reduced. Conclusion A decreased expression pattern of the 4.1R protein was observed in the erythrocytes from patients with atypical NA, which might reflect the expression pattern in the central nervous system, especially basal ganglia, and might lead to dysfunction of AMPA-mediated glutamate transmission. PMID:17298666

Bicycling suppresses abnormal beta synchrony in the Parkinsonian basal ganglia.

PubMed

Storzer, Lena; Butz, Markus; Hirschmann, Jan; Abbasi, Omid; Gratkowski, Maciej; Saupe, Dietmar; Vesper, Jan; Dalal, Sarang S; Schnitzler, Alfons

2017-10-01

Freezing of gait is a poorly understood symptom of Parkinson disease, and can severely disrupt the locomotion of affected patients. However, bicycling ability remains surprisingly unaffected in most patients suffering from freezing, suggesting functional differences in the motor network. The purpose of this study was to characterize and contrast the oscillatory dynamics underlying bicycling and walking in the basal ganglia. We present the first local field potential recordings directly comparing bicycling and walking in Parkinson disease patients with electrodes implanted in the subthalamic nuclei for deep brain stimulation. Low (13-22Hz) and high (23-35Hz) beta power changes were analyzed in 22 subthalamic nuclei from 13 Parkinson disease patients (57.5 ± 5.9 years old, 4 female). The study group consisted of 5 patients with and 8 patients without freezing of gait. In patients without freezing of gait, both bicycling and walking led to a suppression of subthalamic beta power (13-35Hz), and this suppression was stronger for bicycling. Freezers showed a similar pattern in general. Superimposed on this pattern, however, we observed a movement-induced, narrowband power increase around 18Hz, which was evident even in the absence of freezing. These results indicate that bicycling facilitates overall suppression of beta power. Furthermore, movement leads to exaggerated synchronization in the low beta band specifically within the basal ganglia of patients susceptible to freezing. Abnormal ∼18Hz oscillations are implicated in the pathophysiology of freezing of gait, and suppressing them may form a key strategy in developing potential therapies. Ann Neurol 2017;82:592-601. © 2017 American Neurological Association.

Salivary α-amylase and cortisol after exercise in menopause: influence of long-term HRT.

PubMed

Patacchioli, F R; Ghiciuc, C M; Bernardi, M; Dima-Cozma, L C; Fattorini, L; Squeo, M R; Galoppi, P; Brunelli, R; Ferrante, F; Pasquali, V; Perrone, G

2015-01-01

This observational prospective study analyzed the effect of an incremental cardiopulmonary exercise test (CPET) on the secretion of salivary biomarkers of the adrenergic nervous system and hypothalamus-pituitary-adrenal (HPA) axis activity by measuring salivary α-amylase and cortisol diurnal trajectories in the setting of long-term hormone replacement therapy (HRT). Fifteen healthy sedentary postmenopausal women who were current HRT users and 15 women who had never used HRT were consecutively recruited. α-Amylase and cortisol were measured in salivary samples collected on the CPET day and on a rest day. Cardiovascular and respiratory fitness parameters were recorded during the CPET challenge. The participants had very homogeneous somatic characteristics, and they were all in generally good health. The postmenopausal never-HRT users presented an abnormal diurnal pattern of α-amylase at baseline and a flattened response to CPET. In contrast, women on HRT had a physiological α-amylase diurnal pattern and increased salivary α-amylase production during the CPET-induced challenge. The CPET challenge physiologically activated the HPA axis activity, as shown by the increase in the concentration of salivary cortisol during the effort test. HPA axis activity was not affected by long-term HRT. Postmenopausal women using HRT exhibited a cardiorespiratory functional capacity that was significantly (p < 0.05) higher than that of non-users. Our findings show that healthy postmenopausal women present an asymmetry between adrenergic nervous system and HPA axis activities under both basal and stress conditions. HRT was able to modify the abnormal adrenergic nervous system activity, most likely by reducing the sympathetic hyperactivity that characterizes menopause.

d-myo-Inositol-3-Phosphate Affects Phosphatidylinositol-Mediated Endomembrane Function in Arabidopsis and Is Essential for Auxin-Regulated Embryogenesis[W][OA

PubMed Central

Luo, Yu; Qin, Genji; Zhang, Jun; Liang, Yuan; Song, Yingqi; Zhao, Meiping; Tsuge, Tomohiko; Aoyama, Takashi; Liu, Jingjing; Gu, Hongya; Qu, Li-Jia

2011-01-01

In animal cells, myo-inositol is an important regulatory molecule in several physiological and biochemical processes, including signal transduction and membrane biogenesis. However, the fundamental biological functions of myo-inositol are still far from clear in plants. Here, we report the genetic characterization of three Arabidopsis thaliana genes encoding d-myo-inositol-3-phosphate synthase (MIPS), which catalyzes the rate-limiting step in de novo synthesis of myo-inositol. Each of the three MIPS genes rescued the yeast ino1 mutant, which is defective in yeast MIPS gene INO1, and they had different dynamic expression patterns during Arabidopsis embryo development. Although single mips mutants showed no obvious phenotypes, the mips1 mips2 double mutant and the mips1 mips2 mips3 triple mutant were embryo lethal, whereas the mips1 mips3 and mips1 mips2+/− double mutants had abnormal embryos. The mips phenotypes resembled those of auxin mutants. Indeed, the double and triple mips mutants displayed abnormal expression patterns of DR5:green fluorescent protein, an auxin-responsive fusion protein, and they had altered PIN1 subcellular localization. Also, membrane trafficking was affected in mips1 mips3. Interestingly, overexpression of PHOSPHATIDYLINOSITOL SYNTHASE2, which converts myo-inositol to membrane phosphatidylinositol (PtdIns), largely rescued the cotyledon and endomembrane defects in mips1 mips3. We conclude that myo-inositol serves as the main substrate for synthesizing PtdIns and phosphatidylinositides, which are essential for endomembrane structure and trafficking and thus for auxin-regulated embryogenesis. PMID:21505066

Association Between Abnormal Contrast Sensitivity and Mortality Among People With Acquired Immunodeficiency Syndrome

PubMed Central

HOLLAND, GARY N.; KAPPEL, PETER J.; NATTA, MARK L. VAN; PALELLA, FRANK J.; LYON, ALICE T.; SHAH, KAYUR H.; PAVAN, PETER R.; JABS, DOUGLAS A.

2014-01-01

PURPOSE To investigate the relationship between contrast sensitivity (CS) and mortality among people with acquired immunodeficiency syndrome (AIDS); and to explore the hypothesis that abnormal CS is a marker of systemic, life-threatening microvascular disease. DESIGN Longitudinal, observational cohort study. METHODS We evaluated 3395 eyes of 1706 individuals enrolled in the Longitudinal Study of the Complications of AIDS (1998–2008). CS was evaluated as a risk factor for death, and was compared to the presence of systemic diseases characterized by microvasculopathy (diabetes, cardiovascular disease, stroke, renal disease) and to laboratory markers of those diseases. Abnormal CS was defined as logCS <1.5 (lower 2.5th percentile for a normal control population). RESULTS CS was abnormal in 284 of 1691 (16.8%) study participants at enrollment. There was a positive relationship between the presence of abnormal CS at study entry and mortality (relative risk 2.0, 95% confidence interval 1.7-2.3, P < .0001). Abnormal CS was related to the presence of cardiovascular disease, stroke, and renal disease (all P values < .01), but abnormal CS remained associated with death even after adjustment for these diseases and for other known predictors of death among people with AIDS. Diseases characterized by microvasculopathy were more often identified as causes of death among individuals with abnormal CS than among those with normal CS, although the strength of the association was moderate (P = .06). CONCLUSIONS Abnormal CS among people with AIDS is associated with increased mortality, and is independent of other risk factors for death that are monitored routinely. The relationship may indicate life-threatening microvascular disease in other organs. PMID:20399927

Altered Face Scanning and Impaired Recognition of Biological Motion in a 15-Month-Old Infant with Autism

ERIC Educational Resources Information Center

Klin, Ami; Jones, Warren

2008-01-01

Mounting clinical evidence suggests that abnormalities of social engagement in children with autism are present even during infancy. However, direct experimental documentation of these abnormalities is still limited. In this case report of a 15-month-old infant with autism, we measured visual fixation patterns to both naturalistic and ambiguous…

POC1A Truncation Mutation Causes a Ciliopathy in Humans Characterized by Primordial Dwarfism

PubMed Central

Shaheen, Ranad; Faqeih, Eissa; Shamseldin, Hanan E.; Noche, Ramil R.; Sunker, Asma; Alshammari, Muneera J.; Al-Sheddi, Tarfa; Adly, Nouran; Al-Dosari, Mohammed S.; Megason, Sean G.; Al-Husain, Muneera; Al-Mohanna, Futwan; Alkuraya, Fowzan S.

2012-01-01

Primordial dwarfism (PD) is a phenotype characterized by profound growth retardation that is prenatal in onset. Significant strides have been made in the last few years toward improved understanding of the molecular underpinning of the limited growth that characterizes the embryonic and postnatal development of PD individuals. These include impaired mitotic mechanics, abnormal IGF2 expression, perturbed DNA-damage response, defective spliceosomal machinery, and abnormal replication licensing. In three families affected by a distinct form of PD, we identified a founder truncating mutation in POC1A. This gene is one of two vertebrate paralogs of POC1, which encodes one of the most abundant proteins in the Chlamydomonas centriole proteome. Cells derived from the index individual have abnormal mitotic mechanics with multipolar spindles, in addition to clearly impaired ciliogenesis. siRNA knockdown of POC1A in fibroblast cells recapitulates this ciliogenesis defect. Our findings highlight a human ciliopathy syndrome caused by deficiency of a major centriolar protein. PMID:22840364

Neuroanatomical Characterization of Child Offspring of Bipolar Parents

ERIC Educational Resources Information Center

Singh, Manpreet K.; Delbello, Melissa; Adler, Caleb M.; Stanford, Kevin E.; Strakowski, Stephen M.

2008-01-01

A study was conducted to examine the neuroanatomical abnormalities in at-risk children and adolescents of parents with bipolar disorder, and compare them with children of healthy parents. It was found that at-risk children exhibited volumetric abnormalities in portions of the anterior limbic network.

Multifocal visual evoked potentials reveal normal optic nerve projections in human carriers of oculocutaneous albinism type 1a.

PubMed

Hoffmann, Michael B; Wolynski, Barbara; Meltendorf, Synke; Behrens-Baumann, Wolfgang; Käsmann-Kellner, Barbara

2008-06-01

In albinism, part of the temporal retina projects abnormally to the contralateral hemisphere. A residual misprojection is also evident in feline carriers that are heterozygous for tyrosinase-related albinism. This study was conducted to test whether such residual abnormalities can also be identified in human carriers of oculocutaneous tyrosinase-related albinism (OCA1a). In eight carriers heterozygous for OCA1a and in eight age- and sex-matched control subjects, monocular pattern-reversal and -onset multifocal visual evoked potentials (mfVEPs) were recorded at 60 locations comprising a visual field of 44 degrees diameter (VERIS 5.01; EDI, San Mateo, CA). For each eye and each stimulus location, interhemispheric difference potentials were calculated and correlated with each other, to assess the lateralization of the responses: positive and negative correlations indicate lateralizations on the same or opposite hemispheres, respectively. Misrouted optic nerves are expected to yield negative interocular correlations. The analysis also allowed for the assessment of the sensitivity and specificity of the detection of projection abnormalities. No significant differences were obtained for the distributions of the interocular correlation coefficients of controls and carriers. Consequently, no local representation abnormalities were observed in the group of OCA1a carriers. For pattern-reversal and -onset stimulation, an assessment of the control data yielded similar specificity (97.9% and 94.6%) and sensitivity (74.4% and 74.8%) estimates for the detection of projection abnormalities. The absence of evidence for projection abnormalities in human OCA1a carriers contrasts with the previously reported evidence for abnormalities in cat-carriers of tyrosinase-related albinism. This discrepancy suggests that animal models of albinism may not provide a match to human albinism.

The interpretation and management of abnormal liver function tests.

PubMed

Simpson, M A; Freshwater, D A

2015-01-01

Liver function tests (LFTs) are frequently requested as part of routine health assessments on serving members of the Royal Navy (RN). In common with many investigations there are a number of abnormal results in healthy individuals (0.5 - 9% depending on test and study population). There are established patterns of LFT derangement such as cholestatic derangement, hepatocellular derangement, and failure of synthetic function. There can be indicators to the cause of the derangement by assessing the ratios of elevated assays in relation to one another. This article aims to address the definition, potential causes and further investigation of common patterns of LFT derangement found in primary care in the RN.

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.

Placental sulfatase deficiency: maternal and fetal expression of steroid sulfatase deficiency and X-linked ichthyosis.

PubMed

Bradshaw, K D; Carr, B R

1986-07-01

PSD-X-linked ichthyosis are manifestations of a similar disorder of an inborn error of metabolism characterized by a deficiency of steroid sulfatase. The decreased enzyme activity is due to the absence of the expression of enzyme (steroid sulfatase) protein. Affected individuals with this disorder are males (X-linked inheritance) with a frequency of 1/2000 to 1/6000 births. Homozygous females from cosanguineous marriages have been reported with this disorder. The diagnosis is suspected and confirmed by: Low estriol excretion; Negative DHEAS loading test Increased DHEAS in amnionic fluid; Normal DHEAS in cord plasma; Possible delayed or abnormal labor patterns; Decreased sulfatase activity in the placenta, fibroblast, erythrocytes, lymphocytes or leukocytes of affected individuals; Development of ichthyosis in male infants at 2 to 3 months of age.

Kinetic chain abnormalities in the athletic shoulder.

PubMed

Sciascia, Aaron; Thigpen, Charles; Namdari, Surena; Baldwin, Keith

2012-03-01

Overhead activities require the shoulder to be exposed to and sustain repetitive loads. The segmental activation of the body's links, known as the kinetic chain, allows this to occur effectively. Proper muscle activation is achieved through generation of energy from the central segment or core, which then transfers the energy to the terminal links of the shoulder, elbow, and hand. The kinetic chain is best characterized by 3 components: optimized anatomy, reproducible efficient motor patterns, and the sequential generation of forces. However, tissue injury and anatomic deficits such as weakness and/or tightness in the leg, pelvic core, or scapular musculature can lead to overuse shoulder injuries. These injuries can be prevented and maladaptations can be detected with a thorough understanding of biomechanics of the kinetic chain as it relates to overhead activity.

Horseshoe kidney: a review of anatomy and pathology.

PubMed

Natsis, Konstantinos; Piagkou, Maria; Skotsimara, Antonia; Protogerou, Vassilis; Tsitouridis, Ioannis; Skandalakis, Panagiotis

2014-08-01

Horseshoe kidney (HSK) is the most common renal fusion, which is characterized by three anatomic anomalies: ectopia, malrotation and vascular changes. Patients with HSK are prone to a variety of complications, genitourinary and non-genitourinary. In this paper, the anatomy of HSK is delineated with a great emphasis on its blood supply. After reviewing the literature, the arterial supply patterns found by each author were categorized according to the classification system proposed by Graves. The majority of HSKs were found to be supplied by renal arteries derived from the abdominal aorta below the isthmus or by vessels originating from the common iliac arteries. In addition, the abnormalities associated with HSK are highlighted and classified in anatomical variations, congenital anomalies as well as in pathologic conditions related to HSK.

A quantitative estimate of schema abnormality in socially anxious and non-anxious individuals.

PubMed

Wenzel, Amy; Brendle, Jennifer R; Kerr, Patrick L; Purath, Donna; Ferraro, F Richard

2007-01-01

Although cognitive theories of anxiety suggest that anxious individuals are characterized by abnormal threat-relevant schemas, few empirical studies have estimated the nature of these cognitive structures using quantitative methods that lend themselves to inferential statistical analysis. In the present study, socially anxious (n = 55) and non-anxious (n = 62) participants completed 3 Q-Sort tasks to assess their knowledge of events that commonly occur in social or evaluative scenarios. Participants either sorted events according to how commonly they personally believe the events occur (i.e. "self" condition), or to how commonly they estimate that most people believe they occur (i.e. "other" condition). Participants' individual Q-Sorts were correlated with mean sorts obtained from a normative sample to obtain an estimate of schema abnormality, with lower correlations representing greater levels of abnormality. Relative to non-anxious participants, socially anxious participants' sorts were less strongly associated with sorts of the normative sample, particularly in the "self" condition, although secondary analyses suggest that some significant results might be explained, in part, by depression and experience with the scenarios. These results provide empirical support for the theoretical notion that threat-relevant self-schemas of anxious individuals are characterized by some degree of abnormality.

Identification of phenylbutyrate-generated metabolites in Huntington disease patients using parallel liquid chromatography/electrochemical array/mass spectrometry and off-line tandem mass spectrometry.

PubMed

Ebbel, Erika N; Leymarie, Nancy; Schiavo, Susan; Sharma, Swati; Gevorkian, Sona; Hersch, Steven; Matson, Wayne R; Costello, Catherine E

2010-04-15

Oral sodium phenylbutyrate (SPB) is currently under investigation as a histone deacetylation (HDAC) inhibitor in Huntington disease (HD). Ongoing studies indicate that symptoms related to HD genetic abnormalities decrease with SPB therapy. In a recently reported safety and tolerability study of SPB in HD, we analyzed overall chromatographic patterns from a method that employs gradient liquid chromatography with series electrochemical array, ultraviolet (UV), and fluorescence (LCECA/UV/F) for measuring SPB and its metabolite phenylacetate (PA). We found that plasma and urine from SPB-treated patients yielded individual-specific patterns of approximately 20 metabolites that may provide a means for the selection of subjects for extended trials of SPB. The structural identification of these metabolites is of critical importance because their characterization will facilitate understanding the mechanisms of drug action and possible side effects. We have now developed an iterative process with LCECA, parallel LCECA/LCMS, and high-performance tandem MS for metabolite characterization. Here we report the details of this method and its use for identification of 10 plasma and urinary metabolites in treated subjects, including indole species in urine that are not themselves metabolites of SPB. Thus, this approach contributes to understanding metabolic pathways that differ among HD patients being treated with SPB. Copyright 2010 Elsevier Inc. All rights reserved.

Cleidocranial dysplasia

PubMed Central

Dixit, Ramakant; Dixit, Kalpana; Paramez, A. R.

2010-01-01

Cleidocranial dysplasia is a rare autosomal dominant condition with generalized dysplasia of bone, characterized by delayed closer of cranial sutures, hypoplastic or aplastic clavicles, short stature, dental abnormalities and a variety of other skeletal abnormalities. We present a seven-year-old female child presenting with classical features of cleidocranial dysplasia. PMID:20931042

Neurological Abnormalities in Recent-Onset Schizophrenia and Asperger-Syndrome

PubMed Central

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

2014-01-01

Background: Neurological abnormalities including a variety of subtle deficits such as discrete impairments in sensory integration, motor coordination (MOCO), and sequencing of complex motor acts are frequently found in patients with schizophrenia (SZ) and commonly referred to as neurological soft signs (NSS). Asperger-syndrome (AS) is characterized by sensory-motor difficulties as well. However, the question whether the two disorders share a common or a disease-specific pattern of NSS remains unresolved. Method: A total of 78 age- and education-matched participants [26 patients with recent-onset SZ, 26 individuals with AS, and 26 healthy controls (HC)] were recruited for the study. Analyses of covariance (ANCOVAs), with age, years of education, and medication included as covariates, were used to examine group differences on total NSS and the five subscale scores. Discriminant analyses were employed to identify the NSS subscales that maximally discriminate between the three groups. Results: Significant differences among the three groups were found in NSS total score and on the five NSS subscales. The clinical groups differed significantly in the NSS subscale MOCO. The correct discriminant rate between patients with SZ and individuals with AS was 61.5%. The correct discriminant rate was 92.3% between individuals with AS and HC, and 80.8% between SZ patients and HC, respectively. Conclusion: Our findings provide new evidence for the presence of NSS in AS and lend further support to previously reported difficulties in movement control in this disorder. According to the present results, SZ and AS seem to be characterized by both quantitative and qualitative NSS expression. PMID:25147527

Connectomic disturbances in attention-deficit/hyperactivity disorder: a whole-brain tractography analysis.

PubMed

Hong, Soon-Beom; Zalesky, Andrew; Fornito, Alex; Park, Subin; Yang, Young-Hui; Park, Min-Hyeon; Song, In-Chan; Sohn, Chul-Ho; Shin, Min-Sup; Kim, Bung-Nyun; Cho, Soo-Churl; Han, Doug Hyun; Cheong, Jae Hoon; Kim, Jae-Won

2014-10-15

Few studies have sought to identify, in a regionally unbiased way, the precise cortical and subcortical regions that are affected by white matter abnormalities in attention-deficit/hyperactivity disorder (ADHD). This study aimed to derive a comprehensive, whole-brain characterization of connectomic disturbances in ADHD. Using diffusion tensor imaging, whole-brain tractography, and an imaging connectomics approach, we characterized altered white matter connectivity in 71 children and adolescents with ADHD compared with 26 healthy control subjects. White matter differences were further delineated between patients with (n = 40) and without (n = 26) the predominantly hyperactive/impulsive subtype of ADHD. A significant network comprising 25 distinct fiber bundles linking 23 different brain regions spanning frontal, striatal, and cerebellar brain regions showed altered white matter structure in ADHD patients (p < .05, family-wise error-corrected). Moreover, fractional anisotropy in some of these fiber bundles correlated with attentional disturbances. Attention-deficit/hyperactivity disorder subtypes were differentiated by a right-lateralized network (p < .05, family-wise error-corrected) predominantly linking frontal, cingulate, and supplementary motor areas. Fractional anisotropy in this network was also correlated with continuous performance test scores. Using an unbiased, whole-brain, data-driven approach, we demonstrated abnormal white matter connectivity in ADHD. The correlations observed with measures of attentional performance underscore the functional importance of these connectomic disturbances for the clinical phenotype of ADHD. A distributed pattern of white matter microstructural integrity separately involving frontal, striatal, and cerebellar brain regions, rather than direct frontostriatal connectivity, appears to be disrupted in children and adolescents with ADHD. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Patterns in the knee flexion-extension moment profile during stair ascent and descent in patients with total knee arthroplasty.

PubMed

McClelland, Jodie A; Feller, Julian A; Menz, Hylton B; Webster, Kate E

2014-06-03

The aim of this study was to investigate the prevalence of abnormal knee biomechanical patterns in 40 patients with a modern TKA prosthesis, compared to 40 matched control participants when ascending and descending stairs. Fewer patients were able to ascend (65%) or descend stairs (53%) unassisted than controls (83%). Of the participants who could ascend and descend, cluster analysis classified most patients (up to 77%) as demonstrating a similar knee moment pattern as all controls. A small subgroup of patients who completed the tasks did so with distinctly abnormal biomechanics compared to other patients and controls. These findings suggest that recovery of normal stair climbing is possible. However, rehabilitation might be more effective if it were tailored to account for these differences between patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Thoracic computerized tomographic (CT) findings in 2009 influenza A (H1N1) virus infection in Isfahan, Iran

PubMed Central

Rostami, Mojtaba; Javadi, Abbas-Ali; Khorvash, Farzin; Mostafavizadeh, Kamyar; Adibi, Atoosa; Babak, Anahita; Ataei, Behrooz; Meidani, Mohsen; Naeini, Alireza Emami; Salehi, Hasan; Avijgan, Majid; Yazdani, Mohammad Reza; Rezaei, Farshid

2011-01-01

BACKGROUND: Pandemic 2009 H1N1 influenza A virus arrived at Isfahan in August 2009. The virus is still circulating in the world. The abnormal thoracic computerized tomographic (CT) scan findings vary widely among the studies of 2009 H1N1 influenza. We evaluated the thoracic CT findings in patients with 2009 H1N1 virus infection to describe findings compared to previously reported findings, and to suggest patterns that may be suggestive for 2009 influenza A (H1N1) in an appropriate clinical setting. METHODS: Retrospectively, the archive of all patients with a diagnosis of 2009 H1N1 influenza A were reviewed, in Al-Zahra Hospital in Isfahan, central Iran, between September 23rd 2009 to February 20th 2010. Out of 216 patients with confirmed 2009 influenza A (H1N1) virus, 26 cases with abnormal CT were enrolled in the study. Radiologic findings were characterized by the type and pattern of opacities and zonal distribution. RESULTS: Patchy infiltration (34.6%), lobar consolidation (30.8%), and interstitial infiltration (26.9%) with airbronchogram (38.5%) were the predominant findings in our patients. Bilateral distribution was seen in 80.8% of the patients. Only one patient (3.8%) showed ground-glass opacity, predominant radiographic finding in the previous reports and severe acute respiratory syndrome (SARS). CONCLUSIONS: The most common thoracic CT findings in pandemic H1N1 were patchy infiltration, lobar consolidation, and interstitial infiltration with airbronchogram and bilateral distribution. While these findings can be associated with other infections; they may be suggestive to 2009 influenza A (H1N1) in the appropriate clinical setting. Various radiographic patterns can be seen in thoracic CT scans of the influenza patients. Imaging findings are nonspecific. PMID:22091280

Brain 18F-FDG PET Metabolic Abnormalities in Patients with Long-Lasting Macrophagic Myofascitis.

PubMed

Van Der Gucht, Axel; Aoun Sebaiti, Mehdi; Guedj, Eric; Aouizerate, Jessie; Yara, Sabrina; Gherardi, Romain K; Evangelista, Eva; Chalaye, Julia; Cottereau, Anne-Ségolène; Verger, Antoine; Bachoud-Levi, Anne-Catherine; Abulizi, Mukedaisi; Itti, Emmanuel; Authier, François-Jérôme

2017-03-01

The aim of this study was to characterize brain metabolic abnormalities in patients with macrophagic myofascitis (MMF) and the relationship with cognitive dysfunction through the use of PET with 18 F-FDG. Methods: 18 F-FDG PET brain imaging and a comprehensive battery of neuropsychological tests were performed in 100 consecutive MMF patients (age [mean ± SD], 45.9 ± 12 y; 74% women). Images were analyzed with statistical parametric mapping (SPM12). Through the use of analysis of covariance, all 18 F-FDG PET brain images of MMF patients were compared with those of a reference population of 44 healthy subjects similar in age (45.4 ± 16 y; P = 0.87) and sex (73% women; P = 0.88). The neuropsychological assessment identified 4 categories of patients: those with no significant cognitive impairment ( n = 42), those with frontal subcortical (FSC) dysfunction ( n = 29), those with Papez circuit dysfunction ( n = 22), and those with callosal disconnection ( n = 7). Results: In comparison with healthy subjects, the whole population of patients with MMF exhibited a spatial pattern of cerebral glucose hypometabolism ( P < 0.001) involving the occipital lobes, temporal lobes, limbic system, cerebellum, and frontoparietal cortices, as shown by analysis of covariance. The subgroup of patients with FSC dysfunction exhibited a larger extent of involved areas (35,223 voxels vs. 13,680 voxels in the subgroup with Papez circuit dysfunction and 5,453 voxels in patients without cognitive impairment). Nonsignificant results were obtained for the last subgroup because of its small population size. Conclusion: Our study identified a peculiar spatial pattern of cerebral glucose hypometabolism that was most marked in MMF patients with FSC dysfunction. Further studies are needed to determine whether this pattern could represent a diagnostic biomarker of MMF in patients with chronic fatigue syndrome and cognitive dysfunction. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Time course of lung function changes in atypical pneumonia.

PubMed Central

Benusiglio, L N; Stalder, H; Junod, A F

1980-01-01

We measured pulmonary function in each of 21 patients suffering from "atypical", non-bacterial pneumonia during the acute illness and during convalescence (two to 18 months) to study the course and the nature of functional impairment at different stages of the disease. In six patients, no aetiological agent was found. An aetiological agent was identified in 15 of the patients: Mycoplasma pneumoniae (seven patients), influenza A (three patients), parainfluenza 3 (one patient), varicella (two patients), Q fever (one patient), coxsackie B3 (one patient). At the time of admission we observed a restrictive pattern in 52%, an obstructive pattern (decreased FEV1/FVC ratio) in 52% abnormalities in distribution of ventilation (abnormal slope of phase 3) in 63%, and abnormalities in gas exchange (increased AaDO2) in 75% of the patients. The frequency of abnormalities in these pulmonary function tests decreased dramatically after two to four weeks and nearly disappeared in most patients during convalescence. The only major residual abnormality was a decreased FEV1/FVC ratio in five subjects, four of whom were smokers. However, when MMEF and V75 were measured at this stage, their average value for all the groups of patients with the exclusion of the Mycoplasma pneumoniae group, was markedly reduced. These data suggest that small airways involvement can be demonstrated during the convalescence of patients recovering from various types of atypical pneumonia other than those caused by Mycoplasma pneumoniae. PMID:7444825

Novel Analysis Software for Detecting and Classifying Ca2+ Transient Abnormalities in Stem Cell-Derived Cardiomyocytes

PubMed Central

Penttinen, Kirsi; Siirtola, Harri; Àvalos-Salguero, Jorge; Vainio, Tiina; Juhola, Martti; Aalto-Setälä, Katriina

2015-01-01

Comprehensive functioning of Ca2+ cycling is crucial for excitation–contraction coupling of cardiomyocytes (CMs). Abnormal Ca2+ cycling is linked to arrhythmogenesis, which is associated with cardiac disorders and heart failure. Accordingly, we have generated spontaneously beating CMs from induced pluripotent stem cells (iPSC) derived from patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), which is an inherited and severe cardiac disease. Ca2+ cycling studies have revealed substantial abnormalities in these CMs. Ca2+ transient analysis performed manually lacks accepted analysis criteria, and has both low throughput and high variability. To overcome these issues, we have developed a software tool, AnomalyExplorer based on interactive visualization, to assist in the classification of Ca2+ transient patterns detected in CMs. Here, we demonstrate the usability and capability of the software, and we also compare the analysis efficiency to manual analysis. We show that AnomalyExplorer is suitable for detecting normal and abnormal Ca2+ transients; furthermore, this method provides more defined and consistent information regarding the Ca2+ abnormality patterns and cell line specific differences when compared to manual analysis. This tool will facilitate and speed up the analysis of CM Ca2+ transients, making it both more accurate and user-independent. AnomalyExplorer can be exploited in Ca2+ cycling analysis to study basic disease pathology and the effects of different drugs. PMID:26308621

Novel Analysis Software for Detecting and Classifying Ca2+ Transient Abnormalities in Stem Cell-Derived Cardiomyocytes.

PubMed

Penttinen, Kirsi; Siirtola, Harri; Àvalos-Salguero, Jorge; Vainio, Tiina; Juhola, Martti; Aalto-Setälä, Katriina

2015-01-01

Comprehensive functioning of Ca2+ cycling is crucial for excitation-contraction coupling of cardiomyocytes (CMs). Abnormal Ca2+ cycling is linked to arrhythmogenesis, which is associated with cardiac disorders and heart failure. Accordingly, we have generated spontaneously beating CMs from induced pluripotent stem cells (iPSC) derived from patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), which is an inherited and severe cardiac disease. Ca2+ cycling studies have revealed substantial abnormalities in these CMs. Ca2+ transient analysis performed manually lacks accepted analysis criteria, and has both low throughput and high variability. To overcome these issues, we have developed a software tool, AnomalyExplorer based on interactive visualization, to assist in the classification of Ca2+ transient patterns detected in CMs. Here, we demonstrate the usability and capability of the software, and we also compare the analysis efficiency to manual analysis. We show that AnomalyExplorer is suitable for detecting normal and abnormal Ca2+ transients; furthermore, this method provides more defined and consistent information regarding the Ca2+ abnormality patterns and cell line specific differences when compared to manual analysis. This tool will facilitate and speed up the analysis of CM Ca2+ transients, making it both more accurate and user-independent. AnomalyExplorer can be exploited in Ca2+ cycling analysis to study basic disease pathology and the effects of different drugs.

Gamma abnormalities during perception of illusory figures in autism.

PubMed

Brown, Caroline; Gruber, Thomas; Boucher, Jill; Rippon, Gina; Brock, Jon

2005-06-01

This experiment was designed to test the hypothesis that perceptual abnormalities in autism might be associated with alteration of induced gamma activity patterns overlying visual cortical regions. EEG was recorded from six adolescents with autism and eight controls matched on chronological age, and verbal and nonverbal mental age, whilst identifying the presence or absence of an illusory Kanizsa shape. Although there were no reaction time or accuracy differences between the groups there were significant task-related differences in cortical activity. Control participants showed typical gamma-band activity over parietal regions at around 350 msec post onset of shape trials, similar to gamma patterns found in previous studies with non-impaired adults. In contrast, autistic participants showed overall increased activity, including an early 100 msec gamma peak and a late induced peak, 50 to 70 msec earlier than that shown by the control group. We interpret the abnormal gamma activity to reflect decreased "signal to noise" due to decreased inhibitory processing. In this experiment we did not establish a link between altered perception and abnormal gamma, as the autistic participants' behaviour did not differ from the controls. Future work should be designed to replicate this phenomenon and establish the perceptual consequences of altered gamma activity.

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

Poulou, Loukia S., E-mail: ploukia@hotmail.com; Tsangaridou, Iris; Filippoussis, Petros

Bronchiolitis obliterans organizing pneumonia (BOOP) is a nonneoplastic, noninfectious lung disease with a diverse spectrum of imaging abnormalities and nonspecific symptoms diagnosed by open lung biopsy, transbroncial biopsy, and/or video-assisted thoracoscopy. The objective of this study was to retrospectively assess the role of percutaneous computed tomography (CT)-guided biopsy in early diagnosis of the disorder. Fourteen BOOP cases diagnosed by CT-guided biopsy were analyzed in terms of imaging abnormalities and complication rate. All had previously undergone a nondiagnostic procedure (bronchoscopy, transbronchial biopsy, bronchoalveolar lavage) to exclude infection or lung cancer. The most common imaging abnormalities in descending order were bilateral consolidationsmore » (5/14), unilateral tumor-like lesions (5/14), unilateral consolidations (3/14), and diffuse reticular pattern (1/14). Coexistent abnormalities (pleural effusions, nodules, ground-glass opacities) were observed in five patients. The complication rate was 4 of 14 (28.6%), including 2 cases of subclinical pneumothorax and 1 case of minor hemoptysis and local lung injury. None required intervention. We conclude that transthoracic CT-guided biopsy may be used in the diagnosis of BOOP in selected patients with mild complications. For the focal consolidation nodule/mass imaging pattern, CT-guided biopsy may prove to be a reasonable alternative to more invasive procedures.« less

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.

Riser Pattern: Another Determinant of Heart Failure With Preserved Ejection Fraction.

PubMed

Komori, Takahiro; Eguchi, Kazuo; Saito, Toshinobu; Hoshide, Satoshi; Kario, Kazuomi

2016-10-01

Paradoxical increase in blood pressure (BP) during sleep, exceeding those of awake BP, is called the "riser" BP pattern, and known as an abnormal circadian BP rhythm, has been reported to be associated with adverse cardiovascular prognoses. However, the significance of ambulatory BP in heart failure patients with preserved ejection fraction (HFpEF) has never been reported. Here, we tested our hypothesis that abnormal circadian BP rhythm is associated with HFpEF. The authors enrolled 508 patients with hospitalized HF (age 68±13 years; 315 men, 193 women). There were 232 cases of HFpEF and 276 cases of heart failure with reduced ejection fraction (HFrEF). The riser BP pattern was significantly more frequent in the HFpEF (28.9%) group compared with the HFrEF group (19.9%). In a multivariable logistic regression analysis, the riser BP pattern was associated with HFpEF (odds ratio, 1.73; 95% confidence interval, 1.02-2.91; P=.041) independent of the other covariates. In conclusion, the riser BP pattern was associated with HFpEF. ©2016 Wiley Periodicals, Inc.

Fundus autofluorescence and fate of glycoxidized particles injected into subretinal space in rabbit age-related macular degeneration model.

PubMed

Hirata, Megumi; Yasukawa, Tsutomu; Wiedemann, Peter; Kimura, Erika; Kunou, Noriyuki; Eichler, Wolfram; Takase, Ayae; Sato, Rina; Ogura, Yuichiro

2009-07-01

Abnormal fundus autofluorescence (FAF) is associated with the incidence or progression of dry and wet age-related macular degeneration (AMD). We previously developed a rabbit AMD model with drusen and type-1 choroidal neovascularization (CNV) that mimics the accumulation of lipofuscin using artificial glycoxidized particles. The objective of the current study was to investigate in vitro effects of glycoxidized particles on retinal pigment epithelial (RPE) cells, and the FAF and fate of injected particles in this model. Glycoxidized particles were prepared by a 4-day incubation of water-in-oil emulsions of serum albumin and glycolaldehyde to allow glycoxidation and consequent cross-linking. After particles were added in the culture medium of confluent human RPE cells, cell viability, adhesion activity, and proliferation activity were assessed by cell counting. In anesthetized rabbits, 250 microg of glycoxidized particles were injected into the subretinal space to induce experimental AMD. FAF measurement and angiography with sodium fluorescein and indocyanine green were performed periodically using the Heidelberg Retina Angiograph 2 (HRA2). The eyes enucleated, and the lung and the spleen, excised at week 4 or 12, were histologically evaluated by light and fluorescence microscopy. Glycoxidized particles phagocytosed did not impair the cell viability, adhesion, and proliferation of RPE cells, as compared with RPE cells in controls. HRA2 showed different patterns of abnormal FAF in the area with the implanted glycoxidized particles, similar to pathological FAF patterns in aging human eyes with or without AMD. Histologic examination showed accumulated glycoxidized particles and large lipofuscin granules with green autofluorescence in and under the RPE and at the margins of or beneath drusen, possibly associated with abnormal FAF. In addition, some particles were detected in the lung and the spleen. Glycoxidized particles phagocytosed might stay in RPE cells without any acute biological reaction. Our rabbit model of AMD simulated abnormal FAF patterns observed in aging human eyes with or without AMD. Glycoxidized particles phagocytosed by RPE cells could be deposited on Bruch's membrane in rabbits, possibly excreted in part into choroidal circulation. This model may be useful for understanding various patterns of abnormal FAF histologically, and for elucidating the pathogenesis of AMD.

Of Brain and Bone: The Unusual Case of Dr. A

PubMed Central

Narvid, J; Gorno-Tempini, ML; Slavotinek, A; DeArmond, SJ; Cha, YH; Miller, BL; Rankin, K.P

2009-01-01

Frontotemporal dementia (FTD) is a clinical syndrome characterized by progressive decline in social conduct and a focal pattern of frontal and temporal lobe damage. Its biological basis is still poorly understood but the focality of the brain degeneration provides a powerful model to study the cognitive and anatomical basis of social cognition. Here, we present Dr. A, a patient with a rare hereditary bone disease (hereditary multiple exostoses) and FTD (pathologically characterized as Pick’s disease), who presented with a profound behavioral disturbance characterized by acquired sociopathy. We conducted a detailed genetic, pathological, neuroimaging and cognitive study, including a battery of tests designed to investigate Dr. A’s abilities to understand emotional cues and to infer mental states and intentions to others (theory of mind). Dr. A’s genetic profile suggests the possibility that a mutation causing hereditary multiple exostoses, Ext2, may play a role in the pattern of neurodegeneration in frontotemporal dementia since knockout mice deficient in the Ext gene family member, Ext1, show severe CNS defects including loss of olfactory bulbs and abnormally small cerebral cortex. Dr. A showed significant impairment in emotion comprehension, second order theory of mind, attribution of intentions, and empathy despite preserved general cognitive abilities. Voxel-based morphometry on structural MRI images showed significant atrophy in the medial and right orbital frontal and anterior temporal regions with sparing of dorsolateral frontal cortex. This case demonstrates that social and emotional dysfunction in FTD can dissociate from preserved performance on classic executive functioning tasks. The specific pattern of anatomical damage shown by VBM emphasizes the importance of the network including the superior medial frontal gyrus as well as temporal polar areas, in regulation of social cognition and theory of mind. This case provides new evidence regarding the neural basis of social cognition and suggests a possible genetic link between bone disease and FTD. PMID:20183548

Ophthalmologic abnormalities in Mowat-Wilson syndrome and a mutation in ZEB2.

PubMed

Ariss, Michelle; Natan, Kristina; Friedman, Neil; Traboulsi, Elias I

2012-09-01

Mowat-Wilson syndrome is a genetic disorder characterized by a distinct facial appearance, moderate-to-severe mental retardation, microcephaly, agenesis of the corpus callosum, Hirschsprung disease, congenital heart disease, and genital anomalies. Ophthalmological abnormalities have been rarely described in patients with this condition which is caused by mutations in the ZEB2 gene. We report a 9-year-old female with this syndrome who has severe ocular abnormalities including bilateral microphthalmia, cataract, and retinal aplasia.

Autistic Traits and Abnormal Sensory Experiences in Adults

ERIC Educational Resources Information Center

Horder, Jamie; Wilson, C. Ellie; Mendez, M. Andreina; Murphy, Declan G.

2014-01-01

Sensory processing abnormalities are common in autism spectrum disorders (ASD), and now form part of the "Diagnostic and Statistical Manual 5th Edition" (DSM-5) diagnostic criteria, but it is unclear whether they characterize the "broader phenotype" of the disorder. We recruited adults (n = 772) with and without an ASD and…

Response Monitoring, Repetitive Behaviour and Anterior Cingulate Abnormalities in Autism Spectrum Disorders (ASD)

ERIC Educational Resources Information Center

Thakkar, Katharine N.; Polli, Frida E.; Joseph, Robert M.; Tuch, David S.; Hadjikhani, Nouchine; Barton, Jason J. S.; Manoach, Dara S.

2008-01-01

Autism spectrum disorders (ASD) are characterized by inflexible and repetitive behaviour. Response monitoring involves evaluating the consequences of behaviour and making adjustments to optimize outcomes. Deficiencies in this function, and abnormalities in the anterior cingulate cortex (ACC) on which it relies, have been reported as contributing…

Altered Functional Connectivity of the Primary Visual Cortex in Subjects with Amblyopia

PubMed Central

Ding, Kun; Liu, Yong; Yan, Xiaohe; Lin, Xiaoming; Jiang, Tianzi

2013-01-01

Amblyopia, which usually occurs during early childhood and results in poor or blurred vision, is a disorder of the visual system that is characterized by a deficiency in an otherwise physically normal eye or by a deficiency that is out of proportion with the structural or functional abnormalities of the eye. Our previous study demonstrated alterations in the spontaneous activity patterns of some brain regions in individuals with anisometropic amblyopia compared to subjects with normal vision. To date, it remains unknown whether patients with amblyopia show characteristic alterations in the functional connectivity patterns in the visual areas of the brain, particularly the primary visual area. In the present study, we investigated the differences in the functional connectivity of the primary visual area between individuals with amblyopia and normal-sighted subjects using resting functional magnetic resonance imaging. Our findings demonstrated that the cerebellum and the inferior parietal lobule showed altered functional connectivity with the primary visual area in individuals with amblyopia, and this finding provides further evidence for the disruption of the dorsal visual pathway in amblyopic subjects. PMID:23844297

Phenomenology and classification of dystonia: a consensus update

PubMed Central

Albanese, Alberto; Bhatia, Kailash; Bressman, Susan B.; DeLong, Mahlon R.; Fahn, Stanley; Fung, Victor S.C.; Hallett, Mark; Jankovic, Joseph; Jinnah, H.A.; Klein, Christine; Lang, Anthony E.; Mink, Jonathan W.; Teller, Jan K.

2013-01-01

This report describes the consensus outcome of an international panel consisting of investigators with years of experience in this field that reviewed the definition and classification of dystonia. Agreement was obtained based on a consensus development methodology during three in-person meetings and manuscript review by mail. Dystonia is defined as a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. Dystonic movements are typically patterned and twisting, and may be tremulous. Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle activation. Dystonia is classified along two axes: clinical characteristics, including age at onset, body distribution, temporal pattern and associated features (additional movement disorders or neurological features), and etiology, which includes nervous system pathology and inheritance. The clinical characteristics fall into several specific dystonia syndromes that help to guide diagnosis and treatment. We provide here a new general definition of dystonia and propose a new classification. We encourage clinicians and researchers to use these innovative definition and classification and test them in the clinical setting on a variety of patients with dystonia. PMID:23649720

Assessment of transmitral flow after mitral valve edge-to-edge repair using High-speed particle image velocimetry

NASA Astrophysics Data System (ADS)

Jeyhani, Morteza; Shahriari, Shahrokh; Labrosse, Michel; Kadem, Lyes

2013-11-01

Approximately 500,000 people in North America suffer from mitral valve regurgitation (MR). MR is a disorder of the heart in which the mitral valve (MV) leaflets do not close securely during systole. Edge-to-edge repair (EtER) technique can be used to surgically treat MR. This technique produces a double-orifice configuration for the MV. Under these un-physiological conditions, flow downstream of the MV forms a double jet structure that may disturb the intraventricular hemodynamics. Abnormal flow patterns following EtER are mainly characterized by high-shear stress and stagnation zones in the left ventricle (LV), which increase the potential of blood component damage. In this study, a custom-made prosthetic bicuspid MV was used to analyze the LV flow patterns after EtER by means of digital particle image velocimetry (PIV). Although the repair of a MV using EtER technique is an effective approach, this study confirms that EtER leads to changes in the LV flow field, including the generation of a double mitral jet flow and high shear stress regions.

Contemporary review on the pathogenesis of takotsubo syndrome: The heart shedding tears: Norepinephrine churn and foam at the cardiac sympathetic nerve terminals.

PubMed

Y-Hassan, Shams; De Palma, Rodney

2017-02-01

Takotsubo syndrome (TS), an increasingly recognized acute cardiac disease entity, is characterized by a unique pattern of circumferential and typically regional left ventricular wall motion abnormality resulting in a conspicuous transient ballooning of the left ventricle during systole. The mechanism of the disease remains elusive. However, the sudden onset of acute myocardial stunning in a systematic pattern extending beyond a coronary artery territory; the history of a preceding emotional or physical stress factor in two thirds of cases; the signs of sympathetic denervation at the regions of left ventricular dysfunction on sympathetic scintigraphy; the finding of myocardial edema and other signs consistent with (catecholamine-induced) myocarditis shown by cardiac magnetic resonance imaging; and the contraction band necrosis on histopathological examination all argue strongly for the involvement of the cardiac sympathetic nervous system in the pathogenesis of TS. In this narrative review, extensive evidence in support of local cardiac sympathetic nerve hyperactivation, disruption and norepinephrine spillover causing TS in predisposed patients is provided. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Heterogeneity of neuroanatomical patterns in prodromal Alzheimer's disease: links to cognition, progression and biomarkers.

PubMed

Dong, Aoyan; Toledo, Jon B; Honnorat, Nicolas; Doshi, Jimit; Varol, Erdem; Sotiras, Aristeidis; Wolk, David; Trojanowski, John Q; Davatzikos, Christos

2017-03-01

See Coulthard and Knight (doi:10.1093/aww335) for a scientific commentary on this article.Individuals with mild cognitive impairment and Alzheimer's disease clinical diagnoses can display significant phenotypic heterogeneity. This variability likely reflects underlying genetic, environmental and neuropathological differences. Characterizing this heterogeneity is important for precision diagnostics, personalized predictions, and recruitment of relatively homogeneous sets of patients into clinical trials. In this study, we apply state-of-the-art semi-supervised machine learning methods to the Alzheimer's disease Neuroimaging cohort (ADNI) to elucidate the heterogeneity of neuroanatomical differences between subjects with mild cognitive impairment (n = 530) and Alzheimer's disease (n = 314) and cognitively normal individuals (n = 399), thereby adding to an increasing literature aiming to establish neuroanatomical and neuropathological (e.g. amyloid and tau deposition) dimensions in Alzheimer's disease and its prodromal stages. These dimensional approaches aim to provide surrogate measures of heterogeneous underlying pathologic processes leading to cognitive impairment. We relate these neuroimaging patterns to cerebrospinal fluid biomarkers, white matter hyperintensities, cognitive and clinical measures, and longitudinal trajectories. We identified four such atrophy patterns: (i) individuals with largely normal neuroanatomical profiles, who also turned out to have the least abnormal cognitive and cerebrospinal fluid biomarker profiles and the slowest clinical progression during follow-up; (ii) individuals with classical Alzheimer's disease neuroanatomical, cognitive, cerebrospinal fluid biomarkers and clinical profile, who presented the fastest clinical progression; (iii) individuals with a diffuse pattern of atrophy with relatively less pronounced involvement of the medial temporal lobe, abnormal cerebrospinal fluid amyloid-β1-42 values, and proportionally greater executive impairment; and (iv) individuals with notably focal involvement of the medial temporal lobe and a slow steady progression, likely representing in early Alzheimer's disease stages. These four atrophy patterns effectively define a 4-dimensional categorization of neuroanatomical alterations in mild cognitive impairment and Alzheimer's disease that can complement existing dimensional approaches for staging Alzheimer's disease using a variety of biomarkers, which offer the potential for enabling precision diagnostics and prognostics, as well as targeted patient recruitment of relatively homogeneous subgroups of subjects for clinical trials. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

PubMed

Latash, M L; Gutman, S R

1994-01-01

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

Investigation of orbitofrontal sulcogyral pattern in chronic schizophrenia.

PubMed

Cropley, Vanessa L; Bartholomeusz, Cali F; Wu, Peter; Wood, Stephen J; Proffitt, Tina; Brewer, Warrick J; Desmond, Patricia M; Velakoulis, Dennis; Pantelis, Christos

2015-11-30

Abnormalities of orbitofrontal cortex (OFC) pattern type distribution have been associated with schizophrenia-spectrum disorders. We investigated OFC pattern type in a large sample of chronic schizophrenia patients and healthy controls. We found an increased frequency of Type II but no difference in Type I or III folding pattern in the schizophrenia group in comparison to controls. Further large studies are required to investigate the diagnostic specificity of altered OFC pattern type and to confirm the distribution of pattern type in the normal population. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Dermatological and morphological findings in quarter horses with hereditary equine regional dermal asthenia.

PubMed

Badial, Peres R; Oliveira-Filho, José P; Pantoja, José Carlos F; Moreira, José C L; Conceição, Lissandro G; Borges, Alexandre S

2014-12-01

Hereditary equine regional dermal asthenia (HERDA) is an autosomal recessive disorder affecting quarter horses (QHs); affected horses exhibit characteristic skin abnormalities related to abnormal collagen biosynthesis. To characterize the thickness and morphological abnormalities of the skin of HERDA-affected horses and to determine the interobserver agreement and the diagnostic accuracy of histopathological examination of skin biopsies from horses with HERDA. Six affected QHs, confirmed by DNA testing, from a research herd and five unaffected QHs from a stud farm. The skin thickness in 25 distinct body regions was measured on both sides in all affected and unaffected horses. Histopathological and ultrastructural evaluation of skin biopsies was performed. The average skin thickness in all of the evaluated regions was thinner in the affected horses. A statistically significant difference between skin thickness of the affected and unaffected animals was observed only when the average magnitude of difference was ≥38.7% (P = 0.038). The interobserver agreement for the histopathological evaluation was fair to substantial. The histopathological sensitivity for the diagnosis of HERDA was dependent on the evaluator and ranged from 73 to 88%, whereas the specificity was affected by the region sampled and ranged from 35 to 75%. Despite the regional pattern of the cutaneous signs, skin with decreased thickness was not regionally distributed in the HERDA-affected horses. Histopathological evaluation is informative but not conclusive for establishing the diagnosis. Samples of skin from the neck, croup or back are useful for diagnosis of HERDA. However, the final diagnosis must be confirmed using molecular testing. © 2014 ESVD and ACVD.

Rhesus macaque model of chronic opiate dependence and neuro-AIDS: longitudinal assessment of auditory brainstem responses and visual evoked potentials

PubMed Central

Riazi, Mariam; Marcario, Joanne K; Samson, Frank K.; Kenjale, Himanshu; Adany, Istvan; Staggs, Vincent; Ledford, Emily; Marquis, Janet; Narayan, Opendra; Cheney, Paul D.

2013-01-01

Our work characterizes the effects of opiate (morphine) dependence on auditory brainstem and visual evoked responses in a rhesus macaque model of neuro-AIDS utilizing a chronic continuous drug delivery paradigm. The goal of this study was to clarify whether morphine is protective, or if it exacerbates simian immunodeficiency virus (SIV) related systemic and neurological disease. Our model employs a macrophage tropic CD4/CCR5 co-receptor virus, SIVmac239 (R71/E17), which crosses the blood brain barrier shortly after inoculation and closely mimics the natural disease course of human immunodeficiency virus (HIV) infection. The cohort was divided into 3 groups: morphine only, SIV only, and SIV + morphine. Evoked potential (EP) abnormalities in sub-clinically infected macaques were evident as early as eight weeks post-inoculation. Prolongations in EP latencies were observed in SIV-infected macaques across all modalities. Animals with the highest CSF viral loads and clinical disease showed more abnormalities than those with sub-clinical disease, confirming our previous work (Raymond et al, 1998, 1999, 2000). Although some differences were observed in auditory and visual evoked potentials in morphine treated compared to untreated SIV-infected animals, the effects were relatively small and not consistent across evoked potential type. However, morphine treated animals with subclinical disease had a clear tendency toward higher virus loads in peripheral and CNS tissues (Marcario et al., 2008) suggesting that if had been possible to follow all animals to end-stage disease, a clearer pattern of evoked potential abnormality might have emerged. PMID:19283490

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

Dopaminergic circuitry and risk/reward decision making: implications for schizophrenia.

PubMed

Stopper, Colin M; Floresco, Stan B

2015-01-01

Abnormal reinforcement learning and representations of reward value are present in schizophrenia, and these impairments can manifest as deficits in risk/reward decision making. These abnormalities may be due in part to dopaminergic dysfunction within cortico-limbic-striatal circuitry. Evidence from studies with laboratory animal have revealed that normal DA activity within different nodes of these circuits is critical for mediating dissociable processes that can refine decision biases. Moreover, both phasic and tonic dopamine transmission appear to play separate yet complementary roles in these processes. Tonic dopamine release within the prefrontal cortex and nucleus accumbens, serves as a "running rate-meter" of reward and reflects contextual information such as reward uncertainty and overt choice behavior. On the other hand, manipulations of outcome-related phasic dopamine bursts and dips suggest these signals provide rapid feedback to allow for quick adjustments in choice as reward contingencies change. The lateral habenula is a key input to the DA system that phasic signals is necessary for expressing subjective decision biases; as suppression of activity within this nucleus leads to catastrophic impairments in decision making and random patterns of choice behavior. As schizophrenia is characterized by impairments in using positive and negative feedback to appropriately guide decision making, these findings suggest that these deficits in these processes may be mediated, at least in part, by abnormalities in both tonic and phasic dopamine transmission. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Method and system for determining precursors of health abnormalities from processing medical records

DOEpatents

None, None

2013-06-25

Medical reports are converted to document vectors in computing apparatus and sampled by applying a maximum variation sampling function including a fitness function to the document vectors to reduce a number of medical records being processed and to increase the diversity of the medical records being processed. Linguistic phrases are extracted from the medical records and converted to s-grams. A Haar wavelet function is applied to the s-grams over the preselected time interval; and the coefficient results of the Haar wavelet function are examined for patterns representing the likelihood of health abnormalities. This confirms certain s-grams as precursors of the health abnormality and a parameter can be calculated in relation to the occurrence of such a health abnormality.

Identification and handling of artifactual gene expression profiles emerging in microarray hybridization experiments

PubMed Central

Brodsky, Leonid; Leontovich, Andrei; Shtutman, Michael; Feinstein, Elena

2004-01-01

Mathematical methods of analysis of microarray hybridizations deal with gene expression profiles as elementary units. However, some of these profiles do not reflect a biologically relevant transcriptional response, but rather stem from technical artifacts. Here, we describe two technically independent but rationally interconnected methods for identification of such artifactual profiles. Our diagnostics are based on detection of deviations from uniformity, which is assumed as the main underlying principle of microarray design. Method 1 is based on detection of non-uniformity of microarray distribution of printed genes that are clustered based on the similarity of their expression profiles. Method 2 is based on evaluation of the presence of gene-specific microarray spots within the slides’ areas characterized by an abnormal concentration of low/high differential expression values, which we define as ‘patterns of differentials’. Applying two novel algorithms, for nested clustering (method 1) and for pattern detection (method 2), we can make a dual estimation of the profile’s quality for almost every printed gene. Genes with artifactual profiles detected by method 1 may then be removed from further analysis. Suspicious differential expression values detected by method 2 may be either removed or weighted according to the probabilities of patterns that cover them, thus diminishing their input in any further data analysis. PMID:14999086

Remote reprogramming of hepatic circadian transcriptome by breast cancer.

PubMed

Hojo, Hiroaki; Enya, Sora; Arai, Miki; Suzuki, Yutaka; Nojiri, Takashi; Kangawa, Kenji; Koyama, Shinsuke; Kawaoka, Shinpei

2017-05-23

Cancers adversely affect organismal physiology. To date, the genes within a patient responsible for systemically spreading cancer-induced physiological disruption remain elusive. To identify host genes responsible for transmitting disruptive, cancer-driven signals, we thoroughly analyzed the transcriptome of a suite of host organs from mice bearing 4T1 breast cancer, and discovered complexly rewired patterns of circadian gene expression in the liver. Our data revealed that 7 core clock transcription factors, represented by Rev-erba and Rorg, exhibited abnormal daily expression rhythm in the liver of 4T1-bearing mice. Accordingly, expression patterns of specific set of downstream circadian genes were compromised. Osgin1, a marker for oxidative stress, was an example. Specific downstream genes, including E2f8, a transcriptional repressor that controls cellular polyploidy, displayed a striking pattern of disruption, "day-night reversal." Meanwhile, we found that the liver of 4T1-bearing mice suffered from increased oxidative stress. The tetraploid hepatocytes population was concomitantly increased in 4T1-bearing mice, which has not been previously appreciated as a cancer-induced phenotype. In summary, the current study provides a comprehensive characterization of the 4T1-affected hepatic circadian transcriptome that possibly underlies cancer-induced physiological alteration in the liver.

Changing Adolescent Sleep Patterns: Factors Affecting them and the Related Problems.

PubMed

Kaur, Harpreet; Bhoday, Harpreet Singh

2017-03-01

Sleep affects physical growth, behavior and emotional development besides determining cognitive functioning, learning and attention especially of a growing child. Adolescence represents one of the critical transitions in the life span and is characterized by a tremendous pace in growth and change that is second only to that of infancy. Adolescent sleep patterns deserve particular attention because of the potential impact on school performance. Average sleep period in adolescents is reduced during school days to around seven hours. The reasons may be biological mainly the sleep phase delay or psychosocial and environmental. These include academic demands, social activities, sports, internet, television viewing, part-time employment, and use of mobile phone at night, peer and parental influence and socioeconomic status. These changing patterns of sleep in adolescents lead to many behavioral sleep problems like Delayed Sleep-phase Syndrome; Difficulties in falling asleep (insomnia); excessive daytime sleepiness, poor academic performance. Decreased sleep in adolescents also causes obesity and other cardio-metabolic abnormalities. This needs an integrated approach involving adolescents themselves, their parents, teachers and specialized physicians to help improve the sleep quantity and quality and lead to a better quality of life and daytime functioning in adolescents. © Journal of the Association of Physicians of India 2011.

A Multiple Degree of Freedom Lower Extremity Isometric Device to Simultaneously Quantify Hip, Knee and Ankle Torques

PubMed Central

Sánchez, Natalia; Acosta, Ana Maria; Stienen, Arno H.A.

2015-01-01

Characterization of the joint torque coupling strategies used in the lower extremity to generate maximal and submaximal levels of torque at either the hip, knee or ankle is lacking. Currently, there are no available isometric devices that quantify all concurrent joint torques in the hip, knee and ankle of a single leg during maximum voluntary torque generation. Thus, joint-torque coupling strategies in the hip, knee and concurrent torques at ankle and/or coupling patterns at the hip and knee driven by the ankle have yet to be quantified. This manuscript describes the design, implementation and validation of a multiple degree of freedom, lower extremity isometric device (the MultiLEIT) that accurately quantifies simultaneous torques at the hip, knee and ankle. The system was mechanically validated and then implemented with two healthy control individuals and two post-stroke individuals to test usability and patient acceptance. Data indicated different joint torque coupling strategies used by both healthy individuals. In contrast, data showed the same torque coupling patterns in both post-stroke individuals, comparable to those described in the clinic. Successful implementation of the MultiLEIT can contribute to the understanding of the underlying mechanisms responsible for abnormal movement patterns and aid in the design of therapeutic interventions. PMID:25163064

Weakly coupled map lattice models for multicellular patterning and collective normalization of abnormal single-cell states

NASA Astrophysics Data System (ADS)

García-Morales, Vladimir; Manzanares, José A.; Mafe, Salvador

2017-04-01

We present a weakly coupled map lattice model for patterning that explores the effects exerted by weakening the local dynamic rules on model biological and artificial networks composed of two-state building blocks (cells). To this end, we use two cellular automata models based on (i) a smooth majority rule (model I) and (ii) a set of rules similar to those of Conway's Game of Life (model II). The normal and abnormal cell states evolve according to local rules that are modulated by a parameter κ . This parameter quantifies the effective weakening of the prescribed rules due to the limited coupling of each cell to its neighborhood and can be experimentally controlled by appropriate external agents. The emergent spatiotemporal maps of single-cell states should be of significance for positional information processes as well as for intercellular communication in tumorigenesis, where the collective normalization of abnormal single-cell states by a predominantly normal neighborhood may be crucial.

Weakly coupled map lattice models for multicellular patterning and collective normalization of abnormal single-cell states.

PubMed

García-Morales, Vladimir; Manzanares, José A; Mafe, Salvador

2017-04-01

We present a weakly coupled map lattice model for patterning that explores the effects exerted by weakening the local dynamic rules on model biological and artificial networks composed of two-state building blocks (cells). To this end, we use two cellular automata models based on (i) a smooth majority rule (model I) and (ii) a set of rules similar to those of Conway's Game of Life (model II). The normal and abnormal cell states evolve according to local rules that are modulated by a parameter κ. This parameter quantifies the effective weakening of the prescribed rules due to the limited coupling of each cell to its neighborhood and can be experimentally controlled by appropriate external agents. The emergent spatiotemporal maps of single-cell states should be of significance for positional information processes as well as for intercellular communication in tumorigenesis, where the collective normalization of abnormal single-cell states by a predominantly normal neighborhood may be crucial.

Epilepsy

MedlinePlus

... made great strides in detecting patterns of abnormal electrical activity in the brain that cause epileptic seizures. A technology to measure brain activity, called electroencephalography (EEG), became ...

CNS imaging findings associated with Parry-Romberg syndrome and en coup de sabre: correlation to dermatologic and neurologic abnormalities.

PubMed

Doolittle, Derrick A; Lehman, Vance T; Schwartz, Kara M; Wong-Kisiel, Lily C; Lehman, Julia S; Tollefson, Megha M

2015-01-01

Parry-Romberg syndrome (PRS) and en coup de sabre (ECS) are variants of morphea. Although numerous findings on central nervous system (CNS) imaging of PRS and ECS have been reported, the spectrum and frequency of CNS imaging findings and relation to cutaneous and neurologic abnormalities have not been fully characterized. We retrospectively reviewed patients younger than 50 years at our institution over a 16-year interval who had clinical diagnosis of PRS and ECS by a skin or facial subspecialist. Two neuroradiologists evaluated available imaging and characterized CNS imaging findings. Eighty-eight patients with PRS or ECS were identified (62 women [70.4 %]; mean age 28.8 years). Of the 43 patients with CNS imaging, 19 (44 %) had abnormal findings. The only finding in 1 of these 19 patients was lateral ventricle asymmetry; of the other 18, findings were bilateral in 11 (61 %), ipsilateral to the side of facial involvement in 6 (33 %), and contralateral in 1 (6 %). Sixteen patients had serial imaging examinations over an average of 632 days; 13 (81 %) had stable imaging findings, and 3 (19 %) had change over time. Of six patients with progressive cutaneous findings, five (83 %) had stable imaging findings over time. Among the 23 patients with clinical neurologic abnormality and imaging, 12 (52 %) had abnormal imaging findings. All seven patients with seizures (100 %) had abnormal imaging studies. In PRS and ECS, imaging findings often are bilateral and often do not progress, regardless of cutaneous disease activity. Findings are inconsistently associated with clinical abnormalities.

Unknown syndrome: abnormal facies, hypothyroidism, postaxial polydactyly, and severe retardation: a third patient.

PubMed Central

Cavalcanti, D P

1989-01-01

Young and Simpson in 1987 and Fryns and Moerman in 1988 each reported a case of a new unknown syndrome with hypothyroidism, severe global retardation, and abnormal facies, including microcephaly, blepharophimosis, bulbous nose, thin upper lip, low set ears, and micrognathia. A male infant with a similar pattern of malformations and postaxial polydactyly is reported here. Images PMID:2614801

Partial epilepsy and 47,XXX karyotype: report of four cases.

PubMed

Roubertie, Agathe; Humbertclaude, Véronique; Leydet, Julie; Lefort, Geneviève; Echenne, Bernard

2006-07-01

Epilepsy is a common finding in chromosomal imbalances, but only a few chromosome abnormalities have a characteristic electro-clinical pattern. Trisomy X is one of the most common sex chromosome abnormalities in females, and is associated with considerable phenotypic variability. This report describes four 47,XXX females with mental deficiency and epilepsy. Although a specific electro-clinical pattern could not be defined, the epileptic phenotypes of these patients share many features; we suggest that the association 47,XXX/epilepsy/mental retardation may not be coincidental. This report also enlarges the clinical spectrum of the 47,XXX phenotype. Moreover, these observations highlight the critical role of chromosome X in epilepsy and mental retardation.

Abnormal Canine Bone Development Associated with Hypergravity Exposure

NASA Technical Reports Server (NTRS)

Morgan, J. P.; Fisher, G. L.; McNeill, K. L.; Oyama, J.

1979-01-01

Chronic centrifugation of 85- to 92-day-old Beagles at 2.0 x g and 2.6 x g for 26 weeks during the time of active skeletal growth caused skeletal abnormalities in the radius and the ulna of ten of 11 dogs. The pattern of change mimicked that found in naturally occurring and experimentally induced premature distal ulnar physeal closure or delayed growth at this physis. Minimal changes in bone density were detected by sensitive photon absorptiometric techniques. Skeletal abnormalities also were found in five of the six cage-control dogs, although the run-control dogs were radiographically normal.

Oseltamivir use and severe abnormal behavior in Japanese children and adolescents with influenza: Is a self-controlled case series study applicable?

PubMed

Fukushima, Wakaba; Ozasa, Kotaro; Okumura, Akihisa; Mori, Masaaki; Hosoya, Mitsuaki; Nakano, Takashi; Tanabe, Takuya; Yamaguchi, Naoto; Suzuki, Hiroshi; Mori, Mitsuru; Hatayama, Hideaki; Ochiai, Hirotaka; Kondo, Kyoko; Ito, Kazuya; Ohfuji, Satoko; Nakamura, Yosikazu; Hirota, Yoshio

2017-08-24

Since the 1990s, self-controlled designs including self-controlled case series (SCCS) studies have been occasionally used in post-marketing evaluation of drug or vaccine safety. An SCCS study was tentatively applied to evaluate the relationship between oseltamivir use and abnormal behavior Type A (serious abnormal behavior potentially leading to an accident or harm to another person) in influenza patients. From the original prospective cohort study with approximately 10,000 Japanese children and adolescents with influenza (aged <18years), 28 subjects (mean age: 7.3years) who developed abnormal behavior Type A after the first visit to the collaborating hospitals/clinics were analyzed. We hypothesized four combination patterns of the effect period (i.e., the period that effect of oseltamivir on occurrence of abnormal behavior Type A is likely) and the control period. Mantel-Haenszel rate ratio (M-H RR) and its 95% confidence interval (CI) were calculated as the relative risk estimate. Among 28 subjects in the SCCS study, 24 subjects (86%) were administered oseltamivir and 4 subjects (14%) were not. Abnormal behavior Type A was more likely to occur in the effect period than the control period in every pattern (M-H RR: 1.90-29.1). We observed the highest estimate when the effect period was set between the initial intake of oseltamivir and T max (M-H RR: 29.1, 95% CI: 4.21-201). Abnormal behavior Type A was more likely to develop up to approximately 30 times during the period between the initial intake of oseltamivir and T max . However, this period overlapped with the early period of influenza where high fever was observed. Since useful approaches to control the influence of the natural disease course of influenza were not available in this study, we could not deny the possibility that abnormal behavior was induced by influenza itself. The SCCS study was not an optimal method to evaluate the relationship between oseltamivir use and abnormal behavior. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bronchial mucus properties in lung cancer: relationship with site of lesion.

PubMed

Zayas, J G; Rubin, B K; York, E L; Lien, D C; King, M

1999-01-01

To compare the biophysical properties of mucus from the left and right mainstem bronchi in patients undergoing diagnostic bronchoscopy because of a unilateral radiological abnormality. It was hypothesized that abnormalities in the properties of mucus would be greater on the side with the lesion and that this would be most obvious in patients with unilateral lung cancer. Bilateral paired samples of bronchial mucus were taken from 38 nonatopic patients (aged 59.8+/-12.6 years) including 16 nonsmokers, 14 current smokers and eight exsmokers (more than one year). Twenty of the 38 patients had a radiologically defined unilateral abnormality. Eight of these 20, including one nonsmoker, had lung cancer. The viscoelastic properties of the collected mucus were determined by magnetic microrheometry, and the analysis was carried out without knowledge of the histological diagnosis or source. The rheological properties of mucus strongly suggested which was the abnormal side. Within the group of 20 patients with a unilateral radiological abnormality, mucus from the side of the lesion had a lower value of the loss tangent, tan d100 (P=0.004), indicating greater mucus recoil. This is consistent with poor mucus cough clearability on the lesion side. All eight cancer patients fit this mucus rheological pattern with a lower value of tan d100 on the affected side (P=0.007). Four of the five other patients with a similar mucus abnormality were categorized as high cancer risk by other criteria, while six of seven patients with mucus that did not have this abnormality were considered to be lower risk. Based on the mucus analysis done at the time of the bronchoscopy, two of the 'noncancer' patients initially designated as high risk had cancer detected after several months of follow- up. Only two of the 18 patients without a defined unilateral lesion fit the mucus 'cancer pattern'. These findings are consistent with the hypothesis that either abnormalities in mucus properties may represent a risk factor for the development of lung cancer or that bronchial mucus abnormalities may be associated with products secreted by the tumours that, in turn, may suppress mucus clearance.

Cerebellar abnormalities typical of methylmercury poisoning in a fledged saltmarsh sparrow, Ammodramus caudacutus.

PubMed

Scoville, Sheila A; Lane, Oksana P

2013-05-01

A fledged, 12-15 day-old saltmarsh sparrow, Ammodramus caudacutus, was collected from an accidental kill on Cinder Island, Long Island, NY, USA. The sparrow was assessed for feather mercury levels and the brain analyzed for cerebellar abnormalities by microscopic examination. In humans, fetal Minamata disease is caused by maternal ingestion of mercury. It is characterized by disrupted and disordered cerebellar neuronal migration in the fetus or infant. Results from this sparrow show cerebellar abnormalities typical of Minamata disease. It is the first known avian or mammalian specimen taken from the wild to show the abnormalities typical of the human fetal syndrome.

The 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.

Restrictive allograft syndrome after lung transplantation: new radiological insights.

PubMed

Dubbeldam, Adriana; Barthels, Caroline; Coolen, Johan; Verschakelen, Johny A; Verleden, Stijn E; Vos, Robin; Verleden, Geert M; De Wever, Walter

2017-07-01

To describe the CT changes in patients with restrictive allograft syndrome (RAS) after lung transplantation, before and after clinical diagnosis. This retrospective study included 22 patients with clinical diagnosis of RAS. Diagnosis was based on a combination of forced expiratory volume (FEV1) decline (≥20 %) and total lung capacity (TLC) decline (≥10 %). All available CT scans after transplantation were analyzed for the appearance and evolution of lung abnormalities. In 14 patients, non-regressing nodules and reticulations predominantly affecting the upper lobes developed an average of 13.9 months prior to the diagnosis of RAS. Median graft survival after onset of non-regressing abnormalities was 33.5 months, with most patients in follow-up (9/14). In eight patients, a sudden appearance of diffuse consolidations mainly affecting both upper and lower lobes was seen an average of 2.8 months prior to the diagnosis of RAS. Median graft survival was 6.4 months after first onset of non-regressing abnormalities, with graft loss in most patients (6/8). RAS has been previously described as a homogenous group. However, our study shows two different groups of RAS-patients: one with slow progression and one with fast progression. The two groups show different onset and progression patterns of CT abnormalities. • RAS is the newest discovered form of chronic lung allograft dysfunction (CLAD). • RAS is not a homogenous group, as survival varies greatly between patients. • In this study, we see two different CT onset and progression patterns. • These two different CT patterns also correlate with a different survival rate.

POC1A truncation mutation causes a ciliopathy in humans characterized by primordial dwarfism.

PubMed

Shaheen, Ranad; Faqeih, Eissa; Shamseldin, Hanan E; Noche, Ramil R; Sunker, Asma; Alshammari, Muneera J; Al-Sheddi, Tarfa; Adly, Nouran; Al-Dosari, Mohammed S; Megason, Sean G; Al-Husain, Muneera; Al-Mohanna, Futwan; Alkuraya, Fowzan S

2012-08-10

Primordial dwarfism (PD) is a phenotype characterized by profound growth retardation that is prenatal in onset. Significant strides have been made in the last few years toward improved understanding of the molecular underpinning of the limited growth that characterizes the embryonic and postnatal development of PD individuals. These include impaired mitotic mechanics, abnormal IGF2 expression, perturbed DNA-damage response, defective spliceosomal machinery, and abnormal replication licensing. In three families affected by a distinct form of PD, we identified a founder truncating mutation in POC1A. This gene is one of two vertebrate paralogs of POC1, which encodes one of the most abundant proteins in the Chlamydomonas centriole proteome. Cells derived from the index individual have abnormal mitotic mechanics with multipolar spindles, in addition to clearly impaired ciliogenesis. siRNA knockdown of POC1A in fibroblast cells recapitulates this ciliogenesis defect. Our findings highlight a human ciliopathy syndrome caused by deficiency of a major centriolar protein. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Implementation of Fractal Dimension and Self-Organizing Map to Detect Toxic Effects of Toluene on Movement Tracks of Daphnia magna.

PubMed

Liu, Yuedan; Xia, Chunlei; Fan, Zhongya; Wu, Renren; Chen, Xianglin; Liu, Zuoyi

2018-01-01

Movement behaviors of an indicator species, Daphnia magna , in response to contaminants have been implemented to monitor environmental disturbances. Complexity in movement tracks of Daphnia magna was characterized by use of fractal dimension and self-organizing map. The individual movement tracks of D. magna were continuously recorded for 24 hours before and after treatments with toluene at the concentration of 10 mg/L, respectively. The general complexity in movement tracks (10 minutes) was characterized by fractal dimension. Results showed that average fractal dimension of movement tracks was decreased from 1.62 to 1.22 after treatments. The instantaneous movement parameters of movement segments in 5 s were input into the self-organizing map to investigate the swimming pattern changes under stresses of toluene. Abnormal behaviors of D. magna are more frequently observed after treatments than before treatments. Computational methods in ecological informatics could be utilized to obtain the useful information in behavioral data of D. magna and would be further applied as an in situ monitoring tool in water environment.

Translocation (16;20)(p11.2;q13). sole cytogenetic abnormality in a unicameral bone cyst.

PubMed

Richkind, Kathleen E; Mortimer, Errol; Mowery-Rushton, Patricia; Fraire, Armando

2002-09-01

We report the results of cytogenetic analysis of a case of unicameral bone cyst with a t(16;20(p11.2;q13) present as the sole abnormality. To our knowledge, this is only the second report of a cytogenetically characterized tumor of this type.

Nailfold capillaroscopy in 430 patients with rheumatoid arthritis.

PubMed

Rajaei, Alireza; Dehghan, Pooneh; Amiri, Ali

2017-01-01

Microvascular changes are one of the first obvious steps in numerous inflammatory diseases such as rheumatoid arthritis (RA). Nailfold video capillaroscopy (NFC) is an easy, reliable and safe method for evaluating peripheral microangiopathy. The objective of this study was to examine nailfold microcirculation in RA patients, assess morphological and structural changes quantitatively and qualitatively, and recognize useful changes. A total of 430 patients diagnosed with RA were examined in a period of 4 years. NFC was performed on all fingers of both hands in each patient. Different parameters indicating microvascular changes were detected and analyzed; such as microvascular architecture, capillary distribution disturbances, capillary morphology, capillary density, efferent/afferent limb ratio, subpapillary venular plexus and morphological abnormalities. The obtained results were categorized into normal pattern, nonspecific morphological abnormality and scleroderma pattern. The mean age of participants was 51.03±14.54 (19-87 years) that consisted of 359 females and 71 males. Based on the findings, angiogenesis (74.7%) was the most pathological condition observed after tortuosity (99.5%). 7.2% and 20.9% of patients were categorized into normal and scleroderma pattern group, respectively. Among morphological abnormalities, angiogenesis, isolated enlarged loop, irregular enlarged loop and architectural derangement were significantly more frequent in scleroderma than normal pattern (p<0.001). NFC may play an important role in monitoring RA disease and patients' follow-up. Therefore, in our opinion it could be considered in the course and follow-up of rheumatoid arthritis.

Nailfold capillaroscopy in 430 patients with rheumatoid arthritis

PubMed Central

Rajaei, Alireza; Dehghan, Pooneh; Amiri, Ali

2017-01-01

Background: Microvascular changes are one of the first obvious steps in numerous inflammatory diseases such as rheumatoid arthritis (RA). Nailfold video capillaroscopy (NFC) is an easy, reliable and safe method for evaluating peripheral microangiopathy. The objective of this study was to examine nailfold microcirculation in RA patients, assess morphological and structural changes quantitatively and qualitatively, and recognize useful changes. Methods: A total of 430 patients diagnosed with RA were examined in a period of 4 years. NFC was performed on all fingers of both hands in each patient. Different parameters indicating microvascular changes were detected and analyzed; such as microvascular architecture, capillary distribution disturbances, capillary morphology, capillary density, efferent/afferent limb ratio, subpapillary venular plexus and morphological abnormalities. The obtained results were categorized into normal pattern, nonspecific morphological abnormality and scleroderma pattern. Results: The mean age of participants was 51.03±14.54 (19-87 years) that consisted of 359 females and 71 males. Based on the findings, angiogenesis (74.7%) was the most pathological condition observed after tortuosity (99.5%). 7.2% and 20.9% of patients were categorized into normal and scleroderma pattern group, respectively. Among morphological abnormalities, angiogenesis, isolated enlarged loop, irregular enlarged loop and architectural derangement were significantly more frequent in scleroderma than normal pattern (p<0.001). Conclusion: NFC may play an important role in monitoring RA disease and patients’ follow-up. Therefore, in our opinion it could be considered in the course and follow-up of rheumatoid arthritis. PMID:29201317

Excess Secretion of Gel-Forming Mucins and Associated Innate Defense Proteins with Defective Mucin Un-Packaging Underpin Gallbladder Mucocele Formation in Dogs

PubMed Central

Kesimer, Mehmet; Cullen, John; Cao, Rui; Radicioni, Giorgia; Mathews, Kyle G.; Seiler, Gabriela; Gookin, Jody L.

2015-01-01

Mucosal protection of the gallbladder is vital yet we know very little about the mechanisms involved. In domestic dogs, an emergent syndrome referred to as gallbladder mucocele formation is characterized by excessive secretion of abnormal mucus that results in obstruction and rupture of the gallbladder. The cause of gallbladder mucocele formation is unknown. In these first mechanistic studies of this disease, we investigated normal and mucocele-forming dog gallbladders to determine the source, identity, biophysical properties, and protein associates of the culprit mucins with aim to identify causes for abnormal mucus behavior. We established that mucocele formation involves an adoptive excess secretion of gel forming mucins with abnormal properties by the gallbladder epithelium. The mucus is characterized by a disproportionally significant increase in Muc5ac relative to Muc5b, defective mucin un-packaging, and mucin-interacting innate defense proteins that are capable of dramatically altering the physical and functional properties of mucus. These findings provide an explanation for abnormal mucus behavior and based on similarity to mucus observed in the airways of people with cystic fibrosis, suggest that abnormal mechanisms for maintenance of gallbladder epithelial hydration may be an instigating factor for mucocele formation in dogs. PMID:26414376

Curing the Epilepsies: The Promise of Research

MedlinePlus

... Using microelectrodes, researchers are able to better characterize high-frequency oscillations (HFOs). Abnormal HFOs have been linked to ... Using microelectrodes, researchers are able to better characterize high-frequency oscillations. Top Develop New Animal Models for Studying ...

Impact of switching from Caucasian to Indian reference equations for spirometry interpretation.

PubMed

Chhabra, S K; Madan, M

2018-03-01

In the absence of ethnically appropriate prediction equations, spirometry data in Indian subjects are often interpreted using equations for other ethnic populations. To evaluate the impact of switching from Caucasian (National Health and Nutrition Examination Survey III [NHANES III] and Global Lung Function Initiative [GLI]) equations to the recently published North Indian equations on spirometric interpretation, and to examine the suitability of GLI-Mixed equations for this population. Spirometry data on 12 323 North Indian patients were analysed using the North Indian equations as well as NHANES III, GLI-Caucasian and GLI-Mixed equations. Abnormalities and ventilatory patterns were categorised and agreement in interpretation was evaluated. The NHANES III and GLI-Caucasian equations and, to a lesser extent, the GLI-Mixed equations, predicted higher values and labelled more measurements as abnormal. In up to one third of the patients, these differed from Indian equations in the categorisation of ventilatory patterns, with more patients classified as having restrictive and mixed disease. The NHANES III and GLI-Caucasian equations substantially overdiagnose abnormalities and misclassify ventilatory patterns on spirometry in Indian patients. Such errors of interpretation, although less common with the GLI-Mixed equations, remain substantial and are clinically unacceptable. A switch to Indian equations will have a major impact on interpretation.

Pericellular innervation of neurons expressing abnormally hyperphosphorylated tau in the hippocampal formation of Alzheimer's disease patients.

PubMed

Blazquez-Llorca, Lidia; Garcia-Marin, Virginia; Defelipe, Javier

2010-01-01

Neurofibrillary tangles (NFT) represent one of the main neuropathological features in the cerebral cortex associated with Alzheimer's disease (AD). This neurofibrillary lesion involves the accumulation of abnormally hyperphosphorylated or abnormally phosphorylated microtubule-associated protein tau into paired helical filaments (PHF-tau) within neurons. We have used immunocytochemical techniques and confocal microscopy reconstructions to examine the distribution of PHF-tau-immunoreactive (ir) cells, and their perisomatic GABAergic and glutamatergic innervations in the hippocampal formation and adjacent cortex of AD patients. Furthermore, correlative light and electron microscopy was employed to examine these neurons and the perisomatic synapses. We observed two patterns of staining in PHF-tau-ir neurons, pattern I (without NFT) and pattern II (with NFT), the distribution of which varies according to the cortical layer and area. Furthermore, the distribution of both GABAergic and glutamatergic terminals around the soma and proximal processes of PHF-tau-ir neurons does not seem to be altered as it is indistinguishable from both control cases and from adjacent neurons that did not contain PHF-tau. At the electron microscope level, a normal looking neuropil with typical symmetric and asymmetric synapses was observed around PHF-tau-ir neurons. These observations suggest that the synaptic connectivity around the perisomatic region of these PHF-tau-ir neurons was apparently unaltered.

An FMRI study of self-regulatory control and conflict resolution in adolescents with bulimia nervosa.

PubMed

Marsh, Rachel; Horga, Guillermo; Wang, Zhishun; Wang, Pengwei; Klahr, Kristin W; Berner, Laura A; Walsh, B Timothy; Peterson, Bradley S

2011-11-01

The authors examined functional activity in the frontostriatal systems that mediate self-regulatory capacities and conflict resolution in adolescents with bulimia nervosa. Functional magnetic resonance imaging was used to compare blood-oxygen-level-dependent response in 18 female adolescents with bulimia nervosa and 18 healthy female age-matched subjects during performance on a Simon spatial incompatibility task. Bayesian analyses were used to compare the two groups on patterns of brain activation during correct responses to conflict stimuli and to explore the effects of antecedent stimulus context on group differences in self-regulation and conflict resolution. Adolescents with and without bulimia nervosa performed similarly on the task. During correct responses in conflict trials, frontostriatal circuits-including the right inferolateral and dorsolateral prefrontal cortices and putamen-failed to activate to the same degree in adolescents with bulimia nervosa as in healthy comparison subjects. Instead, deactivation was seen in the left inferior frontal gyrus as well as a neural system encompassing the posterior cingulate cortex and superior frontal gyrus. Group differences in cortical and striatal regions were driven by the differential responses to stimuli preceded by conflict and nonconflict stimuli, respectively. When engaging the self-regulatory control processes necessary to resolve conflict, adolescents with bulimia nervosa displayed abnormal patterns of activation in frontostriatal and default-mode systems. Their abnormal processing of the antecedent stimulus context conditioned their brain response to conflict differently from that of healthy comparison subjects, specifically in frontal regions. It is suspected that functional disturbances in frontal portions of frontostriatal systems may release feeding behaviors from regulatory control, thereby perpetuating the conflicting desires to consume fattening foods and avoid weight gain that characterize bulimia nervosa.

How the knowledge of genetic "makeup" and cellular data can affect the analysis of repolarization in surface electrocardiogram.

PubMed

Shimizu, Wataru

2010-01-01

This review article sought to describe patterns of repolarization on the surface electrocardiogram in inherited cardiac arrhythmias and to discuss how the knowledge of genetic makeup and cellular data can affect the analysis based on the data derived from the experimental studies using arterially perfused canine ventricular wedge preparations. Molecular genetic studies have established a link between a number of inherited cardiac arrhythmia syndromes and mutations in genes encoding cardiac ion channels or membrane components during the past 2 decades. Twelve forms of congenital long QT syndrome have been so far identified, and genotype-phenotype correlations have been investigated especially in the 3 major genotypes-LQT1, LQT2, and LQT3. Abnormal T waves are reported in the LQT1, LQT2, and LQT3, and the differences in the time course of repolarization of the epicardial, midmyocardial, and endocardial cells give rise to voltage gradients responsible for the manifestation of phenotypic appearance of abnormal T waves. Brugada syndrome is characterized by ST-segment elevation in leads V1 to V3 and an episode of ventricular fibrillation, in which 7 genotypes have been reported. An intrinsically prominent transient outward current (I(to))-mediated action potential notch and a subsequent loss of action potential dome in the epicardium, but not in the endocardium of the right ventricular outflow tract, give rise to a transmural voltage gradient, resulting in ST-segment elevation, and a subsequent phase 2 reentry-induced ventricular fibrillation. In conclusion, transmural electrical heterogeneity of repolarization across the ventricular wall profoundly affects the phenotypic manifestation of repolarization patterns on the surface electrocardiogram in inherited cardiac arrhythmias. Copyright © 2010 Elsevier Inc. All rights reserved.

An fMRI Study of Self-Regulatory Control and Conflict Resolution in Adolescents With Bulimia Nervosa

PubMed Central

Marsh, Rachel; Horga, Guillermo; Wang, Zhishun; Wang, Pengwei; Klahr, Kristin W.; Berner, Laura A.; Walsh, B. Timothy; Peterson, Bradley S.

2012-01-01

Objective The authors examined functional activity in the frontostriatal systems that mediate self-regulatory capacities and conflict resolution in adolescents with bulimia nervosa. Method Functional magnetic resonance imaging was used to compare blood-oxygen-level-dependent response in 18 female adolescents with bulimia nervosa and 18 healthy female age-matched subjects during performance on a Simon spatial incompatibility task. Bayesian analyses were used to compare the two groups on patterns of brain activation during correct responses to conflict stimuli and to explore the effects of antecedent stimulus context on group differences in self-regulation and conflict resolution. Results Adolescents with and without bulimia nervosa performed similarly on the task. During correct responses in conflict trials, frontostriatal circuits—including the right inferolateral and dorsolateral prefrontal cortices and putamen—failed to activate to the same degree in adolescents with bulimia nervosa as in healthy comparison subjects. Instead, deactivation was seen in the left inferior frontal gyrus as well as a neural system encompassing the posterior cingulate cortex and superior frontal gyrus. Group differences in cortical and striatal regions were driven by the differential responses to stimuli preceded by conflict and nonconflict stimuli, respectively. Conclusions When engaging the self-regulatory control processes necessary to resolve conflict, adolescents with bulimia nervosa displayed abnormal patterns of activation in frontostriatal and default-mode systems. Their abnormal processing of the antecedent stimulus context conditioned their brain response to conflict differently from that of healthy comparison subjects, specifically in frontal regions. It is suspected that functional disturbances in frontal portions of frontostriatal systems may release feeding behaviors from regulatory control, thereby perpetuating the conflicting desires to consume fattening foods and avoid weight gain that characterize bulimia nervosa. PMID:21676991

Cognitive inflexibility in obsessive-compulsive disorder

PubMed Central

Gruner, Patricia; Pittenger, Christopher

2016-01-01

Obsessive-Compulsive Disorder (OCD) is characterized by maladaptive patterns of repetitive, inflexible cognition and behavior that suggest a lack of cognitive flexibility. Consistent with this clinical observation, many neurocognitive studies suggest behavioral and neurobiological abnormalities in cognitive flexibility in individuals with OCD. Meta-analytic reviews support a pattern of cognitive inflexibility, with effect sizes generally in the medium range. Heterogeneity in assessments and the way underlying constructs have been operationalized point to the need for better standardization across studies, as well as more refined overarching models of cognitive flexibility and executive function. Neuropsychological assessments of cognitive flexibility include measures of attentional set shifting, reversal and alternation, cued task switching paradigms, cognitive control measures such as the Trail-Making and Stroop tasks, and several measures of motor inhibition. Differences in the cognitive constructs and neural substrates associated with these measures suggest that performance within these different domains should be examined separately. Additional factors, such as the number of consistent trials prior to a shift and whether a shift is explicitly signaled or must be inferred from a change in reward contingencies, may influence performance, and thus mask or accentuate deficits. Several studies have described abnormalities in neural activation in the absence of differences in behavioral performance, suggesting that our behavioral probes may not be adequately sensitive, but also offering important insights into potential compensatory processes. The fact that deficits of moderate effect size are seen across a broad range of classic neuropsychological tests in OCD presents a conceptual challenge, as clinical symptomatology suggests greater specificity. Traditional cognitive probes may not be sufficient to delineate specific domains of deficit in this and other neuropsychiatric disorders; a new generation of behavioral tasks that test more specific underlying constructs, supplemented by neuroimaging to provide greater insight into the underlying processes, may be needed. PMID:27491478

A study with pharyngeal and esophageal 24-hour pH-impedance monitoring in patients with laryngopharyngeal symptoms refractory to proton pump inhibitors.

PubMed

Dulery, C; Lechot, A; Roman, S; Bastier, P-L; Stoll, D; de Gabory, L; Zerbib, F

2017-01-01

The role of gastroesophageal reflux in chronic laryngeal symptoms is difficult to establish. The aim of this study was to characterize pharyngeal and esophageal pH-impedance reflux patterns in a group of patients with suspected laryngopharyngeal reflux and to determine predictive factors of response to proton pump inhibitors. Patients with chronic pharyngolaryngeal symptoms were evaluated with a symptom score questionnaire, laryngoscopy, and 24-hour pharyngeal and esophageal pH-impedance monitoring at baseline and after 8-week treatment with esomeprazole 40 mg b.i.d. Response to treatment was defined by a diminution of more than 50% of the score for the primary symptom. Reflux patterns and baseline impedance values were compared to those obtained in 46 healthy subjects. Twenty-four patients were included (17 women, median age 54 years), all previously refractory to antisecretory therapy. Symptom scores were 46 (32-62) and 40 (27-76) off and on therapy, respectively (P=.1). There was no significant difference between patients and controls for pH-impedance reflux parameters and baseline values off and on therapy in distal and proximal esophagus and in the pharynx. Median numbers of pharyngeal reflux were 0 and 0 off and on therapy, respectively. Only two patients were responders to treatment, both with excessive distal reflux but no pharyngeal reflux. Only one patient had abnormal pharyngeal reflux but did not respond to proton pump inhibitors. Patients with suspected laryngopharyngeal reflux refractory to therapy do not exhibit abnormal pharyngeal or esophageal pH-impedance reflux. In these patients, laryngopharyngeal reflux is unlikely. © 2016 John Wiley & Sons Ltd.

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

NASA Astrophysics Data System (ADS)

Roman, Diana C.; Gardine, Matthew D.

2013-06-01

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

Age-related differences in autism: The case of white matter microstructure.

PubMed

Koolschijn, P Cédric M P; Caan, Matthan W A; Teeuw, Jalmar; Olabarriaga, Sílvia D; Geurts, Hilde M

2017-01-01

Autism spectrum disorder (ASD) is typified as a brain connectivity disorder in which white matter abnormalities are already present early on in life. However, it is unknown if and to which extent these abnormalities are hard-wired in (older) adults with ASD and how this interacts with age-related white matter changes as observed in typical aging. The aim of this first cross-sectional study in mid- and late-aged adults with ASD was to characterize white matter microstructure and its relationship with age. We utilized diffusion tensor imaging with head motion control in 48 adults with ASD and 48 age-matched controls (30-74 years), who also completed a Flanker task. Intra-individual variability of reaction times (IIVRT) measures based on performance on the Flanker interference task were used to assess IIVRT-white matter microstructure associations. We observed primarily higher mean and radial diffusivity in white matter microstructure in ASD, particularly in long-range fibers, which persisted after taking head motion into account. Importantly, group-by-age interactions revealed higher age-related mean and radial diffusivity in ASD, in projection and association fiber tracts. Subtle dissociations were observed in IIVRT-white matter microstructure relations between groups, with the IIVRT-white matter association pattern in ASD resembling observations in cognitive aging. The observed white matter microstructure differences are lending support to the structural underconnectivity hypothesis in ASD. These reductions seem to have behavioral percussions given the atypical relationship with IIVRT. Taken together, the current results may indicate different age-related patterns of white matter microstructure in adults with ASD. Hum Brain Mapp 38:82-96, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Cluster Analysis Identifies Distinct Pathogenetic Patterns in C3 Glomerulopathies/Immune Complex-Mediated Membranoproliferative GN.

PubMed

Iatropoulos, Paraskevas; Daina, Erica; Curreri, Manuela; Piras, Rossella; Valoti, Elisabetta; Mele, Caterina; Bresin, Elena; Gamba, Sara; Alberti, Marta; Breno, Matteo; Perna, Annalisa; Bettoni, Serena; Sabadini, Ettore; Murer, Luisa; Vivarelli, Marina; Noris, Marina; Remuzzi, Giuseppe

2018-01-01

Membranoproliferative GN (MPGN) was recently reclassified as alternative pathway complement-mediated C3 glomerulopathy (C3G) and immune complex-mediated membranoproliferative GN (IC-MPGN). However, genetic and acquired alternative pathway abnormalities are also observed in IC-MPGN. Here, we explored the presence of distinct disease entities characterized by specific pathophysiologic mechanisms. We performed unsupervised hierarchical clustering, a data-driven statistical approach, on histologic, genetic, and clinical data and data regarding serum/plasma complement parameters from 173 patients with C3G/IC-MPGN. This approach divided patients into four clusters, indicating the existence of four different pathogenetic patterns. Specifically, this analysis separated patients with fluid-phase complement activation (clusters 1-3) who had low serum C3 levels and a high prevalence of genetic and acquired alternative pathway abnormalities from patients with solid-phase complement activation (cluster 4) who had normal or mildly altered serum C3, late disease onset, and poor renal survival. In patients with fluid-phase complement activation, those in clusters 1 and 2 had massive activation of the alternative pathway, including activation of the terminal pathway, and the highest prevalence of subendothelial deposits, but those in cluster 2 had additional activation of the classic pathway and the highest prevalence of nephrotic syndrome at disease onset. Patients in cluster 3 had prevalent activation of C3 convertase and highly electron-dense intramembranous deposits. In addition, we provide a simple algorithm to assign patients with C3G/IC-MPGN to specific clusters. These distinct clusters may facilitate clarification of disease etiology, improve risk assessment for ESRD, and pave the way for personalized treatment. Copyright © 2018 by the American Society of Nephrology.

Noninvasive beat-to-beat finger arterial pressure monitoring during orthostasis: a comprehensive review of normal and abnormal responses at different ages.

PubMed

van Wijnen, V K; Finucane, C; Harms, M P M; Nolan, H; Freeman, R L; Westerhof, B E; Kenny, R A; Ter Maaten, J C; Wieling, W

2017-12-01

Over the past 30 years, noninvasive beat-to-beat blood pressure (BP) monitoring has provided great insight into cardiovascular autonomic regulation during standing. Although traditional sphygmomanometric measurement of BP may be sufficient for detection of sustained orthostatic hypotension, it fails to capture the complexity of the underlying dynamic BP and heart rate responses. With the emerging use of noninvasive beat-to-beat BP monitoring for the assessment of orthostatic BP control in clinical and population studies, various definitions for abnormal orthostatic BP patterns have been used. Here, age-related changes in cardiovascular control in healthy subjects will be reviewed to define the spectrum of the most important abnormal orthostatic BP patterns within the first 180 s of standing. Abnormal orthostatic BP responses can be defined as initial orthostatic hypotension (a transient systolic BP fall of >40 mmHg within 15 s of standing), delayed BP recovery (an inability of systolic BP to recover to a value of >20 mmHg below baseline at 30 s after standing) and sustained orthostatic hypotension (a sustained decline in systolic BP of ≥20 mmHg occurring 60-180 s after standing). In the evaluation of patients with light-headedness, pre(syncope), (unexplained) falls or suspected autonomic dysfunction, it is essential to distinguish between normal cardiovascular autonomic regulation and these abnormal orthostatic BP responses. The prevalence, clinical relevance and underlying pathophysiological mechanisms of these patterns differ significantly across the lifespan. Initial orthostatic hypotension is important for identifying causes of syncope in younger adults, whereas delayed BP recovery and sustained orthostatic hypotension are essential for evaluating the risk of falls in older adults. © 2017 The Authors Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

Characterizing autism spectrum disorders by key biochemical pathways.

PubMed

Subramanian, Megha; Timmerman, Christina K; Schwartz, Joshua L; Pham, Daniel L; Meffert, Mollie K

2015-01-01

The genetic and phenotypic heterogeneity of autism spectrum disorders (ASD) presents a substantial challenge for diagnosis, classification, research, and treatment. Investigations into the underlying molecular etiology of ASD have often yielded mixed and at times opposing findings. Defining the molecular and biochemical underpinnings of heterogeneity in ASD is crucial to our understanding of the pathophysiological development of the disorder, and has the potential to assist in diagnosis and the rational design of clinical trials. In this review, we propose that genetically diverse forms of ASD may be usefully parsed into entities resulting from converse patterns of growth regulation at the molecular level, which lead to the correlates of general synaptic and neural overgrowth or undergrowth. Abnormal brain growth during development is a characteristic feature that has been observed both in children with autism and in mouse models of autism. We review evidence from syndromic and non-syndromic ASD to suggest that entities currently classified as autism may fundamentally differ by underlying pro- or anti-growth abnormalities in key biochemical pathways, giving rise to either excessive or reduced synaptic connectivity in affected brain regions. We posit that this classification strategy has the potential not only to aid research efforts, but also to ultimately facilitate early diagnosis and direct appropriate therapeutic interventions.

Disturbance of the reproductive axis induced by negative energy balance.

PubMed

Judd, S J

1998-01-01

Animal reproduction is impaired when intake of energy is so restricted that activities essential to life are threatened; this is seen as a homeostatic adjustment that restricts wasteful energy expenditure. Fasting or exercising to a degree requiring considerable energy expenditure has major effects on the hypothalamus, including activation of corticotrophin-releasing factor (CRF) neurons, suppression of thyrotrophin-releasing hormone synthesis, and increased growth hormone secretion; these are associated with increased concentrations of hypothalamic neuropeptide Y mRNA and are corrected by administration of leptin, an adipose-tissue protein with a tertiary structure similar to the cytokine interleukin-2. This response to fasting results from a disordered pattern of activity in the gonadotrophin-releasing hormone (GnRH) pacemaker, characterized by reduced luteinizing hormone pulsatility, particularly during daytime. Animal studies have suggested that the response depends on an intact afferent vagal system from the stomach and the presence of oestrogen. Noradrenergic neurons forming the A2 group increase the activity of CRF neurons that, in turn, inhibit GnRH pulsatility. Reproductive impairment due to fasting is reversed by leptin, and abnormalities of leptin are described in individuals who fast or who develop exercise-induced amenorrhoea. This paper discusses these changes induced by negative energy balance and speculates on the involvement of leptin as a contributor to these abnormalities.

Role of the Sensorimotor Cortex in Tourette Syndrome using Multimodal Imaging

PubMed Central

Tinaz, Sule; Belluscio, Beth A.; Malone, Patrick; van der Veen, Jan Willem; Hallett, Mark; Horovitz, Silvina G.

2016-01-01

Tourette syndrome (TS) is a neuropsychiatric disorder characterized by motor and vocal tics. Most patients describe uncomfortable premonitory sensations preceding the tics and a subjective experience of increased sensitivity to tactile stimuli. These reports indicate that a sensory processing disturbance is an important component of TS together with motor phenomena. Thus, we focused our investigation on the role of the sensorimotor cortex (SMC) in TS using multimodal neuroimaging techniques. We measured the gamma-aminobutyric acid (GABA)+/Creatine (Cre) ratio in the SMC using GABA 1H magnetic resonance spectroscopy. We recorded the baseline beta activity in the SMC using magnetoencephalography and correlated GABA+/Cre ratio with baseline beta band power. Finally, we examined the resting state functional connectivity (FC) pattern of the SMC using functional magnetic resonance imaging (fMRI). GABA+/Cre ratio in the SMC did not differ between patients and controls. Correlation between the baseline beta band power and GABA+/Cre ratio was abnormal in patients. The anterior insula showed increased FC with the SMC in patients. These findings suggest that altered limbic input to the SMC and abnormal GABA-mediated beta oscillations in the SMC may underpin some of the sensorimotor processing disturbances in TS and contribute to tic generation. PMID:25044024

The Interplay between Emotion and Cognition in Autism Spectrum Disorder: Implications for Developmental Theory

PubMed Central

Gaigg, Sebastian B.

2012-01-01

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that is clinically defined by abnormalities in reciprocal social and communicative behaviors and an inflexible adherence to routinised patterns of thought and behavior. Laboratory studies repeatedly demonstrate that autistic individuals experience difficulties in recognizing and understanding the emotional expressions of others and naturalistic observations show that they use such expressions infrequently and inappropriately to regulate social exchanges. Dominant theories attribute this facet of the ASD phenotype to abnormalities in a social brain network that mediates social-motivational and social-cognitive processes such as face processing, mental state understanding, and empathy. Such theories imply that only emotion related processes relevant to social cognition are compromised in ASD but accumulating evidence suggests that the disorder may be characterized by more widespread anomalies in the domain of emotions. In this review I summarize the relevant literature and argue that the social-emotional characteristics of ASD may be better understood in terms of a disruption in the domain-general interplay between emotion and cognition. More specifically I will suggest that ASD is the developmental consequence of early emerging anomalies in how emotional responses to the environment modulate a wide range of cognitive processes including those that are relevant to navigating the social world. PMID:23316143

Abnormal Degree Centrality of Bilateral Putamen and Left Superior Frontal Gyrus in Schizophrenia with Auditory Hallucinations: A Resting-state Functional Magnetic Resonance Imaging Study

PubMed Central

Chen, Cheng; Wang, Hui-Ling; Wu, Shi-Hao; Huang, Huan; Zou, Ji-Lin; Chen, Jun; Jiang, Tian-Zi; Zhou, Yuan; Wang, Gao-Hua

2015-01-01

Background: Dysconnectivity hypothesis of schizophrenia has been increasingly emphasized. Recent researches showed that this dysconnectivity might be related to occurrence of auditory hallucination (AH). However, there is still no consistent conclusion. This study aimed to explore intrinsic dysconnectivity pattern of whole-brain functional networks at voxel level in schizophrenic with AH. Methods: Auditory hallucinated patients group (n = 42 APG), no hallucinated patients group (n = 42 NPG) and normal controls (n = 84 NCs) were analyzed by resting-state functional magnetic resonance imaging. The functional connectivity metrics index (degree centrality [DC]) across the entire brain networks was calculated and evaluated among three groups. Results: DC decreased in the bilateral putamen and increased in the left superior frontal gyrus in all the patients. However, in APG, the changes of DC were more obvious compared with NPG. Symptomology scores were negatively correlated with the DC of bilateral putamen in all patients. AH score of APG positively correlated with the DC in left superior frontal gyrus but negatively correlated with the DC in bilateral putamen. Conclusion: Our findings corroborated that schizophrenia was characterized by functional dysconnectivity, and the abnormal DC in bilateral putamen and left superior frontal gyrus might be crucial in the occurrence of AH. PMID:26612293

Long-term effects of marijuana use on the brain

PubMed Central

Filbey, Francesca M.; Aslan, Sina; Calhoun, Vince D.; Spence, Jeffrey S.; Damaraju, Eswar; Caprihan, Arvind; Segall, Judith

2014-01-01

Questions surrounding the effects of chronic marijuana use on brain structure continue to increase. To date, however, findings remain inconclusive. In this comprehensive study that aimed to characterize brain alterations associated with chronic marijuana use, we measured gray matter (GM) volume via structural MRI across the whole brain by using voxel-based morphology, synchrony among abnormal GM regions during resting state via functional connectivity MRI, and white matter integrity (i.e., structural connectivity) between the abnormal GM regions via diffusion tensor imaging in 48 marijuana users and 62 age- and sex-matched nonusing controls. The results showed that compared with controls, marijuana users had significantly less bilateral orbitofrontal gyri volume, higher functional connectivity in the orbitofrontal cortex (OFC) network, and higher structural connectivity in tracts that innervate the OFC (forceps minor) as measured by fractional anisotropy (FA). Increased OFC functional connectivity in marijuana users was associated with earlier age of onset. Lastly, a quadratic trend was observed suggesting that the FA of the forceps minor tract initially increased following regular marijuana use but decreased with protracted regular use. This pattern may indicate differential effects of initial and chronic marijuana use that may reflect complex neuroadaptive processes in response to marijuana use. Despite the observed age of onset effects, longitudinal studies are needed to determine causality of these effects. PMID:25385625

Characterizing autism spectrum disorders by key biochemical pathways

PubMed Central

Subramanian, Megha; Timmerman, Christina K.; Schwartz, Joshua L.; Pham, Daniel L.; Meffert, Mollie K.

2015-01-01

The genetic and phenotypic heterogeneity of autism spectrum disorders (ASD) presents a substantial challenge for diagnosis, classification, research, and treatment. Investigations into the underlying molecular etiology of ASD have often yielded mixed and at times opposing findings. Defining the molecular and biochemical underpinnings of heterogeneity in ASD is crucial to our understanding of the pathophysiological development of the disorder, and has the potential to assist in diagnosis and the rational design of clinical trials. In this review, we propose that genetically diverse forms of ASD may be usefully parsed into entities resulting from converse patterns of growth regulation at the molecular level, which lead to the correlates of general synaptic and neural overgrowth or undergrowth. Abnormal brain growth during development is a characteristic feature that has been observed both in children with autism and in mouse models of autism. We review evidence from syndromic and non-syndromic ASD to suggest that entities currently classified as autism may fundamentally differ by underlying pro- or anti-growth abnormalities in key biochemical pathways, giving rise to either excessive or reduced synaptic connectivity in affected brain regions. We posit that this classification strategy has the potential not only to aid research efforts, but also to ultimately facilitate early diagnosis and direct appropriate therapeutic interventions. PMID:26483618

The Interplay between Emotion and Cognition in Autism Spectrum Disorder: Implications for Developmental Theory.

PubMed

Gaigg, Sebastian B

2012-01-01

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that is clinically defined by abnormalities in reciprocal social and communicative behaviors and an inflexible adherence to routinised patterns of thought and behavior. Laboratory studies repeatedly demonstrate that autistic individuals experience difficulties in recognizing and understanding the emotional expressions of others and naturalistic observations show that they use such expressions infrequently and inappropriately to regulate social exchanges. Dominant theories attribute this facet of the ASD phenotype to abnormalities in a social brain network that mediates social-motivational and social-cognitive processes such as face processing, mental state understanding, and empathy. Such theories imply that only emotion related processes relevant to social cognition are compromised in ASD but accumulating evidence suggests that the disorder may be characterized by more widespread anomalies in the domain of emotions. In this review I summarize the relevant literature and argue that the social-emotional characteristics of ASD may be better understood in terms of a disruption in the domain-general interplay between emotion and cognition. More specifically I will suggest that ASD is the developmental consequence of early emerging anomalies in how emotional responses to the environment modulate a wide range of cognitive processes including those that are relevant to navigating the social world.

Exploring polycythaemia vera with fluorescence in situ hybridization: additional cryptic 9p is the most frequent abnormality detected.

PubMed

Najfeld, Vesna; Montella, Lya; Scalise, Angela; Fruchtman, Steven

2002-11-01

Between 1986 and 2001, 220 patients with polycythaemia vera (PV) were studied using conventional cytogenetics. Of 204 evaluable patients, 52 (25.4%) had clonal abnormalities. The recurrent chromosomal rearrangements were those of chromosome 9 (21.1%), del(20q) (19.2%), trisomy 8 (19.2%), rearrangements of 13q (13.4%), abnormalities of 1q (11.5%), and of chromosomes 5 and 7 (9.6%). Subsequent analysis of 32 patients, performed at follow-up of up to 14.8 years, revealed new clonal abnormalities in five patients and the disappearance of an abnormal clone in four. Eleven patients remained normal up to 11.5 years and seven patients maintained an abnormality for over 10 years. Fifty-three patients were studied retrospectively using interphase fluorescence in situ hybridization (I-FISH), utilizing probes for centromere enumeration of chromosomes 8 and 9, and for 13q14 and 20q12 loci. Conventional cytogenetics demonstrated clonal chromosome abnormalities in 23% of these 53 patients. The addition of I-FISH increased the detection of abnormalities to 29% and permitted clarification of chromosome 9 rearrangements in an additional 5.6% of patients. FISH uncovered rearrangements of chromosome 9 in 53% of patients with an abnormal FISH pattern, which represented the most frequent genomic alteration in this series.

Molecular characterization of a patient with an interstitial 1q deletion [del(1)(q24.1q25.3)] and distinctive skeletal abnormalities.

PubMed

Descartes, Maria; Hain, Julie Zenger; Conklin, Michael; Franklin, Judy; Mikhail, Fady M; Lachman, Ralph S; Nolet, Serge; Messiaen, Ludwine M

2008-11-15

Here we report on a patient with an interstitial deletion on the long(q) arm of chromosome 1 who presents with a unique constellation of anomalies including brachydactyly type E, Müllerian agenesis, growth hormone deficiency, as well as other abnormalities. We present the clinical details of this patient's presentation, the skeletal findings, and provide characterization of the deletion at the molecular level. We postulate that these skeletal anomalies are distinctive to 1q deletions involving the 1q24q25 region. (c) 2008 Wiley-Liss, Inc.

Metabolic Abnormalities Are Common among South American Hispanics Subjects with Normal Weight or Excess Body Weight: The CRONICAS Cohort Study

PubMed Central

Benziger, Catherine P.; Bernabé-Ortiz, Antonio; Gilman, Robert H.; Checkley, William; Smeeth, Liam; Málaga, Germán; Miranda, J. Jaime

2015-01-01

Objective We aimed to characterize metabolic status by body mass index (BMI) status. Methods The CRONICAS longitudinal study was performed in an age-and-sex stratified random sample of participants aged 35 years or older in four Peruvian settings: Lima (Peru’s capital, costal urban, highly urbanized), urban and rural Puno (both high-altitude), and Tumbes (costal semirural). Data from the baseline study, conducted in 2010, was used. Individuals were classified by BMI as normal weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2), and obese (≥30 kg/m2), and as metabolically healthy (0–1 metabolic abnormality) or metabolically unhealthy (≥2 abnormalities). Abnormalities included individual components of the metabolic syndrome, high-sensitivity C-reactive protein, and insulin resistance. Results A total of 3088 (age 55.6±12.6 years, 51.3% females) had all measurements. Of these, 890 (28.8%), 1361 (44.1%) and 837 (27.1%) were normal weight, overweight and obese, respectively. Overall, 19.0% of normal weight in contrast to 54.9% of overweight and 77.7% of obese individuals had ≥3 risk factors (p<0.001). Among normal weight individuals, 43.1% were metabolically unhealthy, and age ≥65 years, female, and highest socioeconomic groups were more likely to have this pattern. In contrast, only 16.4% of overweight and 3.9% of obese individuals were metabolically healthy and, compared to Lima, the rural and urban sites in Puno were more likely to have a metabolically healthier profile. Conclusions Most Peruvians with overweight and obesity have additional risk factors for cardiovascular disease, as well as a majority of those with a healthy weight. Prevention programs aimed at individuals with a normal BMI, and those who are overweight and obese, are urgently needed, such as screening for elevated fasting cholesterol and glucose. PMID:26599322

Metabolic Abnormalities Are Common among South American Hispanics Subjects with Normal Weight or Excess Body Weight: The CRONICAS Cohort Study.

PubMed

Benziger, Catherine P; Bernabé-Ortiz, Antonio; Gilman, Robert H; Checkley, William; Smeeth, Liam; Málaga, Germán; Miranda, J Jaime

2015-01-01

We aimed to characterize metabolic status by body mass index (BMI) status. The CRONICAS longitudinal study was performed in an age-and-sex stratified random sample of participants aged 35 years or older in four Peruvian settings: Lima (Peru's capital, costal urban, highly urbanized), urban and rural Puno (both high-altitude), and Tumbes (costal semirural). Data from the baseline study, conducted in 2010, was used. Individuals were classified by BMI as normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), and obese (≥30 kg/m2), and as metabolically healthy (0-1 metabolic abnormality) or metabolically unhealthy (≥2 abnormalities). Abnormalities included individual components of the metabolic syndrome, high-sensitivity C-reactive protein, and insulin resistance. A total of 3088 (age 55.6±12.6 years, 51.3% females) had all measurements. Of these, 890 (28.8%), 1361 (44.1%) and 837 (27.1%) were normal weight, overweight and obese, respectively. Overall, 19.0% of normal weight in contrast to 54.9% of overweight and 77.7% of obese individuals had ≥3 risk factors (p<0.001). Among normal weight individuals, 43.1% were metabolically unhealthy, and age ≥65 years, female, and highest socioeconomic groups were more likely to have this pattern. In contrast, only 16.4% of overweight and 3.9% of obese individuals were metabolically healthy and, compared to Lima, the rural and urban sites in Puno were more likely to have a metabolically healthier profile. Most Peruvians with overweight and obesity have additional risk factors for cardiovascular disease, as well as a majority of those with a healthy weight. Prevention programs aimed at individuals with a normal BMI, and those who are overweight and obese, are urgently needed, such as screening for elevated fasting cholesterol and glucose.

Habituation and sensitization in primary headaches

PubMed Central

2013-01-01

The phenomena of habituation and sensitization are considered most useful for studying the neuronal substrates of information processing in the CNS. Both were studied in primary headaches, that are functional disorders of the brain characterized by an abnormal responsivity to any kind of incoming innocuous or painful stimuli and it’s cycling pattern over time (interictal, pre-ictal, ictal). The present review summarizes available data on stimulus responsivity in primary headaches obtained with clinical neurophysiology. In migraine, the majority of electrophysiological studies between attacks have shown that, for a number of different sensory modalities, the brain is characterised by a lack of habituation of evoked responses to repeated stimuli. This abnormal processing of the incoming information reaches its maximum a few days before the beginning of an attack, and normalizes during the attack, at a time when sensitization may also manifest itself. An abnormal rhythmic activity between thalamus and cortex, namely thalamocortical dysrhythmia, may be the pathophysiological mechanism subtending abnormal information processing in migraine. In tension-type headache (TTH), only few signs of deficient habituation were observed only in subgroups of patients. By contrast, using grand-average responses indirect evidence for sensitization has been found in chronic TTH with increased nociceptive specific reflexes and evoked potentials. Generalized increased sensitivity to pain (lower thresholds and increased pain rating) and a dysfunction in supraspinal descending pain control systems may contribute to the development and/or maintenance of central sensitization in chronic TTH. Cluster headache patients are chrarcterized during the bout and on the headache side by a pronounced lack of habituation of the brainstem blink reflex and a general sensitization of pain processing. A better insight into the nature of these ictal/interictal electrophysiological dysfunctions in primary headaches paves the way for novel therapeutic targets and may allow a better understanding of the mode of action of available therapies. PMID:23899115

Hypereosinophilia with abnormal T cells, trisomy 7 and elevated TARC serum level.

PubMed

Roumier, A S; Grardel, N; Laï, J L; Becqueriaux, I; Ghomari, K; de Lavareille, A; Roufosse, F; Prin, L; Capron, M

2003-07-01

The idiopathic hypereosinophilic syndrome (HES) is a rare heterogeneous disorder, characterized by persistent blood eosinophilia with possible organ involvement. We describe here the case of a 20-year-old atopic male presenting chronic hypereosinophilia and eczema since childhood. Biological findings included hypereosinophilia (9.5 x 10(9)/L), hyperlymphocytosis (10.9 x 10(9)/L), polyclonal hypergammaglobulinemia and elevated IgE serum level. Flow cytometric analysis of blood lymphoid cells showed a population of CD2+CD3-CD4+TCRab-TCRgd- lymphocytes. These cells displayed a Th0/Th2 cytokine profile, and a clonal TCR rearrangement pattern. A high serum TARC level was observed. Karyotype studies on blood stimulated culture or lymph nodes revealed a cellular hyperdiploïd clone 47, XY, +7. To our knowledge, this chromosomal aberration has never been reported in such case.

Violent somnambulism: a parasomnia of young men with stereotyped dream-like experiences.

PubMed

Szűcs, Anna; Kamondi, Anita; Zoller, Rezső; Barcs, Gábor; Szabó, Pál; Purebl, György

2014-07-01

To characterize a subgroup of arousal parasomnias associated with violent behavior in adults. A pilot study on clinical and polysomnographic data of 13 adult patients seen in a tertiary sleep center for the suspicion of arousal parasomnia associated with violence. Nine young patients (8 males 1 female) had a common pattern of abnormalities: similar 'claustrophobic' dream-like experiences and complex, vehement dream enactments; no REM sleep without atonia on polysomnography. We call this syndrome 'violent somnambulism'. The rest of the patients had alcoholic delirium, partial epilepsy, possible REM sleep behavior disorder and a single sleep walking episode provoked by a sleeping pill. Sleep related violence needs thorough diagnostic evaluation for preventing life-threatening consequences. Violent somnambulism appears to be a distinct NREM sleep-related overlap parasomnia. Copyright © 2014 Elsevier Ltd. All rights reserved.

Hypochondriasis and somatization in college women: a personal projects analysis.

PubMed

Karoly, P; Lecci, L

1993-03-01

Although the descriptive features of hypochondriasis and somatization have been widely studied, the motivational correlates (goal representations) of individuals manifesting abnormal illness patterns have not been considered. The Personal Projects Analysis method (Little, 1983) was used to contrast the health and nonhealth goals of female undergraduates. Subjects selected 10 goals for evaluation along a series of dimensions. When health pursuits alone were examined, hypochondriasis on the Minnesota Multiphasic Personality Inventory was found to correlate directly with goal appraisal dimensions subsumed by an anxiety-absorption factor and inversely with dimensions characterizing rewardingness, thus suggesting a negativity of health goal construal. Somatizers also pursued more health-related projects than did nonsomatizers; nonhealth goal cognition did not relate as strongly to hypochondriasis. Finally, using discriminant function analysis, goal representations were shown to significantly and substantially differentiate somatizers from nonsomatizers.

Correlations Between Anthropometry and Lipid Profile in Women With PCOS.

PubMed

Kiranmayee, Donthu; Kavya, Kothapalli; Himabindu, Yalamanchali; Sriharibabu, Manne; Madhuri, Gadi Leela Jaya; Venu, Swargam

2017-01-01

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in reproductive age women and is associated with both reproductive and metabolic abnormalities. Recent studies have demonstrated an early onset of abnormal cardiovascular risk profile in women with PCOS. Abnormal lipid profile patterns are common in women with PCOS, and these abnormalities are not uniform in all populations. Anthropometry is a simple and commonly used research tool for assessing metabolic risk in women with PCOS. Therefore, this study examined the correlations between anthropometric parameters and lipid profile in women with PCOS. The objectives of the study were (1) To study the anthropometric profile of women with PCOS, (2) To examine the lipid profile pattern of these women with PCOS and (3) To see whether there exists any correlation between these anthropometric parameters and lipid profile. This observational cross-sectional study examined anthropometry and lipid profile in 86 married women with PCOS in the age group of 18-35 years and correlated them by using Pearson's correlation coefficient. More than 80% of the women with PCOS demonstrated abnormal anthropometric parameters, and in more than 70% women, lipid abnormalities such as low levels of high-density lipoprotein (HDL) cholesterol and high levels of triglycerides and low-density lipoprotein cholesterol were observed. Significant positive correlations were seen between body mass index (BMI) and triglycerides ( P ≤ 0.001) and waist circumference (WC) and triglycerides ( P ≤ 0.029). Negative correlations were observed between BMI and HDL cholesterol ( P ≤ 0.013). This study revealed that BMI and WC are the most important anthropometric parameters correlated to dyslipidemia in the south Indian women with PCOS.

Multidimensional analysis of the abnormal neural oscillations associated with lexical processing in schizophrenia.

PubMed

Xu, Tingting; Stephane, Massoud; Parhi, Keshab K

2013-04-01

The neural mechanisms of language abnormalities, the core symptoms in schizophrenia, remain unclear. In this study, a new experimental paradigm, combining magnetoencephalography (MEG) techniques and machine intelligence methodologies, was designed to gain knowledge about the frequency, brain location, and time of occurrence of the neural oscillations that are associated with lexical processing in schizophrenia. The 248-channel MEG recordings were obtained from 12 patients with schizophrenia and 10 healthy controls, during a lexical processing task, where the patients discriminated correct from incorrect lexical stimuli that were visually presented. Event-related desynchronization/synchronization (ERD/ERS) was computed along the frequency, time, and space dimensions combined, that resulted in a large spectral-spatial-temporal ERD/ERS feature set. Machine intelligence techniques were then applied to select a small subset of oscillation patterns that are abnormal in patients with schizophrenia, according to their discriminating power in patient and control classification. Patients with schizophrenia showed abnormal ERD/ERS patterns during both lexical encoding and post-encoding periods. The top-ranked features were located at the occipital and left frontal-temporal areas, and covered a wide frequency range, including δ (1-4 Hz), α (8-12 Hz), β (12-32 Hz), and γ (32-48 Hz) bands. These top features could discriminate the patient group from the control group with 90.91% high accuracy, which demonstrates significant brain oscillation abnormalities in patients with schizophrenia at the specific frequency, time, and brain location indicated by these top features. As neural oscillation abnormality may be due to the mechanisms of the disease, the spectral, spatial, and temporal content of the discriminating features can offer useful information for helping understand the physiological basis of the language disorder in schizophrenia, as well as the pathology of the disease itself.

Glaucomatous patterns in Frequency Doubling Technology (FDT) perimetry data identified by unsupervised machine learning classifiers.

PubMed

Bowd, Christopher; Weinreb, Robert N; Balasubramanian, Madhusudhanan; Lee, Intae; Jang, Giljin; Yousefi, Siamak; Zangwill, Linda M; Medeiros, Felipe A; Girkin, Christopher A; Liebmann, Jeffrey M; Goldbaum, Michael H

2014-01-01

The variational Bayesian independent component analysis-mixture model (VIM), an unsupervised machine-learning classifier, was used to automatically separate Matrix Frequency Doubling Technology (FDT) perimetry data into clusters of healthy and glaucomatous eyes, and to identify axes representing statistically independent patterns of defect in the glaucoma clusters. FDT measurements were obtained from 1,190 eyes with normal FDT results and 786 eyes with abnormal FDT results from the UCSD-based Diagnostic Innovations in Glaucoma Study (DIGS) and African Descent and Glaucoma Evaluation Study (ADAGES). For all eyes, VIM input was 52 threshold test points from the 24-2 test pattern, plus age. FDT mean deviation was -1.00 dB (S.D. = 2.80 dB) and -5.57 dB (S.D. = 5.09 dB) in FDT-normal eyes and FDT-abnormal eyes, respectively (p<0.001). VIM identified meaningful clusters of FDT data and positioned a set of statistically independent axes through the mean of each cluster. The optimal VIM model separated the FDT fields into 3 clusters. Cluster N contained primarily normal fields (1109/1190, specificity 93.1%) and clusters G1 and G2 combined, contained primarily abnormal fields (651/786, sensitivity 82.8%). For clusters G1 and G2 the optimal number of axes were 2 and 5, respectively. Patterns automatically generated along axes within the glaucoma clusters were similar to those known to be indicative of glaucoma. Fields located farther from the normal mean on each glaucoma axis showed increasing field defect severity. VIM successfully separated FDT fields from healthy and glaucoma eyes without a priori information about class membership, and identified familiar glaucomatous patterns of loss.

Investigation of the utility of colorectal function tests and Rome II criteria in dyssynergic defecation (Anismus).

PubMed

Rao, S S C; Mudipalli, R S; Stessman, M; Zimmerman, B

2004-10-01

Although 30-50% of constipated patients exhibit dyssynergia, an optimal method of diagnosis is unclear. Recently, consensus criteria have been proposed but their utility is unknown. To examine the diagnostic yield of colorectal tests, reproducibility of manometry and utility of Rome II criteria. A total of 100 patients with difficult defecation were prospectively evaluated with anorectal manometry, balloon expulsion, colonic transit and defecography. Fifty-three patients had repeat manometry. During attempted defecation, 30 showed normal and 70 one of three abnormal manometric patterns. Forty-six patients fulfilled Rome criteria and showed paradoxical anal contraction (type I) or impaired anal relaxation (type III) with adequate propulsion. However, 24 (34%) showed impaired propulsion (type II). Forty-five (64%) had slow transit, 42 (60%) impaired balloon expulsion and 26 (37%) abnormal defecography. Defecography provided no additional discriminant utility. Evidence of dyssynergia was reproducible in 51 of 53 patients. Symptoms alone could not differentiate dyssynergic subtypes or patients. Dyssynergic patients exhibited three patterns that were reproducible: paradoxical contraction, impaired propulsion and impaired relaxation. Although useful, Rome II criteria may be insufficient to identify or subclassify dyssynergic defecation. Symptoms together with abnormal manometry, abnormal balloon expulsion or colonic marker retention are necessary to optimally identify patients with difficult defecation.

Folding, But Not Surface Area Expansion, Is Associated with Cellular Morphological Maturation in the Fetal Cerebral Cortex

PubMed Central

Studholme, Colin; Frias, Antonio E.

2017-01-01

Altered macroscopic anatomical characteristics of the cerebral cortex have been identified in individuals affected by various neurodevelopmental disorders. However, the cellular developmental mechanisms that give rise to these abnormalities are not understood. Previously, advances in image reconstruction of diffusion magnetic resonance imaging (MRI) have made possible high-resolution in utero measurements of water diffusion anisotropy in the fetal brain. Here, diffusion anisotropy within the developing fetal cerebral cortex is longitudinally characterized in the rhesus macaque, focusing on gestation day (G85) through G135 of the 165 d term. Additionally, for subsets of animals characterized at G90 and G135, immunohistochemical staining was performed, and 3D structure tensor analyses were used to identify the cellular processes that most closely parallel changes in water diffusion anisotropy with cerebral cortical maturation. Strong correlations were found between maturation of dendritic arbors on the cellular level and the loss of diffusion anisotropy with cortical development. In turn, diffusion anisotropy changes were strongly associated both regionally and temporally with cortical folding. Notably, the regional and temporal dependence of diffusion anisotropy and folding were distinct from the patterns observed for cerebral cortical surface area expansion. These findings strengthen the link proposed in previous studies between cellular-level changes in dendrite morphology and noninvasive diffusion MRI measurements of the developing cerebral cortex and support the possibility that, in gyroencephalic species, structural differentiation within the cortex is coupled to the formation of gyri and sulci. SIGNIFICANCE STATEMENT Abnormal brain morphology has been found in populations with neurodevelopmental disorders. However, the mechanisms linking cellular level and macroscopic maturation are poorly understood, even in normal brains. This study contributes new understanding to this subject using serial in utero MRI measurements of rhesus macaque fetuses, from which macroscopic and cellular information can be derived. We found that morphological differentiation of dendrites was strongly associated both regionally and temporally with folding of the cerebral cortex. Interestingly, parallel associations were not observed with cortical surface area expansion. These findings support the possibility that perturbed morphological differentiation of cells within the cortex may underlie abnormal macroscopic characteristics of individuals affected by neurodevelopmental disorders. PMID:28069920

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

Treatment implications of high-resolution manometry findings: options for patients with esophageal dysmotility.

PubMed

Bolkhir, Ahmed; Gyawali, C Prakash

2014-03-01

High-resolution manometry (HRM) has significantly impacted diagnosis and management of achalasia in particular, and has improved characterization of other motor disorders. Achalasia, the most profound esophageal motor disorder, is characterized by esophageal outflow obstruction from abnormal relaxation of the lower esophageal sphincter (LES) during swallowing, and presents with transit symptoms (dysphagia, regurgitation). Esophageal body motor disorders include both inhibitory nerve dysfunction associated with hypermotility or spasm, and hypomotility disorders with poor contraction. The implications of hypermotility disorders are both perceptive and obstructive. On the other hand, hypomotility disorders have reflux implications because of abnormal barrier function at the LES, and abnormal bolus clearance. Esophageal outflow obstruction in achalasia responds favorably to disruption of the LES, and outcome may be predicted by HRM subtyping of achalasia. Identification of dominant (perceptive vs. obstructive) mechanisms of symptom generation help direct therapy of hypermotility disorders, while hypomotility disorders typically require management of concurrent reflux disease.

Dermoscopy of Pigmented Actinic Keratosis of the Face: A Study of 232 Cases.

PubMed

Kelati, A; Baybay, H; Moscarella, E; Argenziano, G; Gallouj, S; Mernissi, F Z

2017-11-01

The diagnosis of pigmented actinic keratosis (PAK) is often challenging because of overlapping features with lentigo maligna. To investigate dermoscopic patterns of PAK according to their different evolutionary stages, and to correlate the pattern with clinical characteristics of the patients. Descriptive and analytical study of 232 PAK. Dermoscopic patterns were divided into two categories: the follicule surroundings' abnormalities (FSA) and follicular keratosis' abnormalities (FKA). FSA and FKA dermoscopic patterns were related to male gender, except for star-like appearance, double white clods and dermoscopic horn (p≤0.04). Rhomboidal, annular granular pattern, gray halo, white circle and double clods were dermoscopic pattern significantly related to xeroderma pigmentosum's type of skin. Based on the evolutionary stages of PAK, the jelly sign was significantly related to thin patches of PAK. Central crusts and scales were related to thick plaques and the star-like appearance to hypertrophic PAK. The presence of 2 or more dermoscopic signs in both FSA and FKA was noticed in 99.1% of lesions. The dermoscopic diagnosis of PAK vary according to the evolutionary stages of the disease, this will increase the diagnosis accuracy, with therapeutic implications. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Changes in shoulder muscle activity pattern on surface electromyography after breast cancer surgery.

PubMed

Yang, Eun Joo; Kwon, YoungOk

2018-02-01

Alterations in muscle activation and restricted shoulder mobility, which are common in breast cancer patients, have been found to affect upper limb function. The purpose of this study was to determine muscle activity patterns, and to compare the prevalence of abnormal patterns among the type of breast surgery. In total, 274 breast cancer patients were recruited after surgery. Type of breast surgery was divided into mastectomy without reconstruction (Mastectomy), reconstruction with tissue expander/implant (TEI), latissimus dorsi (LD) flap, or transverse rectus abdominis flap (TRAM). Activities of shoulder muscles were measured using surface electromyography. Experimental analysis was conducted using a Gaussian filter smoothing method with regression. Patients demonstrated different patterns of muscle activation, such as normal, lower muscle electrical activity, and tightness. After adjusting for BMI and breast surgery, the odds of lower muscle electrical activity and tightness in the TRAM are 40.2% and 38.4% less than in the Mastectomy only group. The prevalence of abnormal patterns was significantly greater in the ALND than SLNB in all except TRAM. Alterations in muscle activity patterns differed by breast surgery and reconstruction type. For breast cancer patients with ALND, TRAM may be the best choice for maintaining upper limb function. © 2017 Wiley Periodicals, Inc.

Altered amygdala-prefrontal response to facial emotion in offspring of parents with bipolar disorder.

PubMed

Manelis, Anna; Ladouceur, Cecile D; Graur, Simona; Monk, Kelly; Bonar, Lisa K; Hickey, Mary Beth; Dwojak, Amanda C; Axelson, David; Goldstein, Benjamin I; Goldstein, Tina R; Bebko, Genna; Bertocci, Michele A; Hafeman, Danella M; Gill, Mary Kay; Birmaher, Boris; Phillips, Mary L

2015-09-01

This study aimed to identify neuroimaging measures associated with risk for, or protection against, bipolar disorder by comparing youth offspring of parents with bipolar disorder versus youth offspring of non-bipolar parents versus offspring of healthy parents in (i) the magnitude of activation within emotional face processing circuitry; and (ii) functional connectivity between this circuitry and frontal emotion regulation regions. The study was conducted at the University of Pittsburgh Medical Centre. Participants included 29 offspring of parents with bipolar disorder (mean age = 13.8 years; 14 females), 29 offspring of non-bipolar parents (mean age = 13.8 years; 12 females) and 23 healthy controls (mean age = 13.7 years; 11 females). Participants were scanned during implicit processing of emerging happy, sad, fearful and angry faces and shapes. The activation analyses revealed greater right amygdala activation to emotional faces versus shapes in offspring of parents with bipolar disorder and offspring of non-bipolar parents than healthy controls. Given that abnormally increased amygdala activation during emotion processing characterized offspring of both patient groups, and that abnormally increased amygdala activation has often been reported in individuals with already developed bipolar disorder and those with major depressive disorder, these neuroimaging findings may represent markers of increased risk for affective disorders in general. The analysis of psychophysiological interaction revealed that offspring of parents with bipolar disorder showed significantly more negative right amygdala-anterior cingulate cortex functional connectivity to emotional faces versus shapes, but significantly more positive right amygdala-left ventrolateral prefrontal cortex functional connectivity to happy faces (all P-values corrected for multiple tests) than offspring of non-bipolar parents and healthy controls. Taken together with findings of increased amygdala-ventrolateral prefrontal cortex functional connectivity, and decreased amygdala-anterior cingulate cortex functional connectivity previously shown in individuals with bipolar disorder, these connectivity patterns in offspring of parents with bipolar disorder may be risk markers for, rather than markers conferring protection against, bipolar disorder in youth. The patterns of activation and functional connectivity remained unchanged after removing medicated participants and those with current psychopathology from analyses. This is the first study to demonstrate that abnormal functional connectivity patterns within face emotion processing circuitry distinguish offspring of parents with bipolar disorder from those of non-bipolar parents and healthy controls. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Gene expression profiling in the early phases of DMD: a constant molecular signature characterizes DMD muscle from early postnatal life throughout disease progression.

PubMed

Pescatori, Mario; Broccolini, Aldobrando; Minetti, Carlo; Bertini, Enrico; Bruno, Claudio; D'amico, Adele; Bernardini, Camilla; Mirabella, Massimiliano; Silvestri, Gabriella; Giglio, Vincenzo; Modoni, Anna; Pedemonte, Marina; Tasca, Giorgio; Galluzzi, Giuliana; Mercuri, Eugenio; Tonali, Pietro A; Ricci, Enzo

2007-04-01

Genome-wide gene expression profiling of skeletal muscle from Duchenne muscular dystrophy (DMD) patients has been used to describe muscle tissue alterations in DMD children older than 5 years. By studying the expression profile of 19 patients younger than 2 years, we describe with high resolution the gene expression signature that characterizes DMD muscle during the initial or "presymptomatic" phase of the disease. We show that in the first 2 years of the disease, DMD muscle is already set to express a distinctive gene expression pattern considerably different from the one expressed by normal, age-matched muscle. This "dystrophic" molecular signature is characterized by a coordinate induction of genes involved in the inflammatory response, extracellular matrix (ECM) remodeling and muscle regeneration, and the reduced transcription of those involved in energy metabolism. Despite the lower degree of muscle dysfunction experienced, our younger patients showed abnormal expression of most of the genes reported as differentially expressed in more advanced stages of the disease. By analyzing our patients as a time series, we provide evidence that some genes, including members of three pathways involved in morphogenetic signaling-Wnt, Notch, and BMP-are progressively induced or repressed in the natural history of DMD.

ACR appropriateness criteria(®) on abnormal vaginal bleeding.

PubMed

Bennett, Genevieve L; Andreotti, Rochelle F; Lee, Susanna I; Dejesus Allison, Sandra O; Brown, Douglas L; Dubinsky, Theodore; Glanc, Phyllis; Mitchell, Donald G; Podrasky, Ann E; Shipp, Thomas D; Siegel, Cary Lynn; Wong-You-Cheong, Jade J; Zelop, Carolyn M

2011-07-01

In evaluating a woman with abnormal vaginal bleeding, imaging cannot replace definitive histologic diagnosis but often plays an important role in screening, characterization of structural abnormalities, and directing appropriate patient care. Transvaginal ultrasound (TVUS) is generally the initial imaging modality of choice, with endometrial thickness a well-established predictor of endometrial disease in postmenopausal women. Endometrial thickness measurements of ≤5 mm and ≤4 mm have been advocated as appropriate upper threshold values to reasonably exclude endometrial carcinoma in postmenopausal women with vaginal bleeding; however, the best upper threshold endometrial thickness in the asymptomatic postmenopausal patient remains a subject of debate. Endometrial thickness in a premenopausal patient is a less reliable indicator of endometrial pathology since this may vary widely depending on the phase of menstrual cycle, and an upper threshold value for normal has not been well-established. Transabdominal ultrasound is generally an adjunct to TVUS and is most helpful when TVUS is not feasible or there is poor visualization of the endometrium. Hysterosonography may also allow for better delineation of both the endometrium and focal abnormalities in the endometrial cavity, leading to hysteroscopically directed biopsy or resection. Color and pulsed Doppler may provide additional characterization of a focal endometrial abnormality by demonstrating vascularity. MRI may also serve as an important problem-solving tool if the endometrium cannot be visualized on TVUS and hysterosonography is not possible, as well as for pretreatment planning of patients with suspected endometrial carcinoma. CT is generally not warranted for the evaluation of patients with abnormal bleeding, and an abnormal endometrium incidentally detected on CT should be further evaluated with TVUS. Copyright © 2011 American College of Radiology. Published by Elsevier Inc. All rights reserved.

White matter correlates of sensory processing in autism spectrum disorders

PubMed Central

Pryweller, Jennifer R.; Schauder, Kimberly B.; Anderson, Adam W.; Heacock, Jessica L.; Foss-Feig, Jennifer H.; Newsom, Cassandra R.; Loring, Whitney A.; Cascio, Carissa J.

2014-01-01

Autism spectrum disorder (ASD) has been characterized by atypical socio-communicative behavior, sensorimotor impairment and abnormal neurodevelopmental trajectories. DTI has been used to determine the presence and nature of abnormality in white matter integrity that may contribute to the behavioral phenomena that characterize ASD. Although atypical patterns of sensory responding in ASD are well documented in the behavioral literature, much less is known about the neural networks associated with aberrant sensory processing. To address the roles of basic sensory, sensory association and early attentional processes in sensory responsiveness in ASD, our investigation focused on five white matter fiber tracts known to be involved in these various stages of sensory processing: superior corona radiata, centrum semiovale, inferior longitudinal fasciculus, posterior limb of the internal capsule, and splenium. We acquired high angular resolution diffusion images from 32 children with ASD and 26 typically developing children between the ages of 5 and 8. We also administered sensory assessments to examine brain-behavior relationships between white matter integrity and sensory variables. Our findings suggest a modulatory role of the inferior longitudinal fasciculus and splenium in atypical sensorimotor and early attention processes in ASD. Increased tactile defensiveness was found to be related to reduced fractional anisotropy in the inferior longitudinal fasciculus, which may reflect an aberrant connection between limbic structures in the temporal lobe and the inferior parietal cortex. Our findings also corroborate the modulatory role of the splenium in attentional orienting, but suggest the possibility of a more diffuse or separable network for social orienting in ASD. Future investigation should consider the use of whole brain analyses for a more robust assessment of white matter microstructure. PMID:25379451

Novel GALNT3 mutations causing hyperostosis-hyperphosphatemia syndrome result in low intact fibroblast growth factor 23 concentrations.

PubMed

Ichikawa, Shoji; Guigonis, Vincent; Imel, Erik A; Courouble, Mélanie; Heissat, Sophie; Henley, John D; Sorenson, Andrea H; Petit, Barbara; Lienhardt, Anne; Econs, Michael J

2007-05-01

Hyperostosis-hyperphosphatemia syndrome (HHS) is a rare metabolic disorder characterized by hyperphosphatemia and localized hyperostosis. HHS is caused by mutations in GALNT3, which encodes UDP-N-acetyl-alpha-D-galactosamine:polypeptide N- acetylgalactosaminyltransferase 3. Familial tumoral calcinosis (TC), characterized by ectopic calcifications and hyperphosphatemia, is caused by mutations in the GALNT3 or fibroblast growth factor 23 (FGF23) genes. Our objective was to identify mutations in FGF23 or GALNT3 and determine serum FGF23 levels in an HHS patient. Mutation detection in FGF23 and GALNT3 was performed by DNA sequencing, and serum FGF23 concentrations were measured by ELISA. A 5-year-old French boy with HHS and his family members participated. The patient presented with painful cortical lesions in his leg. Radiographs of the affected bone showed diaphyseal hyperostosis. The lesional tissue comprised trabeculae of immature, woven bone surrounded by fibrous tissue. Biochemistry revealed elevated phosphate, tubular maximum rate for phosphate reabsorption per deciliter of glomerular filtrate, and 1,25-dihydroxyvitamin D levels. The patient was a compound heterozygote for two novel GALNT3 mutations. His parents and brother were heterozygous for one of the mutations and had no biochemical abnormalities. Intact FGF23 level in the patient was low normal, whereas C-terminal FGF23 was elevated, a pattern similar to TC. The presence of GALNT3 mutations and elevated C-terminal, but low intact serum FGF23, levels in HHS resemble those seen in TC, suggesting that HHS and TC are different manifestations of the same disorder. The absence of biochemical abnormalities in the heterozygous individuals suggests that one normal allele is sufficient for secretion of intact FGF23.

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

PubMed

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

2018-02-01

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

Windows to the soul: vision science as a tool for studying biological mechanisms of information processing deficits in schizophrenia.

PubMed

Yoon, Jong H; Sheremata, Summer L; Rokem, Ariel; Silver, Michael A

2013-10-31

Cognitive and information processing deficits are core features and important sources of disability in schizophrenia. Our understanding of the neural substrates of these deficits remains incomplete, in large part because the complexity of impairments in schizophrenia makes the identification of specific deficits very challenging. Vision science presents unique opportunities in this regard: many years of basic research have led to detailed characterization of relationships between structure and function in the early visual system and have produced sophisticated methods to quantify visual perception and characterize its neural substrates. We present a selective review of research that illustrates the opportunities for discovery provided by visual studies in schizophrenia. We highlight work that has been particularly effective in applying vision science methods to identify specific neural abnormalities underlying information processing deficits in schizophrenia. In addition, we describe studies that have utilized psychophysical experimental designs that mitigate generalized deficit confounds, thereby revealing specific visual impairments in schizophrenia. These studies contribute to accumulating evidence that early visual cortex is a useful experimental system for the study of local cortical circuit abnormalities in schizophrenia. The high degree of similarity across neocortical areas of neuronal subtypes and their patterns of connectivity suggests that insights obtained from the study of early visual cortex may be applicable to other brain regions. We conclude with a discussion of future studies that combine vision science and neuroimaging methods. These studies have the potential to address pressing questions in schizophrenia, including the dissociation of local circuit deficits vs. impairments in feedback modulation by cognitive processes such as spatial attention and working memory, and the relative contributions of glutamatergic and GABAergic deficits.

Body composition in males with adolescent idiopathic scoliosis: a case-control study with dual-energy X-ray absorptiometry.

PubMed

Wang, Weijun; Wang, Zhiwei; Zhu, Zezhang; Zhu, Feng; Qiu, Yong

2016-02-29

In contrast to the well-characterized body growth and development of females with adolescent idiopathic scoliosis (AIS), the pubertal growth pattern of male patients has not been well-documented. Recently, significantly lower body weight (BW) and body mass index (BMI) were reported in males with AIS, and were thought to be related to curve progression. A case-control study was carried out to characterize the body composition and bone status of males with AIS, with the aim of gaining a better understanding of lower BW among these patients. Forty-seven males with AIS and forty age- and gender-matched healthy controls were recruited. Standing height (SH) and BW were measured. The SH of the males who had AIS was corrected using Bjure's equation, and then the BMI was calculated. Body composition, including subcranial fat mass (FM), lean mass (LM), and bone mineral content (BMC), and bone mineral density (BMD) were analyzed using dual-energy X-ray absorptiometry. The LM index (LMi) and the FM index (FMi) were calculated by dividing the FM and LM by the square of the SH. Logistic regression analysis was employed for comparison between AIS and controls. The AIS patients had comparable age and Tanner staging for pubic hair as the controls. After adjustment for age, the AIS patients showed comparable SH but significantly lower BW and BMI than that of the controls. The LM, LMi, BMC and BMD were also significantly lower in the AIS patients than in the controls. However, the difference in BMC between two groups was not significant by adjusting for age, FM and LM. The male AIS patients showed abnormal body composition, presenting as significantly lower LM than the controls. The lower BMC observed in the patients might due to the abnormal body composition.

KNS4/UPEX1: A Type II Arabinogalactan β-(1,3)-Galactosyltransferase Required for Pollen Exine Development1[OPEN

PubMed Central

Suzuki, Toshiya; Narciso, Joan Oñate; Zeng, Wei; van de Meene, Allison; Yasutomi, Masayuki; Takemura, Shunsuke

2017-01-01

Pollen exine is essential for protection from the environment of the male gametes of seed-producing plants, but its assembly and composition remain poorly understood. We previously characterized Arabidopsis (Arabidopsis thaliana) mutants with abnormal pollen exine structure and morphology that we named kaonashi (kns). Here we describe the identification of the causal gene of kns4 that was found to be a member of the CAZy glycosyltransferase 31 gene family, identical to UNEVEN PATTERN OF EXINE1, and the biochemical characterization of the encoded protein. The characteristic exine phenotype in the kns4 mutant is related to an abnormality of the primexine matrix laid on the surface of developing microspores. Using light microscopy with a combination of type II arabinogalactan (AG) antibodies and staining with the arabinogalactan-protein (AGP)-specific β-Glc Yariv reagent, we show that the levels of AGPs in the kns4 microspore primexine are considerably diminished, and their location differs from that of wild type, as does the distribution of pectin labeling. Furthermore, kns4 mutants exhibit reduced fertility as indicated by shorter fruit lengths and lower seed set compared to the wild type, confirming that KNS4 is critical for pollen viability and development. KNS4 was heterologously expressed in Nicotiana benthamiana, and was shown to possess β-(1,3)-galactosyltransferase activity responsible for the synthesis of AG glycans that are present on both AGPs and/or the pectic polysaccharide rhamnogalacturonan I. These data demonstrate that defects in AGP/pectic glycans, caused by disruption of KNS4 function, impact pollen development and viability in Arabidopsis. PMID:27837085

Do You Hear Voices? Problems in Assessment of Mental Status in Deaf Persons with Severe Language Deprivation

ERIC Educational Resources Information Center

Glickman, Neil

2007-01-01

When mental health clinicians perform mental status examinations, they examine the language patterns of patients because abnormal language patterns, sometimes referred to as language dysfluency, may indicate a thought disorder. Performing such examinations with deaf patients is a far more complex task, especially with traditionally underserved…

Touch Processing and Social Behavior in ASD

ERIC Educational Resources Information Center

Miguel, Helga O.; Sampaio, Adriana; Martínez-Regueiro, Rocío; Gómez-Guerrero, Lorena; López-Dóriga, Cristina Gutiérrez; Gómez, Sonia; Carracedo, Ángel; Fernández-Prieto, Montse

2017-01-01

Abnormal patterns of touch processing have been linked to core symptoms in ASD. This study examined the relation between tactile processing patterns and social problems in 44 children and adolescents with ASD, aged 6-14 (M = 8.39 ± 2.35). Multiple linear regression indicated significant associations between touch processing and social problems. No…

Disrupted functional connectivity patterns of the insula subregions in drug-free major depressive disorder.

PubMed

Wang, Chao; Wu, Huawang; Chen, Fangfang; Xu, Jinping; Li, Hongming; Li, Hong; Wang, Jiaojian

2018-07-01

Major depressive disorder (MDD) is characterized by impairments in emotional and cognitive functions. Emerging studies have shown that cognition and emotion interact by reaching identical brain regions, and the insula is one such region with functional and structural heterogeneity. Although previous literatures have shown the role of insula in MDD，it remains unclear whether the insular subregions show differential change patterns in MDD. Using the resting-state fMRI data in a group of 23 drug-free MDD patients and 34 healthy controls (HCs), we investigated whether the abnormal connectivity patterns of insular sub-regions or any behavioural correlates can be detected in MDD. Further hierarchical cluster analysis was used to identify the functional connectivity-clustering patterns of insular sub-regions. Compared with HCs, the MDD exhibited higher connectivities between dorsal agranular insula and inferior parietal lobule and between ventral dysgranular and granular insula and thalamus/habehula, and lower connectivity of hypergranular insula to subgenual anterior cingulate cortex. Moreover, the three subregions with significant group differences were in three separate functional systems along anterior-to-posteior gradient. The anterior and middle insula showed positive correlation with depressive severity, while the posterior insular was to the contrary. The small and unbalanced sample size, only included moderate and severe depression and the possible inter-individual differences may limit the interpretability. These findings provided evidences for the MDD-related effects in functional connectivity patterns of insular subregions, and revealed that the subregions might be involved in different neural circuits associated with the contrary impacts on the depressive symptoms. Copyright © 2017 Elsevier B.V. All rights reserved.

Detection of Abnormal Events via Optical Flow Feature Analysis

PubMed Central

Wang, Tian; Snoussi, Hichem

2015-01-01

In this paper, a novel algorithm is proposed to detect abnormal events in video streams. The algorithm is based on the histogram of the optical flow orientation descriptor and the classification method. The details of the histogram of the optical flow orientation descriptor are illustrated for describing movement information of the global video frame or foreground frame. By combining one-class support vector machine and kernel principal component analysis methods, the abnormal events in the current frame can be detected after a learning period characterizing normal behaviors. The difference abnormal detection results are analyzed and explained. The proposed detection method is tested on benchmark datasets, then the experimental results show the effectiveness of the algorithm. PMID:25811227

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.

Abnormal Grain Growth Suppression in Aluminum Alloys

NASA Technical Reports Server (NTRS)

Hales, Stephen J. (Inventor); Claytor, Harold Dale (Inventor); Alexa, Joel A. (Inventor)

2015-01-01

The present invention provides a process for suppressing abnormal grain growth in friction stir welded aluminum alloys by inserting an intermediate annealing treatment ("IAT") after the welding step on the article. The IAT may be followed by a solution heat treatment (SHT) on the article under effectively high solution heat treatment conditions. In at least some embodiments, a deformation step is conducted on the article under effective spin-forming deformation conditions or under effective superplastic deformation conditions. The invention further provides a welded article having suppressed abnormal grain growth, prepared by the process above. Preferably the article is characterized with greater than about 90% reduction in area fraction abnormal grain growth in any friction-stir-welded nugget.

Patterns of pulmonary maturation in normal and abnormal pregnancy.

PubMed

Goldkrand, J W; Slattery, D S

1979-03-01

Fetal pulmonary maturation may be a variable event depending on various feto-maternal environmental and biochemical influences. The patterns of maturation were studied in 211 amniotic fluid samples from 123 patients (normal 55; diabetes 23; Rh sensitization 19; preeclampsia 26). The phenomenon of globule formation from the amniotic fluid lipid extract and is relation to pulmonary maturity was utilized for this analysis. Validation of this technique is presented. A normal curve was constructed from 22 to 42 weeks; gestation and compared to the abnormal pregnancies. Patients with class A, B, and C diabetes and Rh-sensitized pregnancies had delayed pulmonary maturation. Patients with class D diabetes and preclampsia paralleled the normal course of maturation. A discussion of these results and their possible cause is presented.

Evaluation of Esophageal Motor Function With High-resolution Manometry

PubMed Central

2013-01-01

For several decades esophageal manometry has been the test of choice to evaluate disorders of esophageal motor function. The recent introduction of high-resolution manometry for the study of esophageal motor function simplified performance of esophageal manometry, and revealed previously unidentified patterns of normal and abnormal esophageal motor function. Presentation of pressure data as color contour plots or esophageal pressure topography led to the development of new tools for analyzing and classifying esophageal motor patterns. The current standard and still developing approach to do this is the Chicago classification. While this methodical approach is improving our diagnosis of esophageal motor disorders, it currently does not address all motor abnormalities. We will explore the Chicago classification and disorders that it does not address. PMID:23875094

Supernumerary nipples in association with Hailey-Hailey disease in a Tunisian family.

PubMed

Benmously-Mlika, R; Deghais, S; Bchetnia, M; Charfeddine, C; Mokni, M; Kassar, S; Haouet, S; Boubaker, S; Mokhtar, I; Abdelhak, S; Dhahri, A Ben Osman

2008-06-15

Supernumerary nipples (SNs) or polythelia are developmental abnormalities of breast tissue. They are located along the embryonic mammary lines. Polythelia usually occurs as a sporadic abnormality, although familial aggregation has been occasionally reported. Hailey-Hailey disease is a rare autosomal genodermatosis characterized by disturbed keratinocyte adhesion. These cutaneous disorders have been described in correlation with many other abnormalities. We report here the association of Hailey-Hailey disease and supernumerary nipples in a Northern Tunisian family. To our knowledge, this is the first report of such a clinical association.

Neuromuscular properties of different spastic human joints vary systematically.

PubMed

Mirbagheri, M M; Settle, K

2010-01-01

We quantified the mechanical abnormalities of the spastic wrist in chronic stroke survivors, and determined whether these findings were representative of those recorded at the elbow and ankle joints. System identification techniques were used to characterize the mechanical abnormalities of these joints and to identify the contribution of intrinsic and reflex stiffness to these abnormalities. Modulation of intrinsic and reflex stiffness with the joint angle was studied by applying PRBS perturbations to the joints at different joint angles over the range of motion. Age-matched healthy subjects were used as control.

Hemorheological abnormalities in human arterial hypertension

NASA Astrophysics Data System (ADS)

Lo Presti, Rosalia; Hopps, Eugenia; Caimi, Gregorio

2014-05-01

Blood rheology is impaired in hypertensive patients. The alteration involves blood and plasma viscosity, and the erythrocyte behaviour is often abnormal. The hemorheological pattern appears to be related to some pathophysiological mechanisms of hypertension and to organ damage, in particular left ventricular hypertrophy and myocardial ischemia. Abnormalities have been observed in erythrocyte membrane fluidity, explored by fluorescence spectroscopy and electron spin resonance. This may be relevant for red cell flow in microvessels and oxygen delivery to tissues. Although blood viscosity is not a direct target of antihypertensive therapy, the rheological properties of blood play a role in the pathophysiology of arterial hypertension and its vascular complications.

PASSion: a pattern growth algorithm-based pipeline for splice junction detection in paired-end RNA-Seq data.

PubMed

Zhang, Yanju; Lameijer, Eric-Wubbo; 't Hoen, Peter A C; Ning, Zemin; Slagboom, P Eline; Ye, Kai

2012-02-15

RNA-seq is a powerful technology for the study of transcriptome profiles that uses deep-sequencing technologies. Moreover, it may be used for cellular phenotyping and help establishing the etiology of diseases characterized by abnormal splicing patterns. In RNA-Seq, the exact nature of splicing events is buried in the reads that span exon-exon boundaries. The accurate and efficient mapping of these reads to the reference genome is a major challenge. We developed PASSion, a pattern growth algorithm-based pipeline for splice site detection in paired-end RNA-Seq reads. Comparing the performance of PASSion to three existing RNA-Seq analysis pipelines, TopHat, MapSplice and HMMSplicer, revealed that PASSion is competitive with these packages. Moreover, the performance of PASSion is not affected by read length and coverage. It performs better than the other three approaches when detecting junctions in highly abundant transcripts. PASSion has the ability to detect junctions that do not have known splicing motifs, which cannot be found by the other tools. Of the two public RNA-Seq datasets, PASSion predicted ≈ 137,000 and 173,000 splicing events, of which on average 82 are known junctions annotated in the Ensembl transcript database and 18% are novel. In addition, our package can discover differential and shared splicing patterns among multiple samples. The code and utilities can be freely downloaded from https://trac.nbic.nl/passion and ftp://ftp.sanger.ac.uk/pub/zn1/passion.

Very-Long-Chain Fatty Acids Are Involved in Polar Auxin Transport and Developmental Patterning in Arabidopsis[W

PubMed Central

Roudier, François; Gissot, Lionel; Beaudoin, Frédéric; Haslam, Richard; Michaelson, Louise; Marion, Jessica; Molino, Diana; Lima, Amparo; Bach, Liên; Morin, Halima; Tellier, Frédérique; Palauqui, Jean-Christophe; Bellec, Yannick; Renne, Charlotte; Miquel, Martine; DaCosta, Marco; Vignard, Julien; Rochat, Christine; Markham, Jonathan E.; Moreau, Patrick; Napier, Johnathan; Faure, Jean-Denis

2010-01-01

Very-long-chain fatty acids (VLCFAs) are essential for many aspects of plant development and necessary for the synthesis of seed storage triacylglycerols, epicuticular waxes, and sphingolipids. Identification of the acetyl-CoA carboxylase PASTICCINO3 and the 3-hydroxy acyl-CoA dehydratase PASTICCINO2 revealed that VLCFAs are important for cell proliferation and tissue patterning. Here, we show that the immunophilin PASTICCINO1 (PAS1) is also required for VLCFA synthesis. Impairment of PAS1 function results in reduction of VLCFA levels that particularly affects the composition of sphingolipids, known to be important for cell polarity in animals. Moreover, PAS1 associates with several enzymes of the VLCFA elongase complex in the endoplasmic reticulum. The pas1 mutants are deficient in lateral root formation and are characterized by an abnormal patterning of the embryo apex, which leads to defective cotyledon organogenesis. Our data indicate that in both tissues, defective organogenesis is associated with the mistargeting of the auxin efflux carrier PIN FORMED1 in specific cells, resulting in local alteration of polar auxin distribution. Furthermore, we show that exogenous VLCFAs rescue lateral root organogenesis and polar auxin distribution, indicating their direct involvement in these processes. Based on these data, we propose that PAS1 acts as a molecular scaffold for the fatty acid elongase complex in the endoplasmic reticulum and that the resulting VLCFAs are required for polar auxin transport and tissue patterning during plant development. PMID:20145257

Chronic respiratory disfunction due to diffuse alveolar hemorrhage in patients with systemic lupus erythematosus and primary vasculitis.

PubMed

Pérez Aceves, Eva; Pérez Cristóbal, Mario; Espinola Reyna, Gerardo A; Ariza Andraca, Raul; Xibille Fridmann, Daniel; Barile Fabris, Leonor A

2013-01-01

Pulmonary hemorrhage (PH) occurs in 2-5% of SLE patients, and is associated with a high mortality rate (79-90%). Diagnostic criteria for this complication include: 1) Pulmonary infiltrates, with at least ¾ of lung tissue involved in a chest x ray, 2) Acute respiratory failure, 3) A decrease of 3g/dL or more in hemoglobin levels. PH might lead to organized pneumonia, collagen deposition, and pulmonary fibrosis which in time might cause changes in pulmonary function tests with either restrictive or obstructive patterns. To evaluate the existence of abnormalities in pulmonary function tests after a PH episode. We included patients with SLE and primary vasculitis that developed PH. During the acute episode, we measured SLEDAI in SLE patients, five factor score in microscopic polyangiitis (MPA) and Birmingham Vasculitis Activity Store (BVAS) in granulomatosis with polyangiitis (GPA) (Wegener). We determined the number of PH events, treatment, and ventilator assistance requirements and correlated its association with abnormal pulmonary function tests. We included 10 patients, 7 with SLE, 2 with MPA and 1 with GPA (Wegener). The mean activity measures were: SLEDAI 20.4 ± 7.5, FFS 2, and BVAS 36. Treatment consisted in methylprednisolone (MPD) in 3 patients, MPD plus cyclophosphamide (CY) in 6 patients, and MPD, CY, IV immunoglobulin, and plasmapheresis in one patient. Five patients required ventilatory support. We found abnormalities in pulmonary function tests in 8 patients, three had an obstructive pattern and five a restrictive pattern; 2 patients did not show any change. We did not find a significant association with any of the studied variables. PH might cause abnormalities in pulmonary function tests and prolonged immunosuppressive treatment could be required. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Levothyroxine treatment generates an abnormal uterine contractility patterns in an in vitro animal model.

PubMed

Corriveau, Stéphanie; Blouin, Simon; Raiche, Évelyne; Nolin, Marc-Antoine; Rousseau, Éric; Pasquier, Jean-Charles

2015-12-01

Abnormal uterine contraction patterns were recently demonstrated in uterine strips from pregnant women treated with Levothyroxine (T4). These abnormalities were correlated with an increased risk of C-section delivery and associated surgical complications. To date, no study has investigated whether uterine contractility is modified by hypothyroidism or T4 treatment. Herein, we analyze the physiological role of T4 on uterine contractions. Female non-pregnant Sprague-Dawley rats ( N  = 22) were used and divided into four groups: 1) control, 2) hypothyroidism, 3) hypothyroidism treated with low T4 doses (20 μg/kg/day) and 4) with high T4 doses (100 μg/kg/day). Hypothyroidism was induced by an iodine-deficient diet. Isometric tension measurements were performed in vitro on myometrium tissues in isolated organ baths. Contractile activity parameters were quantified (amplitude, duration, frequency and area under the curve) using pharmacological tools to assess their effect. Screening of thyroid function confirmed a hypothyroid state for all rats under iodine-free diet to which T4 was subsequently administered to counterbalance hypothyroidism. Results demonstrate that hypothyroidism significantly decreased contractile duration (-17%) and increased contractile frequency (+26%), while high doses of T4 increased duration (+200%) and decreased frequency (-51%). These results thus mimic the pattern of abnormal contractions previously observed in uterine tissue from T4-treated hypothyroid pregnant women. Our data suggest that changes in myometrial reactivity are induced by T4 treatment. Thus, in conjunction with our previous observations on human myometrial strips, management of hypothyroidism should be improved to reduce the rate of C-sections in this group of patients.

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.

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.

The role of transvaginal power Doppler ultrasound in the differential diagnosis of benign intrauterine focal lesions.

PubMed

Cogendez, Ebru; Eken, Meryem Kurek; Bakal, Nuray; Gun, Ismet; Kaygusuz, Ecmel Isik; Karateke, Ates

2015-10-01

The purpose of this prospective study was to assess the role of power Doppler imaging in the differential diagnosis of benign intrauterine focal lesions such as endometrial polyps and submucous myomas using the characteristics of power Doppler flow mapping. A total of 480 premenopausal patients with abnormal uterine bleeding were evaluated by transvaginal ultrasonography (TVS) searching for intrauterine pathology. Sixty-four patients with a suspicious focal endometrial lesion received saline infusion sonography (SIS) after TVS. Fifty-eight patients with focal endometrial lesions underwent power Doppler ultrasound (PDUS). Three different vascular flow patterns were defined: Single vessel pattern, multiple vessel pattern, and circular flow pattern. Finally, hysteroscopic resection was performed in all cases, and Doppler flow characteristics were then compared with the final histopathological findings. Histopathological results were as follows: endometrial polyp: 40 (69 %), submucous myoma: 18 (31 %). Of the cases with endometrial polyps, 80 % demonstrated a single vessel pattern, 7.5 % a multiple vessel pattern, and 0 % a circular pattern. Vascularization was not observed in 12.5 % of patients with polyps. Of the cases with submucousal myomas, 72.2 % demonstrated a circular flow pattern, 27.8 % a multiple vessel pattern, and none of them showed a single vessel pattern. The sensitivity, specificity, and positive and negative predictive values of the single vessel pattern in diagnosing endometrial polyps were 80, 100, 100, and 69.2 %, respectively; and for the circular pattern in diagnosing submucous myoma, these were 72.2, 100, 100, and 88.9 %, respectively. Power Doppler blood flow mapping is a useful, practical, and noninvasive diagnostic method for the differential diagnosis of benign intrauterine focal lesions. Especially in cases of recurrent abnormal uterine bleeding, recurrent abortion, and infertility, PDUS can be preferred as a first-line diagnostic method.

Psychologic management of brace therapy for patients with idiopathic scoliosis.

PubMed

Matsunaga, Shunji; Hayashi, Kyoji; Naruo, Tetsuro; Nozoe, Shin-ichi; Komiya, Setsuro

2005-03-01

A trial of brace therapy modified by a measured personality pattern of patients with idiopathic scoliosis was performed. To evaluate the effectiveness of performing personality tests for patients with idiopathic scoliosis who undergo brace therapy. Brace therapy has often been used for the treatment of scoliosis. However, emotional distress can result from this therapy. Few attempts have been made to reduce such stress. A test using the Maudsley Personality Inventory was performed on 145 adolescent females with idiopathic scoliosis, treated with brace therapy alone, before the start of brace therapy and 1 month after the start of brace therapy. On the basis of test results, the patients were rated as normal type and four abnormal types. Brace therapy was continued considering the personality pattern of patients. For all patients, changes in psychologic test results, compliance with braces wearing instructions, and correction of scoliosis were analyzed. Of the 134 patients rated as normal before the start of therapy, 108 patients were rated as abnormal pattern when tested 1 month after the start of therapy. After performing autogenic training for patients with E-N+ and E-N- personalities, and giving advice to school teachers to decrease the emotional stress for patients with E+N+ personality, 47 patients were finally rated as abnormal pattern. In total, 12 (8%) of the 145 patients dropped out. In dropouts, the average pretreatment deformity of 29 degrees (range: 21 degrees -37 degrees ) had increased to an average of 37 degrees (range, 31 degrees -48 degrees ). Psychologic tests may be useful and provide a means of modifying brace therapy tailored to the psychologic conditions of individual patients.

Rare copy number variations in congenital heart disease patients identify unique genes in left-right patterning

PubMed Central

Fakhro, Khalid A.; Choi, Murim; Ware, Stephanie M.; Belmont, John W.; Towbin, Jeffrey A.; Lifton, Richard P.; Khokha, Mustafa K.; Brueckner, Martina

2011-01-01

Dominant human genetic diseases that impair reproductive fitness and have high locus heterogeneity constitute a problem for gene discovery because the usual criterion of finding more mutations in specific genes than expected by chance may require extremely large populations. Heterotaxy (Htx), a congenital heart disease resulting from abnormalities in left-right (LR) body patterning, has features suggesting that many cases fall into this category. In this setting, appropriate model systems may provide a means to support implication of specific genes. By high-resolution genotyping of 262 Htx subjects and 991 controls, we identify a twofold excess of subjects with rare genic copy number variations in Htx (14.5% vs. 7.4%, P = 1.5 × 10−4). Although 7 of 45 Htx copy number variations were large chromosomal abnormalities, 38 smaller copy number variations altered a total of 61 genes, 22 of which had Xenopus orthologs. In situ hybridization identified 7 of these 22 genes with expression in the ciliated LR organizer (gastrocoel roof plate), a marked enrichment compared with 40 of 845 previously studied genes (sevenfold enrichment, P < 10−6). Morpholino knockdown in Xenopus of Htx candidates demonstrated that five (NEK2, ROCK2, TGFBR2, GALNT11, and NUP188) strongly disrupted both morphological LR development and expression of pitx2, a molecular marker of LR patterning. These effects were specific, because 0 of 13 control genes from rare Htx or control copy number variations produced significant LR abnormalities (P = 0.001). These findings identify genes not previously implicated in LR patterning. PMID:21282601

Rare copy number variations in congenital heart disease patients identify unique genes in left-right patterning.

PubMed

Fakhro, Khalid A; Choi, Murim; Ware, Stephanie M; Belmont, John W; Towbin, Jeffrey A; Lifton, Richard P; Khokha, Mustafa K; Brueckner, Martina

2011-02-15

Dominant human genetic diseases that impair reproductive fitness and have high locus heterogeneity constitute a problem for gene discovery because the usual criterion of finding more mutations in specific genes than expected by chance may require extremely large populations. Heterotaxy (Htx), a congenital heart disease resulting from abnormalities in left-right (LR) body patterning, has features suggesting that many cases fall into this category. In this setting, appropriate model systems may provide a means to support implication of specific genes. By high-resolution genotyping of 262 Htx subjects and 991 controls, we identify a twofold excess of subjects with rare genic copy number variations in Htx (14.5% vs. 7.4%, P = 1.5 × 10(-4)). Although 7 of 45 Htx copy number variations were large chromosomal abnormalities, 38 smaller copy number variations altered a total of 61 genes, 22 of which had Xenopus orthologs. In situ hybridization identified 7 of these 22 genes with expression in the ciliated LR organizer (gastrocoel roof plate), a marked enrichment compared with 40 of 845 previously studied genes (sevenfold enrichment, P < 10(-6)). Morpholino knockdown in Xenopus of Htx candidates demonstrated that five (NEK2, ROCK2, TGFBR2, GALNT11, and NUP188) strongly disrupted both morphological LR development and expression of pitx2, a molecular marker of LR patterning. These effects were specific, because 0 of 13 control genes from rare Htx or control copy number variations produced significant LR abnormalities (P = 0.001). These findings identify genes not previously implicated in LR patterning.

Altered expression pattern of molecular factors involved in colonic smooth muscle functions: an immunohistochemical study in patients with diverticular disease.

PubMed

Mattii, Letizia; Ippolito, Chiara; Segnani, Cristina; Battolla, Barbara; Colucci, Rocchina; Dolfi, Amelio; Bassotti, Gabrio; Blandizzi, Corrado; Bernardini, Nunzia

2013-01-01

The pathogenesis of diverticular disease (DD) is thought to result from complex interactions among dietary habits, genetic factors and coexistence of other bowel abnormalities. These conditions lead to alterations in colonic pressure and motility, facilitating the formation of diverticula. Although electrophysiological studies on smooth muscle cells (SMCs) have investigated colonic motor dysfunctions, scarce attention has been paid to their molecular abnormalities, and data on SMCs in DD are lacking. Accordingly, the main purpose of this study was to evaluate the expression patterns of molecular factors involved in the contractile functions of SMCs in the tunica muscularis of colonic specimens from patients with DD. By means of immunohistochemistry and image analysis, we examined the expression of Cx26 and Cx43, which are prominent components of gap junctions in human colonic SMCs, as well as pS368-Cx43, PKCps, RhoA and αSMA, all known to regulate the functions of gap junctions and the contractile activity of SMCs. The immunohistochemical analysis revealed significant abnormalities in DD samples, concerning both the expression and distribution patterns of most of the investigated molecular factors. This study demonstrates, for the first time, that an altered pattern of factors involved in SMC contractility is present at level of the tunica muscularis of DD patients. Moreover, considering that our analysis was conducted on colonic tissues not directly affected by diverticular lesions or inflammatory reactions, it is conceivable that these molecular alterations may precede and predispose to the formation of diverticula, rather than being mere consequences of the disease.

Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates

PubMed Central

Ances, Beau M.; Vitaliani, Roberta; Taylor, Robert A.; Liebeskind, David S.; Voloschin, Alfredo; Houghton, David J.; Galetta, Steven L.; Dichter, Marc; Alavi, Abass; Rosenfeld, Myrna R.; Dalmau, Josep

2007-01-01

We report seven patients, six from a single institution, who developed subacute limbic encephalitis initially considered of uncertain aetiology. Four patients presented with symptoms of hippocampal dysfunction (i.e. severe short-term memory loss) and three with extensive limbic dysfunction (i.e. confusion, seizures and suspected psychosis). Brain MRI and [18F]fluorodeoxyglucose (FDG)-PET complemented each other but did not overlap in 50% of the patients. Combining both tests, all patients had temporal lobe abnormalities, five with additional areas involved. In one patient, FDG hyperactivity in the brainstem that was normal on MRI correlated with central hypoventilation; in another case, hyperactivity in the cerebellum anticipated ataxia. All patients had abnormal CSF: six pleocytosis, six had increased protein concentration, and three of five examined had oligoclonal bands. A tumour was identified and removed in four patients (mediastinal teratoma, thymoma, thymic carcinoma and thyroid cancer) and not treated in one (ovarian teratoma). An immunohistochemical technique that facilitates the detection of antibodies to cell surface or synaptic proteins demonstrated that six patients had antibodies to the neuropil of hippocampus or cerebellum, and one to intraneuronal antigens. Only one of the neuropil antibodies corresponded to voltage-gated potassium channel (VGKC) antibodies; the other five (two with identical specificity) reacted with antigens concentrated in areas of high dendritic density or synaptic-enriched regions of the hippocampus or cerebellum. Preliminary characterization of these antigens indicates that they are diverse and expressed on the neuronal cell membrane and dendrites; they do not co-localize with VGKCs, but partially co-localize with spinophilin. A target autoantigen in one of the patients co-localizes with a cell surface protein involved in hippocampal dendritic development. All patients except the one with antibodies to intracellular antigens had dramatic clinical and neuroimaging responses to immunotherapy or tumour resection; two patients had neurological relapse and improved with immunotherapy. Overall, the phenotype associated with the novel neuropil antibodies includes dominant behavioural and psychiatric symptoms and seizures that often interfere with the evaluation of cognition and memory, and brain MRI or FDG-PET abnormalities less frequently restricted to the medial temporal lobes than in patients with classical paraneoplastic or VGKC antibodies. When compared with patients with VGKC antibodies, patients with these novel antibodies are more likely to have CSF inflammatory abnormalities and systemic tumours (teratoma and thymoma), and they do not develop SIADH-like hyponatraemia. Although most autoantigens await characterization, all share intense expression by the neuropil of hippocampus, with patterns of immunolabelling characteristic enough to suggest the diagnosis of these disorders and predict response to treatment. PMID:15888538

Pulmonary Arterial Hypertension With Abnormal V/Q Single-Photon Emission Computed Tomography.

PubMed

Chan, Kenneth; Ioannidis, Stefanos; Coghlan, John G; Hall, Margaret; Schreiber, Benjamin E

2017-10-16

This study aimed to evaluate the incidence and clinical outcomes of abnormal ventilation/perfusion (V/Q) single-photon emission computed tomography (SPECT) without thromboembolism, especially in patients with group I pulmonary arterial hypertension (PAH). American Heart Association/American College of Cardiology and European Society of Cardiology guidelines recommend V/Q scan for screening for chronic thromboembolic pulmonary hypertension. The significance of patients with abnormal V/Q SPECT findings but no thromboembolism demonstrated in further investigations remained unclear. A distinct pattern of global patchy changes not typical of thromboembolism is recognized, but guidelines for reporting these in the context of PAH are lacking. A total of 136 patients who underwent V/Q SPECT and right-sided heart catheterization showing mean pulmonary arterial pressure ≥25 mm Hg were included. V/Q SPECT findings were reported using European Association of Nuclear Medicine criteria for pulmonary embolism followed by computed tomography pulmonary angiography screening for positive thromboembolism and further invasive pulmonary angiography for distal thromboembolism. The abnormal V/Q SPECT images were further analyzed according to perfusion pattern into focal or global perfusion defects. V/Q SPECT showed thromboembolic disease in 44 patients, but 19 of these patients had no thromboembolism demonstrated by pulmonary angiography. Among these patients, 15 of 19 (78.9%) had group I PAH, and the majority had diffuse, patchy perfusion defects. After redefining V/Q SPECT images according to the perfusion pattern, those patients with global perfusion defects had higher mean pulmonary arterial pressure compared with patients with focal perfusion defects and normal scans (mean difference +13.9 and +6.2 mm Hg, respectively; p = 0.0002), as well as higher pulmonary vascular resistance (mean difference +316.6 and +226.3 absolute resistance units, respectively; p = 0.004). Among patients with PAH, global perfusion defects were associated with higher all-cause mortality with a hazard ratio of 5.63 (95% confidence interval: 1.11 to 28.5) compared with patients with focal or no perfusion abnormalities. There is a high incidence of abnormal V/Q SPECT scans in nonthromboembolic PAH. Further studies are needed to investigate the poor outcome associated with abnormal V/Q SPECT findings in the context of PAH. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Abnormal patterns of displacement activities: a review and reinterpretation.

PubMed

Anselme, Patrick

2008-09-01

A series of important theoretical contributions flourished in the years 1950-1970 about displacement activities -- those 'out-of-context' actions expressed by organisms in stressful situations. Nothing really new has appeared thereafter. Although the models address different issues, such as causal factors of displacement, it appears obvious that they do not provide a unified (coherent) approach; they often explain the same phenomena using very different means and turn out to be contradictory on several points. In addition, some problems currently remain unsolved, especially concerning the fact that displacement activities exhibit 'abnormalities' of expression in comparison with the same activities performed in usual context. Each model is here described and criticized in order to evaluate its explanatory power and allow the identification of specific limits. A new, integrative model -- the Anticipatory Dynamics Model (or ADM) -- then attempts to overcome the failures of previous models. The ADM suggests that abnormal patterns of displacement activities result from attentional interference caused by a thwarting experience or conflicting motivations. At least one theoretical prediction of the ADM can be differentiated from that of any other model.

Infrared Surveys of Hawaiian Volcanoes: Aerial surveys with infrared imaging radiometer depict volcanic thermal patterns and structural features.

PubMed

Fisher, W A; Moxham, R M; Polcyn, F; Landis, G H

1964-11-06

Aerial infrared-sensor surveys of Kilauea volcano have depicted the areal extent and the relative intensity of abnormal thermal features in the caldera area of the volcano and along its associated rift zones. Many of these anomalies show correlation with visible steaming and reflect convective transfer of heat to the surface from subterranean sources. Structural details of the volcano, some not evident from surface observation, are also delineated by their thermal abnormalities. Several changes were observed in the patterns of infrared emission during the period of study; two such changes show correlation in location with subsequent eruptions, but the cause-and-effect relationship is uncertain. Thermal anomalies were also observed on the southwest flank of Mauna Loa; images of other volcanoes on the island of Hawaii, and of Haleakala on the island of Maui, revealed no thermal abnormalities. Approximately 25 large springs issuing into the ocean around the periphery of Hawaii have been detected. Infrared emission varies widely with surface texture and composition, suggesting that similar observations may have value for estimating surface conditions on the moon or planets.

Correlative anatomy of the pleura and pleural spaces.

PubMed

Liang, Chen; Shuang, Li; Wei, Liu; Bolduc, Jean-Philippe; Deslauriers, Jean

2011-05-01

Although pleural disorders are commonly encountered in the daily practices of thoracic surgeons, their assessment can be difficult. Being able to correlate normal and abnormal anatomy with imaging characteristics provides additional information that can be useful not only to accurately locate pleuropulmonary lesions but also to characterize abnormalities, such as pleural thickening or malignant processes. Copyright © 2011 Elsevier Inc. All rights reserved.

Sensory Processing in Low-Functioning Adults with Autism Spectrum Disorder: Distinct Sensory Profiles and Their Relationships with Behavioral Dysfunction

ERIC Educational Resources Information Center

Gonthier, Corentin; Longuépée, Lucie; Bouvard, Martine

2016-01-01

Sensory processing abnormalities are relatively universal in individuals with autism spectrum disorder, and can be very disabling. Surprisingly, very few studies have investigated these abnormalities in low-functioning adults with autism. The goals of the present study were (a) to characterize distinct profiles of sensory dysfunction, and (b) to…

Increased ventilatory variability and complexity in patients with hyperventilation disorder.

PubMed

Bokov, Plamen; Fiamma, Marie-Noëlle; Chevalier-Bidaud, Brigitte; Chenivesse, Cécile; Straus, Christian; Similowski, Thomas; Delclaux, Christophe

2016-05-15

It has been hypothesized that hyperventilation disorders could be characterized by an abnormal ventilatory control leading to enhanced variability of resting ventilation. The variability of tidal volume (VT) often depicts a nonnormal distribution that can be described by the negative slope characterizing augmented breaths formed by the relationship between the probability density distribution of VT and VT on a log-log scale. The objectives of this study were to describe the variability of resting ventilation [coefficient of variation (CV) of VT and slope], the stability in respiratory control (loop, controller and plant gains characterizing ventilatory-chemoresponsiveness interactions) and the chaotic-like dynamics (embedding dimension, Kappa values characterizing complexity) of resting ventilation in patients with a well-defined dysfunctional breathing pattern characterized by air hunger and constantly decreased PaCO2 during a cardiopulmonary exercise test. Compared with 14 healthy subjects with similar anthropometrics, 23 patients with hyperventilation were characterized by increased variability of resting tidal ventilation (CV of VT median [interquartile]: 26% [19-35] vs. 36% [28-48], P = 0.020; slope: -6.63 [-7.65; -5.36] vs. -3.88 [-5.91; -2.66], P = 0.004) that was not related to increased chemical drive (loop gain: 0.051 [0.039-0.221] vs. 0.044 [0.012-0.087], P = 0.149) but that was related to an increased ventilatory complexity (Kappa values, P < 0.05). Plant gain was decreased in patients and correlated with complexity (with Kappa 5 - degree 5: Rho = -0.48, P = 0.006). In conclusion, well-defined patients suffering from hyperventilation disorder are characterized by increased variability of their resting ventilation due to increased ventilatory complexity with stable ventilatory-chemoresponsiveness interactions. Copyright © 2016 the American Physiological Society.

Leukoencephalopathy with thalamus and brainstem involvement and high lactate 'LTBL' caused by EARS2 mutations.

PubMed

Steenweg, Marjan E; Ghezzi, Daniele; Haack, Tobias; Abbink, Truus E M; Martinelli, Diego; van Berkel, Carola G M; Bley, Annette; Diogo, Luisa; Grillo, Eugenio; Te Water Naudé, Johann; Strom, Tim M; Bertini, Enrico; Prokisch, Holger; van der Knaap, Marjo S; Zeviani, Massimo

2012-05-01

In the large group of genetically undetermined infantile-onset mitochondrial encephalopathies, multiple defects of mitochondrial DNA-related respiratory-chain complexes constitute a frequent biochemical signature. In order to identify responsible genes, we used exome-next-generation sequencing in a selected cohort of patients with this biochemical signature. In an isolated patient, we found two mutant alleles for EARS2, the gene encoding mitochondrial glutamyl-tRNA synthetase. The brain magnetic resonance imaging of this patient was hallmarked by extensive symmetrical cerebral white matter abnormalities sparing the periventricular rim and symmetrical signal abnormalities of the thalami, midbrain, pons, medulla oblongata and cerebellar white matter. Proton magnetic resonance spectroscopy showed increased lactate. We matched this magnetic resonance imaging pattern with that of a cohort of 11 previously selected unrelated cases. We found mutations in the EARS2 gene in all. Subsequent detailed clinical and magnetic resonance imaging based phenotyping revealed two distinct groups: mild and severe. All 12 patients shared an infantile onset and rapidly progressive disease with severe magnetic resonance imaging abnormalities and increased lactate in body fluids and proton magnetic resonance spectroscopy. Patients in the 'mild' group partially recovered and regained milestones in the following years with striking magnetic resonance imaging improvement and declining lactate levels, whereas those of the 'severe' group were characterized by clinical stagnation, brain atrophy on magnetic resonance imaging and persistent lactate increases. This new neurological disease, early-onset leukoencephalopathy with thalamus and brainstem involvement and high lactate, is hallmarked by unique magnetic resonance imaging features, defined by a peculiar biphasic clinical course and caused by mutations in a single gene, EARS2, expanding the list of medically relevant defects of mitochondrial DNA translation.

Postnatal Anthropometric and Body Composition Profiles in Infants with Intrauterine Growth Restriction Identified by Prenatal Doppler

PubMed Central

Mazarico, E.; Martinez-Cumplido, R.; Díaz, M.; Sebastiani, G.; Ibáñez, L.; Gómez-Roig, M. D.

2016-01-01

Introduction Infant anthropometry and body composition have been previously assessed to gauge the impact of intrauterine growth restriction (IUGR) at birth, but the interplay between prenatal Doppler measurements and postnatal development has not been studied in this setting. The present investigation was performed to assess the significance of prenatal Doppler findings relative to postnatal anthropometrics and body composition in IUGR newborns over the first 12 months of life. Patients and Methods Consecutive cases of singleton pregnancies with suspected IUGR were prospectively enrolled over 12 months. Fetal biometry and prenatal Doppler ultrasound examinations were performed. Body composition was assessed by absorptiometry at ages 10 days, and at 4 and12 months. Results A total of 48 pregnancies qualifying as IUGR were studied. Doppler parameters were normal in 26 pregnancies. The remaining 22 deviated from normal, marked by an Umbilical Artery Pulsatility Index (UA-PI) >95th centil or Cerebro-placental ratio (CPR) <5th centile. No significant differences emerged when comparing anthropometry and body composition at each time point, in relation to Doppler findings. Specifically, those IUGR newborns with and without abnormal Doppler findings had similar weight, length, body mass index, lean and fat mass, and bone mineral content throughout the first 12 months of life. In a separate analysis, when comparing IUGR newborns by Doppler (abnormal UA-PI vs. abnormal CPR), anthropometry and body composition did not differ significantly. Conclusions Infants with IUGR maintain a pattern of body composition during the first year of life that is independent of prenatal Doppler findings. Future studies with larger sample sizes and correlating with hormonal status are warranted to further extend the phenotypic characterization of the various conditions now classified under the common label of IUGR. PMID:26938993

The management of children with gastroenteritis and dehydration in the emergency department.

PubMed

Colletti, James E; Brown, Kathleen M; Sharieff, Ghazala Q; Barata, Isabel A; Ishimine, Paul

2010-06-01

Acute gastroenteritis is characterized by diarrhea, which may be accompanied by nausea, vomiting, fever, and abdominal pain. To review the evidence on the assessment of dehydration, methods of rehydration, and the utility of antiemetics in the child presenting with acute gastroenteritis. The evidence suggests that the three most useful predictors of 5% or more dehydration are abnormal capillary refill, abnormal skin turgor, and abnormal respiratory pattern. Studies are conflicting on whether blood urea nitrogen (BUN) or BUN/creatinine ratio correlates with dehydration, but several studies found that low serum bicarbonate combined with certain clinical parameters predicts dehydration. In most studies, oral or nasogastric rehydration with an oral rehydration solution was equally efficacious as intravenous (i.v.) rehydration. Many experts discourage the routine use of antiemetics in young children. However, children receiving ondensetron are less likely to vomit, have greater oral intake, and are less likely to be treated by intravenous rehydration. Mean length of Emergency Department (ED) stay is also less, and very few serious side effects have been reported. In the ED, dehydration is evaluated by synthesizing the historical and physical examination, and obtaining laboratory data points in select patients. No single laboratory value has been found to be accurate in predicting the degree of dehydration and this is not routinely recommended. The evidence suggests that the majority of children with mild to moderate dehydration can be treated successfully with oral rehydration therapy. Ondansetron (orally or intravenously) may be effective in decreasing the rate of vomiting, improving the success rate of oral hydration, preventing the need for i.v. hydration, and preventing the need for hospital admission in those receiving i.v. hydration. Copyright 2010. Published by Elsevier Inc.

Social anhedonia is associated with neural abnormalities during face emotion processing.

PubMed

Germine, Laura T; Garrido, Lucia; Bruce, Lori; Hooker, Christine

2011-10-01

Human beings are social organisms with an intrinsic desire to seek and participate in social interactions. Social anhedonia is a personality trait characterized by a reduced desire for social affiliation and reduced pleasure derived from interpersonal interactions. Abnormally high levels of social anhedonia prospectively predict the development of schizophrenia and contribute to poorer outcomes for schizophrenia patients. Despite the strong association between social anhedonia and schizophrenia, the neural mechanisms that underlie individual differences in social anhedonia have not been studied and are thus poorly understood. Deficits in face emotion recognition are related to poorer social outcomes in schizophrenia, and it has been suggested that face emotion recognition deficits may be a behavioral marker for schizophrenia liability. In the current study, we used functional magnetic resonance imaging (fMRI) to see whether there are differences in the brain networks underlying basic face emotion processing in a community sample of individuals low vs. high in social anhedonia. We isolated the neural mechanisms related to face emotion processing by comparing face emotion discrimination with four other baseline conditions (identity discrimination of emotional faces, identity discrimination of neutral faces, object discrimination, and pattern discrimination). Results showed a group (high/low social anhedonia) × condition (emotion discrimination/control condition) interaction in the anterior portion of the rostral medial prefrontal cortex, right superior temporal gyrus, and left somatosensory cortex. As predicted, high (relative to low) social anhedonia participants showed less neural activity in face emotion processing regions during emotion discrimination as compared to each control condition. The findings suggest that social anhedonia is associated with abnormalities in networks responsible for basic processes associated with social cognition, and provide a starting point for understanding the neural basis of social motivation and our drive to seek social affiliation. Copyright © 2011 Elsevier Inc. All rights reserved.

Mesh-free based variational level set evolution for breast region segmentation and abnormality detection using mammograms.

PubMed

Kashyap, Kanchan L; Bajpai, Manish K; Khanna, Pritee; Giakos, George

2018-01-01

Automatic segmentation of abnormal region is a crucial task in computer-aided detection system using mammograms. In this work, an automatic abnormality detection algorithm using mammographic images is proposed. In the preprocessing step, partial differential equation-based variational level set method is used for breast region extraction. The evolution of the level set method is done by applying mesh-free-based radial basis function (RBF). The limitation of mesh-based approach is removed by using mesh-free-based RBF method. The evolution of variational level set function is also done by mesh-based finite difference method for comparison purpose. Unsharp masking and median filtering is used for mammogram enhancement. Suspicious abnormal regions are segmented by applying fuzzy c-means clustering. Texture features are extracted from the segmented suspicious regions by computing local binary pattern and dominated rotated local binary pattern (DRLBP). Finally, suspicious regions are classified as normal or abnormal regions by means of support vector machine with linear, multilayer perceptron, radial basis, and polynomial kernel function. The algorithm is validated on 322 sample mammograms of mammographic image analysis society (MIAS) and 500 mammograms from digital database for screening mammography (DDSM) datasets. Proficiency of the algorithm is quantified by using sensitivity, specificity, and accuracy. The highest sensitivity, specificity, and accuracy of 93.96%, 95.01%, and 94.48%, respectively, are obtained on MIAS dataset using DRLBP feature with RBF kernel function. Whereas, the highest 92.31% sensitivity, 98.45% specificity, and 96.21% accuracy are achieved on DDSM dataset using DRLBP feature with RBF kernel function. Copyright © 2017 John Wiley & Sons, Ltd.

Ultrasonography and detection of subclinical joints and tendons involvements in Systemic Lupus erythematosus (SLE) patients: A cross-sectional multicenter study.

PubMed

Salliot, Carine; Denis, Amélie; Dernis, Emmanuelle; Andre, Vincent; Perdriger, Aleth; Albert, Jean-David; Mammou Mraghni, Saloua; Griffoul-Espitalier, Isabelle; Hamidou, Mohamed; Le Goff, Benoit; Joulin, Sandrine Jousse; Marhadour, Thierry; Richez, Christophe; Poursac, Nicolas; Lazaro, Estebaliz; Rist, Stéphanie; Corondan, Anca; Quinten, Clara; Martaillé, Virginie; Valéry, Antoine; Ducourau, Emilie

2018-02-15

The aims of this study in SLE population were (1) to describe ultrasonography (US) joint abnormalities, (2) to estimate the reliability of clinical swollen joint count (C-SJC) and SLEDAI (C-SLEDAI) versus US-SJC and US-SLEDAI scores, (3) to highlight specific patterns of lupus patients with Power Doppler (PD) abnormalities. For this cross-sectional multicenter study, 151 consecutive adult SLE patients were recruited. Evaluation included a clinical standardized joint assessment, B-mode and PD US of 40 joints and 26 tendons blinded for clinical examination. Reliability and agreement between clinical and B-mode US were calculated using the intraclass correlation coefficients (ICC [95% Confidence Interval]). We found a very high frequency of subclinical US abnormalities in asymptomatic patients: 85% of patients without joint symptoms had at least 1 US abnormality. Among them 46 patients (87%) had a history of joint involvement. The most frequent abnormalities were joint effusmaions (108 patients), synovial hypertrophy (SH, 109 patients) and synovitis (61 patients). Joint or tendon PD signal (grade>1) was found in 44% of patients (67/151). Synovitis were mainly located especially on MCPs and wrists. Even if reliability between clinical and grey-scale US SJC assessments was poor, reliability between clinical and US SLEDAI was good. Comparison between SLE patients with and without PD signal did not show any specific SLE pattern. US may be useful to assess joint involvement in SLE patients but did not significantly change SLEDAI score. Copyright © 2018. Published by Elsevier SAS.

Evaluation of esophageal motility utilizing the functional lumen imaging probe (FLIP)

PubMed Central

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.

2016-01-01

Background 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. Methods 145 patients (ages 18 – 85, 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 mm2/mmHg or contractility pattern demonstrated absent contractility or repetitive, retrograde contractions. Results HRM was abnormal in 111 (77%) patients: 70 achalasia (19 type I, 39 type II, 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. 17 (50%) had abnormal FLIP topography including 13 (37%) with abnormal EGJ-DI. Conclusions 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. PMID:27725650

Utilisation of a direct access echocardiography service by general practitioners in a remote and rural area--distance and rurality are not barriers to referral.

PubMed

Choo, Wai K; McGeary, Katie; Farman, Colin; Greyling, Andre; Cross, Stephen J; Leslie, Stephen J

2014-01-01

This study aimed to examine whether general practitioner (GP) practice locations in remote and rural areas affected the pattern of direct access echocardiography referral and to assess any variations in echocardiographic findings. All referrals made by all GP practices in the Scottish Highlands over a 36-month period were analysed. Referral patterns were examined according to distance and rurality based on the Scottish Government's Urban-Rural Classification. Reasons for referral and cardiac abnormality detection rates were also examined. In total, 1188 referrals were made from 49 different GP practices; range of referral rates was 0.3-20.1 per 1000 population with a mean of 6.5 referrals per 1000 population. Referral rates were not significantly different between urban and rural practices after correction for population size. There was no correlation between the referral rates and the distance from the centre (r2=0.004, p=0.65). The most common reason for referral was the presence of new murmur (46%). The most common presenting symptom was breathlessness (44%). Overall, 28% of studies had significant abnormal findings requiring direct input from a cardiologist. There was no clear relationship between referral rates and cardiac abnormality detection rates (r2=0.07, p=0.37). The average cardiac abnormality detection rate was 56%, (range 52-60%), with no variation based on rurality (p=0.891). In this cohort, rurality and distance were not barriers to an equitable direct access echocardiography service. Cardiac abnormality detection rates are consistent with that of other studies.

[Immunohistochemical expression of the E-cadherin-catenin complex in gastric cancer].

PubMed

Guzmán, Pablo; Araya, Juan; Villaseca, Miguel; Roa, Iván; Melo, Angélica; Muñoz, Sergio; Roa, Juan

2006-08-01

The E-cadherin/catenin complex plays an essential role in the control of epithelial differentiation. Abnormal expression in tumors correlates with histological grade, advanced stage and poor prognosis. To evaluate the expression pattern of E-cadherin/catenin complex in gastric carcinoma and analyze their association with tumor clinicopathological features and patient survival. Inmunohistochemical staining of E-cadherin, alpha and ss-catenin was performed from paraffin specimens of 65 gastric carcinomas. Abnormal expression of E-cadherin, alpha and ss-catenin was demonstrated in 82%, 85% and 88% of gastric carcinomas, respectively. There was a significant correlation between abnormal expression and Lauren pathological classification and depth of infiltration, but not with tumor stage, positive lymph node metastases and survival. Abnormal expression of E-cadherin, alpha and ss-catenin occurs frequently in gastric carcinoma and correlates with histological grade.

Isolation and Characterization of Sex-Linked Female-Sterile Mutants in DROSOPHILA MELANOGASTER with Special Attention to Eggshell Mutants

PubMed Central

Komitopoulou, Katia; Gans, Madeleine; Margaritis, Lukas H.; Kafatos, Fotis C.; Masson, Michele

1983-01-01

To study genes that function mainly or exclusively during oogenesis, we have isolated and analyzed female-sterile mutations, with special emphasis on those that affect eggshell formation. Following treatment that induced 61 to 66% lethals, 8.1% of the 1071 X chromosomes tested carried recessive female sterility mutations (87 isolates), and 8.0% carried partial female-sterile mutations (86 isolates), respectively. In addition, three dominant female steriles were recovered. Some of the mutants had very low fecundity, and others laid morphologically normal eggs that failed to develop. A third category included 29 mutants that laid eggs with morphological abnormalities: 26 were female steriles, two were partial female steriles and one was fertile. Mutants of this third category were characterized in some detail and compared with 40 previously isolated mutants that laid similarly abnormal eggs. Approximately 28–31 complementation groups with morphological abnormalities were detected, some of which were large allelic series (11, 9, 7, 6 and 5 alleles). Twenty-four groups were mapped genetically or cytogenetically, and 21 were partially characterized by ultrastructural and biochemical procedures. Of the latter, one group showed clear deficiency of yolk proteins, and nine showed prominent ultrastructural defects in the chorion (at least eight accompanied by deficiencies in characterized chorion proteins). At least six groups with clear-cut effects were found at loci not previously identified with known chorion structural genes. PMID:17246182

Progress in Mathematical Modeling of Gastrointestinal Slow Wave Abnormalities

PubMed Central

Du, Peng; Calder, Stefan; Angeli, Timothy R.; Sathar, Shameer; Paskaranandavadivel, Niranchan; O'Grady, Gregory; Cheng, Leo K.

2018-01-01

Gastrointestinal (GI) motility is regulated in part by electrophysiological events called slow waves, which are generated by the interstitial cells of Cajal (ICC). Slow waves propagate by a process of “entrainment,” which occurs over a decreasing gradient of intrinsic frequencies in the antegrade direction across much of the GI tract. Abnormal initiation and conduction of slow waves have been demonstrated in, and linked to, a number of GI motility disorders. A range of mathematical models have been developed to study abnormal slow waves and applied to propose novel methods for non-invasive detection and therapy. This review provides a general outline of GI slow wave abnormalities and their recent classification using multi-electrode (high-resolution) mapping methods, with a particular emphasis on the spatial patterns of these abnormal activities. The recently-developed mathematical models are introduced in order of their biophysical scale from cellular to whole-organ levels. The modeling techniques, main findings from the simulations, and potential future directions arising from notable studies are discussed. PMID:29379448

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.

Diagnostic classification of macular ganglion cell and retinal nerve fiber layer analysis: differentiation of false-positives from glaucoma.

PubMed

Kim, Ko Eun; Jeoung, Jin Wook; Park, Ki Ho; Kim, Dong Myung; Kim, Seok Hwan

2015-03-01

To investigate the rate and associated factors of false-positive diagnostic classification of ganglion cell analysis (GCA) and retinal nerve fiber layer (RNFL) maps, and characteristic false-positive patterns on optical coherence tomography (OCT) deviation maps. Prospective, cross-sectional study. A total of 104 healthy eyes of 104 normal participants. All participants underwent peripapillary and macular spectral-domain (Cirrus-HD, Carl Zeiss Meditec Inc, Dublin, CA) OCT scans. False-positive diagnostic classification was defined as yellow or red color-coded areas for GCA and RNFL maps. Univariate and multivariate logistic regression analyses were used to determine associated factors. Eyes with abnormal OCT deviation maps were categorized on the basis of the shape and location of abnormal color-coded area. Differences in clinical characteristics among the subgroups were compared. (1) The rate and associated factors of false-positive OCT maps; (2) patterns of false-positive, color-coded areas on the GCA deviation map and associated clinical characteristics. Of the 104 healthy eyes, 42 (40.4%) and 32 (30.8%) showed abnormal diagnostic classifications on any of the GCA and RNFL maps, respectively. Multivariate analysis revealed that false-positive GCA diagnostic classification was associated with longer axial length and larger fovea-disc angle, whereas longer axial length and smaller disc area were associated with abnormal RNFL maps. Eyes with abnormal GCA deviation map were categorized as group A (donut-shaped round area around the inner annulus), group B (island-like isolated area), and group C (diffuse, circular area with an irregular inner margin in either). The axial length showed a significant increasing trend from group A to C (P=0.001), and likewise, the refractive error was more myopic in group C than in groups A (P=0.015) and B (P=0.014). Group C had thinner average ganglion cell-inner plexiform layer thickness compared with other groups (group A=B>C, P=0.004). Abnormal OCT diagnostic classification should be interpreted with caution, especially in eyes with long axial lengths, large fovea-disc angles, and small optic discs. Our findings suggest that the characteristic patterns of OCT deviation map can provide useful clues to distinguish glaucomatous changes from false-positive findings. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Network Disruption and Cerebrospinal Fluid Amyloid-Beta and Phospho-Tau Levels in Mild Cognitive Impairment.

PubMed

Canuet, Leonides; Pusil, Sandra; López, María Eugenia; Bajo, Ricardo; Pineda-Pardo, José Ángel; Cuesta, Pablo; Gálvez, Gerardo; Gaztelu, José María; Lourido, Daniel; García-Ribas, Guillermo; Maestú, Fernando

2015-07-15

Synaptic dysfunction is a core deficit in Alzheimer's disease, preceding hallmark pathological abnormalities. Resting-state magnetoencephalography (MEG) was used to assess whether functional connectivity patterns, as an index of synaptic dysfunction, are associated with CSF biomarkers [i.e., phospho-tau (p-tau) and amyloid beta (Aβ42) levels]. We studied 12 human subjects diagnosed with mild cognitive impairment due to Alzheimer's disease, comparing those with normal and abnormal CSF levels of the biomarkers. We also evaluated the association between aberrant functional connections and structural connectivity abnormalities, measured with diffusion tensor imaging, as well as the convergent impact of cognitive deficits and CSF variables on network disorganization. One-third of the patients converted to Alzheimer's disease during a follow-up period of 2.5 years. Patients with abnomal CSF p-tau and Aβ42 levels exhibited both reduced and increased functional connectivity affecting limbic structures such as the anterior/posterior cingulate cortex, orbitofrontal cortex, and medial temporal areas in different frequency bands. A reduction in posterior cingulate functional connectivity mediated by p-tau was associated with impaired axonal integrity of the hippocampal cingulum. We noted that several connectivity abnormalities were predicted by CSF biomarkers and cognitive scores. These preliminary results indicate that CSF markers of amyloid deposition and neuronal injury in early Alzheimer's disease associate with a dual pattern of cortical network disruption, affecting key regions of the default mode network and the temporal cortex. MEG is useful to detect early synaptic dysfunction associated with Alzheimer's disease brain pathology in terms of functional network organization. In this preliminary study, we used magnetoencephalography and an integrative approach to explore the impact of CSF biomarkers, neuropsychological scores, and white matter structural abnormalities on neural function in mild cognitive impairment. Disruption in functional connectivity between several pairs of cortical regions associated with abnormal levels of biomarkers, cognitive deficits, or with impaired axonal integrity of hippocampal tracts. Amyloid deposition and tau protein-related neuronal injury in early Alzheimer's disease are associated with synaptic dysfunction and a dual pattern of cortical network disorganization (i.e., desynchronization and hypersynchronization) that affects key regions of the default mode network and temporal areas. Copyright © 2015 the authors 0270-6474/15/3510326-06$15.00/0.

A retrospective study of two populations to test a simple rule for spirometry.

PubMed

Ohar, Jill A; Yawn, Barbara P; Ruppel, Gregg L; Donohue, James F

2016-06-04

Chronic lung disease is common and often under-diagnosed. To test a simple rule for conducting spirometry we reviewed spirograms from two populations, occupational medicine evaluations (OME) conducted by Saint Louis and Wake Forest Universities at 3 sites (n = 3260, mean age 64.14 years, 95 % CI 58.94-69.34, 97 % men) and conducted by Wake Forest University preop clinic (POC) at one site (n = 845, mean age 62.10 years, 95 % CI 50.46-73.74, 57 % men). This retrospective review of database information that the first author collected prospectively identified rates, types, sensitivity, specificity and positive and negative predictive value for lung function abnormalities and associated mortality rate found when conducting spirometry based on the 20/40 rule (≥20 years of smoking in those aged ≥ 40 years) in the OME population. To determine the reproducibility of the 20/40 rule for conducting spirometry, the rule was applied to the POC population. A lung function abnormality was found in 74 % of the OME population and 67 % of the POC population. Sensitivity of the rule was 85 % for an obstructive pattern and 77 % for any abnormality on spirometry. Positive and negative predictive values of the rule for a spirometric abnormality were 74 and 55 %, respectively. Patients with an obstructive pattern were at greater risk of coronary heart disease (odds ratio (OR) 1.39 [confidence interval (CI) 1.00-1.93] vs. normal) and death (hazard ratio (HR) 1.53, 95 % CI 1.20-1.84) than subjects with normal spirometry. Restricted spirometry patterns were also associated with greater risk of coronary disease (odds ratio (OR) 1.7 [CI 1.23-2.35]) and death (Hazard ratio 1.40, 95 % CI 1.08-1.72). Smokers (≥ 20 pack years) age ≥ 40 years are at an increased risk for lung function abnormalities and those abnormalities are associated with greater presence of coronary heart disease and increased all-cause mortality. Use of the 20/40 rule could provide a simple method to enhance selection of candidates for spirometry evaluation in the primary care setting.

Time-Lapse Analysis of Human Embryonic Stem Cells Reveals Multiple Bottlenecks Restricting Colony Formation and Their Relief upon Culture Adaptation

PubMed Central

Barbaric, Ivana; Biga, Veronica; Gokhale, Paul J.; Jones, Mark; Stavish, Dylan; Glen, Adam; Coca, Daniel; Andrews, Peter W.

2014-01-01

Summary Using time-lapse imaging, we have identified a series of bottlenecks that restrict growth of early-passage human embryonic stem cells (hESCs) and that are relieved by karyotypically abnormal variants that are selected by prolonged culture. Only a minority of karyotypically normal cells divided after plating, and these were mainly cells in the later stages of cell cycle at the time of plating. Furthermore, the daughter cells showed a continued pattern of cell death after division, so that few formed long-term proliferating colonies. These colony-forming cells showed distinct patterns of cell movement. Increasing cell density enhanced cell movement facilitating cell:cell contact, which resulted in increased proportion of dividing cells and improved survival postplating of normal hESCs. In contrast, most of the karyotypically abnormal cells reentered the cell cycle on plating and gave rise to healthy progeny, without the need for cell:cell contacts and independent of their motility patterns. PMID:25068128

Fetal heart rate abnormalities during and after external cephalic version: Which fetuses are at risk and how are they delivered?

PubMed

Kuppens, Simone M; Smailbegovic, Ida; Houterman, Saskia; de Leeuw, Ingrid; Hasaart, Tom H

2017-10-17

Fetal heart rate abnormalities (FHR) during and after external cephalic version (ECV) are relatively frequent. They may raise concern about fetal wellbeing. Only occasionally they may lead to an emergency cesarean section. Prospective cohort study in 980 women (> 34 weeks gestation) with a singleton fetus in breech presentation. During and after external cephalic version (ECV) FHR abnormalities were recorded. Obstetric variables and delivery outcome were evaluated. Primary outcome was to identify which fetuses are at risk for FHR abnormalities. Secondary outcome was to identify a possible relationship between FHR abnormalities during and after ECV and mode of delivery and fetal distress during subsequent labor. The overall success rate of ECV was 60% and in 9% of the attempts there was an abnormal FHR pattern. In two cases FHR abnormalities after ECV led to an emergency CS. Estimated fetal weight per 100 g (OR 0.90, CI: 0.87-0.94) and longer duration of the ECV-procedure (OR 1.13, CI: 1.05-1.21) were factors significantly associated with the occurrence of FHR abnormalities. FHR abnormalities were not associated with the mode of delivery or the occurrence of fetal distress during subsequent labor. FHR abnormalities during and after ECV are more frequent with lower estimated fetal weight and longer duration of the procedure. FHR abnormalities during and after ECV have no consequences for subsequent mode of delivery. They do not predict whether fetal distress will occur during labor. The Eindhoven Breech Intervention Study, NCT00516555 . Date of registration: August 13, 2007.

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

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

PubMed

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

2018-06-08

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

Association between dietary patterns and the risk of metabolic syndrome among Lebanese adults.

PubMed

Naja, F; Nasreddine, L; Itani, L; Adra, N; Sibai, A M; Hwalla, N

2013-02-01

The main objective of this study was to evaluate the association between dietary patterns and the metabolic syndrome (MetS) and its metabolic abnormalities among Lebanese adults, using data from a national nutrition survey. A cross-sectional analysis involving adults aged ≥ 18 years (n = 323) with no prior history of chronic diseases was conducted. Participants completed a brief sociodemographic and 61-item food frequency questionnaire. Anthropometric measurements and fasting blood samples were also obtained. The International Diabetes Federation criteria were used to classify study participants with the metabolic syndrome. Dietary patterns were identified by factor analysis. Multivariate logistic regression analysis was used to evaluate the associations of extracted patterns with MetS and its metabolic abnormalities. Out of 323 participants, 112 (34.6%) were classified as having MetS. Three dietary patterns were identified: "Fast Food/Dessert," "Traditional Lebanese," and "High Protein." Compared with participants in the lowest quintile of the Fast Food/Dessert pattern, those in the highest quintile had significantly higher odds for MetS (OR, 3.13; 95% CI: 1.36-7.22) and hyperglycemia (OR, 3.81; 95% CI: 159-9.14). Subjects with the highest intake of the High Protein pattern had an increased risk for hypertension (OR, 2.98; 95% CI: 1.26-7.02). The Traditional Lebanese pattern showed no association with MetS or its components. The findings of this study demonstrate a positive association of the Fast Food/Dessert pattern with MetS and hyperglycemia among Lebanese adults. These results may guide the development of improved preventive nutrition interventions in this adult population.

Flow Behavior in the Left Heart Ventricle Following Apico-Aortic Bypass Surgery

NASA Astrophysics Data System (ADS)

Shahriari, Shahrokh; Jeyhani, Morteza; Labrosse, Michel; Kadem, Lyes

2013-11-01

Apico-aortic bypass (AAB) surgery is an alternative for transcatheter aortic valve implantation (TAVI) to reduce left ventricle (LV) overload in patients with severe aortic stenosis (AS). It consists in connecting the apex of the LV to the descending thoracic aorta with a valved conduit. Postoperative flow assessments show that two thirds of the outflow is conducted from the LV apex to the conduit, while only one third crosses the native aortic valve. In this study, we performed high speed particle image velocimetry (PIV) measurements of flow pattern within an in vitro elastic model of LV in the presence of a very severe AS, before and after AAB. Results indicate that AAB effectively relieves the LV outflow obstruction; however, it also leads to abnormal ventricular flow patterns. Normal LV flow dynamics is characterized by an emerging mitral jet flow followed by the development of a vortical flow with velocities directed towards the aortic valve, while measurements in the presence of AAB show systolic flow bifurcating to the apical conduit and to the aortic valve outflow tract. This study provides the first insight into the LV flow structure after AAB including outflow jets and disturbed stagnation regions.

Fgf8 expression in the Tbx1 domain causes skeletal abnormalities and modifies the aortic arch but not the outflow tract phenotype of Tbx1 mutants

PubMed Central

Vitelli, Francesca; Zhang, Zhen; Huynh, Tuong; Sobotka, Angela; Mupo, Annalisa; Baldini, Antonio

2007-01-01

Fgf8 and Tbx1 have been shown to interact in patterning the aortic arch, and both genes are required in formation and growth of the outflow tract of the heart. However, the nature of the interaction of the two genes is unclear. We have utilized a novel Tbx1Fgf8 allele which drives Fgf8 expression in Tbx1-positive cells and an inducible Cre-LoxP recombination system to address the role of Fgf8 in Tbx1 positive cells in modulating cardiovascular development. Results support a requirement of Fgf8 in Tbx1 expressing cells to finely control patterning of the aortic arch and great arteries specifically during the pharyngeal arch artery remodeling process and indicate that the endoderm is the most likely site of this interaction. Furthermore, our data suggest that Fgf8 and Tbx1 play independent roles in regulating outflow tract development. This finding is clinically relevant since TBX1 is the candidate for DGS/VCFS, characterized clinically by variable expressivity and reduced penetrance of cardiovascular defects; Fgf8 gene variants may provide molecular clues to this variability. PMID:16696966

Natural progression of blood-induced joint damage in patients with haemophilia: clinical relevance and reproducibility of three-dimensional gait analysis.

PubMed

Lobet, S; Detrembleur, C; Francq, B; Hermans, C

2010-09-01

A major complication in haemophilia is the destruction of joint cartilage because of recurrent intraarticular and intramuscular bleeds. Therefore, joint assessment is critical to quantify the extent of joint damage, which has traditionally been evaluated using both radiological and clinical joint scores. Our study aimed to evaluate the natural progression of haemophilic arthopathy using three-dimensional gait analysis (3DGA) and to assess the reproducibility of this technique. We hypothesized that the musculoskeletal function was relatively stable in patients with haemophilia. Eighteen adults with established haemophilic arthropathies were evaluated twice by 3DGA (mean follow-up: 18 +/- 5 weeks). Unexpectedly, our findings revealed infraclinical deterioration of gait pattern, characterized by a 3.2% decrease in the recovery index, which is indicative of the subject's ability to save energy while walking. A tendency towards modification of segmental joint function was also observed. Gait analysis was sufficiently reproducible with regards to spatiotemporal parameters as well as kinetic, mechanical and energetic gait variables. The kinematic variables were reproducible in both the sagittal and frontal planes. In conclusion, 3DGA is a reproducible tool to assess abnormal gait patterns and monitor natural disease progression in haemophilic patients.

Phenomenology and classification of dystonia: a consensus update.

PubMed

Albanese, Alberto; Bhatia, Kailash; Bressman, Susan B; Delong, Mahlon R; Fahn, Stanley; Fung, Victor S C; Hallett, Mark; Jankovic, Joseph; Jinnah, Hyder A; Klein, Christine; Lang, Anthony E; Mink, Jonathan W; Teller, Jan K

2013-06-15

This report describes the consensus outcome of an international panel consisting of investigators with years of experience in this field that reviewed the definition and classification of dystonia. Agreement was obtained based on a consensus development methodology during 3 in-person meetings and manuscript review by mail. Dystonia is defined as a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. Dystonic movements are typically patterned and twisting, and may be tremulous. Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle activation. Dystonia is classified along 2 axes: clinical characteristics, including age at onset, body distribution, temporal pattern and associated features (additional movement disorders or neurological features); and etiology, which includes nervous system pathology and inheritance. The clinical characteristics fall into several specific dystonia syndromes that help to guide diagnosis and treatment. We provide here a new general definition of dystonia and propose a new classification. We encourage clinicians and researchers to use these innovative definition and classification and test them in the clinical setting on a variety of patients with dystonia. © 2013 Movement Disorder Society. © 2013 Movement Disorder Society.

Spectral changes in spontaneous MEG activity across the lifespan

NASA Astrophysics Data System (ADS)

Gómez, Carlos; Pérez-Macías, Jose M.; Poza, Jesús; Fernández, Alberto; Hornero, Roberto

2013-12-01

Objective. The aim of this study is to explore the spectral patterns of spontaneous magnetoencephalography (MEG) activity across the lifespan. Approach. Relative power (RP) in six frequency bands (delta, theta, alpha, beta-1, beta-2 and gamma) was calculated in a sample of 220 healthy subjects with ages ranging from 7 to 84 years. Main results. A significant RP decrease in low-frequency bands (i.e. delta and theta) and a significant increase in high bands (mainly beta-1 and beta-2) were found from childhood to adolescence. This trend was observed until the sixth decade of life, though only slight changes were found. Additionally, healthy aging was characterized by a power increase in low-frequency bands. Our results show that spectral changes across the lifespan may follow a quadratic relationship in delta, theta, alpha, beta-2 and gamma bands with peak ages being reached around the fifth or sixth decade of life. Significance. Our findings provide original insights into the definition of the ‘normal’ behavior of age-related MEG spectral patterns. Furthermore, our study can be useful for the forthcoming MEG research focused on the description of the abnormalities of different brain diseases in comparison to cognitive decline in normal aging.

Disrupted Topological Patterns of Large-Scale Network in Conduct Disorder

PubMed Central

Jiang, Yali; Liu, Weixiang; Ming, Qingsen; Gao, Yidian; Ma, Ren; Zhang, Xiaocui; Situ, Weijun; Wang, Xiang; Yao, Shuqiao; Huang, Bingsheng

2016-01-01

Regional abnormalities in brain structure and function, as well as disrupted connectivity, have been found repeatedly in adolescents with conduct disorder (CD). Yet, the large-scale brain topology associated with CD is not well characterized, and little is known about the systematic neural mechanisms of CD. We employed graphic theory to investigate systematically the structural connectivity derived from cortical thickness correlation in a group of patients with CD (N = 43) and healthy controls (HCs, N = 73). Nonparametric permutation tests were applied for between-group comparisons of graphical metrics. Compared with HCs, network measures including global/local efficiency and modularity all pointed to hypo-functioning in CD, despite of preserved small-world organization in both groups. The hubs distribution is only partially overlapped with each other. These results indicate that CD is accompanied by both impaired integration and segregation patterns of brain networks, and the distribution of highly connected neural network ‘hubs’ is also distinct between groups. Such misconfiguration extends our understanding regarding how structural neural network disruptions may underlie behavioral disturbances in adolescents with CD, and potentially, implicates an aberrant cytoarchitectonic profiles in the brain of CD patients. PMID:27841320

Adolescent Alcohol Exposure: Burden of Epigenetic Reprogramming, Synaptic Remodeling, and Adult Psychopathology

PubMed Central

Kyzar, Evan J.; Floreani, Christina; Teppen, Tara L.; Pandey, Subhash C.

2016-01-01

Adolescence represents a crucial phase of synaptic maturation characterized by molecular changes in the developing brain that shape normal behavioral patterns. Epigenetic mechanisms play an important role in these neuromaturation processes. Perturbations of normal epigenetic programming during adolescence by ethanol can disrupt these molecular events, leading to synaptic remodeling and abnormal adult behaviors. Repeated exposure to binge levels of alcohol increases the risk for alcohol use disorder (AUD) and comorbid psychopathology including anxiety in adulthood. Recent studies in the field clearly suggest that adolescent alcohol exposure causes widespread and persistent changes in epigenetic, neurotrophic, and neuroimmune pathways in the brain. These changes are manifested by altered synaptic remodeling and neurogenesis in key brain regions leading to adult psychopathology such as anxiety and alcoholism. This review details the molecular mechanisms underlying adolescent alcohol exposure-induced changes in synaptic plasticity and the development of alcohol addiction-related phenotypes in adulthood. PMID:27303256

Targets for Drug Therapy for Autism Spectrum Disorder: Challenges and Future Directions.

PubMed

Lacivita, Enza; Perrone, Roberto; Margari, Lucia; Leopoldo, Marcello

2017-11-22

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by persistent deficits in social communication and interaction and restricted, repetitive patterns of behavior, interests, and activities. Various factors are involved in the etiopathogenesis of ASD, including genetic factors, environmental toxins and stressors, impaired immune responses, mitochondrial dysfunction, and neuroinflammation. The heterogeneity in the phenotype among ASD patients and the complex etiology of the condition have long impeded the advancement of the development of pharmacological therapies. In the recent years, the integration of findings from mouse models to human genetics resulted in considerable progress toward the understanding of ASD pathophysiology. Currently, strategies to treat core symptoms of ASD are directed to correct synaptic dysfunctions, abnormalities in central oxytocin, vasopressin, and serotonin neurotransmission, and neuroinflammation. Here, we present a survey of the studies that have suggested molecular targets for drug development for ASD and the state-of-the-art of medicinal chemistry efforts in related areas.

Suppression of self-organized surface nanopatterning on GaSb/InAs multilayers induced by low energy oxygen ion bombardment by using simultaneously sample rotation and oxygen flooding

NASA Astrophysics Data System (ADS)

Beainy, Georges; Cerba, Tiphaine; Bassani, Franck; Martin, Mickaël; Baron, Thierry; Barnes, Jean-Paul

2018-05-01

Time of flight secondary ion mass spectrometry (ToF-SIMS) is a well-adapted analytical method for the chemical characterization of concentration profiles in layered or multilayered materials. However, under ion beam bombardment, initially smooth material surface becomes morphologically unstable. This leads to abnormal secondary ion yields and depth profile distortions. In this contribution, we explore the surface topography and roughening evolution induced by O2+ ion bombardment on GaSb/InAs multilayers. We demonstrate the formation of nanodots and ripples patterning according to the ion beam energy. Since the latter are undesirable for ToF-SIMS analysis, we managed to totally stop their growth by using simultaneously sample rotation and oxygen flooding. This unprecedented coupling between these two latter mechanisms leads to a significant enhancement in depth profiles resolution.

Effect of proximal vagotomy and Roux-en-Y diversion on gastric emptying kinetics in asymptomatic patients.

PubMed

Urbain, J L; Penninckx, F; Siegel, J A; Vandenborre, P; Van Cutsem, E; Vandenmaegdenbergh, V; De Roo, M

1990-10-01

The role of the distal stomach in gastric emptying was studied. Ten patients with proximal gastric vagotomy (PV) and 10 age-matched patients with Roux-en-Y gastro-jejunostomy (R-Y) were compared with 10 healthy controls. Gastric emptying of solids and liquids was determined by the use of Tc-99m SC scrambled eggs and In-111 DTPA. In PV, gastric emptying of both solids and liquids was delayed; the prolongation with solids was mainly accounted for by an abnormal lag phase. In R-Y patients, no lag phase was observed, and the solid emptying curve pattern was characterized by early rapid emptying followed by very slow emptying. Both the solid and liquid phases were prolonged. The lag phase is affected by proximal vagotomy and is mainly determined by the distal stomach, which appears to be essential for normal emptying.

Botulinum toxin for treatment of the focal dystonia.

PubMed

Nakamura, Yusaku

2017-07-29

Dystonia is defined as a movement disorder characterized by sustained or intermittent muscles contraction causing abnormal, often repetitive, movements, postures, or both. Dystonic movements are typically patterned and twisting, and may be tremulous. The precis diagnosis of dystonia is difficult for physicians because neurological brain imaging does not provide enough practical information. The diagnosis is depend on clinical experience of physicians. Botulinum toxin treatment is the accepted standard of care for patients with focal dystonia. Botulinum toxin treatment results in significant improvement of decreasing the symptom of dystonia. The success of treatment is dependent on muscle selection for treating involved muscles. Usually performance of botulinum toxin treatment is injected according to clinical experience of surface anatomy or clinical location method. However, the benefit of guidance of botulinum toxin treatment is improve outcome in dystonia. Injection techniques with ultra sound echogram or EMG guidance to identify dystonic muscles can be more benefit for patients.

Early functional impairment of sensory-motor connectivity in a mouse model of spinal muscular atrophy

PubMed Central

Mentis, George Z.; Blivis, Dvir; Liu, Wenfang; Drobac, Estelle; Crowder, Melissa E.; Kong, Lingling; Alvarez, Francisco J.; Sumner, Charlotte J.; O'Donovan, Michael J.

2011-01-01

SUMMARY To define alterations of neuronal connectivity that occur during motor neuron degeneration, we characterized the function and structure of spinal circuitry in spinal muscular atrophy (SMA) model mice. SMA motor neurons show reduced proprioceptive reflexes that correlate with decreased number and function of synapses on motor neuron somata and proximal dendrites. These abnormalities occur at an early stage of disease in motor neurons innervating proximal hindlimb muscles and medial motor neurons innervating axial muscles, but only at end-stage disease in motor neurons innervating distal hindlimb muscles. Motor neuron loss follows afferent synapse loss with the same temporal and topographical pattern. Trichostatin A, which improves motor behavior and survival of SMA mice, partially restores spinal reflexes illustrating the reversibility of these synaptic defects. De-afferentation of motor neurons is an early event in SMA and may be a primary cause of motor dysfunction that is amenable to therapeutic intervention. PMID:21315257

Studying groundwater and surface water interactions using airborne remote sensing in Heihe River basin, northwest China

NASA Astrophysics Data System (ADS)

Liu, C.; Liu, J.; Hu, Y.; Zheng, C.

2015-05-01

Managing surface water and groundwater as a unified system is important for water resource exploitation and aquatic ecosystem conservation. The unified approach to water management needs accurate characterization of surface water and groundwater interactions. Temperature is a natural tracer for identifying surface water and groundwater interactions, and the use of remote sensing techniques facilitates basin-scale temperature measurement. This study focuses on the Heihe River basin, the second largest inland river basin in the arid and semi-arid northwest of China where surface water and groundwater undergoes dynamic exchanges. The spatially continuous river-surface temperature of the midstream section of the Heihe River was obtained by using an airborne pushbroom hyperspectral thermal sensor system. By using the hot spot analysis toolkit in the ArcGIS software, abnormally cold water zones were identified as indicators of the spatial pattern of groundwater discharge to the river.

[Research on the incidence and prevalence of congenital abnormalities in Iaşi district and Iaşi city, from 2001 to 2008].

PubMed

Chiosac, Alina Andreea Andreescu; Manole, Alina; Gorduza, E V; Stamatin, Maria; Titianus, Monica; Ivan, A

2010-01-01

Congenital abnormalities (CA) are deviations from the normal embryonic development that appear antenatal and they are characterized by the alteration of the morphology and function of an organ, system of organs or even of the entire body. The study, on a period of eight years, included 1685 children with CA, from which 58% were males and 50% were from the country-side. It has been observed that 36% of the CA cases were premature births and 64% were normal term births. Also, 21% of the children with CA weighed less than 2700 grams at birth and 79% weighed more than 2700 grams at birth. The birth's APGAR score has been less than 7 in 30% of the cases and higher than 7 in 70% of the cases. 72% of the cases were natural births and 28% were caesarian births. 88% of the CA cases were singular congenital abnormalities and 12% were multiple congenital abnormalities. 24% of the CA were cardiac abnormalities and 21% were skeletal abnormalities. 3% of the subjects of the study have died, of which 69% died from cardiac abnormalities, 22% from hydrocephalus abnormalities, 7% from diaphragmatic hernia and 2% from renal congenital abnormalities.

COMPARISON OF REAL-TIME MICROVASCULAR ABNORMALITIES IN PEDIATRIC AND ADULT SICKLE CELL ANEMIA PATIENTS

PubMed Central

Cheung, Anthony T.W.; Miller, Joshua W.; Craig, Sarah M.; To, Patricia L.; Lin, Xin; Samarron, Sandra L.; Chen, Peter C.Y.; Zwerdling, Theodore; Wun, Ted; Li, Chin-Shang; Green, Ralph

2010-01-01

The conjunctival microcirculation in 14 pediatric and 8 adult sickle cell anemia (SCA) patients was studied using computer-assisted intravital microscopy. The bulbar conjunctiva in SCA patients in both age groups exhibited a blanched/avascular appearance characterized by decreased vascularity. SCA patients from both age groups had many of the same abnormal morphometric {vessel diameter, vessel distribution, morphometry (shape), tortuosity, arteriole:venule (A:V) ratio, and hemosiderin deposits} and dynamic {vessel sludging/sludged flow, boxcar blood (trickled) flow and abnormal flow velocity} abnormalities. A severity index (SI) was computed to quantify the degree of vasculopathy for comparison between groups. The severity of vasculopathy differed significantly between the pediatric and adult patients (SI: 4.2 ± 1.8 vs 6.6 ± 2.4; p=0.028), indicative of a lesser degree of overall severity in the pediatric patients. Specific abnormalities that were less prominent in the pediatric patients included abnormal vessel morphometry and tortuosity. Sludged flow, abnormal vessel distribution, abnormal A:V ratio, and boxcar flow, appeared in high prevalence in both age groups. The results indicate that SCA microvascular abnormalities develop in childhood and the severity of vasculopathy likely progresses with age. Intervention and effective treatment/management modalities should target pediatric patients to ameliorate, slow down or prevent progressive microvascular deterioration. PMID:20872552

Left globus pallidus abnormality in never-medicated patients with schizophrenia

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

Early, T.S.; Reiman, E.M.; Raichle, M.E.

1987-01-01

Schizophrenia is a severe psychiatric disorder characterized by onset in young adulthood, the occurrence of hallucinations and delusions, and the development of enduring psychosocial disability. The pathophysiology of this disorder remains unknown. Studies of cerebral blood flow and metabolism designed to identify brain abnormalities in schizophrenia have been limited by inadequate methods of anatomical localization and the possibility of persistent medication effects. The authors have now used positron emission tomography and a validated method of anatomical localization in an attempt to identify abnormalities of regional cerebral blood flow in newly diagnosed never-medicated patients with schizophrenia. An exploratory study of 5more » patients and 10 normal control subjects identified abnormally high blood flow in the left globus pallidus of patients with schizophrenia. A replication study of 5 additional patients and 10 additional control subjects confirmed this finding. No other abnormalities were found.« less

Characterization and prognostic implication of 17 chromosome abnormalities in myelodysplastic syndrome.

PubMed

Sánchez-Castro, Judit; Marco-Betés, Víctor; Gómez-Arbonés, Xavier; Arenillas, Leonor; Valcarcel, David; Vallespí, Teresa; Costa, Dolors; Nomdedeu, Benet; Jimenez, María José; Granada, Isabel; Grau, Javier; Ardanaz, María T; de la Serna, Javier; Carbonell, Félix; Cervera, José; Sierra, Adriana; Luño, Elisa; Cervero, Carlos J; Falantes, José; Calasanz, María J; González-Porrás, José R; Bailén, Alicia; Amigo, M Luz; Sanz, Guillermo; Solé, Francesc

2013-07-01

The prognosis of chromosome 17 (chr17) abnormalities in patients with primary myelodysplastic syndrome (MDS) remains unclear. The revised International Prognostic Scoring System (IPSS-R) includes these abnormalities within the intermediate cytogenetic risk group. This study assessed the impact on overall survival (OS) and risk of acute myeloid leukemia transformation (AMLt) of chr17 abnormalities in 88 patients with primary MDS. We have compared this group with 1346 patients with primary MDS and abnormal karyotype without chr17 involved. The alterations of chr17 should be considered within group of poor prognosis. The different types of alterations of chromosome 17 behave different prognosis. The study confirms the intermediate prognostic impact of the i(17q), as stated in IPSS-R. The results of the study, however, provide valuable new information on the prognostic impact of alterations of chromosome 17 in complex karyotypes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Developing Gene Silencing for the Study and Treatment of Dystonia

DTIC Science & Technology

2015-11-01

cause abnormal twisting postures. DYT1 dystonia is an autosomal dominant disease with onset of dystonia during childhood . The most common early onset...SUPPLEMENTARY NOTES 14. ABSTRACT Dystonia is a debilitating neurological disease with no cure. In dystonia, there are involuntary muscle contractions that...is a debilitating neurological disease with no cure that is characterized by involuntary muscle contractions that cause abnormal twisting postures

Dorsal midbrain syndrome associated with persistent neck extension: Clinical and diagnostic imaging findings in 2 dogs

PubMed Central

Canal, Sara; Baroni, Massimo; Falzone, Cristian; De Benedictis, Giulia M.; Bernardini, Marco

2015-01-01

Two young dogs were evaluated for an acute onset of abnormal head posture and eye movement. Neurological examination was characterized mostly by permanent neck extension, abnormalities of pupils, and eye movement. A mesencephalic mass lesion was detected on magnetic resonance imaging in both cases. Neurophysiological pathways likely responsible for this peculiar clinical presentation are discussed. PMID:26663922

The non-motor syndrome of primary dystonia: clinical and pathophysiological implications

PubMed Central

Stamelou, Maria; Edwards, Mark J.; Hallett, Mark

2012-01-01

Dystonia is typically considered a movement disorder characterized by motor manifestations, primarily involuntary muscle contractions causing twisting movements and abnormal postures. However, growing evidence indicates an important non-motor component to primary dystonia, including abnormalities in sensory and perceptual functions, as well as neuropsychiatric, cognitive and sleep domains. Here, we review this evidence and discuss its clinical and pathophysiological implications. PMID:21933808

Abnormal Vestibulo-Ocular Reflexes in Autism: A Potential Endophenotype

DTIC Science & Technology

2013-06-01

Annual Report for 15 May 2012 – 14 May 2013 8 Table 5. Summary of Gaze Evoked Nystagmus Tests (no differences between groups) Target...abnormalities of vestibulo-ocular reflexes (VOR) in Autism Spectrum Disorder (ASD). Specific Aim 1: Characterize horizontal VOR post-rotary nystagmus ...without optokinetic feedback using a velocity step test. We hypothesize that in ASD vertical eye movement intrusions during horizontal nystagmus will

Simpson-Golabi-Behmel syndrome types I and II.

PubMed

Tenorio, Jair; Arias, Pedro; Martínez-Glez, Víctor; Santos, Fernando; García-Miñaur, Sixto; Nevado, Julián; Lapunzina, Pablo

2014-09-20

Simpson-Golabi-Behmel syndrome (SGBS) is a rare overgrowth syndrome clinically characterized by multiple congenital abnormalities, pre/postnatal overgrowth, distinctive craniofacial features, macrocephaly, and organomegaly. Abnormalities of the skeletal system, heart, central nervous system, kidney, and gastrointestinal tract may also be observed. Intellectual disability, early motor milestones and speech delay are sometimes present; however, there are a considerable number of individuals with normal intelligence.

Metacarpophalangeal pattern profile analysis: useful diagnostic tool for differentiating between dyschondrosteosis, Turner syndrome, and hypochondroplasia.

PubMed

Laurencikas, E; Sävendahl, L; Jorulf, H

2006-06-01

To assess the value of the metacarpophalangeal pattern profile (MCPP) analysis as a diagnostic tool for differentiating between patients with dyschondrosteosis, Turner syndrome, and hypochondroplasia. Radiographic and clinical data from 135 patients between 1 and 51 years of age were collected and analyzed. The study included 25 patients with hypochondroplasia (HCP), 39 with dyschondrosteosis (LWD), and 71 with Turner syndrome (TS). Hand pattern profiles were calculated and compared with those of 110 normal individuals. Pearson correlation coefficient (r) and multivariate discriminant analysis were used for pattern profile analysis. Pattern variability index, a measure of dysmorphogenesis, was calculated for LWD, TS, HCP, and normal controls. Our results demonstrate that patients with LWD, TS, or HCP have distinct pattern profiles that are significantly different from each other and from those of normal controls. Discriminant analysis yielded correct classification of normal versus abnormal individuals in 84% of cases. Classification of the patients into LWD, TS, and HCP groups was successful in 75%. The correct classification rate was higher (85%) when differentiating two pathological groups at a time. Pattern variability index was not helpful for differential diagnosis of LWD, TS, and HCP. Patients with LWD, TS, or HCP have distinct MCPPs and can be successfully differentiated from each other using advanced MCPP analysis. Discriminant analysis is to be preferred over Pearson correlation coefficient because it is a more sensitive and specific technique. MCPP analysis is a helpful tool for differentiating between syndromes with similar clinical and radiological abnormalities.

Transient Maternal Hypothyroidism Alters Neural Progenitor Expression Resulting in Abnormal Brain Development

EPA Science Inventory

Heterotopias are a birth defect of the brain, and have varying etiologies in humans. They are characterized as clusters of mislocalized neurons, and are associated with disorders such as autism, epilepsy, and learning disabilities. We have previously characterized the robust pene...

Transient Maternal Hypothyroidism Alters Neural Progenitors Resulting in Abnormal Brain Development

EPA Science Inventory

Heterotopias are a birth defect of the brain and have varying etiologies in humans. They are characterized as clusters of mislocalized neurons and are associated with disorders such as autism, epilepsy, and learning disabilities. We have previously characterized the robust penetr...

Manometric characterization of rectal dysfunction following radical hysterectomy.

PubMed

Barnes, W; Waggoner, S; Delgado, G; Maher, K; Potkul, R; Barter, J; Benjamin, S

1991-08-01

Bladder dysfunction thought to be due to partial denervation has been described following radical hysterectomy. Some patients experience acute and chronic rectal dysfunction characterized by difficulty with defecation and loss of defecatory urge. To define this abnormality, anorectal pressure profiles were examined in 15 patients with Stage I carcinoma of the cervix before and after radical hysterectomy. Profiles were done using standard anorectal manometry with a water-infused system. In all patients preoperative manometric profiles were normal; postoperative studies were abnormal in all patients. Features seen include altered relaxation of the internal sphincter, increased distension needed to trigger relaxation, and decreased rectal sensation; external sphincters and resting internal sphincters were unchanged. Postoperatively, 12 patients reported problems with rectal function. A physiologic defect is definable in patients undergoing radical hysterectomy; this suggests disruption of the spinal reflex arcs controlling rectal emptying. These physiologic abnormalities correlate with the clinical symptomatology experienced by some patients. Continuing definition and evaluation of management options in this situation should be useful in developing effective therapy for rectal dysfunction following radical hysterectomy.