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Sample records for behavioral abnormalities ventricular

  1. Abnormal right ventricular relaxation in pulmonary hypertension

    PubMed Central

    La Gerche, Andre; Roberts, Timothy J.; Prior, David L.; MacIsaac, Andrew I.; Burns, Andrew T.

    2015-01-01

    Abstract Left ventricular diastolic dysfunction is a well-described complication of systemic hypertension. However, less is known regarding the effect of chronic pressure overload on right ventricular (RV) diastolic function. We hypothesized that pulmonary hypertension (PHT) is associated with abnormal RV early relaxation and that this would be best shown by invasive pressure measurement. Twenty-five patients undergoing right heart catheterization for investigation of breathlessness and/or suspected PHT were studied. In addition to standard measurements, RV pressure was sampled with a high-fidelity micromanometer, and RV pressure/time curves were analyzed. Patients were divided into a PHT group and a non-PHT group on the basis of a derived mean pulmonary artery systolic pressure of 25 mmHg. Eleven patients were classified to the PHT group. This group had significantly higher RV minimum diastolic pressure ( vs. mmHg, ) and RV end-diastolic pressure (RVEDP; vs. mmHg, ), and RV τ was significantly prolonged ( vs. ms, ). There were strong correlations between RV τ and RV minimum diastolic pressure (, ) and between RV τ and RVEDP (, ). There was a trend toward increased RV contractility (end-systolic elastance) in the PHT group ( vs. mmHg/mL, ) and a correlation between RV systolic pressure and first derivative of maximum pressure change (, ). Stroke volumes were similar. Invasive measures of RV early relaxation are abnormal in patients with PHT, whereas measured contractility is static or increasing, which suggests that diastolic dysfunction may precede systolic dysfunction. Furthermore, there is a strong association between measures of RV relaxation and RV filling pressures. PMID:26064464

  2. Neurological and behavioral abnormalities, ventricular dilatation, altered cellular functions, inflammation, and neuronal injury in brains of mice due to common, persistent, parasitic infection

    PubMed Central

    Hermes, Gretchen; Ajioka, James W; Kelly, Krystyna A; Mui, Ernest; Roberts, Fiona; Kasza, Kristen; Mayr, Thomas; Kirisits, Michael J; Wollmann, Robert; Ferguson, David JP; Roberts, Craig W; Hwang, Jong-Hee; Trendler, Toria; Kennan, Richard P; Suzuki, Yasuhiro; Reardon, Catherine; Hickey, William F; Chen, Lieping; McLeod, Rima

    2008-01-01

    Background Worldwide, approximately two billion people are chronically infected with Toxoplasma gondii with largely unknown consequences. Methods To better understand long-term effects and pathogenesis of this common, persistent brain infection, mice were infected at a time in human years equivalent to early to mid adulthood and studied 5–12 months later. Appearance, behavior, neurologic function and brain MRIs were studied. Additional analyses of pathogenesis included: correlation of brain weight and neurologic findings; histopathology focusing on brain regions; full genome microarrays; immunohistochemistry characterizing inflammatory cells; determination of presence of tachyzoites and bradyzoites; electron microscopy; and study of markers of inflammation in serum. Histopathology in genetically resistant mice and cytokine and NRAMP knockout mice, effects of inoculation of isolated parasites, and treatment with sulfadiazine or αPD1 ligand were studied. Results Twelve months after infection, a time equivalent to middle to early elderly ages, mice had behavioral and neurological deficits, and brain MRIs showed mild to moderate ventricular dilatation. Lower brain weight correlated with greater magnitude of neurologic abnormalities and inflammation. Full genome microarrays of brains reflected inflammation causing neuronal damage (Gfap), effects on host cell protein processing (ubiquitin ligase), synapse remodeling (Complement 1q), and also increased expression of PD-1L (a ligand that allows persistent LCMV brain infection) and CD 36 (a fatty acid translocase and oxidized LDL receptor that mediates innate immune response to beta amyloid which is associated with pro-inflammation in Alzheimer's disease). Immunostaining detected no inflammation around intra-neuronal cysts, practically no free tachyzoites, and only rare bradyzoites. Nonetheless, there were perivascular, leptomeningeal inflammatory cells, particularly contiguous to the aqueduct of Sylvius and hippocampus

  3. Abnormal subendocardial function in restrictive left ventricular disease.

    PubMed Central

    Henein, M Y; Gibson, D G

    1994-01-01

    OBJECTIVE--To study possible disturbances in left ventricular long axis function in patients with a restrictive filling pattern. DESIGN--Prospective examination of the left ventricular transverse and longitudinal axes, transmitral flow, and the apexcardiogram. SETTING--A tertiary referral centre for cardiac diseases. SUBJECTS--21 normal subjects, age (SD) 51(11); 30 patients of similar age with a restrictive left ventricular filling pattern, defined as short early diastolic deceleration time less than the lower 95% confidence limit of the normal value (120 ms). 20 patients had a normal and 10 had an increased left ventricular end diastolic cavity size. RESULTS--Mitral Doppler echocardiography: E wave velocity was high only in patients with a normal cavity size. A wave velocity was greatly reduced in the two groups (P < 0.001) so that the E/A ratio was abnormally high. The relative A wave amplitude on the apexcardiogram was greatly increased in the two groups: 46(15)% (mean (SD)) and 54(4)% v 15(5)%. Minor axis: Fractional shortening was reduced from 30(10)% to 17(7)% in patients with normal cavity size and to 13(4.2)% in those with a dilated cavity (P < 0.001), as was the posterior wall thickening fraction from 100(30)% to 42(20)% and 50(25)% respectively (P < 0.001). Total systolic epicardial motion was normal and isovolumic relaxation time was short in the two groups. Long axis: Left ventricular abnormalities included reduced total amplitude of motion and its component during atrial systole (P < 0.001 for the two groups at both sites). Peak long axis shortening and lengthening were decreased at both left ventricular sites (P < 0.001). The time intervals from q wave of the electrocardiogram and A2 (aortic valve closure) to the onset of shortening and lengthening respectively were increased (both P < 0.001). Right ventricular long axis function was similarly affected but to a lesser extent. CONCLUSION--Left ventricular long axis function is consistently abnormal in

  4. Bioenergetic abnormalities associated with severe left ventricular hypertrophy.

    PubMed Central

    Zhang, J; Merkle, H; Hendrich, K; Garwood, M; From, A H; Ugurbil, K; Bache, R J

    1993-01-01

    Transmurally localized 31P-nuclear magnetic resonance spectroscopy (NMR) was used to study the effect of severe pressure overload left ventricular hypertrophy (LVH) on myocardial high energy phosphate content. Studies were performed on 8 normal dogs and 12 dogs with severe left ventricular hypertrophy produced by banding the ascending aorta at 8 wk of age. Spatially localized 31P-NMR spectroscopy provided measurements of the transmural distribution of myocardial ATP, phosphocreatine (CP), and inorganic phosphate (Pi); spectra were calibrated from measurements of ATP content in myocardial biopsies using HPLC. Blood flow was measured with microspheres. In hypertrophied hearts during basal conditions, ATP was decreased by 42%, CP by 58%, and the CP/ATP ratio by 32% in comparison with normal. Increasing myocardial blood flow with adenosine did not correct these abnormalities, indicating that they were not the result of persistent hypoperfusion. Atrial pacing at 200 and 240 beats per min caused no change in high energy phosphate content in normal hearts but resulted in further CP depletion with Pi accumulation in the inner left ventricular layers of the hypertrophied hearts. These changes were correlated with redistribution of blood flow away from the subendocardium in LVH hearts. These findings demonstrate that high energy phosphate levels and the CP/ATP ratio are significantly decreased in severe LVH. These abnormalities are proportional to the degree of hypertrophy but are not the result of persistent abnormalities of myocardial perfusion. In contrast, depletion of CP and accumulation of Pi during tachycardia in LVH are closely related to the pacing-induced perfusion abnormalities and likely reflect subendocardial ischemia. PMID:8349829

  5. Abnormal ventricular development in preterm neonates with visually normal MRIs

    NASA Astrophysics Data System (ADS)

    Shi, Jie; Wang, Yalin; Lao, Yi; Ceschin, Rafael; Mi, Liang; Nelson, Marvin D.; Panigrahy, Ashok; Leporé, Natasha

    2015-12-01

    Children born preterm are at risk for a wide range of neurocognitive and neurobehavioral disorders. Some of these may stem from early brain abnormalities at the neonatal age. Hence, a precise characterization of neonatal neuroanatomy may help inform treatment strategies. In particular, the ventricles are often enlarged in neurocognitive disorders, due to atrophy of surrounding tissues. Here we present a new pipeline for the detection of morphological and relative pose differences in the ventricles of premature neonates compared to controls. To this end, we use a new hyperbolic Ricci flow based mapping of the ventricular surfaces of each subjects to the Poincaré disk. Resulting surfaces are then registered to a template, and a between group comparison is performed using multivariate tensor-based morphometry. We also statistically compare the relative pose of the ventricles within the brain between the two groups, by performing a Procrustes alignment between each subject's ventricles and an average shape. For both types of analyses, differences were found in the left ventricles between the two groups.

  6. Right Ventricular Outflow Tract Tachycardia with Structural Abnormalities of the Right Ventricle and Left Ventricular Diverticulum

    PubMed Central

    Martini, Bortolo; Trevisi, Nicola; Martini, Nicolò; Zhang, Li

    2015-01-01

    A 43-year-old woman presented to the emergency room with a sustained ventricular tachycardia (VT). ECG showed a QRS in left bundle branch block morphology with inferior axis. Echocardiography, ventricular angiography, and cardiac magnetic resonance imaging (CMRI) revealed a normal right ventricle and a left ventricular diverticulum. Electrophysiology studies with epicardial voltage mapping identified a large fibrotic area in the inferolateral layer of the right ventricular wall and a small area of fibrotic tissue at the anterior right ventricular outflow tract. VT ablation was successfully performed with combined epicardial and endocardial approaches. PMID:26509086

  7. Increase in the embedding dimension in the heart rate variability associated with left ventricular abnormalities

    NASA Astrophysics Data System (ADS)

    Andrés, D. S.; Irurzun, I. M.; Mitelman, J.; Mola, E. E.

    2006-10-01

    In the present study, the authors report evidence that the existence of premature ventricular contractions increases the embedding dimension of the cardiac dynamics. They also analyze patients with congestive heart failure, a severe clinical condition associated with abnormal left ventricular function. Results also show an increase in the embedding dimension of the heart rate variability. They used electrocardiograms collected by themselves with quality standards that make them comparable with other databases.

  8. Different effects of abnormal activation and myocardial disease on left ventricular ejection and filling times

    PubMed Central

    Zhou, Q; Henein, M; Coats, A; Gibson, D

    2000-01-01

    BACKGROUND—Ventricular activation is often abnormal in patients with dilated cardiomyopathy, but its specific effects on timing remain undetermined.
OBJECTIVE—To investigate the use of the ratio of the sum of left ventricular ejection and filling times to the total RR interval (Z ratio) to dissociate the effects of abnormal activation from those of cavity dilatation.
METHODS—Subjects were 20 normal individuals, 11 patients with isolated left bundle branch block (LBBB, QRS duration > 120 ms), 17 with dilated cardiomyopathy and normal activation, and 23 with dilated cardiomyopathy and LBBB. An additional 30 patients (nine with normal ventricular systolic function and 21 with dilated cardiomyopathy) were studied before and after right ventricular pacing. Left ventricular ejection and filling times were measured by pulsed wave Doppler and cavity size by M mode echocardiography.
RESULTS—Z ratio was independent of RR interval in all groups. Mean (SD) Z ratio was 82 (10)% for normal subjects, 66 (10)% for isolated LBBB (p < 0.01 v normal), 77 (7)% for dilated cardiomyopathy without LBBB (NS v normal), and 61 (7)% for dilated cardiomyopathy with LBBB (p < 0.01 v normal). In the nine patients with normal left ventricular size and QRS duration, Z ratio fell from 88 (6)% in sinus rhythm to 77 (10)% with right ventricular pacing (p = 0.26). In the 21 patients with dilated cardiomyopathy and LBBB, Z ratio rose from 59 (10)% in sinus rhythm to 74 (9)% with right ventricular DDD pacing (p < 0.001).
CONCLUSIONS—Z ratio dissociates the effects of abnormal ventricular activation and systolic disease. It also clearly differentiates right ventricular pacing from LBBB. It may thus be useful in comparing the haemodynamic effects of different pacing modes in patients with or without left ventricular disease.


Keywords: dilated cardiomyopathy; pacemaker; left bundle branch block; echocardiography. PMID:10956289

  9. Behavioral abnormalities in captive nonhuman primates.

    PubMed

    Mallapur, Avanti; Choudhury, B C

    2003-01-01

    In this study, we dealt with 11 species of nonhuman primates across 10 zoos in India. We recorded behavior as instantaneous scans between 9 a.m. and 5 p.m. In the study, we segregated behaviors for analyses into abnormal, undesirable, active, and resting. The 4 types of abnormal behavior exhibited included floating limb, self-biting, self-clasping, and stereotypic pacing. In the study, we recorded 2 types of undesirable behavior: autoerotic stimulation and begging. Langurs and group-housed macaques did not exhibit undesirable behaviors. A male lion-tailed macaque and a male gibbon exhibited begging behavior. autoerotic stimulation and self-biting occurred rarely. Males exhibited higher levels of undesirable behavior than did females. Animals confiscated from touring zoos, circuses, and animal traders exhibited higher levels of abnormal behaviors than did animals reared in larger, recognized zoos. The stump-tailed macaque was the only species to exhibit floating limb, autoerotic stimulation, self-biting, and self-clasping. Our results show that rearing experience and group composition influence the proportions of abnormal behavior exhibited by nonhuman primates in captivity. The history of early social and environmental deprivation in these species of captive nonhuman primates probably is critical in the development of behavioral pathologies. Establishing this will require further research. PMID:14965782

  10. Conduction abnormalities and ventricular arrhythmogenesis: The roles of sodium channels and gap junctions

    PubMed Central

    Tse, Gary; Yeo, Jie Ming

    2015-01-01

    Ventricular arrhythmias arise from disruptions in the normal orderly sequence of electrical activation and recovery of the heart. They can be categorized into disorders affecting predominantly cellular depolarization or repolarization, or those involving action potential (AP) conduction. This article briefly discusses the factors causing conduction abnormalities in the form of unidirectional conduction block and reduced conduction velocity (CV). It then examines the roles that sodium channels and gap junctions play in AP conduction. Finally, it synthesizes experimental results to illustrate molecular mechanisms of how abnormalities in these proteins contribute to such conduction abnormalities and hence ventricular arrhythmogenesis, in acquired pathologies such as acute ischaemia and heart failure, as well as inherited arrhythmic syndromes. PMID:26839915

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

    SciTech Connect

    Botvinick, E.H.; Frais, M.A.; Shosa, D.W.; O'Connell, J.W.; Pacheco-Alvarez, J.A.; Scheinman, M.; Hattner, R.S.; Morady, F.; Faulkner, D.B.

    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 and 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.

  12. [Subarachnoid hemorrhage complicated with different manifestations of transient abnormal left ventricular wall motion: two case reports].

    PubMed

    Inoue, Fumitaka; Tsuzuki, Takashi; Thoma, Yoshiki; Shiono, Shigeru; Tabuse, Hisayuki; Hoshida, Thoru; Saito, Yoshihiko

    2006-05-01

    Two patients with subarachnoid hemorrhage presented with transient abnormal left ventricular wall motion. Case 1 was a 56-year-old man. Electrocardiography showed ST segment elevation in leads I, II, II, aVL, aVF, V3-V6. Echocardiography showed localized left ventricular hypokinesis around the apical area (takotsubo-like cardiomyopathy). Ejection fraction was 20% (1st hospital day). Troponin T was positive. Case 2 was a 48-year-old woman. Electrocardiography showed ST segment elevation in leads I, aVL, V2-V6 and ST segment depression in leads II, III, aVF, V1. Echocardiography showed diffuse left ventricular hypokinesis. Ejection fraction was 21% (1st hospital day). Troponin T was positive. These two patients had no history of cardiac disease, and coronary angiography showed no stenosis or obstruction. Catecholamine was given for 1 day(Case 1) and for about 2 weeks (Case 2). Pimobendane was given to Case 2. Ejection fraction was 57% in Case 1 (2nd hospital day) and 33% (6th hospital day), 43% (7th hospital day)and 58% (16th hospital day)in Case 2. The recovery period of left ventricular abnormal wall motion and the medication period were longer in Case 2 showing diffuse hypokinesis than in Case 1 showing takotsubo-like cardiomyopathy. PMID:16764331

  13. Implications of abnormal right ventricular thallium uptake in acute myocardial infarction

    SciTech Connect

    Nestico, P.F.; Hakki, A.H.; Felsher, J.; Heo, J.; Iskandrian, A.S.

    1986-08-01

    The correlates of abnormal right ventricular (RV) thallium uptake were examined in 116 patients with documented acute myocardial infarction (AMI) who underwent predischarge thallium-201 scintigraphy at rest, radionuclide angiography and 24-hour ambulatory electrocardiography. The patients were separated into 2 groups: patients group 1 (n = 31) had increased RV thallium uptake and those in group 2 (n = 85) had no such uptake. The 2 groups were comparable in age, type and site of AMI, peak creatine kinase level, systolic blood pressure and heart rate. However, compared with group 2, group 1 had a lower mean left ventricular (LV) ejection fraction (33 +/- 15% vs 39 +/- 14%, p less than 0.05), higher prevalence of increased lung thallium uptake (45% vs 22%, p less than 0.02), more extensive LV perfusion defects (4.4 +/- 2.9 vs 3.0 +/- 3.0 segments, p less than 0.03) and more complex ventricular arrhythmias (55% vs 35%, p less than 0.05). At a mean follow-up of 6 months, 17 patients (8 in group 1 and 9 in group 2) died from cardiac causes. Actuarial life-table analysis showed that the survival rate was better in group 2 than in group 1 (Mantel-Cox statistics = 4.62, p = 0.03). Thus, patients with AMI and abnormal RV thallium uptake have worse LV function, more complex ventricular arrhythmias and worse prognosis.

  14. Abnormal behaviors detection using particle motion model

    NASA Astrophysics Data System (ADS)

    Chen, Yutao; Zhang, Hong; Cheng, Feiyang; Yuan, Ding; You, Yuhu

    2015-03-01

    Human abnormal behaviors detection is one of the most challenging tasks in the video surveillance for the public security control. Interaction Energy Potential model is an effective and competitive method published recently to detect abnormal behaviors, but their model of abnormal behaviors is not accurate enough, so it has some limitations. In order to solve this problem, we propose a novel Particle Motion model. Firstly, we extract the foreground to improve the accuracy of interest points detection since the complex background usually degrade the effectiveness of interest points detection largely. Secondly, we detect the interest points using the graphics features. Here, the movement of each human target can be represented by the movements of detected interest points of the target. Then, we track these interest points in videos to record their positions and velocities. In this way, the velocity angles, position angles and distance between each two points can be calculated. Finally, we proposed a Particle Motion model to calculate the eigenvalue of each frame. An adaptive threshold method is proposed to detect abnormal behaviors. Experimental results on the BEHAVE dataset and online videos show that our method could detect fight and robbery events effectively and has a promising performance.

  15. Usefulness of verapamil for congestive heart failure associated with abnormal left ventricular diastolic filling and normal left ventricular systolic performance

    SciTech Connect

    Setaro, J.F.; Zaret, B.L.; Schulman, D.S.; Black, H.R.; Soufer, R. )

    1990-10-15

    Normal left ventricular systolic performance with impaired left ventricular diastolic filling may be present in a substantial number of patients with congestive heart failure (CHF). To evaluate the effect of oral verapamil in this subset, 20 men (mean age 68 +/- 5 years) with CHF, intact left ventricular function (ejection fraction greater than 45%) and abnormal diastolic filling (peak filling rate less than 2.5 end-diastolic volumes per second (edv/s)) were studied in a placebo-controlled, double-blind 5-week crossover trial. All patients underwent echocardiography to rule out significant valvular disease, and thallium-201 stress scintigraphy to exclude major active ischemia. Compared to baseline values, verapamil significantly improved exercise capacity by 33% (13.9 +/- 4.3 vs 10.7 +/- 3.4 minutes at baseline) and peak filling rate by 30% (2.29 +/- 0.54 vs 1.85 +/- 0.45 edv/s at baseline) (all p less than 0.05). Placebo values were 12.3 +/- 4.0 minutes and 2.16 +/- 0.48 edv/s, respectively (difference not significant for both). Improvement from baseline in an objective clinico-radiographic heart failure score (scale 0 to 13) was significantly greater with verapamil compared to placebo (median improvement in score: 3 vs 1, p less than 0.01). Mean ejection fraction and systolic blood pressure were unchanged from baseline; diastolic blood pressure and heart rate decreased to a small degree. Verapamil may have therapeutic efficacy in patients with CHF, preserved systolic function and impaired diastolic filling.

  16. Abnormal Behavior in Relation to Cage Size in Rhesus Monkeys

    ERIC Educational Resources Information Center

    Paulk, H. H.; And Others

    1977-01-01

    Examines the effects of cage size on stereotyped and normal locomotion and on other abnormal behaviors in singly caged animals, whether observed abnormal behaviors tend to co-occur, and if the development of an abnormal behavior repertoire leads to reduction in the number of normal behavior categories. (Author/RK)

  17. Abnormal left ventricular torsion and cardiac autonomic dysfunction in subjects with type 1 diabetes mellitus

    PubMed Central

    Piya, Milan K.; Shivu, Ganesh Nallur; Tahrani, Abd; Dubb, Kiran; Abozguia, Khalid; Phan, T.T.; Narendran, Parth; Pop-Busui, Rodica; Frenneaux, Michael; Stevens, Martin J.

    2011-01-01

    Left ventricular torsion is increased and cardiac energetics are reduced in uncomplicated type 1 diabetes mellitus (T1DM). Our aim was to determine the relationships of these abnormalities to cardiovascular autonomic neuropathy (CAN) in subjects with T1DM. A cross-sectional study was conducted in 20 subjects with T1DM free of known coronary heart disease attending an outpatient clinic. Cardiovascular autonomic neuropathy was assessed using heart rate variability studies and the continuous wavelet transform method. Left ventricular function was determined by speckle tracking echocardiography. Magnetic resonance spectroscopy and stress magnetic resonance imaging were used to measure cardiac energetics and myocardial perfusion reserve index, respectively. Twenty subjects (age, 35 ± 8 years; diabetes duration, 16 ± 9 years; hemoglobin A1c, 8.0% ± 1.1%) were recruited. Forty percent of the subjects exhibited definite or borderline CAN. Log peak radial strain was significantly increased in subjects with CAN compared with those without (1.56 ± 0.06 vs 1.43 ± 0.14, respectively; P = .011). Data were adjusted for log duration of diabetes, and log left ventricular torsion correlated (r = 0.593, P = .01) with log low-frequency to high-frequency ratio during the Valsalva maneuver. Log isovolumic relaxation time correlated significantly with log Valsalva ratio and log proportion of differences in consecutive RR intervals of normal beats greater than 50 milliseconds during deep breathing. However, CAN did not correlate with cardiac energetics or myocardial perfusion reserve index. Spectral analysis of low-frequency to high-frequency ratio power during the Valsalva maneuver is associated with altered left ventricular torsion in subjects with T1DM. Parasympathetic dysfunction is closely associated with diastolic deficits. Cardiovascular autonomic neuropathy is not however the principal cause of impaired cardiac energetics. The role of CAN in the development of cardiomyopathy

  18. Comparison of diagnostic accuracy, time dependency, and prognostic impact of abnormal Q waves, combined electrocardiographic criteria, and ST segment abnormalities in right ventricular infarction.

    PubMed Central

    Zehender, M; Kasper, W; Kauder, E; Schönthaler, M; Olschewski, M; Just, H

    1994-01-01

    OBJECTIVE--To determine the diagnostic and prognostic impact of abnormal Q waves in comparison to or in combination with ST segment abnormalities in the right precordial and inferior leads as indicators of right ventricular infarction during the acute phase of inferior myocardial infarction. DESIGN--Prospective study of a consecutive series of 200 patients with acute inferior myocardial infarction with and without right ventricular infarction. SETTING--Department of internal medicine, university clinic. RESULTS--Right ventricular infarction was diagnosed in 106 (57%) out of 187 patients from the results of coronary angiography, technetium pyrophosphate scanning, and measurement of haemodynamic variables or at necropsy, or both. In the acute phase of inferior infarction ST segment elevation > or = 0.1 mV in any of the right precordial leads V4-6R was the most reliable criterion for right ventricular infarction (sensitivity, 89%; specificity, 83%). Abnormal Q waves in the right precordial leads, the most specific criterion (91%) for right ventricular infarction, were superior to ST segment elevation in patients admitted > 12 hours after the onset of symptoms. Both ST segment elevation in leads V4-6R (increase in in hospital mortality, 6.2-times; P < 0.001; major complications, 2.3-times; P < 0.01) and abnormal Q waves (2.3-times, P < 0.05; 1.8-times, P < 0.05) on admission were highly predictive of a worse outcome during the in hospital period. In the presence of inferior myocardial infarction previously proposed combined electrocardiographic criteria were not better diagnostically or prognostically than ST segment abnormalities and abnormal Q waves alone. CONCLUSIONS--During the first 24 hours of inferior myocardial infarction ST segment elevation and abnormal Q waves derived from the right precordial leads are complementary rather than competitive criteria for reliably diagnosing right ventricular infarction, both indicating a worse in hospital course for the

  19. Abnormal behavior in caged birds kept as pets.

    PubMed

    van Hoek, C S; ten Cate, C

    1998-01-01

    There are a limited number of studies dealing with abnormal behavior in caged birds kept as pets. However, these studies demonstrate the presence of abnormal behavior in both songbirds and parrots. Ethological studies on these birds, as well as studies on domestic and zoo birds, indicate that inappropriate rearing and housing conditions may lead to behavioral abnormalities. Together these data indicate that behavioral abnormalities occur among both wild-caught and domesticated pet birds. The severity and magnitude of these abnormalities is probably underestimated, and there is a need for systematic studies on the nature, origin, variability, species-specificity, and reversibility of behavioral problems in pet birds. Abnormal behavior in caged birds may to some extent be prevented and reduced by environmental enrichment. However, most enrichment studies are anecdotal and not based on a thorough analysis of the behavioral abnormalities, which may lead to measures resulting in a reduction of symptoms rather than the underlying causes. Although it is likely that several of these problems could be reduced by modifying rearing and housing conditions, the current insights into the causal mechanisms underlying abnormal behavior of domesticated and wild-caught pet birds are limited, as are the insights into the possibilities of preventing or curing abnormal behavior. PMID:16363987

  20. A hemodynamics model to study the collective behavior of the ventricular-arterial system

    NASA Astrophysics Data System (ADS)

    Lin Wang, Yuh-Ying; Wang, Wei-Kung

    2013-01-01

    Applying principles from complex systems to study the efficacy of integrative therapies has become a new interest in medical research. We aimed to construct a concise model for the ventricular-arterial (VA) system and to provide a systematic method for exploring its overall behavior. The transportation of blood from the heart to the peripheral arterioles via hydraulic pressure forces was described by a multi-rank model. Parts of the VA system that have strong mutual interactions were combined into a single sub system. Sub systems of four different ranks were characterized. We then applied the multi-rank model to analyze the aortic pressure wave generated by the periodic ventricular blood ejection, the renal pressure in response to the input from the VA system, and the blood flowing from the renal artery to its arterioles. Maintaining the pressure distribution along the main arteries and in all of the organs with the lowest possible ventricular input turned out to be the first principle for the operation of an efficient VA system. By this principle, we pointed out the benefit of some arterial structures in mammals, derived specific regulation rules and deduced some fundamental concepts for healing. The justification of the biomechanics in our model that differed greatly from those in the prevailing models was given. We concluded that the oscillatory motion and the pressure pulse of the arterial system can be analyzed as steady states with resonance behaviors and suggested utilizing this model to construct integrative therapies for diseases correlated with abnormality in blood circulation.

  1. Cell Junction Pathology of Neural Stem Cells Is Associated With Ventricular Zone Disruption, Hydrocephalus, and Abnormal Neurogenesis.

    PubMed

    Guerra, María Montserrat; Henzi, Roberto; Ortloff, Alexander; Lichtin, Nicole; Vío, Karin; Jiménez, Antonio J; Dominguez-Pinos, María Dolores; González, César; Jara, Maria Clara; Hinostroza, Fernando; Rodríguez, Sara; Jara, Maryoris; Ortega, Eduardo; Guerra, Francisco; Sival, Deborah A; den Dunnen, Wilfred F A; Pérez-Fígares, José M; McAllister, James P; Johanson, Conrad E; Rodríguez, Esteban M

    2015-07-01

    Fetal-onset hydrocephalus affects 1 to 3 per 1,000 live births. It is not only a disorder of cerebrospinal fluid dynamics but also a brain disorder that corrective surgery does not ameliorate. We hypothesized that cell junction abnormalities of neural stem cells (NSCs) lead to the inseparable phenomena of fetal-onset hydrocephalus and abnormal neurogenesis. We used bromodeoxyuridine labeling, immunocytochemistry, electron microscopy, and cell culture to study the telencephalon of hydrocephalic HTx rats and correlated our findings with those in human hydrocephalic and nonhydrocephalic human fetal brains (n = 12 each). Our results suggest that abnormal expression of the intercellular junction proteins N-cadherin and connexin-43 in NSC leads to 1) disruption of the ventricular and subventricular zones, loss of NSCs and neural progenitor cells; and 2) abnormalities in neurogenesis such as periventricular heterotopias and abnormal neuroblast migration. In HTx rats, the disrupted NSC and progenitor cells are shed into the cerebrospinal fluid and can be grown into neurospheres that display intercellular junction abnormalities similar to those of NSC of the disrupted ventricular zone; nevertheless, they maintain their potential for differentiating into neurons and glia. These NSCs can be used to investigate cellular and molecular mechanisms underlying this condition, thereby opening the avenue for stem cell therapy. PMID:26079447

  2. Neurobiology of social behavior abnormalities in autism and Williams syndrome.

    PubMed

    Barak, Boaz; Feng, Guoping

    2016-04-26

    Social behavior is a basic behavior mediated by multiple brain regions and neural circuits, and is crucial for the survival and development of animals and humans. Two neuropsychiatric disorders that have prominent social behavior abnormalities are autism spectrum disorders (ASD), which is characterized mainly by hyposociability, and Williams syndrome (WS), whose subjects exhibit hypersociability. Here we review the unique properties of social behavior in ASD and WS, and discuss the major theories in social behavior in the context of these disorders. We conclude with a discussion of the research questions needing further exploration to enhance our understanding of social behavior abnormalities. PMID:27116389

  3. Freud Was Right. . . about the Origins of Abnormal Behavior

    ERIC Educational Resources Information Center

    Muris, Peter

    2006-01-01

    Freud's psychodynamic theory is predominantly based on case histories of patients who displayed abnormal behavior. From a scientific point of view, Freud's analyses of these cases are unacceptable because the key concepts of his theory cannot be tested empirically. However, in one respect, Freud was totally right: most forms of abnormal behavior…

  4. Studying ventricular abnormalities in mild cognitive impairment with hyperbolic Ricci flow and tensor-based morphometry.

    PubMed

    Shi, Jie; Stonnington, Cynthia M; Thompson, Paul M; Chen, Kewei; Gutman, Boris; Reschke, Cole; Baxter, Leslie C; Reiman, Eric M; Caselli, Richard J; Wang, Yalin

    2015-01-01

    Mild Cognitive Impairment (MCI) is a transitional stage between normal aging and dementia and people with MCI are at high risk of progression to dementia. MCI is attracting increasing attention, as it offers an opportunity to target the disease process during an early symptomatic stage. Structural magnetic resonance imaging (MRI) measures have been the mainstay of Alzheimer's disease (AD) imaging research, however, ventricular morphometry analysis remains challenging because of its complicated topological structure. Here we describe a novel ventricular morphometry system based on the hyperbolic Ricci flow method and tensor-based morphometry (TBM) statistics. Unlike prior ventricular surface parameterization methods, hyperbolic conformal parameterization is angle-preserving and does not have any singularities. Our system generates a one-to-one diffeomorphic mapping between ventricular surfaces with consistent boundary matching conditions. The TBM statistics encode a great deal of surface deformation information that could be inaccessible or overlooked by other methods. We applied our system to the baseline MRI scans of a set of MCI subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI: 71 MCI converters vs. 62 MCI stable). Although the combined ventricular area and volume features did not differ between the two groups, our fine-grained surface analysis revealed significant differences in the ventricular regions close to the temporal lobe and posterior cingulate, structures that are affected early in AD. Significant correlations were also detected between ventricular morphometry, neuropsychological measures, and a previously described imaging index based on fluorodeoxyglucose positron emission tomography (FDG-PET) scans. This novel ventricular morphometry method may offer a new and more sensitive approach to study preclinical and early symptomatic stage AD. PMID:25285374

  5. STUDYING VENTRICULAR ABNORMALITIES IN MILD COGNITIVE IMPAIRMENT WITH HYPERBOLIC RICCI FLOW AND TENSOR-BASED MORPHOMETRY

    PubMed Central

    Shi, Jie; Stonnington, Cynthia M.; Thompson, Paul M.; Chen, Kewei; Gutman, Boris; Reschke, Cole; Baxter, Leslie C.; Reiman, Eric M.; Caselli, Richard J.; Wang, Yalin

    2014-01-01

    Mild Cognitive Impairment (MCI) is a transitional stage between normal aging and dementia and people with MCI are at high risk of progression to dementia. MCI is attracting increasing attention, as it offers an opportunity to target the disease process during an early symptomatic stage. Structural magnetic resonance imaging (MRI) measures have been the mainstay of Alzheimer’s disease (AD) imaging research, however, ventricular morphometry analysis remains challenging because of its complicated topological structure. Here we describe a novel ventricular morphometry system based on the hyperbolic Ricci flow method and tensor-based morphometry (TBM) statistics. Unlike prior ventricular surface parameterization methods, hyperbolic conformal parameterization is angle-preserving and does not have any singularities. Our system generates a one-to-one diffeomorphic mapping between ventricular surfaces with consistent boundary matching conditions. The TBM statistics encode a great deal of surface deformation information that could be inaccessible or overlooked by other methods. We applied our system to the baseline MRI scans of a set of MCI subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI: 71 MCI converters vs. 62 MCI stable). Although the combined ventricular area and volume features did not differ between the two groups, our fine-grained surface analysis revealed significant differences in the ventricular regions close to the temporal lobe and posterior cingulate, structures that are affected early in AD. Significant correlations were also detected between ventricular morphometry, neuropsychological measures, and a previously described imaging index based on fluorodeoxyglucose positron emission tomography (FDG-PET) scans. This novel ventricular morphometry method may offer a new and more sensitive approach to study preclinical and early symptomatic stage AD. PMID:25285374

  6. Clinical significance of exercise-induced left ventricular wall motion abnormality occurring at a low heart rate

    SciTech Connect

    Kimchi, A.; Rozanski, A.; Fletcher, C.; Maddahi, J.; Swan, H.J.; Berman, D.S.

    1987-10-01

    We studied the relationship between the heart rate at the time of onset of exercise-induced wall motion abnormality and the severity of coronary artery disease in 89 patients who underwent exercise equilibrium radionuclide ventriculography as part of their evaluation for coronary artery disease. Segmental wall motion was scored with a five-point system (3 = normal; -1 = dyskinesis); a decrease of one score defined the onset of wall motion abnormality. The onset of wall motion abnormality at less than or equal to 70% of maximal predicted heart rate had 100% predictive accuracy for coronary artery disease and higher sensitivity than the onset of ischemic ST segment depression at similar heart rate during exercise: 36% (25 of 69 patients with coronary disease) vs 19% (13 of 69 patients), p = 0.01. Wall motion abnormality occurring at less than or equal to 70% of maximal predicted heart rate was present in 49% of patients (23 of 47) with critical stenosis (greater than or equal to 90% luminal diameter narrowing), and in only 5% of patients (2 of 42) without such severe stenosis, p less than 0.001. The sensitivity of exercise-induced wall motion abnormality occurring at a low heart rate for the presence of severe coronary artery disease was similar to that of a deterioration in wall motion by more than two scores during exercise (49% vs 53%) or an absolute decrease of greater than or equal to 5% in exercise left ventricular ejection fraction (49% vs 45%).

  7. Sb (111) Abnormal Behavior under Ion Etching

    NASA Astrophysics Data System (ADS)

    Smirnov, A. A.; Bozhko, S. I.; Ionov, A. M.; Protasova, S. G.; Chekmazov, S. V.; Kapustin, A. A.

    Due to a strong spin-orbit interaction (SOI), the surface states of Sb (111) are similar to those for topological insulators (TI) Sugawara et al. (2006). The surface states are protected by time-reversal symmetry and energy dispersion is a linear function of momentum. Defects in crystal structure lead to a local break of the surface translational symmetry and can modify surface states. It is the primary reason to study defects of Sb crystal structure and their effect on the surface states dispersion. Etching of the Sb (111) surface using Ar+ ions is a common way to create defects both in a bulk and on the surface of the crystal. Sb (111) ion etching at room temperature reveals anomalous behavior of surface crystal structure. It results in formation of flat terraces of 2 nm in size. Investigation of electronic structure of the etched Sb (111) surface has demonstrated increase of density of states (DOS) at the Fermi level. The results are discussed in terms of local break of conditions of Peierls transition.

  8. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders.

    PubMed

    Hsiao, Elaine Y; McBride, Sara W; Hsien, Sophia; Sharon, Gil; Hyde, Embriette R; McCue, Tyler; Codelli, Julian A; Chow, Janet; Reisman, Sarah E; Petrosino, Joseph F; Patterson, Paul H; Mazmanian, Sarkis K

    2013-12-19

    Neurodevelopmental disorders, including autism spectrum disorder (ASD), are defined by core behavioral impairments; however, subsets of individuals display a spectrum of gastrointestinal (GI) abnormalities. We demonstrate GI barrier defects and microbiota alterations in the maternal immune activation (MIA) mouse model that is known to display features of ASD. Oral treatment of MIA offspring with the human commensal Bacteroides fragilis corrects gut permeability, alters microbial composition, and ameliorates defects in communicative, stereotypic, anxiety-like and sensorimotor behaviors. MIA offspring display an altered serum metabolomic profile, and B. fragilis modulates levels of several metabolites. Treating naive mice with a metabolite that is increased by MIA and restored by B. fragilis causes certain behavioral abnormalities, suggesting that gut bacterial effects on the host metabolome impact behavior. Taken together, these findings support a gut-microbiome-brain connection in a mouse model of ASD and identify a potential probiotic therapy for GI and particular behavioral symptoms in human neurodevelopmental disorders. PMID:24315484

  9. Insights regarding the normal and abnormal formation of the atrial and ventricular septal structures.

    PubMed

    Anderson, Robert H; Brown, Nigel A; Mohun, Timothy J

    2016-04-01

    Knowledge of cardiac development can provide the basis for understanding the morphogenesis of congenital cardiac malformations. Only recently, however, has the quality of information regarding cardiac embryology been sufficient to justify this approach. In this review, we show how such knowledge of development of the normal atrial and ventricular septal structures underscores the interpretation of the lesions that provide the basis for interatrial and interventricular shunting of blood. We show that current concepts of atrial septation, which frequently depend on a suggested formation of an extensive secondary septum, are simplistic. There are additional contributions beyond growth of the primary septum, but the new tissue is added to form the ventral buttress of the definitive atrial septum, rather than its cranial margin, as is usually depicted. We show that the ventricular septum possesses muscular and membranous components, with the entirety of the muscular septum produced concomitant with the so-called ballooning of the apical ventricular component. It is expansion of the atrioventricular canal that creates the inlet of the right ventricle, with no separate formation of an "inlet" septum. The proximal parts of the outflow cushions initially form a septal structure between the developing ventricular outlets, but this becomes converted into the free-standing muscular subpulmonary infundibulum as the aortic outlet is transferred to the left ventricle. These features of normal development are then shown to provide the basis for understanding of the channels that provide the means for interatrial and interventricular shunting. PMID:26378977

  10. Personality theory, abnormal psychology, and psychological measurement. A psychological behaviorism.

    PubMed

    Staats, A W

    1993-01-01

    Behaviorism, because it has not had a theory of personality, has been separated from the rest of psychology, unable in large part to draw from or contribute to it. Traditional psychology has not had a theory of personality that says what personality is, how it comes about, or how it functions. An antagonism has resulted that weakens rather than complements each tradition. Psychological behaviorism presents a new type of theory of personality. Derived from experimentation, it is constructed from basic theories of emotion, language, and sensory-motor behavior. It says personality is composed of learned basic behavioral repertoires (BBRs) that affect behavior. Personality measurement instruments are analyzed in terms of the BBRs, beginning the behaviorization of this field and calling for much additional research. These multilevel developments are then basic in psychological behaviorism's theory of abnormal behavior and of clinical treatment. The approach opens many new avenues of empirical and theoretical work. PMID:8439278

  11. Detecting abnormalities in left ventricular function during exercise by respiratory measurement

    SciTech Connect

    Koike, A.; Itoh, H.; Taniguchi, K.; Hiroe, M. )

    1989-12-01

    The degree of exercise-induced cardiac dysfunction and its relation to the anaerobic threshold were evaluated in 23 patients with chronic heart disease. A symptom-limited exercise test was performed with a cycle ergometer with work rate increased by 1 W every 6 seconds. Left ventricular function, as reflected by ejection fraction, was continuously monitored with a computerized cadmium telluride detector after the intravenous injection of technetium-labeled red blood cells. The anaerobic threshold (mean, 727 {plus minus} 166 ml/min) was determined by the noninvasive measurement of respiratory gas exchange. As work rate rose, the left ventricular ejection fraction increased but reached a peak value at the anaerobic threshold and then fell below resting levels. Ejection fraction at rest, anaerobic threshold, and peak exercise were 41.4 {plus minus} 11.3%, 46.5 {plus minus} 12.0%, and 37.2 {plus minus} 11.0%, respectively. Stroke volume also increased from rest (54.6 {plus minus} 17.0 ml/beat) to the point of the anaerobic threshold (65.0 {plus minus} 21.2 ml/beat) and then decreased at peak exercise (52.4 {plus minus} 18.7 ml/beat). The slope of the plot of cardiac output versus work rate decreased above the anaerobic threshold. The anaerobic threshold occurred at the work rate above which left ventricular function decreased during exercise. Accurate determination of the anaerobic threshold provides an objective, noninvasive measure of the oxygen uptake above which exercise-induced deterioration in left ventricular function occurs in patients with chronic heart disease.

  12. Possible Electromagnetic Effects on Abnormal Animal Behavior Before an Earthquake

    PubMed Central

    Hayakawa, Masashi

    2013-01-01

    Simple Summary Possible electromagnetic effects on abnormal animal behavior before earthquakes. Abstract The former statistical properties summarized by Rikitake (1998) on unusual animal behavior before an earthquake (EQ) have first been presented by using two parameters (epicentral distance (D) of an anomaly and its precursor (or lead) time (T)). Three plots are utilized to characterize the unusual animal behavior; (i) EQ magnitude (M) versus D, (ii) log T versus M, and (iii) occurrence histogram of log T. These plots are compared with the corresponding plots for different seismo-electromagnetic effects (radio emissions in different frequency ranges, seismo-atmospheric and -ionospheric perturbations) extensively obtained during the last 15–20 years. From the results of comparisons in terms of three plots, it is likely that lower frequency (ULF (ultra-low-frequency, f ≤ 1 Hz) and ELF (extremely-low-frequency, f ≤ a few hundreds Hz)) electromagnetic emissions exhibit a very similar temporal evolution with that of abnormal animal behavior. It is also suggested that a quantity of field intensity multiplied by the persistent time (or duration) of noise would play the primary role in abnormal animal behavior before an EQ. PMID:26487307

  13. Usefulness of noninvasive detection of left ventricular diastolic abnormalities during isometric stress in hypertrophic cardiomyopathy and in athletes.

    PubMed

    Manolas, J; Kyriakidis, M; Anastasakis, A; Pegas, P; Rigopoulos, A; Theopistou, A; Toutouzas, P

    1998-02-01

    We showed previously that the handgrip apexcardiographic test (HAT) is a useful method for detecting left ventricular (LV) diastolic abnormalities in patients with coronary artery disease and systemic hypertension. This study evaluates the use of HAT for assessing the prevalence and types of exercise-induced diastolic abnormalities in patients with obstructive (n = 31) and nonobstructive (n = 35) hypertrophic cardiomyopathy (HC) as well as its potential value for separating healthy subjects and athletes from patients with HC. We obtained a HAT in 66 consecutive patients with HC and in 72 controls (52 healthy volunteers and 20 athletes). A positive HAT was defined by the presence of one of the following: (1) relative A wave to total height (A/H) during or after handgrip > 21% (compliance type), (2) total apexcardiographic relaxation time (TART) > 143 ms or the heart rate corrected TART (TARTI) during handgrip < 0.14, (relaxation type), (3) both types present (mixed type), and (4) diastolic amplitude time index (DATI = TARTI/[A/D]) during handgrip < 0.27. Of the controls, only 1 of 52 healthy subjects and 1 of 20 athletes showed a positive HAT, whereas of the total HC cohort 63 of 66 patients (95%) had a positive result. There was no significant difference in the distribution of these types between obstructive and nonobstructive HC. Further, no LV diastolic abnormalities were present in 10 of 35 patients (29%) with nonobstructive HC at rest and in 3 of 35 patients (9%) during handgrip, whereas of the patients with obstructive HC only 1 of 31 (3%) had no LV diastolic abnormalities at rest and none during handgrip. Based on HAT data, our study demonstrates that in HC (1) LV diastolic abnormalities are very frequent during handgrip; (2) patients with nonobstructive HC show significantly fewer LV diastolic abnormalities at rest than those with obstructive HC; and (3) no significant difference exists between obstructive and nonobstructive HC in the prevalence of types of

  14. Spent fuel behavior under abnormal thermal transients during dry storage

    SciTech Connect

    Stahl, D.; Landow, M.P.; Burian, R.J.; Pasupathi, V.

    1986-01-01

    This study was performed to determine the effects of abnormally high temperatures on spent fuel behavior. Prior to testing, calculations using the CIRFI3 code were used to determine the steady-state fuel and cask component temperatures. The TRUMP code was used to determine transient heating rates under postulated abnormal events during which convection cooling of the cask surfaces was obstructed by a debris bed covering the cask. The peak rate of temperature rise during the first 6 h was calculated to be about 15/sup 0/C/h, followed by a rate of about 1/sup 0/C/h. A Turkey Point spent fuel rod segment was heated to approx. 800/sup 0/C. The segment deformed uniformly with an average strain of 17% at failure and a local strain of 60%. Pretest characterization of the spent fuel consisted of visual examination, profilometry, eddy-current examination, gamma scanning, fission gas collection, void volume measurement, fission gas analysis, hydrogen analysis of the cladding, burnup analysis, cladding metallography, and fuel ceramography. Post-test characterization showed that the failure was a pinhole cladding breach. The results of the tests showed that spent fuel temperatures in excess of 700/sup 0/C are required to produce a cladding breach in fuel rods pressurized to 500 psing (3.45 MPa) under postulated abnormal thermal transient cask conditions. The pinhole cladding breach that developed would be too small to compromise the confinement of spent fuel particles during an abnormal event or after normal cooling conditions are restored. This behavior is similar to that found in other slow ramp tests with irradiated and nonirradiated rod sections and nonirradiated whole rods under conditions that bracketed postulated abnormal heating rates. This similarity is attributed to annealing of the irradiation-strengthened Zircaloy cladding during heating. In both cases, the failure was a benign, ductile pinhole rupture.

  15. Abnormal Ca2+ Cycling in Failing Ventricular Myocytes: Role of NOS1-Mediated Nitroso-Redox Balance

    PubMed Central

    Houser, Steven R.

    2014-01-01

    Abstract Significance: Heart failure (HF) results from poor heart function and is the leading cause of death in Western society. Abnormalities of Ca2+ handling at the level of the ventricular myocyte are largely responsible for much of the poor heart function. Recent Advances: Although studies have unraveled numerous mechanisms for the abnormal Ca2+ handling, investigations over the past decade have indicated that much of the contractile dysfunction and adverse remodeling that occurs in HF involves oxidative stress. Critical Issues: Regrettably, antioxidant therapy has been an immense disappointment in clinical trials. Thus, redox signaling is being reassessed to elucidate why antioxidants failed to treat HF. Future Directions: A recently identified aspect of redox signaling (specifically the superoxide anion radical) is its interaction with nitric oxide, known as the nitroso-redox balance. There is a large nitroso-redox imbalance with HF, and we suggest that correcting this imbalance may be able to restore myocyte contraction and improve heart function. Antioxid. Redox Signal. 21, 2044–2059. PMID:24801117

  16. Possible Electromagnetic Effects on Abnormal Animal Behavior Before an Earthquake.

    PubMed

    Hayakawa, Masashi

    2013-01-01

    The former statistical properties summarized by Rikitake (1998) on unusual animal behavior before an earthquake (EQ) have first been presented by using two parameters (epicentral distance (D) of an anomaly and its precursor (or lead) time (T)). Three plots are utilized to characterize the unusual animal behavior; (i) EQ magnitude (M) versus D, (ii) log T versus M, and (iii) occurrence histogram of log T. These plots are compared with the corresponding plots for different seismo-electromagnetic effects (radio emissions in different frequency ranges, seismo-atmospheric and -ionospheric perturbations) extensively obtained during the last 15-20 years. From the results of comparisons in terms of three plots, it is likely that lower frequency (ULF (ultra-low-frequency, f ≤ 1 Hz) and ELF (extremely-low-frequency, f ≤ a few hundreds Hz)) electromagnetic emissions exhibit a very similar temporal evolution with that of abnormal animal behavior. It is also suggested that a quantity of field intensity multiplied by the persistent time (or duration) of noise would play the primary role in abnormal animal behavior before an EQ. PMID:26487307

  17. Abnormal magnetization behaviors in Sm-Ni-Fe-Cu alloys

    NASA Astrophysics Data System (ADS)

    Yang, W. Y.; Zhang, Y. F.; Zhao, H.; Chen, G. F.; Zhang, Y.; Du, H. L.; Liu, S. Q.; Wang, C. S.; Han, J. Z.; Yang, Y. C.; Yang, J. B.

    2016-06-01

    The magnetization behaviors in Sm-Ni-Fe-Cu alloys at low temperatures have been investigated. It was found that the hysteresis loops show wasp-waisted character at low temperatures, which has been proved to be related to the existence of multi-phases, the Fe/Ni soft magnetic phases and the CaCu5-type hard magnetic phase. A smooth-jump behavior of the magnetization is observed at T>5 K, whereas a step-like magnetization process appears at T<5 K. The CaCu5-type phase is responsible for such abnormal magnetization behavior. The magnetic moment reversal model with thermal activation is used to explain the relation of the critical magnetic field (Hcm) to the temperature (T>5 K). The reversal of the moment direction has to cross over an energy barrier of about 6.6×10-15 erg. The step-like jumps of the magnetization below 5 K is proposed to be resulted from a sharp increase of the sample temperature under the heat released by the irreversible domain wall motion.

  18. Abnormal Elastic and Vibrational Behaviors of Magnetite at High Pressures

    PubMed Central

    Lin, Jung-Fu; Wu, Junjie; Zhu, Jie; Mao, Zhu; Said, Ayman H.; Leu, Bogdan M.; Cheng, Jinguang; Uwatoko, Yoshiya; Jin, Changqing; Zhou, Jianshi

    2014-01-01

    Magnetite exhibits unique electronic, magnetic, and structural properties in extreme conditions that are of great research interest. Previous studies have suggested a number of transitional models, although the nature of magnetite at high pressure remains elusive. We have studied a highly stoichiometric magnetite using inelastic X-ray scattering, X-ray diffraction and emission, and Raman spectroscopies in diamond anvil cells up to ~20 GPa, while complementary electrical conductivity measurements were conducted in a cubic anvil cell up to 8.5 GPa. We have observed an elastic softening in the diagonal elastic constants (C11 and C44) and a hardening in the off-diagonal constant (C12) at ~8 GPa where significant elastic anisotropies in longitudinal and transverse acoustic waves occur, especially along the [110] direction. An additional vibrational Raman band between the A1g and T2g modes was also detected at the transition pressure. These abnormal elastic and vibrational behaviors of magnetite are attributed to the occurrence of the octahedrally-coordinated Fe2+-Fe3+-Fe2+ ions charge-ordering along the [110] direction in the inverse spinel structure. We propose a new phase diagram of magnetite in which the temperature for the metal-insulator and distorted structural transitions decreases with increasing pressure while the charge-ordering transition occurs at ~8 GPa and room temperature. PMID:25186916

  19. Abnormal Elastic and Vibrational Behaviors of Magnetite at High Pressures

    NASA Astrophysics Data System (ADS)

    Lin, Jung-Fu; Wu, Junjie; Zhu, Jie; Mao, Zhu; Said, Ayman H.; Leu, Bogdan M.; Cheng, Jinguang; Uwatoko, Yoshiya; Jin, Changqing; Zhou, Jianshi

    2014-09-01

    Magnetite exhibits unique electronic, magnetic, and structural properties in extreme conditions that are of great research interest. Previous studies have suggested a number of transitional models, although the nature of magnetite at high pressure remains elusive. We have studied a highly stoichiometric magnetite using inelastic X-ray scattering, X-ray diffraction and emission, and Raman spectroscopies in diamond anvil cells up to ~20 GPa, while complementary electrical conductivity measurements were conducted in a cubic anvil cell up to 8.5 GPa. We have observed an elastic softening in the diagonal elastic constants (C11 and C44) and a hardening in the off-diagonal constant (C12) at ~8 GPa where significant elastic anisotropies in longitudinal and transverse acoustic waves occur, especially along the [110] direction. An additional vibrational Raman band between the A1g and T2g modes was also detected at the transition pressure. These abnormal elastic and vibrational behaviors of magnetite are attributed to the occurrence of the octahedrally-coordinated Fe2+-Fe3+-Fe2+ ions charge-ordering along the [110] direction in the inverse spinel structure. We propose a new phase diagram of magnetite in which the temperature for the metal-insulator and distorted structural transitions decreases with increasing pressure while the charge-ordering transition occurs at ~8 GPa and room temperature.

  20. Abnormal elastic and vibrational behaviors of magnetite at high pressures.

    PubMed

    Lin, Jung-Fu; Wu, Junjie; Zhu, Jie; Mao, Zhu; Said, Ayman H; Leu, Bogdan M; Cheng, Jinguang; Uwatoko, Yoshiya; Jin, Changqing; Zhou, Jianshi

    2014-01-01

    Magnetite exhibits unique electronic, magnetic, and structural properties in extreme conditions that are of great research interest. Previous studies have suggested a number of transitional models, although the nature of magnetite at high pressure remains elusive. We have studied a highly stoichiometric magnetite using inelastic X-ray scattering, X-ray diffraction and emission, and Raman spectroscopies in diamond anvil cells up to ~20 GPa, while complementary electrical conductivity measurements were conducted in a cubic anvil cell up to 8.5 GPa. We have observed an elastic softening in the diagonal elastic constants (C11 and C44) and a hardening in the off-diagonal constant (C12) at ~8 GPa where significant elastic anisotropies in longitudinal and transverse acoustic waves occur, especially along the [110] direction. An additional vibrational Raman band between the A1g and T2g modes was also detected at the transition pressure. These abnormal elastic and vibrational behaviors of magnetite are attributed to the occurrence of the octahedrally-coordinated Fe(2+)-Fe(3+)-Fe(2+) ions charge-ordering along the [110] direction in the inverse spinel structure. We propose a new phase diagram of magnetite in which the temperature for the metal-insulator and distorted structural transitions decreases with increasing pressure while the charge-ordering transition occurs at ~8 GPa and room temperature. PMID:25186916

  1. BETA-ENDORPHIN LEVELS IN LONGTAILED AND PIGTAILED MACAQUES VARY BY ABNORMAL BEHAVIOR RATING AND SEX

    PubMed Central

    Crockett, Carolyn M.; Sackett, Gene P.; Sandman, Curt A.; Chicz-DeMet, Aleksandra; Bentson, Kathleen L.

    2007-01-01

    Frequent or severe abnormal behavior may be associated with the release of endorphins that positively reinforce the behavior with an opiate euphoria or analgesia. One line of research exploring this association involves the superhormone, proopiomelanocortin (POMC). The products of POMC appear to be dysregulated in some human subjects who exhibit self-injurious behavior (SIB). Macaque monkeys have POMC very similar to humans, and some laboratory macaques display SIB or frequent stereotypies. We investigated associations between plasma levels of three immunoreactive POMC fragments with possible opioid action and abnormal behavior ratings in macaques. In 58 adult male and female macaques (24 Macaca fascicularis and 34 M. nemestrina), plasma levels of intact beta-endorphin (βE) and the N-terminal fragment (BEN) were significantly higher in animals with higher levels of abnormal behavior. The C-terminal fragment (BEC) was significantly higher in males but unrelated to ratings of abnormal behavior. Levels of ACTH, cortisol, and (βE-ACTH)/βE dysregulation index were unrelated to abnormal behavior. None of the POMC products differed significantly by subjects' species, age, or weight. The finding that intact beta-endorphin is positively related to abnormal behavior in two species of macaque is consistent with some previous research on human subjects and nonprimates. The positive relation of the N-terminal fragment of βE to abnormal behavior is a new finding. PMID:17719139

  2. Normal behavior and the clinical implications of abnormal behavior in guinea pigs.

    PubMed

    Bradley, T A

    2001-09-01

    Cavies are becoming more popular as pets because they are relatively easy to care for and provide never-ending love and entertainment with their curious but gentle nature. As with other species, the best way to learn about guinea pig behavior is to own guinea pigs. Understanding normal behavior provides the practitioner with the ability to more easily recognize pathology and abnormal behavior. This allows the veterinarian to provide necessary supportive care and pain management more quickly while performing diagnostics and determining the need for therapeutics. Understanding the behavior of cavies allows the clinician to better educate guinea pig-owning clients and to better and more quickly serve the needs of their guinea pig patients. PMID:11601108

  3. Effects of chronic beta-adrenergic blockade on the left ventricular and cardiocyte abnormalities of chronic canine mitral regurgitation.

    PubMed Central

    Tsutsui, H; Spinale, F G; Nagatsu, M; Schmid, P G; Ishihara, K; DeFreyte, G; Cooper, G; Carabello, B A

    1994-01-01

    The mechanism by which beta blockade improves left ventricular dysfunction in various cardiomyopathies has been ascribed to improved contractile function of the myocardium or to improved beta-adrenergic responsiveness. In this study we tested two hypotheses: (a) that chronic beta blockade would improve the left ventricular dysfunction which develops in mitral regurgitation, and (b) that an important mechanism of this effect would be improved innate contractile function of the myocardium. Two groups of six dogs with chronic severe mitral regurgitation were studied. After 3 mo both groups had developed similar and significant left ventricular dysfunction. One group was then gradually beta-blocked while the second group continued to be observed without further intervention. In the group that remained unblocked, contractile function remained depressed. However, in the group that received chronic beta blockade, contractile function improved substantially. The contractility of cardiocytes isolated from the unblocked hearts and then studied in the absence of beta receptor stimulation was extremely depressed. However, contractility of cardiocytes isolated from the beta-blocked ventricles was virtually normal. Consistent with these data, myofibrillar density was much higher, 55 +/- 4% in the beta-blocked group vs. 39 +/- 2% (P < 0.01) in the unblocked group; thus, there were more contractile elements to generate force in the beta-blocked group. We conclude that chronic beta blockade improves left ventricular function in chronic experimental mitral regurgitation. This improvement was associated with an improvement in the innate contractile function of isolated cardiocytes, which in turn is associated with an increase in the number of contractile elements. Images PMID:7911128

  4. Abnormal behavior and associated risk factors in captive baboons (Papio hamadryas spp.).

    PubMed

    Lutz, Corrine K; Williams, Priscilla C; Sharp, R Mark

    2014-04-01

    Abnormal behavior, ranging from motor stereotypies to self-injurious behavior, has been documented in captive nonhuman primates, with risk factors including nursery rearing, single housing, and veterinary procedures. Much of this research has focused on macaque monkeys; less is known about the extent of and risk factors for abnormal behavior in baboons. Because abnormal behavior can be indicative of poor welfare, either past or present, the purpose of this study was to survey the presence of abnormal behavior in captive baboons and to identify potential risk factors for these behaviors with an aim of prevention. Subjects were 144 baboons (119 females, 25 males) aged 3-29 (median = 9.18) years temporarily singly housed for research or clinical reasons. A 15-min focal observation was conducted on each subject using the Noldus Observer® program. Abnormal behavior was observed in 26% of the subjects, with motor stereotypy (e.g., pace, rock, swing) being the most common. Motor stereotypy was negatively associated with age when first singly housed (P < 0.005) while self-directed behavior (e.g., hair pull, self-bite) was positively associated with the lifetime number of days singly housed (P < 0.05) and the average number of blood draws per year (P < 0.05). In addition, abnormal appetitive behavior was associated with being male (P < 0.05). Although the baboons in this study exhibited relatively low levels of abnormal behavior, the risk factors for these behaviors (e.g., social restriction, routine veterinary procedures, and sex) appear to remain consistent across primate species. PMID:24323406

  5. Deletion of ETS-1, a gene in the Jacobsen syndrome critical region, causes ventricular septal defects and abnormal ventricular morphology in mice

    PubMed Central

    Ye, Maoqing; Coldren, Chris; Liang, Xingqun; Mattina, Teresa; Goldmuntz, Elizabeth; Benson, D. Woodrow; Ivy, Dunbar; Perryman, M.B.; Garrett-Sinha, Lee Ann; Grossfeld, Paul

    2010-01-01

    Congenital heart defects comprise the most common form of major birth defects, affecting 0.7% of all newborn infants. Jacobsen syndrome (11q-) is a rare chromosomal disorder caused by deletions in distal 11q. We have previously determined that a wide spectrum of the most common congenital heart defects occur in 11q-, including an unprecedented high frequency of hypoplastic left heart syndrome (HLHS). We identified an ∼7 Mb ‘cardiac critical region’ in distal 11q that contains a putative causative gene(s) for congenital heart disease. In this study, we utilized chromosomal microarray mapping to characterize three patients with 11q- and congenital heart defects that carry interstitial deletions overlapping the 7 Mb cardiac critical region. We propose that this 1.2 Mb region of overlap harbors a gene(s) that causes at least a subset of the congenital heart defects that occur in 11q-. We demonstrate that one gene in this region, ETS-1 (a member of the ETS family of transcription factors), is expressed in the endocardium and neural crest during early mouse heart development. Gene-targeted deletion of ETS-1 in mice in a C57/B6 background causes, with high penetrance, large membranous ventricular septal defects and a bifid cardiac apex, and less frequently a non-apex-forming left ventricle (one of the hallmarks of HLHS). Our results implicate an important role for the ETS-1 transcription factor in mammalian heart development and should provide important insights into some of the most common forms of congenital heart disease. PMID:19942620

  6. Abnormalities in aortic properties: a potential link between left ventricular diastolic function and ventricular-aortic coupling in sickle cell disease.

    PubMed

    Bollache, Emilie; Kachenoura, Nadjia; Lang, Roberto M; Desai, Ankit A; Mor-Avi, Victor; Patel, Amit R

    2016-06-01

    Left ventricular (LV) diastolic dysfunction in patients with sickle cell disease (SCD) is associated with increased mortality. However, its mechanisms are not well known, preventing the development of effective therapies. We hypothesized that patients with SCD have altered aortic properties despite normal blood pressure, which may contribute towards the development of diastolic dysfunction. We studied 31 stable adult patients with SCD (32 ± 7 years) and 12 healthy controls of similar age (29 ± 10 years) who underwent echocardiography and cardiovascular magnetic resonance (CMR) imaging on the same day. Echocardiographic measurements of mitral inflow and mitral annulus velocities were used to evaluate LV diastolic function. CMR imaging included standard LV function evaluation and myocardial tissue characterization as well as velocity-encoded images of the ascending aorta to measure aortic diastolic cross-sectional area, distensibility, as well as peaks and volumes of the global, forward and backward blood flow rate. Compared to controls, SCD patients had increased aortic diastolic area, global stroke volume, and both forward and backward flow, while aortic distensibility and peripheral blood pressure were similar. Furthermore, peak backward flow rate and volume were able to discriminate between patients with and without diastolic dysfunction. Our findings show that some aortic properties are altered in SCD patients and may be associated with diastolic dysfunction despite normal systolic blood pressure. If confirmed in larger studies, these aortic changes could be a novel therapeutic target to prevent or delay the development of LV diastolic dysfunction in SCD and thus potentially improve outcomes in these patients. PMID:26907920

  7. Macro- and microscopic spectral-polarization characteristics of the structure of normal and abnormally located chordae tendianeae of left ventricular

    NASA Astrophysics Data System (ADS)

    Malyk, Yu. Yu.; Prydij, O. G.; Zymnyakov, D. A.; Alonova, M. V.; Ushakova, O. V.

    2013-12-01

    The morphological peculiarities of TS mitral valve of the heart of man in normal and abnormal spaced strings of the left ventricle and the study of their structural features depending on the location was studied. There are given the results of comparative statistics, correlation and fractal study population Mueller-matrix images (MMI) of healthy and abnormal (early forms that are not diagnosed by histological methods) BT normal and abnormally located tendon strings left ventricle of the human heart. Abnormalities in the structure of the wings, tendon strings (TS), mastoid muscle (MM) in inconsistencies elements and harmonized operation of all valve complex shown in the features of the polarization manifestations of it laser images.

  8. Behavioral abnormalities in mice lacking mesenchyme-specific Pten.

    PubMed

    Borniger, Jeremy C; Cissé, Yasmine M; Cantemir-Stone, Carmen Z; Bolon, Brad; Nelson, Randy J; Marsh, Clay B

    2016-05-01

    Phosphatase and tensin homolog (Pten) is a negative regulator of cell proliferation and growth. Using a Cre-recombinase approach with Lox sequences flanking the fibroblast-specific protein 1 (Fsp1 aka S100A4; a mesenchymal marker), we probed sites of expression using a β-galactosidase Rosa26(LoxP) reporter allele; the transgene driving deletion of Pten (exons 4-5) was found throughout the brain parenchyma and pituitary, suggesting that deletion of Pten in Fsp1-positive cells may influence behavior. Because CNS-specific deletion of Pten influences social and anxiety-like behaviors and S100A4 is expressed in astrocytes, we predicted that loss of Pten in Fsp1-expressing cells would result in deficits in social interaction and increased anxiety. We further predicted that environmental enrichment would compensate for genetic deficits in these behaviors. We conducted a battery of behavioral assays on Fsp1-Cre;Pten(LoxP/LoxP) male and female homozygous knockouts (Pten(-/-)) and compared their behavior to Pten(LoxP/LoxP) (Pten(+/+)) conspecifics. Despite extensive physical differences (including reduced hippocampal size) and deficits in sensorimotor function, Pten(-/-) mice behaved remarkably similar to control mice on nearly all behavioral tasks. These results suggest that the social and anxiety-like phenotypes observed in CNS-specific Pten(-/-) mice may depend on neuronal Pten, as lack of Pten in Fsp1-expressing cells of the CNS had little effect on these behaviors. PMID:26876012

  9. Allergies: The Key to Many Childhood Behavior Abnormalities.

    ERIC Educational Resources Information Center

    Vass, Molly; Rasmussen, Betty

    1984-01-01

    Describes the role of allergies in childhood behavior problems and discusses the role of school counselors in identifying allergic responses. Includes a list of references and resources on allergies, nutrition, support groups, and environmental care units. (JAC)

  10. PLEKHM2 mutation leads to abnormal localization of lysosomes, impaired autophagy flux and associates with recessive dilated cardiomyopathy and left ventricular noncompaction.

    PubMed

    Muhammad, Emad; Levitas, Aviva; Singh, Sonia R; Braiman, Alex; Ofir, Rivka; Etzion, Sharon; Sheffield, Val C; Etzion, Yoram; Carrier, Lucie; Parvari, Ruti

    2015-12-20

    Gene mutations, mostly segregating with a dominant mode of inheritance, are important causes of dilated cardiomyopathy (DCM), a disease characterized by enlarged ventricular dimensions, impaired cardiac function, heart failure and high risk of death. Another myocardial abnormality often linked to gene mutations is left ventricular noncompaction (LVNC) characterized by a typical diffuse spongy appearance of the left ventricle. Here, we describe a large Bedouin family presenting with a severe recessive DCM and LVNC. Homozygosity mapping and exome sequencing identified a single gene variant that segregated as expected and was neither reported in databases nor in Bedouin population controls. The PLEKHM2 cDNA2156_2157delAG variant causes the frameshift p.Lys645AlafsTer12 and/or the skipping of exon 11 that results in deletion of 30 highly conserved amino acids. PLEKHM2 is known to interact with several Rabs and with kinesin-1, affecting endosomal trafficking. Accordingly, patients' primary fibroblasts exhibited abnormal subcellular distribution of endosomes marked by Rab5, Rab7 and Rab9, as well as the Golgi apparatus. In addition, lysosomes appeared to be concentrated in the perinuclear region, and autophagy flux was impaired. Transfection of wild-type PLEKHM2 cDNA into patient's fibroblasts corrected the subcellular distribution of the lysosomes, supporting the causal effect of PLEKHM2 mutation. PLEKHM2 joins LAMP-2 and BAG3 as a disease gene altering autophagy resulting in an isolated cardiac phenotype. The association of PLEKHM2 mutation with DCM and LVNC supports the importance of autophagy for normal cardiac function. PMID:26464484

  11. Autism-related behavioral abnormalities in synapsin knockout mice

    PubMed Central

    Greco, Barbara; Managò, Francesca; Tucci, Valter; Kao, Hung-Teh; Valtorta, Flavia; Benfenati, Fabio

    2013-01-01

    Several synaptic genes predisposing to autism-spectrum disorder (ASD) have been identified. Nonsense and missense mutations in the SYN1 gene encoding for Synapsin I have been identified in families segregating for idiopathic epilepsy and ASD and genetic mapping analyses have identified variations in the SYN2 gene as significantly contributing to epilepsy predisposition. Synapsins (Syn I/II/III) are a multigene family of synaptic vesicle-associated phosphoproteins playing multiple roles in synaptic development, transmission and plasticity. Lack of SynI and/or SynII triggers a strong epileptic phenotype in mice associated with mild cognitive impairments that are also present in the non-epileptic SynIII−/− mice. SynII−/− and SynIII−/− mice also display schizophrenia-like traits, suggesting that Syns could be involved in the regulation of social behavior. Here, we studied social interaction and novelty, social recognition and social dominance, social transmission of food preference and social memory in groups of male SynI−/−, SynII−/− and SynIII−/− mice before and after the appearance of the epileptic phenotype and compared their performances with control mice. We found that deletion of Syn isoforms widely impairs social behaviors and repetitive behaviors, resulting in ASD-related phenotypes. SynI or SynIII deletion altered social behavior, whereas SynII deletion extensively impaired various aspects of social behavior and memory, altered exploration of a novel environment and increased self-grooming. Social impairments of SynI−/− and SynII−/− mice were evident also before the onset of seizures. The results demonstrate an involvement of Syns in generation of the behavioral traits of ASD and identify Syn knockout mice as a useful experimental model of ASD and epilepsy. PMID:23280234

  12. HINT1 is involved in the behavioral abnormalities induced by social isolation rearing.

    PubMed

    Dang, Yong-hui; Liu, Peng; Ma, Rui; Chu, Zheng; Liu, You-ping; Wang, Jia-bei; Ma, Xian-cang; Gao, Cheng-ge

    2015-10-21

    Social isolation (SI) rearing has been demonstrated to induce behavioral abnormalities like anxiety, impulsivity, aggression, and learning and memory deficits which are relevant to core symptoms in patients with some certain neuropsychiatric disorders. But the underlying pathophysiological mechanisms remain unclear. Recent studies have revealed HINT1 has close relation with diverse neuropsychiatric diseases. In this present study, the SI rearing mice exhibited depression-like and aggressive behavior. Besides, HINT1 protein levels decreased in PFC but increased in HIP. Based on the data obtained, we concluded that HINT1 is involved in the behavioral abnormalities induced by social isolation and exerts distinct roles in different encephalic regions. PMID:26300541

  13. Risk factors for behavioral abnormalities in mild cognitive impairment and mild Alzheimer's disease

    PubMed Central

    Apostolova, Liana G.; Di, Li Jie; Duffy, Erin L.; Brook, Jenny; Elashoff, David; Tseng, Chi-Hong; Fairbanks, Lynn; Cummings, Jeffrey L.

    2014-01-01

    Background Behavioral symptoms are common in both MCI and AD. Methods We analyzed the Neuropsychiatric Inventory Questionnaire data of 3456 MCI and 2641 mild AD NACC participants. Using factor analysis and logistic regression we estimated the effects of age, sex, race, education, MMSE, functional impairment, marital status and family history on presence of behavioral symptoms. We also compared the observed prevalence of behavioral symptoms between amnestic and nonamnestic MCI. Results Four factors were identified: affective behaviors (depression, apathy and anxiety); distress/tension behaviors (irritability and agitation); impulse control behaviors (disinhibition, elation and aberrant motor behavior), and psychotic behaviors (delusions and hallucinations). Male gender was significantly associated with all factors. Younger age was associated with higher prevalence of distress/tension, impulse control and psychotic behaviors. Being married was protective against psychotic behaviors. Lower education was associated with the presence of distress/tension behaviors. Caucasians showed higher prevalence of affective behaviors. Functional impairment was strongly associated with all behavioral abnormalities. Amnestic MCI had more elation and agitation relative to nonamnestic MCI. Conclusions Younger age, male gender and greater functional impairment were associated with higher overall presence of behavioral abnormalities in MCI and mild AD. Marital status, lower education and race had effect on selected behaviors. PMID:24481207

  14. Characterizing abnormal behavior in a large population of zoo-housed chimpanzees: prevalence and potential influencing factors.

    PubMed

    Jacobson, Sarah L; Ross, Stephen R; Bloomsmith, Mollie A

    2016-01-01

    Abnormal behaviors in captive animals are generally defined as behaviors that are atypical for the species and are often considered to be indicators of poor welfare. Although some abnormal behaviors have been empirically linked to conditions related to elevated stress and compromised welfare in primates, others have little or no evidence on which to base such a relationship. The objective of this study was to investigate a recent claim that abnormal behavior is endemic in the captive population by surveying a broad sample of chimpanzees (Pan troglodytes), while also considering factors associated with the origins of these behaviors. We surveyed animal care staff from 26 accredited zoos to assess the prevalence of abnormal behavior in a large sample of chimpanzees in the United States for which we had information on origin and rearing history. Our results demonstrated that 64% of this sample was reported to engage in some form of abnormal behavior in the past two years and 48% of chimpanzees engaged in abnormal behavior other than coprophagy. Logistic regression models were used to analyze the historical variables that best predicted the occurrence of all abnormal behavior, any abnormal behavior that was not coprophagy, and coprophagy. Rearing had opposing effects on the occurrence of coprophagy and the other abnormal behaviors such that mother-reared individuals were more likely to perform coprophagy, whereas non-mother-reared individuals were more likely to perform other abnormal behaviors. These results support the assertion that coprophagy may be classified separately when assessing abnormal behavior and the welfare of captive chimpanzees. This robust evaluation of the prevalence of abnormal behavior in our sample from the U.S. zoo population also demonstrates the importance of considering the contribution of historical variables to present behavior, in order to better understand the causes of these behaviors and any potential relationship to psychological

  15. Characterizing abnormal behavior in a large population of zoo-housed chimpanzees: prevalence and potential influencing factors

    PubMed Central

    Jacobson, Sarah L.; Bloomsmith, Mollie A.

    2016-01-01

    Abnormal behaviors in captive animals are generally defined as behaviors that are atypical for the species and are often considered to be indicators of poor welfare. Although some abnormal behaviors have been empirically linked to conditions related to elevated stress and compromised welfare in primates, others have little or no evidence on which to base such a relationship. The objective of this study was to investigate a recent claim that abnormal behavior is endemic in the captive population by surveying a broad sample of chimpanzees (Pan troglodytes), while also considering factors associated with the origins of these behaviors. We surveyed animal care staff from 26 accredited zoos to assess the prevalence of abnormal behavior in a large sample of chimpanzees in the United States for which we had information on origin and rearing history. Our results demonstrated that 64% of this sample was reported to engage in some form of abnormal behavior in the past two years and 48% of chimpanzees engaged in abnormal behavior other than coprophagy. Logistic regression models were used to analyze the historical variables that best predicted the occurrence of all abnormal behavior, any abnormal behavior that was not coprophagy, and coprophagy. Rearing had opposing effects on the occurrence of coprophagy and the other abnormal behaviors such that mother-reared individuals were more likely to perform coprophagy, whereas non-mother-reared individuals were more likely to perform other abnormal behaviors. These results support the assertion that coprophagy may be classified separately when assessing abnormal behavior and the welfare of captive chimpanzees. This robust evaluation of the prevalence of abnormal behavior in our sample from the U.S. zoo population also demonstrates the importance of considering the contribution of historical variables to present behavior, in order to better understand the causes of these behaviors and any potential relationship to psychological

  16. Abnormal repetitive behaviors in dogs and cats: a guide for practitioners.

    PubMed

    Tynes, Valarie V; Sinn, Leslie

    2014-05-01

    Abnormal repetitive behaviors (ARBs) represent a diverse group of behaviors whose underlying mechanism is poorly understood. Their neurobiology likely involves several different neurotransmitter systems. These behaviors have been referred to as compulsive disorders, obsessive compulsive disorders and stereotypies. Underlying medical conditions and pain can often cause changes in behavior that are mistaken for ARBs. A complete medical work-up is always indicated prior to reaching a presumptive diagnosis. The frequency of ARBs can be reduced but not always eliminated with the use of selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs) in conjunction with behavior modification and environmental enrichment. PMID:24766699

  17. Early cognitive changes and nondementing behavioral abnormalities in Parkinson's disease.

    PubMed

    Levin, Bonnie E; Katzen, Heather L

    2005-01-01

    Early cognitive changes in patients with PD are often subtle and influenced by factors that interact with the disease process, including age of disease onset, medication, and the specific constellation of motor symptoms. These factors notwithstanding, ample evidence exists that specific cognitive changes occur early in the course of PD. This evidence does not imply that cognitive deficits are pervasive during the early stages. To the contrary, they are usually subtle and often difficult to detect without formal neuropsychological testing. Executive-function deficits are the most frequently reported cognitive problems and, given that executive skills are an integral part of many tasks, it follows that subtle difficulties may be seen on a wide range of cognitive measures, particularly in working memory and visuospatial dysfunction, two areas that rely heavily on executive skills. Whereas apraxia and language processing deficits occur infrequently, subtle changes in olfaction and contrast sensitivity have also been repeatedly observed. Finally, depressive symptoms are also common in the early stages of the disease. The significance of the early behavioral changes and their prognostic implications are largely unknown. Prospective studies are needed to understand the longitudinal course of early cognitive changes to determine whether they remain as circumscribed impairments or represent a precursor to a more widespread dementia. PMID:16383214

  18. A Quantitative Comparison of the Behavior of Human Ventricular Cardiac Electrophysiology Models in Tissue

    PubMed Central

    Elshrif, Mohamed M.; Cherry, Elizabeth M.

    2014-01-01

    Numerical integration of mathematical models of heart cell electrophysiology provides an important computational tool for studying cardiac arrhythmias, but the abundance of available models complicates selecting an appropriate model. We study the behavior of two recently published models of human ventricular action potentials, the Grandi-Pasqualini-Bers (GPB) and the O'Hara-Virág-Varró-Rudy (OVVR) models, and compare the results with four previously published models and with available experimental and clinical data. We find the shapes and durations of action potentials and calcium transients differ between the GPB and OVVR models, as do the magnitudes and rate-dependent properties of transmembrane currents and the calcium transient. Differences also occur in the steady-state and S1–S2 action potential duration and conduction velocity restitution curves, including a maximum conduction velocity for the OVVR model roughly half that of the GPB model and well below clinical values. Between single cells and tissue, both models exhibit differences in properties, including maximum upstroke velocity, action potential amplitude, and minimum diastolic interval. Compared to experimental data, action potential durations for the GPB and OVVR models agree fairly well (although OVVR epicardial action potentials are shorter), but maximum slopes of steady-state restitution curves are smaller. Although studies show alternans in normal hearts, it occurs only in the OVVR model, and only for a narrow range of cycle lengths. We find initiated spiral waves do not progress to sustained breakup for either model. The dominant spiral wave period of the GPB model falls within clinically relevant values for ventricular tachycardia (VT), but for the OVVR model, the dominant period is longer than periods associated with VT. Our results should facilitate choosing a model to match properties of interest in human cardiac tissue and to replicate arrhythmia behavior more closely. Furthermore, by

  19. Olfaction in eating disorders and abnormal eating behavior: a systematic review

    PubMed Central

    Islam, Mohammed A.; Fagundo, Ana B.; Arcelus, Jon; Agüera, Zaida; Jiménez-Murcia, Susana; Fernández-Real, José M.; Tinahones, Francisco J.; de la Torre, Rafael; Botella, Cristina; Frühbeck, Gema; Casanueva, Felipe F.; Menchón, José M.; Fernandez-Aranda, Fernando

    2015-01-01

    The study provides a systematic review that explores the current literature on olfactory capacity in abnormal eating behavior. The objective is to present a basis for discussion on whether research in olfaction in eating disorders may offer additional insight with regard to the complex etiopathology of eating disorders (ED) and abnormal eating behaviors. Electronic databases (Medline, PsycINFO, PubMed, Science Direct, and Web of Science) were searched using the components in relation to olfaction and combining them with the components related to abnormal eating behavior. Out of 1352 articles, titles were first excluded by title (n = 64) and then by abstract and fulltext resulting in a final selection of 14 articles (820 patients and 385 control participants) for this review. The highest number of existing literature on olfaction in ED were carried out with AN patients (78.6%) followed by BN patients (35.7%) and obese individuals (14.3%). Most studies were only conducted on females. The general findings support that olfaction is altered in AN and in obesity and indicates toward there being little to no difference in olfactory capacity between BN patients and the general population. Due to the limited number of studies and heterogeneity this review stresses on the importance of more research on olfaction and abnormal eating behavior. PMID:26483708

  20. Teaching a Course in Abnormal Psychology and Behavior Intervention Skills for Nursing Home Aides.

    ERIC Educational Resources Information Center

    Glenwick, David S.; Slutzsky, Mitchel R.; Garfinkel, Eric

    2001-01-01

    Describes an 11-week course given at a nursing home to nursing home aides that focused on abnormal psychology and behavior intervention skills. Discusses the course goals, class composition, and course description. Addresses the problems and issues encountered with teaching this course to a nontraditional population in an unconventional setting.…

  1. Abnormal Nocturnal Behavior due to Hypoglycemia in a Patient with Type 2 Diabetes.

    PubMed

    Yang, Kwang Ik; Kim, Hyung Ki; Baek, Jeehun; Kim, Doh-Eui; Park, Hyung Kook

    2016-04-01

    Abnormal nocturnal behavior can have many causes, including primary sleep disorder, nocturnal seizures, and underlying medical or neurological disorders. A 79-year-old woman with type 2 diabetes was admitted for evaluation of abnormal nocturnal behavior. Every night at around 04:30 she was observed displaying abnormal behavior including leg shaking, fumbling with bedclothes, crawling around the room with her eyes closed, and non-responsiveness to verbal communication. Polysomnography with 20-channel electroencephalography (EEG) was performed. EEG showed that the posterior dominant rhythm was slower than that observed in the initial EEG, with diffuse theta and delta activities intermixed, and no epileptiform activity. The serum glucose level was 35 mg/dL at that time, and both the EEG findings and clinical symptoms were resolved after an intravenous injection of 50 mL of 50% glucose. These results indicate that nocturnal hypoglycemia should be considered as one of the possible etiologies in patients presenting with abnormal nocturnal behavior. PMID:26943712

  2. Ultrastructural correlates of left ventricular contraction abnormalities in patients with chronic ischemic heart disease: determinants of reversible segmental asynergy postrevascularization surgery.

    PubMed

    Flameng, W; Suy, R; Schwarz, F; Borgers, M; Piessens, J; Thone, F; Van Ermen, H; De Geest, H

    1981-11-01

    The relationships between structural alterations and left ventricular (LV) contraction abnormalities were studied in patients with coronary artery disease (CAD). Transmural biopsies of the LV anterior free wall were taken during aortocoronary bypass surgery (CABG) in 62 patients. When preoperative anterior wall motion (AWM) was reduced, significant myocardial cell degeneration was found in patients with as well as without previous anterior infarction (MI). The amount of myocardial fibrosis was increased only in patients with ECG evidence of previous anterior MI (p less than 0.001). In a second series of 139 CAD patients, cineventriculograms performed before and 8 months after CABG were examined. In patients with patent grafts to the LV anterior wall not previously infarcted, reduced AWM became normal. In patients with previous anterior MI the outcome of AWM was unpredictable (usually unimproved). Thus the histologic correlate of reduced AWM in segments not previously infarcted was progressive loss of contractile material in otherwise viable myocardial cells. Some reversibility was suggested by restoration of resting function after CABG. Unpredictable results in segments associated with pathologic Q waves appear related to the fibrous component of these previously infarcted areas. PMID:6975559

  3. Incidence and behavioral correlates of epileptiform abnormalities in autism spectrum disorders.

    PubMed

    Mulligan, Caitlin K; Trauner, Doris A

    2014-02-01

    Autism spectrum disorders (ASD) are associated with an increased incidence of epilepsy and of epileptiform discharges on electroencephalograms. It is unknown whether epileptiform discharges correlate with symptoms of ASD. We completed a retrospective chart review of 101 patients with ASD who had overnight electroencephalograms. We looked for a relationship between epileptiform abnormalities and diagnosis, history of regression, communication skills, and other features associated with ASD. There was a higher incidence of epileptiform activity in children with stereotypies and aggressive behavior. The incidence of epileptiform abnormalities was significantly lower in Asperger's compared with more severe forms of autism. Results suggest that increasing severity of autistic symptoms may be associated with higher likelihood of epileptiform abnormalities. Whether treatment alters outcome is unknown. PMID:23872941

  4. Omnivores Going Astray: A Review and New Synthesis of Abnormal Behavior in Pigs and Laying Hens

    PubMed Central

    Brunberg, Emma I.; Rodenburg, T. Bas; Rydhmer, Lotta; Kjaer, Joergen B.; Jensen, Per; Keeling, Linda J.

    2016-01-01

    Pigs and poultry are by far the most omnivorous of the domesticated farm animals and it is in their nature to be highly explorative. In the barren production environments, this motivation to explore can be expressed as abnormal oral manipulation directed toward pen mates. Tail biting (TB) in pigs and feather pecking (FP) in laying hens are examples of unwanted behaviors that are detrimental to the welfare of the animals. The aim of this review is to draw these two seemingly similar abnormalities together in a common framework, in order to seek underlying mechanisms and principles. Both TB and FP are affected by the physical and social environment, but not all individuals in a group express these behaviors and individual genetic and neurobiological characteristics play an important role. By synthesizing what is known about environmental and individual influences, we suggest a novel possible mechanism, common for pigs and poultry, involving the brain–gut–microbiota axis. PMID:27500137

  5. Omnivores Going Astray: A Review and New Synthesis of Abnormal Behavior in Pigs and Laying Hens.

    PubMed

    Brunberg, Emma I; Rodenburg, T Bas; Rydhmer, Lotta; Kjaer, Joergen B; Jensen, Per; Keeling, Linda J

    2016-01-01

    Pigs and poultry are by far the most omnivorous of the domesticated farm animals and it is in their nature to be highly explorative. In the barren production environments, this motivation to explore can be expressed as abnormal oral manipulation directed toward pen mates. Tail biting (TB) in pigs and feather pecking (FP) in laying hens are examples of unwanted behaviors that are detrimental to the welfare of the animals. The aim of this review is to draw these two seemingly similar abnormalities together in a common framework, in order to seek underlying mechanisms and principles. Both TB and FP are affected by the physical and social environment, but not all individuals in a group express these behaviors and individual genetic and neurobiological characteristics play an important role. By synthesizing what is known about environmental and individual influences, we suggest a novel possible mechanism, common for pigs and poultry, involving the brain-gut-microbiota axis. PMID:27500137

  6. Cnga2 Knockout Mice Display Alzheimer's-Like Behavior Abnormities and Pathological Changes.

    PubMed

    Xie, Ao-Ji; Liu, En-Jie; Huang, He-Zhou; Hu, Yu; Li, Ke; Lu, Youming; Wang, Jian-Zhi; Zhu, Ling-Qiang

    2016-09-01

    Olfactory dysfunction is recognized as a potential risk factor for Alzheimer's disease (AD). We have reported previously that olfactory deprivation by olfactory bulbectomy (OBX) induced Alzheimer's-like pathological changes and behavioral abnormalities. However, the acute OBX model undergoes surgical-induced brain parenchyma loss and unexpected massive hemorrhage so that it cannot fully mimic the progressive olfactory loss and neurodegeneration in AD. Here, we employed the mice loss of cyclic nucleotide-gated channel alpha 2 (Cnga2) which is critical for olfactory sensory transduction, to investigate the role of olfactory dysfunction in AD pathological process. We found that impaired learning and memory abilities, loss of dendrite spines, as well as decrement of synaptic proteins were displayed in Cnga2 knockout mice. Moreover, Aβ overproduction, tau hyperphosphorylation, and somatodendritic translocation were also found in Cnga2 knockout mice. Our findings suggest that progressive olfactory loss leads to Alzheimer's-like behavior abnormities and pathological changes. PMID:26377105

  7. Studies of planning behavior of aircraft pilots in normal, abnormal and emergency situations

    NASA Technical Reports Server (NTRS)

    Johannsen, G.; Rouse, W. B.; Hillmann, K.

    1981-01-01

    A methodology for the study of planning is presented and the results of applying the methodology within two experimental investigations of planning behavior of aircraft pilots in normal, abnormal, and emergency situations are discussed. Beyond showing that the methodology yields consistent results, these experiments also lead to concepts in terms of a dichotomy between event driven and time driven planning, subtle effects of automation on planning, and the relationship of planning to workload and flight performance.

  8. Brain gene expression differences are associated with abnormal tail biting behavior in pigs.

    PubMed

    Brunberg, E; Jensen, P; Isaksson, A; Keeling, L J

    2013-03-01

    Knowledge about gene expression in animals involved in abnormal behaviors can contribute to the understanding of underlying biological mechanisms. This study aimed to explore the motivational background to tail biting, an abnormal injurious behavior and severe welfare problem in pig production. Affymetrix microarrays were used to investigate gene expression differences in the hypothalamus and prefrontal cortex of pigs performing tail biting, pigs receiving bites to the tail and neutral pigs who were not involved in the behavior. In the hypothalamus, 32 transcripts were differentially expressed (P < 0.05) when tail biters were compared with neutral pigs, 130 when comparing receiver pigs with neutrals, and two when tail biters were compared with receivers. In the prefrontal cortex, seven transcripts were differently expressed in tail biters when compared with neutrals, seven in receivers vs. neutrals and none in the tail biters vs. receivers. In total, 19 genes showed a different expression pattern in neutral pigs when compared with both performers and receivers. This implies that the functions of these may provide knowledge about why the neutral pigs are not involved in tail biting behavior as performers or receivers. Among these 19 transcripts were genes associated with production traits in pigs (PDK4), sociality in humans and mice (GTF2I) and novelty seeking in humans (EGF). These are in line with hypotheses linking tail biting with reduced back fat thickness and explorative behavior. PMID:23146156

  9. Studies of planning behavior of aircraft pilots in normal, abnormal, and emergency situations

    NASA Technical Reports Server (NTRS)

    Johannsen, G.; Rouse, W. B.; Hillmann, K.

    1981-01-01

    A methodology for the study of human planning behavior in complex dynamic systems is presented and applied to the study of aircraft pilot behavior in normal, abnormal and emergency situations. The method measures the depth of planning, that is the level of detail employed with respect to a specific task, according to responses to a verbal questionnaire, and compares planning depth with variables relating to time, task criticality and the probability of increased task difficulty. In two series of experiments, depth of planning was measured on a five- or ten-point scale during various phases of flight in a HFB-320 simulator under normal flight conditions, abnormal scenarios involving temporary runway closure due to snow removal or temporary CAT-III conditions due to a dense fog, and emergency scenarios involving engine shut-down or hydraulic pressure loss. Results reveal a dichotomy between event-driven and time-driven planning, different effects of automation in abnormal and emergency scenarios and a low correlation between depth of planning and workload or flight performance.

  10. Antisocial behavior, psychopathic features and abnormalities in reward and punishment processing in youth.

    PubMed

    Byrd, Amy L; Loeber, Rolf; Pardini, Dustin A

    2014-06-01

    A better understanding of what leads youth to initially engage in antisocial behavior (ASB) and more importantly persist with such behaviors into adulthood has significant implications for prevention and intervention efforts. A considerable number of studies using behavioral and neuroimaging techniques have investigated abnormalities in reward and punishment processing as potential causal mechanisms underlying ASB. However, this literature has yet to be critically evaluated, and there are no comprehensive reviews that systematically examine and synthesize these findings. The goal of the present review is twofold. The first aim is to examine the extent to which youth with ASB are characterized by abnormalities in (1) reward processing; (2) punishment processing; or (3) both reward and punishment processing. The second aim is to evaluate whether aberrant reward and/or punishment processing is specific to or most pronounced in a subgroup of antisocial youth with psychopathic features. Studies utilizing behavioral methods are first reviewed, followed by studies using functional magnetic resonance imaging. An integration of theory and research across multiple levels of analysis is presented in order to provide a more comprehensive understanding of reward and punishment processing in antisocial youth. Findings are discussed in terms of developmental and contextual considerations, proposed future directions and implications for intervention. PMID:24357109

  11. Abnormal animal behavior prior to the Vrancea (Romania) major subcrustal earthquakes

    NASA Astrophysics Data System (ADS)

    Constantin, Angela; Pantea, Aurelian

    2013-04-01

    The goal of this paper is to present some observations about abnormal animal behavior prior and during of some Romanian subcrustal earthquakes. The major Vrancea earthquakes of 4 March 1977 (Mw = 7.4, Imax = IX-X MSK), 30 August 1986 (Mw = 7.1, Io = VIII-IX MSK) and 30 May 1990 (Mw = 6.9, Io = VIII MSK), were preceded by extensive occurrences of anomalous animal behavior. These data were collected immediately after the earthquakes from the areas affected by these. Some species of animals became excited, nervous and panicked before and during the earthquakes, such as: dogs (barking and running in panic), cats, snakes, mice and rats (came into the houses and have lost their fear), birds (hens, geese, parrots), horses, fishes etc. These strange manifestations of the animals were observed on the entire territory of country, especially in the extra-Carpathian area. This unusual behavior was noticed within a few hours to days before the seismic events, but for the most of cases the time of occurrence was within two hours of the quakes. We can hope that maybe one day the abnormal animal behavior will be used as a reliable seismic precursor for the intermediate depth earthquakes.

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

    SciTech Connect

    Brunner, H.G. ); Nelen, M.; Ropers, H.H.; van Oost, B.A. )

    1993-10-22

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

  13. Who Should Report Abnormal Behavior at Preschool Age? The Case of Behavioral Inhibition

    ERIC Educational Resources Information Center

    Ballespi, Sergi; Jane, Ma Claustre; Riba, Ma Dolors

    2012-01-01

    Children who are behaviorally "inhibited"--a condition at the extreme of the behavioral inhibition dimension--experience distress in uncertain social situations. Although parents and teachers are in the best position to detect this condition, they rarely agree. This study aims to analyze the agreement between parents and teachers and to examine…

  14. Repeated transcranial direct current stimulation prevents abnormal behaviors associated with abstinence from chronic nicotine consumption.

    PubMed

    Pedron, Solène; Monnin, Julie; Haffen, Emmanuel; Sechter, Daniel; Van Waes, Vincent

    2014-03-01

    Successful available treatments to quit smoking remain scarce. Recently, the potential of transcranial direct current stimulation (tDCS) as a tool to reduce craving for nicotine has gained interest. However, there is no documented animal model to assess the neurobiological mechanisms of tDCS on addiction-related behaviors. To address this topic, we have developed a model of repeated tDCS in mice and used it to validate its effectiveness in relieving nicotine addiction. Anodal repeated tDCS was applied over the frontal cortex of Swiss female mice. The stimulation electrode (anode) was fixed directly onto the cranium, and the reference electrode was placed onto the ventral thorax. A 2 × 20 min/day stimulation paradigm for five consecutive days was used (0.2 mA). In the first study, we screened for behaviors altered by the stimulation. Second, we tested whether tDCS could alleviate abnormal behaviors associated with abstinence from nicotine consumption. In naive animals, repeated tDCS had antidepressant-like properties 3 weeks after the last stimulation, improved working memory, and decreased conditioned place preference for nicotine without affecting locomotor activity and anxiety-related behavior. Importantly, abnormal behaviors associated with chronic nicotine exposure (ie, depression-like behavior, increase in nicotine-induced place preference) were normalized by repeated tDCS. Our data show for the first time in an animal model that repeated tDCS is a promising, non-expensive clinical tool that could be used to reduce smoking craving and facilitate smoking cessation. Our animal model will be useful to investigate the mechanisms underlying the effects of tDCS on addiction and other psychiatric disorders. PMID:24154668

  15. Behavioral and regulatory abnormalities in mice deficient in the NPAS1 and NPAS3 transcription factors.

    PubMed

    Erbel-Sieler, Claudia; Dudley, Carol; Zhou, Yudong; Wu, Xinle; Estill, Sandi Jo; Han, Tina; Diaz-Arrastia, Ramon; Brunskill, Eric W; Potter, S Steven; McKnight, Steven L

    2004-09-14

    Laboratory mice bearing inactivating mutations in the genes encoding the NPAS1 and NPAS3 transcription factors have been shown to exhibit a spectrum of behavioral and neurochemical abnormalities. Behavioral abnormalities included diminished startle response, as measured by prepulse inhibition, and impaired social recognition. NPAS1/NPAS3-deficient mice also exhibited stereotypic darting behavior at weaning and increased locomotor activity. Immunohistochemical staining assays showed that the NPAS1 and NPAS3 proteins are expressed in inhibitory interneurons and that the viability and anatomical distribution of these neurons are unaffected by the absence of either transcription factor. Adult brain tissues from NPAS3- and NPAS1/NPAS3-deficient mice exhibited a distinct reduction in reelin, a large, secreted protein whose expression has been reported to be attenuated in the postmortem brain tissue of patients with schizophrenia. These observations raise the possibility that a regulatory program controlled in inhibitory interneurons by the NPAS1 and NPAS3 transcription factors may be either substantively or tangentially relevant to psychosis. PMID:15347806

  16. A survey of abnormal repetitive behaviors in North American river otters housed in zoos.

    PubMed

    Morabito, Paige; Bashaw, Meredith J

    2012-01-01

    Stereotypic behaviors, indicating poor welfare and studied in a variety of species (especially carnivores), appear related to characteristics of current and past environments. Although North American river otters (Lontra canadensis) often develop abnormal, repetitive, possibly stereotypic behaviors, no published reports describe otter housing and management or characterize how these variables relate to abnormal repetitive behavior (ARB) occurrence. The first author developed surveys to gather data on housing, individual history, management, and the prevalence of ARBs in otters housed in facilities accredited by the Association of Zoos and Aquariums. Consistent with anecdotal evidence that otters are prone to ARBs, 46% of river otters in the study exhibit them. ARBs were mostly locomotor and often preceded feeding. Exhibits where otters were fed and trained housed a greater percentage of nonhuman animals with ARBs. This study supports the Tarou, Bloomsmith, and Maple (2005) report that more hands-on management is associated with higher levels of ARBs because management efforts are only for animals with ARBs. Escape motivation, breeding season, feeding cues, and ability to forage may affect ARBs in river otters and should be investigated. PMID:22742198

  17. Scaling behavior and a Markov model for ventricular fibrillation generated by ectopic beats

    NASA Astrophysics Data System (ADS)

    Hastings, Harold; Evans, Steven; Zaharakis, Alex; Hilaire, Christian

    2006-03-01

    Sudden cardiac death is a major cause of death in the industrialized world, responsible for 300,000 deaths per year in the US. Although the cardiac electrical system normally produces one ventricular activation in response to each stimulus from the sinus node, ``spontaneous'' activations, called premature ventricular contractions (PVCs), can arise in the ventricles themselves, and propagate through the ventricles. Although usually harmless in the absence of underlying disease, PVCs can generate broken wavefronts when they meet gradients of refractoriness generated by other beats. These broken wavefronts may generate spiral waves producing ventricular tachycardia and ultimately degenerate into ventricular fibrillation (VF), causing sudden cardiac death. When does a PVC lead to ventricular fibrillation ? This is a stiff problem, involving time scales from milliseconds to many years. We overcome this problem by developing universal scaling properties and using these rules to drive a Markov process. We find two significant ``amplifiers'' and discuss consequences for variability of VF rates in human populations. We thank Elizabeth Cherry, Flavio Fenton, Anna Gelzer and James Glimm for helpful discussions.

  18. Trichloroethylene exposure aggravates behavioral abnormalities in mice that are deficient in superoxide dismutase.

    PubMed

    Otsuki, Noriyuki; Homma, Takujiro; Fujiwara, Hiroki; Kaneko, Kenya; Hozumi, Yasukazu; Shichiri, Mototada; Takashima, Mizuki; Ito, Junitsu; Konno, Tasuku; Kurahashi, Toshihiro; Yoshida, Yasukazu; Goto, Kaoru; Fujii, Satoshi; Fujii, Junichi

    2016-08-01

    Trichloroethylene (TCE) has been implicated as a causative agent for Parkinson's disease (PD). The administration of TCE to rodents induces neurotoxicity associated with dopaminergic neuron death, and evidence suggests that oxidative stress as a major player in the progression of PD. Here we report on TCE-induced behavioral abnormality in mice that are deficient in superoxide dismutase 1 (SOD1). Wild-type (WT) and SOD1-deficient (Sod1(-/-)) mice were intraperitoneally administered TCE (500 mg/kg) over a period of 4 weeks. Although the TCE-administrated Sod1(-/-) mice showed marked abnormal motor behavior, no significant differences were observed among the experimental groups by biochemical and histopathological analyses. However, treating mouse neuroblastoma-derived NB2a cells with TCE resulted in the down regulation of the SOD1 protein and elevated oxidative stress under conditions where SOD1 production was suppressed. Taken together, these data indicate that SOD1 plays a pivotal role in protecting motor neuron function against TCE toxicity. PMID:27166294

  19. Elevated PEM (Phasic Electromyographic Metric) Rates Identify Rapid Eye Movement Behavior Disorder Patients on Nights Without Behavioral Abnormalities

    PubMed Central

    Bliwise, Donald L.; Rye, David B.

    2008-01-01

    Objective: To determine the validity of the phasic electromyographic metric (PEM) to differentiate patients with a history suggestive of rapid eye movement behavior disorder (REMBD) on laboratory nights without overt dream-enactment behavior. Methods: PEM was quantified as the % of 2.5-sec intervals with phasic muscle activity of 100-msec duration with an amplitude of at least 4 times background activity in 11 patients and 31 elderly controls. Data were derived from both REM and NREM sleep from 5 muscle groups (mentalis, left/right anterior tibialis, left/right brachioradialis). Results: Relative to controls, REMBD patients had significantly higher levels of PEM activity in all recordings. The largest differences occurred during REM sleep for the mentalis and brachioradialis channels. Similar results were obtained by limiting quantification of PEM to the final REM period of the night and could be accomplished by individuals with no previous familiarity with polysomnography. Discussion: PEM may be a useful metric to characterize the REM related phasic muscle activity on patients with a history of REMBD, even when no overt dream-enactment behaviors are detected on a laboratory night. Citation: Bliwise DL; Rye DB. Elevated PEM (phasic electromyographic metric) rates identify rapid eye movement behavior disorder patients on nights without behavioral abnormalities. SLEEP 2008;31(6):853–857. PMID:18548830

  20. Reproductive and behavioral abnormalities in tree swallows with high levels of PCB contamination

    SciTech Connect

    McCarty, J.; Secord, A.; Tillitt, D.

    1995-12-31

    Tree Swallows (Tachycineta bicolor) breeding along the Hudson River forage extensively on PCB contaminated insects that emerge from the river. The authors studied the reproductive ecology and behavior of tree swallows breeding at several sites along the Hudson River. These sites vary in the severity of PCB contamination. PCB levels in both eggs and chicks were found to be among the highest ever reported in this species, with concentrations comparable to those found in aquatic organisms in the Hudson River. In 1994 reproductive success at PCB contaminated sites was significantly impaired, relative to other sites in New York. Reduced reproductive success was largely attributed to high levels of nest abandonment during incubation and reduced hatchability of eggs. Growth and development of nestlings was not significantly impaired. Abnormal nest building behavior was also noted in 1994, and this was studied in detail in 1995. Nests from contaminated areas are significantly smaller than those at a nearby reference site and at other sites in New York. The authors suggest that the reduced reproductive outputs at these sites are, in large part, a result of effects on the behavior of incubating females. The population-level implications of these patterns are unknown.

  1. Decomposition of abnormal free locomotor behavior in a rat model of Parkinson's disease

    PubMed Central

    Grieb, Benjamin; von Nicolai, Constantin; Engler, Gerhard; Sharott, Andrew; Papageorgiou, Ismini; Hamel, Wolfgang; Engel, Andreas K.; Moll, Christian K.

    2013-01-01

    Poverty of spontaneous movement, slowed execution and reduced amplitudes of movement (akinesia, brady- and hypokinesia) are cardinal motor manifestations of Parkinson's disease that can be modeled in experimental animals by brain lesions affecting midbrain dopaminergic neurons. Most behavioral investigations in experimental parkinsonism have employed short-term observation windows to assess motor impairments. We postulated that an analysis of longer-term free exploratory behavior could provide further insights into the complex fine structure of altered locomotor activity in parkinsonian animals. To this end, we video-monitored 23 h of free locomotor behavior and extracted several behavioral measures before and after the expression of a severe parkinsonian phenotype following bilateral 6-hydroxydopamine (6-OHDA) lesions of the rat dopaminergic substantia nigra. Unbiased stereological cell counting verified the degree of midbrain tyrosine hydroxylase positive cell loss in the substantia nigra and ventral tegmental area. In line with previous reports, overall covered distance and maximal motion speed of lesioned animals were found to be significantly reduced compared to controls. Before lesion surgery, exploratory rat behavior exhibited a bimodal distribution of maximal speed values obtained for single movement episodes, corresponding to a “first” and “second gear” of motion. 6-OHDA injections significantly reduced the incidence of second gear motion episodes and also resulted in an abnormal prolongation of these fast motion events. Likewise, the spatial spread of such episodes was increased in 6-OHDA rats. The increase in curvature of motion tracks was increased in both lesioned and control animals. We conclude that the discrimination of distinct modes of motion by statistical decomposition of longer-term spontaneous locomotion provides useful insights into the fine structure of fluctuating motor functions in a rat analog of Parkinson's disease. PMID:24348346

  2. Variables influencing the origins of diverse abnormal behaviors in a large sample of captive chimpanzees (Pan troglodytes).

    PubMed

    Nash, L T; Fritz, J; Alford, P A; Brent, L

    1999-01-01

    The developmental origin of abnormal behaviors is generally associated with early rearing environments that lack sufficient physical and sensory stimulation. However, other factors should also be considered. A large sample of captive chimpanzees (128 males and 140 females) was surveyed for the presence or absence of 18 abnormal behaviors. Origin variables included the subject's source (zoo, pet, performer, or laboratory), rearing (mother- or hand-reared), and sex. Animals were assessed while held at the Primate Foundation of Arizona, University of Texas M. D. Anderson Cancer Center, or White Sands Research Center. There was a confound among origin variables; more hand-reared animals than expected were from laboratories. Logistic regression tested the relationship of rearing and source, with sex as a secondary predictor variable, to each of the abnormal behaviors. There was no clear association between any abnormal behavior and source. However, for coprophagy, relative to animals from the laboratory, zoo animals tended to show a higher prevalence, while performers tended to show a lower prevalence (when rearing and sex were controlled). Rocking and self-sucking were significantly more likely in hand-reared animals. Coprophagy and depilation of self were significantly more likely in mother-reared animals. When rearing and source were statistically controlled, the only significant sex difference was a higher prevalence of coprophagy in females and a higher prevalence of rocking in males. In a second, smaller sample of 25 males and 33 females from Southwest Foundation for Biomedical Research, no significant sex association was found for coprophagy, urophagy, rocking, or self-depilation. In this second sample, coprophagy was also significantly more likely in mother-reared than hand-reared subjects. The association of some abnormal behaviors with mother-rearing suggests that some form of social learning may be involved in the origin of some of these behavior patterns

  3. GABAergic influences on ORX receptor-dependent abnormal motor behaviors and neurodegenerative events in fish

    SciTech Connect

    Facciolo, Rosa Maria; Crudo, Michele; Giusi, Giuseppina; Canonaco, Marcello

    2010-02-15

    At date the major neuroreceptors i.e. gamma-aminobutyric acid{sub A} (GABA{sub A}R) and orexin (ORXR) systems are beginning to be linked to homeostasis, neuroendocrine and emotional states. In this study, intraperitoneal treatment of the marine teleost Thalassoma pavo with the highly selective GABA{sub A}R agonist (muscimol, MUS; 0,1 mug/g body weight) and/or its antagonist bicuculline (BIC; 1 mug/g body weight) have corroborated a GABA{sub A}ergic role on motor behaviors. In particular, MUS induced moderate (p < 0.05) and great (p < 0.01) increases of swimming towards food sources and resting states after 24 (1 dose) and 96 (4 doses) h treatment sessions, respectively, when compared to controls. Conversely, BIC caused a very strong (p < 0.001) reduction of the former behavior and in some cases convulsive swimming. From the correlation of BIC-dependent behavioral changes to neuronal morphological and ORXR transcriptional variations, it appeared that the disinhibitory action of GABA{sub A}R was very likely responsible for very strong and strong ORXR mRNA reductions in cerebellum valvula and torus longitudinalis, respectively. Moreover these effects were linked to evident ultra-structural changes such as shrunken cell membranes and loss of cytoplasmic architecture. In contrast, MUS supplied a very low, if any, argyrophilic reaction in hypothalamic and mesencephalic regions plus a scarce level of ultra-structural damages. Interestingly, combined administrations of MUS + BIC were not related to consistent damages, aside mild neuronal alterations in motor-related areas such as optic tectum. Overall it is tempting to suggest, for the first time, a neuroprotective role of GABA{sub A}R inhibitory actions against the overexcitatory ORXR-dependent neurodegeneration and consequently abnormal swimming events in fish.

  4. Loss of prion protein leads to age-dependent behavioral abnormalities and changes in cytoskeletal protein expression

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cellular prion protein (PrPC) is a multifunctional protein, whose exact physiological role remains elusive. Since previous studies indicated a neuroprotective function of PrPC, we investigated whether Prnp knockout mice(Prnp0/0)display age-dependent behavioral abnormalities. Matched sets of Prnp0/0 ...

  5. Dido mutations trigger perinatal death and generate brain abnormalities and behavioral alterations in surviving adult mice.

    PubMed

    Villares, Ricardo; Gutiérrez, Julio; Fütterer, Agnes; Trachana, Varvara; Gutiérrez del Burgo, Fernando; Martínez-A, Carlos

    2015-04-14

    Nearly all vertebrate cells have a single cilium protruding from their surface. This threadlike organelle, once considered vestigial, is now seen as a pivotal element for detection of extracellular signals that trigger crucial morphogenetic pathways. We recently proposed a role for Dido3, the main product of the death inducer-obliterator (dido) gene, in histone deacetylase 6 delivery to the primary cilium [Sánchez de Diego A, et al. (2014) Nat Commun 5:3500]. Here we used mice that express truncated forms of Dido proteins to determine the link with cilium-associated disorders. We describe dido mutant mice with high incidence of perinatal lethality and distinct neurodevelopmental, morphogenetic, and metabolic alterations. The anatomical abnormalities were related to brain and orofacial development, consistent with the known roles of primary cilia in brain patterning, hydrocephalus incidence, and cleft palate. Mutant mice that reached adulthood showed reduced life expectancy, brain malformations including hippocampus hypoplasia and agenesis of corpus callosum, as well as neuromuscular and behavioral alterations. These mice can be considered a model for the study of ciliopathies and provide information for assessing diagnosis and therapy of genetic disorders linked to the deregulation of primary cilia. PMID:25825751

  6. Dido mutations trigger perinatal death and generate brain abnormalities and behavioral alterations in surviving adult mice

    PubMed Central

    Villares, Ricardo; Gutiérrez, Julio; Fütterer, Agnes; Trachana, Varvara; Gutiérrez del Burgo, Fernando; Martínez-A, Carlos

    2015-01-01

    Nearly all vertebrate cells have a single cilium protruding from their surface. This threadlike organelle, once considered vestigial, is now seen as a pivotal element for detection of extracellular signals that trigger crucial morphogenetic pathways. We recently proposed a role for Dido3, the main product of the death inducer-obliterator (dido) gene, in histone deacetylase 6 delivery to the primary cilium [Sánchez de Diego A, et al. (2014) Nat Commun 5:3500]. Here we used mice that express truncated forms of Dido proteins to determine the link with cilium-associated disorders. We describe dido mutant mice with high incidence of perinatal lethality and distinct neurodevelopmental, morphogenetic, and metabolic alterations. The anatomical abnormalities were related to brain and orofacial development, consistent with the known roles of primary cilia in brain patterning, hydrocephalus incidence, and cleft palate. Mutant mice that reached adulthood showed reduced life expectancy, brain malformations including hippocampus hypoplasia and agenesis of corpus callosum, as well as neuromuscular and behavioral alterations. These mice can be considered a model for the study of ciliopathies and provide information for assessing diagnosis and therapy of genetic disorders linked to the deregulation of primary cilia. PMID:25825751

  7. Periventricular white matter abnormalities and restricted repetitive behavior in autism spectrum disorder

    PubMed Central

    Blackmon, Karen; Ben-Avi, Emma; Wang, Xiuyuan; Pardoe, Heath R.; Di Martino, Adriana; Halgren, Eric; Devinsky, Orrin; Thesen, Thomas; Kuzniecky, Ruben

    2015-01-01

    Malformations of cortical development are found at higher rates in autism spectrum disorder (ASD) than in healthy controls on postmortem neuropathological evaluation but are more variably observed on visual review of in-vivo MRI brain scans. This may be due to the visually elusive nature of many malformations on MRI. Here, we utilize a quantitative approach to determine whether a volumetric measure of heterotopic gray matter in the white matter is elevated in people with ASD, relative to typically developing controls (TDC). Data from a primary sample of 48 children/young adults with ASD and 48 age-, and gender-matched TDCs, selected from the Autism Brain Imaging Data Exchange (ABIDE) open-access database, were analyzed to compare groups on (1) blinded review of high-resolution T1-weighted research sequences; and (2) quantitative measurement of white matter hypointensity (WMH) volume calculated from the same T1-weighted scans. Groupwise WMH volume comparisons were repeated in an independent, multi-site sample (80 ASD/80 TDC), also selected from ABIDE. Visual review resulted in equivalent proportions of imaging abnormalities in the ASD and TDC group. However, quantitative analysis revealed elevated periventricular and deep subcortical WMH volumes in ASD. This finding was replicated in the independent, multi-site sample. Periventricular WMH volume was not associated with age but was associated with greater restricted repetitive behaviors on both parent-reported and clinician-rated assessment inventories. Thus, findings demonstrate that periventricular WMH volume is elevated in ASD and associated with a higher degree of repetitive behaviors and restricted interests. Although the etiology of focal WMH clusters is unknown, the absence of age effects suggests that they may reflect a static anomaly. PMID:26693400

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

    PubMed Central

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

    2012-01-01

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

  9. Albuminuria is Independently Associated with Cardiac Remodeling, Abnormal Right and Left Ventricular Function, and Worse Outcomes in Heart Failure with Preserved Ejection Fraction

    PubMed Central

    Katz, Daniel H.; Burns, Jacob A.; Aguilar, Frank G.; Beussink, Lauren; Shah, Sanjiv J.

    2014-01-01

    Objectives To determine the relationship between albuminuria and cardiac structure/function in heart failure with preserved ejection fraction (HFpEF). Background Albuminuria, a marker of endothelial dysfunction, has been associated with adverse cardiovascular outcomes in HFpEF. However, the relationship between albuminuria and cardiac structure/function in HFpEF has not been well studied. Methods We measured urinary albumin-to-creatinine ratio (UACR) and performed comprehensive echocardiography, including tissue Doppler imaging and right ventricular (RV) evaluation, in a prospective study of 144 patients with HFpEF. Multivariable-adjusted linear regression was used to determine the association between UACR and echocardiographic parameters. Cox proportional hazards analyses were used to determine the association between UACR and outcomes. Results The mean age was 66±11 years, 62% were female, and 42% were African-American. Higher UACR was associated with greater left ventricular (LV) mass, lower preload-recruitable stroke work, and lower global longitudinal strain. Higher UACR was also significantly associated with RV remodeling (for each doubling of UACR, RV wall thickness was 0.9 mm higher [95% confidence interval (CI) 0.05–0.14 mm; P=0.001, adjusted P=0.01]) and worse RV systolic function (for each doubling of UACR, RV fractional area change was 0.56% lower [95% CI 0.14–0.98%; P=0.01, adjusted P=0.03]. The association between UACR and RV parameters persisted after excluding patients with macroalbuminuria (UACR > 300 mg/g). Increased UACR was also independently associated with worse outcomes. Conclusions In HFpEF, increased UACR is a prognostic marker and is associated with increased RV and LV remodeling, and longitudinal systolic dysfunction. PMID:25282032

  10. In vivo characterization of metabotropic glutamate receptor type 5 abnormalities in behavioral variant FTD.

    PubMed

    Leuzy, Antoine; Zimmer, Eduardo Rigon; Dubois, Jonathan; Pruessner, Jens; Cooperman, Cory; Soucy, Jean-Paul; Kostikov, Alexey; Schirmaccher, Esther; Désautels, René; Gauthier, Serge; Rosa-Neto, Pedro

    2016-04-01

    Although the pathogenesis underlying behavioral variant frontotemporal dementia (bvFTD) has yet to be fully understood, glutamatergic abnormalities have been hypothesized to play an important role. The aim of the present study was to determine the availability of the metabotropic glutamate receptor type 5 (mGluR5) using a novel positron emission tomography (PET) radiopharmaceutical with high selectivity for mGluR5 ([(11)C]ABP688) in a sample of bvFTD patients. In addition, we sought to determine the overlap between availability of mGluR5 and neurodegeneration, as measured using [(18)F]FDG-PET and voxel-based morphometry (VBM). Availability of mGluR5 and glucose metabolism ([(18)F]FDG) were measured in bvFTD (n = 5) and cognitively normal (CN) subjects (n = 10). [(11)C]ABP688 binding potential maps (BPND) were calculated using the cerebellum as a reference region, with [(18)F]FDG standardized uptake ratio maps (SUVR) normalized to the pons. Grey matter (GM) concentrations were determined using VBM. Voxel-based group differences were obtained using RMINC. BvFTD patients showed widespread decrements in [(11)C]ABP688 BPND throughout frontal, temporal and subcortical areas. These areas were likewise characterized by significant hypometabolism and GM loss, with overlap between reduced [(11)C]ABP688 BPND and hypometabolism superior to that for GM atrophy. Several regions were characterized only by decreased binding of [(11)C]ABP688. The present findings represent the first in vivo report of decreased availability of mGluR5 in bvFTD. This study suggests that glutamate excitotoxicity may play a role in the pathogenesis of bvFTD and that [(11)C]ABP688 may prove a suitable marker of glutamatergic neurotransmission in vivo. PMID:25596865

  11. Behavioral abnormalities are common and severe in patients with distal 22q11.2 microdeletions and microduplications

    PubMed Central

    Lindgren, Valerie; McRae, Anne; Dineen, Richard; Saulsberry, Alexandria; Hoganson, George; Schrift, Michael

    2015-01-01

    We describe six individuals with microdeletions and microduplications in the distal 22q11.2 region detected by microarray. Five of the abnormalities have breakpoints in the low-copy repeats (LCR) in this region and one patient has an atypical rearrangement. Two of the six patients with abnormalities in the region between LCR22 D–E have hearing loss, which has previously been reported only once in association with these abnormalities. We especially note the behavioral/neuropsychiatric problems, including the severity and early onset, in patients with distal 22q11.2 rearrangements. Our patients add to the genotype–phenotype correlations which are still being generated for these chromosomal anomalies. PMID:26247050

  12. GLP-1 receptor agonist liraglutide reverses long-term atypical antipsychotic treatment associated behavioral depression and metabolic abnormalities in rats.

    PubMed

    Sharma, Ajaykumar N; Ligade, Sagar S; Sharma, Jay N; Shukla, Praveen; Elased, Khalid M; Lucot, James B

    2015-04-01

    Mood disorder patients that are on long-term atypical antipsychotics treatment frequently experience metabolic dysfunctions. In addition to this, accumulating evidences points to increased risk of structural abnormalities, brain volume changes, altered neuroplasticity and behavioral depression with long-term antipsychotics use. However, there is paucity of preclinical evidences for long-term antipsychotic associated depression-like behavior. The objectives of the present study were: (1) to evaluate influence of long-term antipsychotic (olanzapine) treatment on rat behavior in forced swim test (FST) as a model for depression and; (2) to examine impact of glucagon-like peptide 1 (GLP-1) receptor agonist liraglutide - an antidiabetic medication for type II diabetes, on long-term olanzapine associated metabolic and behavioral changes in rats. Daily olanzapine treatment (0.5 mg/kg; p.o.) for 8-9 weeks significantly increased body weights, food and water intake, plasma cholesterol and triglycerides and immobility time in FST with parallel reduction in plasma HDL cholesterol levels. These results points to development of metabolic abnormalities and depression-like behavior with long-term olanzapine treatment. Acute liraglutide (50 μg/kg; i.p.) and imipramine (10 mg/kg, i. p.) treatment per se significantly decreased duration of immobility in FST compared to vehicle treated rats. Additionally, 3-week liraglutide treatment (50 μg/kg; i.p., daily) partially reversed metabolic abnormalities and depression-like behavior with long-term olanzapine-treatment in rats. None of these treatment regimens affected locomotor behavior of rats. In summary, add-on GLP-1 receptor agonists promise novel alternatives to counteract long-term antipsychotics associated behavioral and metabolic complications. PMID:25023888

  13. Abnormal sexual behavior during sleep in temporal lobe epilepsy: a case report.

    PubMed

    Pelin, Zerrin; Yazla, Ece

    2012-06-01

    Herein, we describe a case who presented with abnormal sexual behaviour during sleep. Video-electroencephalography monitoring during sleep revealed an abnormality suggesting an epileptic basis. The patient was successfully treated with carbamazepin. The psychiatric symptoms that were thought to be related to abnormal sexual behaviours were controlled with antipsychotic treatment. Our findings strongly emphasize the fact that efforts should be spent to increase awareness of seizure activity at night, which can be misinterpreted as benign parasomnias. Such a misinterpretation may have serious consequences, such as insufficient seizure control, progressive personality changes, and cognitive impairment. PMID:25206999

  14. Unipolar resistance switching and abnormal reset behaviors in Pt/CuO/Pt and Cu/CuO/Pt structures

    NASA Astrophysics Data System (ADS)

    Wu, Liang; Li, Xiaomin; Gao, Xiangdong; Zheng, Renkui; Zhang, Feng; Liu, Xinjun; Wang, Qun

    2012-07-01

    The effects of Pt and Cu top electrodes on resistance switching properties were investigated for CuO thin films with Pt/CuO/Pt and Cu/CuO/Pt sandwich structures. Typical unipolar resistance switching (URS) behaviors and two different kinds of resistance changes in the reset process were observed in both structures. When voltages were applied to the film, the low-resistance state (LRS) with relatively low resistance value (<30 Ω) was switched to the high-resistance state (HRS), exhibiting normal reset behavior. For LRS with relatively high resistance value (>50 Ω), the resistance first decreased then increased to HRS, showing abnormal reset behavior. The former variation of LRS could be ascribed to the decrease in filament size induced by Joule heating, while the latter one could be ascribed to the growth of disconnected filaments induced by high electric fields. This study indicates that the switching modes and the abnormal reset behaviors in CuO thin films are not due to Pt and Cu top electrodes, but the intrinsic properties of CuO film.

  15. The Relationship between Personality Dimensions and Resiliency to Environmental Stress in Orange-Winged Amazon Parrots (Amazona amazonica), as Indicated by the Development of Abnormal Behaviors.

    PubMed

    Cussen, Victoria A; Mench, Joy A

    2015-01-01

    Parrots are popular companion animals, but are frequently relinquished because of behavioral problems, including abnormal repetitive behaviors like feather damaging behavior and stereotypy. In addition to contributing to pet relinquishment, these behaviors are important as potential indicators of diminished psychological well-being. While abnormal behaviors are common in captive animals, their presence and/or severity varies between animals of the same species that are experiencing the same environmental conditions. Personality differences could contribute to this observed individual variation, as they are known risk factors for stress sensitivity and affective disorders in humans. The goal of this study was to assess the relationship between personality and the development and severity of abnormal behaviors in captive-bred orange-winged Amazon parrots (Amazona amazonica). We monitored between-individual behavioral differences in enrichment-reared parrots of known personality types before, during, and after enrichment deprivation. We predicted that parrots with higher scores for neurotic-like personality traits would be more susceptible to enrichment deprivation and develop more abnormal behaviors. Our results partially supported this hypothesis, but also showed that distinct personality dimensions were related to different forms of abnormal behavior. While neuroticism-like traits were linked to feather damaging behavior, extraversion-like traits were negatively related to stereotypic behavior. More extraverted birds showed resiliency to environmental stress, developing fewer stereotypies during enrichment deprivation and showing lower levels of these behaviors following re-enrichment. Our data, together with the results of the few studies conducted on other species, suggest that, as in humans, certain personality types render individual animals more susceptible or resilient to environmental stress. Further, this susceptibility/resiliency can have a long

  16. The Relationship between Personality Dimensions and Resiliency to Environmental Stress in Orange-Winged Amazon Parrots (Amazona amazonica), as Indicated by the Development of Abnormal Behaviors

    PubMed Central

    Cussen, Victoria A.; Mench, Joy A.

    2015-01-01

    Parrots are popular companion animals, but are frequently relinquished because of behavioral problems, including abnormal repetitive behaviors like feather damaging behavior and stereotypy. In addition to contributing to pet relinquishment, these behaviors are important as potential indicators of diminished psychological well-being. While abnormal behaviors are common in captive animals, their presence and/or severity varies between animals of the same species that are experiencing the same environmental conditions. Personality differences could contribute to this observed individual variation, as they are known risk factors for stress sensitivity and affective disorders in humans. The goal of this study was to assess the relationship between personality and the development and severity of abnormal behaviors in captive-bred orange-winged Amazon parrots (Amazona amazonica). We monitored between-individual behavioral differences in enrichment-reared parrots of known personality types before, during, and after enrichment deprivation. We predicted that parrots with higher scores for neurotic-like personality traits would be more susceptible to enrichment deprivation and develop more abnormal behaviors. Our results partially supported this hypothesis, but also showed that distinct personality dimensions were related to different forms of abnormal behavior. While neuroticism-like traits were linked to feather damaging behavior, extraversion-like traits were negatively related to stereotypic behavior. More extraverted birds showed resiliency to environmental stress, developing fewer stereotypies during enrichment deprivation and showing lower levels of these behaviors following re-enrichment. Our data, together with the results of the few studies conducted on other species, suggest that, as in humans, certain personality types render individual animals more susceptible or resilient to environmental stress. Further, this susceptibility/resiliency can have a long

  17. Abnormalities of physics and mechanical properties, behavior of helium and hydrogen in the V-Ti alloys (Overview)

    NASA Astrophysics Data System (ADS)

    Staltsov, M. S.; Chernov, I. I.; Kalin, B. A.; Korchagin, O. N.; Anan'in, V. M.

    2016-04-01

    The paper presents the results of studies of physical and mechanical properties, helium and hydrogen behavior in vanadium-titanium alloys depending on titanium content. In particular, the results of helium swelling research, thermal desorption studies of helium and hydrogen behavior, results of internal friction measurements, measuring amount of hydrogen retained introduced by various methods. It was shown that the addition of titanium to vanadium have nonmonotonic influence on the behavior of implanted helium and hydrogen, as well as on the physical and mechanical and radiation properties known in literature. It is expected that such an abnormal influence of titanium on various properties of vanadium-titanium alloys occurs because of the interaction of vanadium and titanium atoms with atoms of interstitial impurities.

  18. Abnormal bipolar resistive switching behavior in a Pt/GaO{sub 1.3}/Pt structure

    SciTech Connect

    Guo, D. Y.; Wu, Z. P.; Zhang, L. J.; Yang, T.; Hu, Q. R.; Lei, M.; Tang, W. H. E-mail: pgli@zstu.edu.cn; Li, P. G. E-mail: pgli@zstu.edu.cn; Li, L. H.

    2015-07-20

    A stable and repeatable abnormal bipolar resistive switching behavior was observed in a Pt/GaO{sub 1.3}/Pt sandwich structure without an electroforming process. The low resistance state (LRS) and the high resistance state (HRS) of the device can be distinguished clearly and be switched reversibly under a train of the voltage pulses. The LRS exhibits a conduction of electron tunneling, while the HRS shows a conduction of Schottky-type. The observed phenomena are considered to be related to the migration of oxygen vacancies which changes the space charge region width of the metal/semiconductor interface and results in a different electron transport mechanism.

  19. High-resolution imaging of cardiomyocyte behavior reveals two distinct steps in ventricular trabeculation

    PubMed Central

    Staudt, David W.; Liu, Jiandong; Thorn, Kurt S.; Stuurman, Nico; Liebling, Michael; Stainier, Didier Y. R.

    2014-01-01

    Over the course of development, the vertebrate heart undergoes a series of complex morphogenetic processes that transforms it from a simple myocardial epithelium to the complex 3D structure required for its function. One of these processes leads to the formation of trabeculae to optimize the internal structure of the ventricle for efficient conduction and contraction. Despite the important role of trabeculae in the development and physiology of the heart, little is known about their mechanism of formation. Using 3D time-lapse imaging of beating zebrafish hearts, we observed that the initiation of cardiac trabeculation can be divided into two processes. Before any myocardial cell bodies have entered the trabecular layer, cardiomyocytes extend protrusions that invade luminally along neighboring cell-cell junctions. These protrusions can interact within the trabecular layer to form new cell-cell contacts. Subsequently, cardiomyocytes constrict their abluminal surface, moving their cell bodies into the trabecular layer while elaborating more protrusions. We also examined the formation of these protrusions in trabeculation-deficient animals, including erbb2 mutants, tnnt2a morphants, which lack cardiac contractions and flow, and myh6 morphants, which lack atrial contraction and exhibit reduced flow. We found that, compared with cardiomyocytes in wild-type hearts, those in erbb2 mutants were less likely to form protrusions, those in tnnt2a morphants formed less stable protrusions, and those in myh6 morphants extended fewer protrusions per cell. Thus, through detailed 4D imaging of beating hearts, we have identified novel cellular behaviors underlying cardiac trabeculation. PMID:24401373

  20. Tau deposition drives neuropathological, inflammatory and behavioral abnormalities independently of neuronal loss in a novel mouse model

    PubMed Central

    Cook, Casey; Kang, Silvia S.; Carlomagno, Yari; Lin, Wen-Lang; Yue, Mei; Kurti, Aishe; Shinohara, Mitsuru; Jansen-West, Karen; Perkerson, Emilie; Castanedes-Casey, Monica; Rousseau, Linda; Phillips, Virginia; Bu, Guojun; Dickson, Dennis W.; Petrucelli, Leonard; Fryer, John D.

    2015-01-01

    Aberrant tau protein accumulation drives neurofibrillary tangle (NFT) formation in several neurodegenerative diseases. Currently, efforts to elucidate pathogenic mechanisms and assess the efficacy of therapeutic targets are limited by constraints of existing models of tauopathy. In order to generate a more versatile mouse model of tauopathy, somatic brain transgenesis was utilized to deliver adeno-associated virus serotype 1 (AAV1) encoding human mutant P301L-tau compared with GFP control. At 6 months of age, we observed widespread human tau expression with concomitant accumulation of hyperphosphorylated and abnormally folded proteinase K resistant tau. However, no overt neuronal loss was observed, though significant abnormalities were noted in the postsynaptic scaffolding protein PSD95. Neurofibrillary pathology was also detected with Gallyas silver stain and Thioflavin-S, and electron microscopy revealed the deposition of closely packed filaments. In addition to classic markers of tauopathy, significant neuroinflammation and extensive gliosis were detected in AAV1-TauP301L mice. This model also recapitulates the behavioral phenotype characteristic of mouse models of tauopathy, including abnormalities in exploration, anxiety, and learning and memory. These findings indicate that biochemical and neuropathological hallmarks of tauopathies are accurately conserved and are independent of cell death in this novel AAV-based model of tauopathy, which offers exceptional versatility and speed in comparison with existing transgenic models. Therefore, we anticipate this approach will facilitate the identification and validation of genetic modifiers of disease, as well as accelerate preclinical assessment of potential therapeutic targets. PMID:26276810

  1. Abnormal behavioral responses to fenfluramine in patients with affective and personality disorders. Correlation with increased serotonergic responsivity.

    PubMed

    Myers, J E; Mieczkowski, T; Perel, J; Abbondanza, D; Cooper, T B; Mann, J J

    1994-01-15

    Serotonergic responsivity was assessed in 20 psychiatric patients by the prolactin response to a fenfluramine challenge test. During the fenfluramine challenge 6 of 20 patients (30%) spontaneously reported psychopathologic reactions that included: increased anxiety/agitation, psychotic symptoms, illusions, mood elevation, and anergia. The time of peak behavioral symptoms (2.5 +/- 0.8 hrs) corresponded closely to the time of peak increase in prolactin levels (3.0 +/- 1.1 hr). Abnormal behavioral responders had statistically significant greater increases in prolactin 1 to 4 hr after fenfluramine when compared to normal responders. Patients who developed an abnormal psychopathologic response to fenfluramine were characterized by higher levels of anxiety and agitation at the time of admission to the hospital but otherwise were not distinguishable on the basis of severity of other psychiatric symptoms. This study suggests that increased serotonergic transmission may trigger anxiety, psychosis, and mood elevation in specific vulnerable individuals, whereas other patients with similar psychiatric illnesses are not affected. PMID:8167207

  2. Abnormal vibrissa-related behavior and loss of barrel field inhibitory neurons in 5xFAD transgenics

    PubMed Central

    Flanigan, Timothy J.; Xue, Yi; Rao, Shailaja Kishan; Anandh, Dhanushkodi; McDonald, Michael P.

    2014-01-01

    A recent study reported lower anxiety in the 5xFAD transgenic mouse model of Alzheimer's disease, as measured by reduced time on the open arms of an elevated plus maze. This is important because all behaviors in experimental animals must be interpreted in light of basal anxiety and response to novel environments. We conducted a comprehensive anxiety battery in the 5xFAD transgenics and replicated the plus-maze phenotype. However, we found that it did not reflect reduced anxiety, but rather abnormal avoidance of the closed arms on the part of transgenics and within-session habituation to the closed arms on the part of wild-type controls. We noticed that the 5xFAD transgenics did not engage in the whisker-barbering behavior typical of mice of this background strain. This is suggestive of abnormal social behavior, and we suspected it might be related to their avoidance of the closed arms on the plus maze. Indeed, transgenic mice exhibited excessive home-cage social behavior and impaired social recognition, and did not permit barbering by wild-type mice when pair-housed. When their whiskers were snipped the 5xFAD transgenics no longer avoided the closed arms on the plus maze. Examination of parvalbumin (PV) staining showed a 28.9% reduction in PV+ inhibitory interneurons in the in barrel fields of 5xFAD mice, and loss of PV+ fibers in layers IV and V. This loss of vibrissal inhibition suggests a putatively aversive overstimulation that may be responsible for the transgenics’ avoidance of the closed arms in the plus maze. PMID:24655396

  3. Ventricular tachycardia

    MedlinePlus

    ... of implanting a device called an implantable cardioverter defibrillator (ICD). The ICD is most often implanted in ... tachycardia; V tach; Tachycardia - ventricular Images Implantable cardioverter-defibrillator References Olgin JE, Zipes DP. Specific Arrhythmias: Diagnosis ...

  4. Ventricular fibrillation

    MedlinePlus

    ... Fibrillation is an uncontrolled twitching or quivering of muscle fibers (fibrils). When it occurs in the lower chambers of the heart, it is called ventricular fibrillation. During ... the heart muscle does not get enough oxygen for any reason. ...

  5. Behavioral Abnormality Induced by Enhanced Hypothalamo-Pituitary-Adrenocortical Axis Activity under Dietary Zinc Deficiency and Its Usefulness as a Model

    PubMed Central

    Takeda, Atsushi; Tamano, Haruna; Nishio, Ryusuke; Murakami, Taku

    2016-01-01

    Dietary zinc deficiency increases glucocorticoid secretion from the adrenal cortex via enhanced hypothalamo-pituitary-adrenocortical (HPA) axis activity and induces neuropsychological symptoms, i.e., behavioral abnormality. Behavioral abnormality is due to the increase in glucocorticoid secretion rather than disturbance of brain zinc homeostasis, which occurs after the increase in glucocorticoid secretion. A major target of glucocorticoids is the hippocampus and their actions are often associated with disturbance of glutamatergic neurotransmission, which may be linked to behavioral abnormality, such as depressive symptoms and aggressive behavior under zinc deficiency. Glucocorticoid-mediated disturbance of glutamatergic neurotransmission in the hippocampus is also involved in the pathophysiology of, not only psychiatric disorders, such as depression, but also neurodegenerative disorders, e.g., Alzheimer’s disease. The evidence suggests that zinc-deficient animals are models for behavioral and psychological symptoms of dementia (BPSD), as well as depression. To understand validity to apply zinc-deficient animals as a behavioral abnormality model, this paper deals with the effect of antidepressive drugs and herbal medicines on hippocampal dysfunctions and behavioral abnormality, which are induced by enhanced HPA axis activity under dietary zinc deficiency. PMID:27438830

  6. Behavioral Abnormality Induced by Enhanced Hypothalamo-Pituitary-Adrenocortical Axis Activity under Dietary Zinc Deficiency and Its Usefulness as a Model.

    PubMed

    Takeda, Atsushi; Tamano, Haruna; Nishio, Ryusuke; Murakami, Taku

    2016-01-01

    Dietary zinc deficiency increases glucocorticoid secretion from the adrenal cortex via enhanced hypothalamo-pituitary-adrenocortical (HPA) axis activity and induces neuropsychological symptoms, i.e., behavioral abnormality. Behavioral abnormality is due to the increase in glucocorticoid secretion rather than disturbance of brain zinc homeostasis, which occurs after the increase in glucocorticoid secretion. A major target of glucocorticoids is the hippocampus and their actions are often associated with disturbance of glutamatergic neurotransmission, which may be linked to behavioral abnormality, such as depressive symptoms and aggressive behavior under zinc deficiency. Glucocorticoid-mediated disturbance of glutamatergic neurotransmission in the hippocampus is also involved in the pathophysiology of, not only psychiatric disorders, such as depression, but also neurodegenerative disorders, e.g., Alzheimer's disease. The evidence suggests that zinc-deficient animals are models for behavioral and psychological symptoms of dementia (BPSD), as well as depression. To understand validity to apply zinc-deficient animals as a behavioral abnormality model, this paper deals with the effect of antidepressive drugs and herbal medicines on hippocampal dysfunctions and behavioral abnormality, which are induced by enhanced HPA axis activity under dietary zinc deficiency. PMID:27438830

  7. Abnormal relationship between GABA, neurophysiology and impulsive behavior in neurofibromatosis type 1

    PubMed Central

    Ribeiro, Maria J.; Violante, Inês R.; Bernardino, Inês; Edden, Richard A.E.; Castelo-Branco, Miguel

    2016-01-01

    Neurofibromatosis type 1 (NF1) is a neurodevelopmental disorder characterized by a broad spectrum of cognitive deficits. In particular, executive dysfunction is recognized as a core deficit of NF1, including impairments in executive attention and inhibitory control. Yet, the neural mechanisms behind these important deficits are still unknown. Here, we studied inhibitory control in a visual go/no-go task in children and adolescents with NF1 and age- and gender-matched controls (n = 16 per group). We applied a multimodal approach using high-density electroencephalography (EEG), to study the evoked brain responses, and magnetic resonance spectroscopy (MRS) to measure the levels of GABA and glutamate + glutamine in the medial frontal cortex, a brain region that plays a pivotal role in inhibitory control, and also in a control region, the occipital cortex. Finally, we run correlation analyses to identify the relationship between inhibitory control, levels of neurotransmitters, and EEG markers of neural function. Individuals with NF1 showed impaired impulse control and reduced EEG correlates of early visual processing (parieto-occipital P1) and inhibitory control (frontal P3). MRS data revealed a reduction in medial frontal GABA+/tCr (total Creatine) levels in the NF1 group, in parallel with the already reported reduced occipital GABA levels. In contrast, glutamate + glutamine/tCr levels were normal, suggesting the existence of abnormal inhibition/excitation balance in this disorder. Notably, medial frontal but not occipital GABA levels correlated with general intellectual abilities (IQ) in NF1, and inhibitory control in both groups. Surprisingly, the relationship between inhibitory control and medial frontal GABA was reversed in NF1: higher GABA was associated with a faster response style whereas in controls it was related to a cautious strategy. Abnormal GABAergic physiology appears, thus, as an important factor underlying impaired cognition in NF1, in a level and

  8. The aggression and behavioral abnormalities associated with monoamine oxidase A deficiency are rescued by acute inhibition of serotonin reuptake.

    PubMed

    Godar, Sean C; Bortolato, Marco; Castelli, M Paola; Casti, Alberto; Casu, Angelo; Chen, Kevin; Ennas, M Grazia; Tambaro, Simone; Shih, Jean C

    2014-09-01

    The termination of serotonin (5-hydroxytryptamine, 5-HT) neurotransmission is regulated by its uptake by the 5-HT transporter (5-HTT), as well as its degradation by monoamine oxidase (MAO)-A. MAO-A deficiency results in a wide set of behavioral alterations, including perseverative behaviors and social deficits. These anomalies are likely related to 5-HTergic homeostatic imbalances; however, the role of 5-HTT in these abnormalities remains unclear. To ascertain the role of 5-HTT in the behavioral anomalies associated to MAO-A deficiency, we tested the behavioral effects of its blocker fluoxetine on perseverative, social and aggressive behaviors in transgenic animals with hypomorphic or null-allele MAO-A mutations. Acute treatment with the 5-HTT blocker fluoxetine (10 mg/kg, i.p.) reduced aggressive behavior in MAO-A knockout (KO) mice and social deficits in hypomorphic MAO-A(Neo) mice. Furthermore, this treatment also reduced perseverative responses (including marble burying and water mist-induced grooming) in both MAO-A mutant genotypes. Both MAO-A mutant lines displayed significant reductions in 5-HTT expression across the prefrontal cortex, amygdala and striatum, as quantified by immunohistochemical detection; however, the down-regulation of 5-HTT in MAO-A(Neo) mice was more pervasive and widespread than in their KO counterparts, possibly indicating a greater ability of the hypomorphic line to enact compensatory mechanisms with respect to 5-HT homeostasis. Collectively, these findings suggest that the behavioral deficits associated with low MAO-A activity may reflect developmental alterations of 5-HTT within 5-HTergic neurons. Furthermore, the translational implications of our results highlight 5-HT reuptake inhibition as an interesting approach for the control of aggressive outbursts in MAO-A deficient individuals. PMID:24882701

  9. Ventricular-Vascular Interaction in Heart Failure

    PubMed Central

    Borlaug, Barry A.; Kass, David A.

    2008-01-01

    Synopsis Nearly half of all patients with heart failure have preserved ejection fraction (HFpEF). HFpEF patients tend to be older, female, and hypertensive, and characteristically display increased ventricular and arterial stiffening. In this review, we discuss the pathophysiology of abnormal ventriculoarterial stiffening and how the latter affects ventricular function, cardiovascular hemodynamics, reserve capacity, and symptoms. We conclude by exploring how novel treatment strategies targeting abnormal ventricular-arterial interaction might prove useful in the treatment of patients with HFpEF. PMID:18313622

  10. Behavioral and neurochemical abnormalities after exposure to low doses of high-energy iron particles.

    PubMed

    Hunt, W A; Joseph, J A; Rabin, B M

    1989-01-01

    Exposure of rats to high-energy iron particles (600 MeV/amu) has been found to alter behavior after doses as low as 10 rads. The performance of a task that measures upper body strength was significantly degraded after irradiation. In addition, an impairment in the regulation of dopamine release in the caudate nucleus (a motor center in the brain), lasting at least 6 months, was also found and correlated with the performance deficits. A general indication of behavioral toxicity and an index of nausea and emesis, the conditioned taste aversion, was also evident. The sensitivity to iron particles was 10-600 times greater than to gamma photons. These results suggest that behavioral and neurobiological damage may be a consequence of exposure to low doses of heavy particles and that this possibility should be extensively studied. PMID:11537313

  11. Behavioral and neurochemical abnormalities after exposure to low doses of high-energy iron particles

    NASA Astrophysics Data System (ADS)

    Hunt, Walter A.; Joseph, James A.; Rabin, Bernard M.

    Exposure of rats to high-energy iron particles (600 MeV/amu) has been found to alter behavior after doses as low as 10 rads. The performance of a task that measures upper body strength was significantly degraded after irradiation. In addition, an impairment in the regulation of dopamine release in the caudate nucleus (a motor center in the brain), lasting at least 6 months, was also found and correlated with the performance deficits. A general indication of behavioral toxicity and an index of nausea and emesis, the conditioned taste aversion, was also evident. The sensitivity to iron particles was 10-600 times greater than to gamma photons. These results suggest that behavioral and neurobiological damage may be a consequence of exposure to low doses of heavy particles and that this possibility should be extensively studied.

  12. Behavioral and neurochemical abnormalities after exposure to low doses of high-energy iron particles

    SciTech Connect

    Hunt, W.A.; Joseph, J.A.; Rabin, B.M.

    1989-01-01

    Exposure of rats to high-energy iron particles (600 MeV/amu) has been found to alter behavior after doses as low as 10 rads. The performance of a task that measures upper body strength was significantly degraded after irradiation. In addition, an impairment in the regulation of dopamine release in the caudate nucleus (a motor center in the brain), lasting at least 6 months, was also found and correlated with the performance deficits. A general indication of behavioral toxicity and an index of nausea and emesis, the conditioned taste aversion, was also evident. The sensitivity to iron particles was 10-600 times greater than to gamma photons. These results suggest that behavioral and neurobiological damage may be a consequence of exposure to low doses of heavy particles and that this possibility should be extensively studied.

  13. LIN-41 inactivation leads to delayed centrosome elimination and abnormal chromosome behavior during female meiosis in Caenorhabditis elegans

    PubMed Central

    Matsuura, Rieko; Ashikawa, Tomoko; Nozaki, Yuka; Kitagawa, Daiju

    2016-01-01

    During oogenesis, two successive meiotic cell divisions occur without functional centrosomes because of the inactivation and subsequent elimination of maternal centrosomes during the diplotene stage of meiosis I. Despite being a conserved phenomenon in most metazoans, the means by which this centrosome behavior is controlled during female meiosis remain elusive. Here, we conducted a targeted RNAi screening in the Caenorhabditis elegans gonad to identify novel regulators of centrosome behavior during oogenesis. We screened 513 genes known to be essential for embryo production and directly visualized GFP–γ-tubulin to monitor centrosome behavior at all stages of oogenesis. In the screening, we found that RNAi-mediated inactivation of 33 genes delayed the elimination of GFP–γ-tubulin at centrosomes during oogenesis, whereas inactivation of nine genes accelerated the process. Depletion of the TRIM-NHL protein LIN-41 led to a significant delay in centrosome elimination and to the separation and reactivation of centrosomes during oogenesis. Upon LIN-41 depletion, meiotic chromosomes were abnormally condensed and pulled toward one of the two spindle poles around late pachytene even though the spindle microtubules emanated from both centrosomes. Overall, our work provides new insights into the regulation of centrosome behavior to ensure critical meiotic events and the generation of intact oocytes. PMID:26764090

  14. Regional brain abnormalities in 22q11.2 deletion syndrome: association with cognitive abilities and behavioral symptoms.

    PubMed

    Bearden, Carrie E; van Erp, Theo G M; Monterosso, John R; Simon, Tony J; Glahn, David C; Saleh, Peter A; Hill, Nicole M; McDonald-McGinn, Donna M; Zackai, Elaine; Emanuel, Beverly S; Cannon, Tyrone D

    2004-06-01

    Children with 22q11.2 microdeletions (Velocardiofacial Syndrome; VCFS) have previously been shown to exhibit learning deficits and elevated rates of psychopathology. The aim of this study was to assess regional brain abnormalities in children with 22q11DS, and to determine the relationship of these measures to neurocognitive and behavioral function. Thirteen children with confirmed deletions and 9 demographically matched comparison subjects were assessed with a neurocognitive battery, behavioral measures, and high-resolution MRI. Twenty-two qllDS children showed a nonsignificant 4.3% global decrease in total brain volume as compared to healthy controls,with differential reduction in white matter, and significantly increased sulcal cerebrospinal fluid (CSF) in temporal and posterior brain regions. In 22q11 DS subjects, but not controls, bilateral temporal gray and white matter volumes were significant predictors of overall cognitive performance. Further, reduced temporal gray matter was associated with elevated Thought Problems score on the CBCL. Results indicate that global alterations in brain volume are common in children with 22q deletions, particularly those with low IQ and/or behavioral disturbance. Although preliminary,these findings suggest a possible underlying pathophysiology of the cognitive deficits seen in this syndrome,and provide insight into complex gene-brain-behavior relationships. PMID:15788257

  15. Behavioral, neurochemical and neuroendocrine effects of abnormal savda munziq in the chronic stress mice.

    PubMed

    Amat, Nurmuhammat; Hoxur, Parida; Ming, Dang; Matsidik, Aynur; Kijjoa, Anake; Upur, Halmurat

    2012-01-01

    Oral administration of Abnormal Savda Munsiq (ASMq), a herbal preparation used in Traditional Uighur Medicine, was found to exert a memory-enhancing effect in the chronic stressed mice, induced by electric foot-shock. The memory improvement of the stressed mice was shown by an increase of the latency time in the step-through test and the decrease of the latency time in the Y-maze test. Treatment with ASMq was found to significantly decrease the serum levels of adrenocorticotropic hormone (ACTH), corticosterone (CORT) and β-endorphin (β-EP) as well as the brain and serum level of norepinephrine (NE). Furthermore, ASMq was able to significantly reverse the chronic stress by decreasing the brain and serum levels of the monoamine neurotransmitters dopamine (DA), 5-hydroxytryptamine (5-HT) and 3,4-dihydroxyphenylalanine (DOPAC). The results obtained from this study suggested that the memory-enhancing effect of ASMq was mediated through regulations of neurochemical and neuroendocrine systems. PMID:22919413

  16. Modulation of Serotonin Transporter Function during Fetal Development Causes Dilated Heart Cardiomyopathy and Lifelong Behavioral Abnormalities

    PubMed Central

    Noorlander, Cornelle W.; Ververs, Frederique F. T.; Nikkels, Peter G. J.; van Echteld, Cees J. A.; Visser, Gerard H. A.; Smidt, Marten P.

    2008-01-01

    Background Women are at great risk for mood and anxiety disorders during their childbearing years and may become pregnant while taking antidepressant drugs. In the treatment of depression and anxiety disorders, selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed drugs, while it is largely unknown whether this medication affects the development of the central nervous system of the fetus. The possible effects are the product of placental transfer efficiency, time of administration and dose of the respective SSRI. Methodology/Principal Findings In order to attain this information we have setup a study in which these parameters were measured and the consequences in terms of physiology and behavior are mapped. The placental transfer of fluoxetine and fluvoxamine, two commonly used SSRIs, was similar between mouse and human, indicating that the fetal exposure of these SSRIs in mice is comparable with the human situation. Fluvoxamine displayed a relatively low placental transfer, while fluoxetine showed a relatively high placental transfer. Using clinical doses of fluoxetine the mortality of the offspring increased dramatically, whereas the mortality was unaffected after fluvoxamine exposure. The majority of the fluoxetine-exposed offspring died postnatally of severe heart failure caused by dilated cardiomyopathy. Molecular analysis of fluoxetine-exposed offspring showed long-term alterations in serotonin transporter levels in the raphe nucleus. Furthermore, prenatal fluoxetine exposure resulted in depressive- and anxiety-related behavior in adult mice. In contrast, fluvoxamine-exposed mice did not show alterations in behavior and serotonin transporter levels. Decreasing the dose of fluoxetine resulted in higher survival rates and less dramatic effects on the long-term behavior in the offspring. Conclusions These results indicate that prenatal fluoxetine exposure affects fetal development, resulting in cardiomyopathy and a higher

  17. Rest and exercise ventricular function in adults with congenital ventricular septal defects

    SciTech Connect

    Jablonsky, G.; Hilton, J.D.; Liu, P.P.; Morch, J.E.; Druck, M.N.; Bar-Shlomo, B.Z.; McLaughlin, P.R.

    1983-01-15

    Rest and exercise right and left ventricular function were compared using equilibrium gated radionuclide angiography in 19 normal sedentary control subjects and 34 patients with hemodynamically documented congenital ventricular septal defect (VSD). Gated radionuclide angiography was performed at rest and during each level of graded supine bicycle exercise to fatigue. Heart rate, blood pressure, maximal work load achieved, and right and left ventricular ejection fractions were assessed. The control subjects demonstrated an increase in both the left and right ventricular ejection fractions with exercise. All study groups failed to demonstrate an increase in ejection fraction in either ventricle with exercise. Furthermore, resting left ventricular ejection fraction in Groups 2 and 3 was lower than that in the control subjects and resting right ventricular ejection fraction was lower in Group 3 versus control subjects. Thus left and right ventricular function on exercise were abnormal in patients with residual VSD as compared with control subjects; rest and exercise left ventricular ejection fractions remained abnormal despite surgical closure of VSD in the remote past; resting left and right ventricular function was abnormal in patients with Eisenmenger's complex; lifelong volume overload may be detrimental to myocardial function.

  18. Prenatal rapamycin results in early and late behavioral abnormalities in wildtype C57Bl/6 mice

    PubMed Central

    Tsai, Peter T.; Green-Colozzi, Emily; Goto, June; Anderl, Stefanie; Kwiatkowski, David; Sahin, Mustafa

    2012-01-01

    Mammalian target of rapamycin (mTOR) signaling has been shown to be deregulated in a number of genetic, neurodevelopmental disorders including Tuberous Sclerosis Complex, Neurofibromatosis, Fragile X, and Rett syndromes. As a result, mTOR inhibitors, such as rapamycin and its analogs, offer potential therapeutic avenues for these disorders. Some of these disorders – such as Tuberous Sclerosis Complex – can be diagnosed prenatally. Thus, prenatal administration of these inhibitors could potentially prevent the development of the devastating symptoms associated with these disorders. To assess the possible detrimental effects of prenatal rapamycin treatment, we evaluated both early and late behavioral effects of a single rapamycin treatment at embryonic day 16.5 in wildtype C57Bl/6 mice. This treatment adversely impacted early developmental milestones as well as motor function in adult animals. Rapamycin also resulted in anxiety-like behaviors during both early development and adulthood but did not affect adult social behaviors. Together, these results indicate that a single, prenatal rapamycin treatment not only adversely affects early postnatal development but also results in long lasting negative effects, persisting into adulthood. These findings are of importance in considering prenatal administration of rapamycin and related drugs in the treatment of patients with neurogenetic, neurodevelopmental disorders. PMID:23229624

  19. Early life seizures in female rats lead to anxiety-related behavior and abnormal social behavior characterized by reduced motivation to novelty and deficit in social discrimination.

    PubMed

    Castelhano, Adelisandra Silva Santos; Ramos, Fabiane Ochai; Scorza, Fulvio Alexandre; Cysneiros, Roberta Monterazzo

    2015-03-01

    Previously, we demonstrated that male Wistar rats submitted to neonatal status epilepticus showed abnormal social behavior characterized by deficit in social discrimination and enhanced emotionality. Taking into account that early insult can produce different biological manifestations in a gender-dependent manner, we aimed to investigate the social behavior and anxiety-like behavior in female Wistar rats following early life seizures. Neonate female Wistar rats at 9 days postnatal were subject to pilocarpine-induced status epilepticus and the control received saline. Behavioral tests started from 60 days postnatal and were carried out only during the diestrus phase of the reproductive cycle. In sociability test experimental animals exhibited reduced motivation for social encounter and deficit in social discrimination. In open field and the elevated plus maze, experimental animals showed enhanced emotionality with no changes in basal locomotor activity. The results showed that female rats submitted to neonatal status epipepticus showed impaired social behavior, characterized by reduced motivation to novelty and deficit in social discrimination in addition to enhanced emotionality. PMID:25139483

  20. Increased apoptosis and abnormal visual behavior by histone modifications with exposure to para-xylene in developing Xenopus.

    PubMed

    Gao, Juanmei; Ruan, Hangze; Qi, Xianjie; Guo, Xia; Zheng, Jingna; Liu, Cong; Fang, Yanxiao; Huang, Minjiao; Xu, Miao; Shen, Wanhua

    2016-09-01

    Xylene and its derivatives are raw materials widely used in industry and known to be toxic to animals. However, the mechanism underlying the neurotoxicity of para-xylene (PX) to the central nervous system (CNS) in vivo is less clear. Here, we exposed Xenopus laevis tadpoles to sub-lethal concentrations of PX during the critical period of brain development to determine the effects of PX on Xenopus development and visual behavior. We found that the abnormality rate was significantly increased with exposure to increasing concentrations of PX. In particular, the number of apoptotic cells in the optic tectum was dramatically increased with exposure to PX at 2mM. Long-term PX exposure also resulted in significant deficits in visually guided avoidance behavior. Strikingly, co-incubation with PX and d-glucuronolactone (GA) decreased the number of apoptotic cells and rescued the avoidance behavior. Furthermore, we found that the acetylation of H4K12 (H4K12ac) and the dimethylation of H3K9 (H3K9me2) in the optic tectum were significantly increased in PX-treated animals, and these effects were suppressed by GA treatment. In particular, the increase in apoptotic cells in PX-treated brains was also inhibited by GA treatment. These effects indicate that epigenetic regulation plays a key role in PX-induced apoptosis and animal behavior. In an effort to characterize the neurotoxic effects of PX on brain development and behavior, these results suggest that the neurotoxicity of PX requires further evaluation regarding the safety of commercial and industrial uses. PMID:27343828

  1. Loss of GSK-3 Causes Abnormal Astrogenesis and Behavior in Mice.

    PubMed

    Jung, Eui-Man; Ka, Minhan; Kim, Woo-Yang

    2016-08-01

    Altered activity of glycogen synthase kinase-3 (GSK-3) is associated with psychiatric diseases and neurodegenerative diseases. GSK-3 is a key regulator in multiple aspects of neuronal differentiation in the brain. However, little is known about the role of GSK-3 in astrocyte development. To examine the role of GSK-3 in astrocytes, we generated a conditional knockout mouse using a glial fibrillary acidic protein (GFAP)-cre driver, in which the GSK-3 alpha and beta genes are deleted in astrocytes. We found that GFAP-cre-mediated GSK-3 deletion led to a larger brain. The number and size of astrocytes were increased in GSK-3 mutant brains. The levels of GFAP and phospho-STAT3, indicators of astrogenesis, were elevated in GSK-3 mutants. Furthermore, we found upregulation of astrocyte regulatory molecules such as phospho-AKT, phospho-S6, and cyclin D in GSK-3 mutant brains. Finally, GSK-3 mutant mice exhibited aberrant anxiety and social behavior. Our results suggest that GSK-3 plays a significant role in astrocyte development and behavioral control in mice. PMID:26179612

  2. Tspyl2 Loss-of-Function Causes Neurodevelopmental Brain and Behavior Abnormalities in Mice.

    PubMed

    Li, Qi; Chan, Siu Yuen; Wong, Kwun K; Wei, Ran; Leung, Yu On; Ding, Abby Y; Hui, Tomy C K; Cheung, Charlton; Chua, Siew E; Sham, Pak C; Wu, Ed X; McAlonan, Grainne M

    2016-07-01

    Testis specific protein, Y-encoded-like 2 (TSPYL2) regulates the expression of genes encoding glutamate receptors. Glutamate pathology is implicated in neurodevelopmental conditions such as autism spectrum disorder, attention deficit hyperactivity disorder (ADHD) and schizophrenia. In line with this, a microduplication incorporating the TSPYL2 locus has been reported in people with ADHD. However, the role of Tspyl2 remains unclear. Therefore here we used a Tspyl2 loss-of-function mouse model to directly examine how this gene impacts upon behavior and brain anatomy. We hypothesized that Tspyl2 knockout (KO) would precipitate a phenotype relevant to neurodevelopmental conditions. In line with this prediction, we found that Tspyl2 KO mice were marginally more active, had significantly impaired prepulse inhibition, and were significantly more 'sensitive' to the dopamine agonist amphetamine. In addition, the lateral ventricles were significantly smaller in KO mice. These findings suggest that disrupting Tspyl2 gene expression leads to behavioral and brain morphological alterations that mirror a number of neurodevelopmental psychiatric traits. PMID:26826030

  3. Abnormal behavior of midgap electron trap in HB-GaAs during thermal annealing

    NASA Astrophysics Data System (ADS)

    Min, Suk-Ki; Kim, Eun Kyu; Cho, Hoon Young

    1988-05-01

    The behavior of the EL2 family in horizontal Bridgman-(HB) grown GaAs by two thermal annealing methods, furnace annealing and rapid thermal annealing, was studied through deep level transient spectroscopy (DLTS) measurements, and a similar behavior of another group of electron traps was observed. As the annealing time is increased, the EL2 trap (Ec-0.81 eV) is transformed to the new trap, EX2 (Ec-0.73 eV), and finally to the other new trap, EX1 (Ec-0.86 eV). Also the EL6 group (Ec-0.18, 0.22, 0.27, and 0.35 eV) varied similarly to the EL2 family as a trap (Ec-0.27 eV) is transformed to the first trap (Ec-0.18 eV) and then the second trap (Ec-0.22 eV). This result revealed that the EL2 family is related to the EL6 group. From the study of photocapacitance quenching, the existence of metastable states of the EL2 family is identified. These results suggest that the atomic structure of the EL2 trap may be an arsenic antisite with an interstitial arsenic and a double vacancy, such as VAsAsIVGaAsGa or its complex.

  4. Cocaine Self-Administration Experience Induces Pathological Phasic Accumbens Dopamine Signals and Abnormal Incentive Behaviors in Drug-Abstinent Rats

    PubMed Central

    Wang, Xuefei; Sugam, Jonathan A.; Carelli, Regina M.

    2016-01-01

    Chronic exposure to drugs of abuse is linked to long-lasting alterations in the function of limbic system structures, including the nucleus accumbens (NAc). Although cocaine acts via dopaminergic mechanisms within the NAc, less is known about whether phasic dopamine (DA) signaling in the NAc is altered in animals with cocaine self-administration experience or if these animals learn and interact normally with stimuli in their environment. Here, separate groups of rats self-administered either intravenous cocaine or water to a receptacle (controls), followed by 30 d of enforced abstinence. Next, all rats learned an appetitive Pavlovian discrimination and voltammetric recordings of real-time DA release were taken in either the NAc core or shell of cocaine and control subjects. Cocaine experience differentially impaired DA signaling in the core and shell relative to controls. Although phasic DA signals in the shell were essentially abolished for all stimuli, in the core, DA did not distinguish between cues and was abnormally biased toward reward delivery. Further, cocaine rats were unable to learn higher-order associations and even altered simple conditioned approach behaviors, displaying enhanced preoccupation with cue-associated stimuli (sign-tracking; ST) but diminished time at the food cup awaiting reward delivery (goal-tracking). Critically, whereas control DA signaling correlated with ST behaviors, cocaine experience abolished this relationship. These findings show that cocaine has persistent, differential, and pathological effects on both DA signaling and DA-dependent behaviors and suggest that psychostimulant experience may remodel the very circuits that bias organisms toward repeated relapse. SIGNIFICANCE STATEMENT Relapsing to drug abuse despite periods of abstinence and sincere attempts to quit is one of the most pernicious facets of addiction. Unfortunately, little is known about how the dopamine (DA) system functions after periods of drug abstinence

  5. Pattern Organization of Premature Ventricular Heartbeats

    NASA Astrophysics Data System (ADS)

    Schulte-Frohlinde, Verena; Ashkenazy, Yosef; Ivanov, Plamen; Stanley, H. Eugene; Stanley, Gene; Goldberger, Ary L.

    2000-03-01

    Increased number of premature (abnormal) ventricular beats in a record of heartbeat intervals are known to be associated with an advanced stage of pathology (e.g. congestive heart failure). These abnormal beats usually occur in repeated bursts for relatively short periods of time. Here we ask the question if particular abnormal patterns appear throughout records of heartbeat intervals. We study the temporal organization of specific patterns of ventricular beats in long 24 hour records and their relation to different stages of disease. We analyze the statistical properties of such patterns and combination of patterns by means of crosscorrelation matrices.

  6. Dietary glycemic index modulates the behavioral and biochemical abnormalities associated with autism spectrum disorder.

    PubMed

    Currais, A; Farrokhi, C; Dargusch, R; Goujon-Svrzic, M; Maher, P

    2016-03-01

    Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder of unknown etiology, but very likely resulting from both genetic and environmental factors. There is good evidence for immune system dysregulation in individuals with ASD. However, the contribution of insults such as dietary factors that can also activate the immune system have not been explored in the context of ASD. In this paper, we show that the dietary glycemic index has a significant impact on the ASD phenotype. By using BTBR mice, an inbred strain that displays behavioral traits that reflect the diagnostic symptoms of human ASD, we found that the diet modulates plasma metabolites, neuroinflammation and brain markers of neurogenesis in a manner that is highly reflective of ASD in humans. Overall, the manuscript supports the idea that ASD results from gene-environment interactions and that in the presence of a genetic predisposition to ASD, diet can make a large difference in the expression of the condition. PMID:26055422

  7. Consequences of long-term treatment with agomelatine on depressive-like behavior and neurobiological abnormalities in pinealectomized rats.

    PubMed

    Tchekalarova, Jana; Nenchovska, Zlatina; Atanasova, Dimitrina; Atanasova, Milena; Kortenska, Lidia; Stefanova, Miroslava; Alova, Liana; Lazarov, Nikolai

    2016-04-01

    Previous data have shown that the rat model of melatonin deficit can cause a number of neurobiological aberrations. The aim of the present study was to determine whether the antidepressant drug agomelatine, a MT1/MT2 melatoninergic receptor agonist/5-HT2C receptor antagonist is able to prevent some of the behavioral, biochemical and cellular abnormalities induced by pinealectomy. The injection of agomelatine (40 mg/kg, i.p. for 5 weeks)/vehicle started after pinealectomy/sham procedure in Wistar rats. Animals were tested in different behavioral tests for anxiety and depression during the period of agomelatine treatment (chronic effect) and two months later (plastic effect). The effect of agomelatine on KCl-evoked serotonin (5-HT) release from the hippocampus, the activity of the hypothalamic-pituitary-adrenal (HPA) axis and neuronal loss in pinealectomized rats were assessed. Our results showed that agomelatine not only did not prevent the disturbed emotional arousal/anxiety behavior in pinealectomized rats during the treatment but the enhanced motor activity and decreased anxiety state was still observed two months after the discontinuation of treatment. However, the drug corrected a depressive-like behavior (chronic and plastic effect), alleviated the enhanced KCl-evoked 5-HT release in the hippocampus, recovered the suppressed negative feedback inhibition of HPA axis and exerted a neuroprotection in pinealectomized rats. Our findings suggest that pinealectomy can model melancholic depression disorder while the antidepressant action of agomelatine is associated with a correction of 5-HT release in the hippocampus, dysregulated HPA system and neuroprotection in limbic structures. PMID:26779670

  8. Epilepsy, Behavioral Abnormalities, and Physiological Comorbidities in Syntaxin-Binding Protein 1 (STXBP1) Mutant Zebrafish

    PubMed Central

    Grone, Brian P.; Marchese, Maria; Hamling, Kyla R.; Kumar, Maneesh G.; Krasniak, Christopher S.; Sicca, Federico; Santorelli, Filippo M.; Patel, Manisha; Baraban, Scott C.

    2016-01-01

    Mutations in the synaptic machinery gene syntaxin-binding protein 1, STXBP1 (also known as MUNC18-1), are linked to childhood epilepsies and other neurodevelopmental disorders. Zebrafish STXBP1 homologs (stxbp1a and stxbp1b) have highly conserved sequence and are prominently expressed in the larval zebrafish brain. To understand the functions of stxbp1a and stxbp1b, we generated loss-of-function mutations using CRISPR/Cas9 gene editing and studied brain electrical activity, behavior, development, heart physiology, metabolism, and survival in larval zebrafish. Homozygous stxbp1a mutants exhibited a profound lack of movement, low electrical brain activity, low heart rate, decreased glucose and mitochondrial metabolism, and early fatality compared to controls. On the other hand, homozygous stxbp1b mutants had spontaneous electrographic seizures, and reduced locomotor activity response to a movement-inducing “dark-flash” visual stimulus, despite showing normal metabolism, heart rate, survival, and baseline locomotor activity. Our findings in these newly generated mutant lines of zebrafish suggest that zebrafish recapitulate clinical phenotypes associated with human syntaxin-binding protein 1 mutations. PMID:26963117

  9. High Fat Diet Produces Brain Insulin Resistance, Synaptodendritic Abnormalities and Altered Behavior in Mice

    PubMed Central

    Arnold, Steven E.; Lucki, Irwin; Brookshire, Bethany R.; Carlson, Gregory C.; Browne, Carolyn A.; Kazi, Hala; Bang, Sookhee; Choi, Bo-Ran; Chen, Yong; McMullen, Mary F.; Kim, Sangwon F.

    2014-01-01

    Insulin resistance and other features of the metabolic syndrome are increasingly recognized for their effects on cognitive health. To ascertain mechanisms by which this occurs, we fed mice a very high fat diet (60% kcal by fat) for 17 days or a moderate high fat diet (HFD, 45% kcal by fat) for 8 weeks and examined changes in brain insulin signaling responses, hippocampal synaptodendritic protein expression, and spatial working memory. Compared to normal control diet mice, cerebral cortex tissues of HFD mice were insulin-resistant as evidenced by failed activation of Akt, S6 and GSK3β with ex-vivo insulin stimulation. Importantly, we found that expression of brain IPMK, which is necessary for mTOR/Akt signaling, remained decreased in HFD mice upon activation of AMPK. HFD mouse hippocampus exhibited increased expression of serine-phosphorylated insulin receptor substrate 1 (IRS1-pS616), a marker of insulin resistance, as well as decreased expression of PSD-95, a scaffolding protein enriched in post-synaptic densities, and synaptopodin, an actin-associated protein enriched in spine apparatuses. Spatial working memory was impaired as assessed by decreased spontaneous alternation in a T-maze. These findings indicate that HFD is associated with telencephalic insulin resistance and deleterious effects on synaptic integrity and cognitive behaviors. PMID:24686304

  10. Behavioral abnormalities and Parkinson’s-like histological changes resulting from Id2 inactivation in mice

    PubMed Central

    Havrda, Matthew C.; Paolella, Brenton R.; Ward, Nora M.; Holroyd, Kathryn B.

    2013-01-01

    SUMMARY Characterizing dopaminergic neuronal development and function in novel genetic animal models might uncover strategies for researchers to develop disease-modifying treatments for neurologic disorders. Id2 is a transcription factor expressed in the developing central nervous system. Id2−/− mice have fewer dopaminergic neurons in the olfactory bulb and reduced olfactory discrimination, a pre-clinical marker of Parkinson’s disease. Here, we summarize behavioral, histological and in vitro molecular biological analyses to determine whether midbrain dopaminergic neurons are affected by Id2 loss. Id2−/− mice were hyperactive at 1 and 3 months of age, but by 6 months showed reduced activity. Id2−/− mice showed age-dependent histological alterations in dopaminergic neurons of the substantia nigra pars compacta (SNpC) associated with changes in locomotor activity. Reduced dopamine transporter (DAT) expression was observed at early ages in Id2−/− mice and DAT expression was dependent on Id2 expression in an in vitro dopaminergic differentiation model. Evidence of neurodegeneration, including activated caspase-3 and glial infiltration, were noted in the SNpC of older Id2−/− mice. These findings document a novel role for Id2 in the maintenance of midbrain dopamine neurons. The Id2−/− mouse should provide unique opportunities to study the progression of neurodegenerative disorders involving the dopamine system. PMID:23264561

  11. Surface Structure Evolution and Abnormal Wear Behavior of the TiNiNb Alloy under Impact Load

    NASA Astrophysics Data System (ADS)

    Zhang, Jianjun; Zhu, Jinhua

    2009-05-01

    The TiNiNb alloy exhibits a linear increase in wear with a number of impacts at the low impact energy density E im of 1.6 J/cm2. However, a change in the volume wear occurs on the wear curve when E im is increased to 2.42 J/cm2. In this case, when the number of impacts N is more than 3 × 105 cycles, the wear rate decreases from 5.8 × 10-6 to 1.9 × 10-6 mm3/cycle, which is only one-half of that under low E im (1.6 J/cm2). It is significant for practical applications because impact energy increases while the wear rate decreases. X-ray diffraction (XRD) and transmission electron microscopy (TEM) analyses show that a large number of amorphous structures are produced on the sample surface at high E im , while no new crystalline phases appear. The abnormal wear behavior of the TiNiNb alloy can be attributed to the excellent wear behavior of amorphous structure and the consumption of impact energy during amorphous structure production.

  12. Acid sphingomyelinase (aSMase) deficiency leads to abnormal microglia behavior and disturbed retinal function

    SciTech Connect

    Dannhausen, Katharina; Karlstetter, Marcus; Caramoy, Albert; Volz, Cornelia; Jägle, Herbert; Liebisch, Gerhard; Utermöhlen, Olaf; Langmann, Thomas

    2015-08-21

    Mutations in the acid sphingomyelinase (aSMase) coding gene sphingomyelin phosphodiesterase 1 (SMPD1) cause Niemann-Pick disease (NPD) type A and B. Sphingomyelin storage in cells of the mononuclear phagocyte system cause hepatosplenomegaly and severe neurodegeneration in the brain of NPD patients. However, the effects of aSMase deficiency on retinal structure and microglial behavior have not been addressed in detail yet. Here, we demonstrate that retinas of aSMase{sup −/−} mice did not display overt neuronal degeneration but showed significantly reduced scotopic and photopic responses in electroretinography. In vivo fundus imaging of aSMase{sup −/−} mice showed many hyperreflective spots and staining for the retinal microglia marker Iba1 revealed massive proliferation of retinal microglia that had significantly enlarged somata. Nile red staining detected prominent phospholipid inclusions in microglia and lipid analysis showed significantly increased sphingomyelin levels in retinas of aSMase{sup −/−} mice. In conclusion, the aSMase-deficient mouse is the first example in which microglial lipid inclusions are directly related to a loss of retinal function. - Highlights: • aSMase-deficient mice show impaired retinal function and reactive microgliosis. • aSMase-deficient microglia express pro-inflammatory transcripts. • aSMase-deficient microglia proliferate and have increased cell body size. • In vivo imaging shows hyperreflective spots in the fundus of aSMase-deficient mice. • aSMase-deficient microglia accumulate sphingolipid-rich intracellular deposits.

  13. Aberrant IgG isotype generation in mice with abnormal behaviors.

    PubMed

    Kim, So-Nam; Jo, Gwang-Ho; Kim, Hyoung-Ah; Heo, Yong

    2016-01-01

    BTBR T+tf/J (BTBR) mice were recently cited as a suitable animal model for the study of autism because of their behavioral characteristics and immunological changes similar to those reported from autistic subjects. The BTBR mouse was reported to have significantly higher levels of serum IgG, brain IgG deposits and anti-brain IgG than highly social C57BL/6 mice, suggesting involvement of aberrant immune responses in the occurrence of autism. Up-regulation of IgG production was investigated here, with a focus on the pattern of IgG isotype distribution compared with that in FVB/NJ (FVB) mice, another highly social control strain. The results indicated that levels of serum IgG1, IgG2b and IgG3 in post-natal day 21 BTBR mice was significantly higher than FVB mice, regardless of sex, resulting in higher IgG1:IgG2a ratios in BTBR mice than in FVB mice (statistical significance in males). A similar outcome regarding the IgG1:IgG2a ratio was observed in culture supernatants of bone marrow cells from these hosts. A presence of brain-reactive IgG in the sera of BTBR was higher than in FVB mice; levels of brain-reactive IgG against whole brain homogenates were higher in BTBR than in FVB mice, with significant differences seen in the striatum and substantia nigra regions. Levels of IgG1 deposited in the cerebellum, cortex, hippocampus or striatum of both BTBR male and female mice were significantly higher than in FVB counterparts. Overall, these results suggest that alterations in IgG isotype production or deposition in the brain could be implicated in the aberrant immune reactivities of BTBR mice. PMID:25691089

  14. Left ventricular function in patients with ventricular arrhythmias and aortic valve disease

    SciTech Connect

    Santinga, J.T.; Kirsh, M.M.; Brady, T.J.; Thrall, J.; Pitt, B.

    1983-02-01

    Forty patients having aortic valve replacement were evaluated preoperatively for ventricular arrhythmia and left ventricular ejection fraction. Arrhythmias were classified as complex or simple using the Lown criteria on the 24-hour ambulatory electrocardiogram; ejection fractions were determined by radionuclide gated blood pool analysis and contrast angiography. The ejection fractions determined by radionuclide angiography were 59.1 +/- 13.1% for 26 patients with simple or no ventricular arrhythmias, and 43.9 +/- 20.3% for 14 patients with complex ventricular arrhythmias (p less than 0.01). Ejection fractions determined by angiography, available for 31 patients, were also lower in patients with complex ventricular arrhythmias (61.1 +/- 16.3% versus 51.4 +/- 13.4%; p less than 0.05). Seven of 9 patients showing conduction abnormalities on the electrocardiogram had complex ventricular arrhythmias. Eight of 20 patients with aortic stenosis had complex ventricular arrhythmias, while 2 of 13 patients with aortic insufficiency had such arrhythmias. It is concluded that decreased left ventricular ejection fraction, intraventricular conduction abnormalities, and aortic stenosis are associated with an increased frequency of complex ventricular arrhythmias in patients with aortic valve disease.

  15. Are There Gender-Specific Pathways from Early Adolescence Psychological Distress Symptoms toward the Development of Substance Use and Abnormal Eating Behavior?

    ERIC Educational Resources Information Center

    Beato-Fernandez, Luis; Rodriguez-Cano, Teresa; Pelayo-Delgado, Esther; Calaf, Myralys

    2007-01-01

    The aim of the present longitudinal community study was to test whether psychological distress at 13 years of age predicted reported substance use problems in boys and abnormal eating behavior in girls 2 years later. The sample consisted of 500 male and 576 female students. The use of substances was evaluated using a semi-structured interview,…

  16. Beneficial effects of sodium butyrate in 6-OHDA induced neurotoxicity and behavioral abnormalities: Modulation of histone deacetylase activity.

    PubMed

    Sharma, Sorabh; Taliyan, Rajeev; Singh, Sumel

    2015-09-15

    Parkinson's disease (PD) is the second most common neurodegenerative disorder. Recent studies have investigated the involvement of epigenetic modifications in PD. Histone deacetylase (HDAC) inhibitors have been reported to be beneficial in cognitive and motor deficit states. The present study was designed to investigate the effect of sodium butyrate, a HDAC inhibitor in 6-hydroxydopamine (6-OHDA) - induced experimental PD like symptoms in rats. To produce motor deficit, 6-OHDA was administered unilaterally in the right medial forebrain bundle. Three weeks after 6-OHDA administration, the rats were challenged with apomorphine. Following this, the animals were treated with sodium butyrate (150 and 300 mg/kg i.p.) once daily for 14 days. Movement abnormalities were assessed by battery of behavioral tests. Biochemically, oxidative stress markers, neuroinflammation and dopamine were measured in striatal brain homogenate. Further, to explore the molecular mechanism(s), we measured the level of global H3 histone acetylation and brain derived neurotrophic factor (BDNF). 6-OHDA administration results in significant motor deficit along with reduction in striatal dopamine level. 6-OHDA treated rats showed elevated oxidative stress and neuroinflammatory markers. Treatment with sodium butyrate results in significant attenuation of motor deficits and increased striatal dopamine level. Moreover, sodium butyrate treatment attenuated the oxidative stress and neuroinflammatory markers. These effects occur concurrently with increased global H3 histone acetylation and BDNF levels. Thus, the observed results of the present study are indicative for the therapeutic potential of HDAC inhibitors in PD. PMID:26048426

  17. Early Social Enrichment Rescues Adult Behavioral and Brain Abnormalities in a Mouse Model of Fragile X Syndrome

    PubMed Central

    Oddi, Diego; Subashi, Enejda; Middei, Silvia; Bellocchio, Luigi; Lemaire-Mayo, Valerie; Guzmán, Manuel; Crusio, Wim E; D'Amato, Francesca R; Pietropaolo, Susanna

    2015-01-01

    Converging lines of evidence support the use of environmental stimulation to ameliorate the symptoms of a variety of neurodevelopmental disorders. Applying these interventions at very early ages is critical to achieve a marked reduction of the pathological phenotypes. Here we evaluated the impact of early social enrichment in Fmr1-KO mice, a genetic mouse model of fragile X syndrome (FXS), a major developmental disorder and the most frequent monogenic cause of autism. Enrichment was achieved by providing male KO pups and their WT littermates with enhanced social stimulation, housing them from birth until weaning with the mother and an additional nonlactating female. At adulthood they were tested for locomotor, social, and cognitive abilities; furthermore, dendritic alterations were assessed in the hippocampus and amygdala, two brain regions known to be involved in the control of the examined behaviors and affected by spine pathology in Fmr1-KOs. Enrichment rescued the behavioral FXS-like deficits displayed in adulthood by Fmr1-KO mice, that is, hyperactivity, reduced social interactions, and cognitive deficits. Early social enrichment also eliminated the abnormalities shown by adult KO mice in the morphology of hippocampal and amygdala dendritic spines, namely an enhanced density of immature vs mature types. Importantly, enrichment did not induce neurobehavioral changes in WT mice, thus supporting specific effects on FXS-like pathology. These findings show that early environmental stimulation has profound and long-term beneficial effects on the pathological FXS phenotype, thereby encouraging the use of nonpharmacological interventions for the treatment of this and perhaps other neurodevelopmental diseases. PMID:25348604

  18. Respiratory acoustic impedance in left ventricular failure.

    PubMed

    Depeursinge, F B; Feihl, F; Depeursinge, C; Perret, C H

    1989-12-01

    The measurement of respiratory acoustic impedance (Zrs) by forced pseudorandom noise provides a simple means of assessing respiratory mechanics in nonintubated intensive care patients. To characterize the lung mechanical alterations induced by acute vascular congestion of the lung, Zrs was measured in 14 spontaneously breathing patients hospitalized for acute left ventricular failure. The Zrs data in the cardiac patients were compared with those of 48 semirecumbent normal subjects and those of 23 sitting asthmatic patients during allergen-induced bronchospasm. In the patients with acute left ventricular failure, the Zrs abnormalities noted were an excessive frequency dependence of resistance from 10 to 20 Hz and an abnormally low reactance at all frequencies, abnormalities qualitatively similar to those observed in the asthmatic patients but of lesser magnitude. Acute lung vascular congestion modifies the acoustic impedance of the respiratory system. Reflex-induced bronchospasm might be the main mechanism altering respiratory acoustic impedance in acute left ventricular failure. PMID:2582846

  19. Arrhythmogenic Right Ventricular Dysplasia

    MedlinePlus

    MENU Return to Web version Arrhythmogenic Right Ventricular Dysplasia Overview What is arrhythmogenic right ventricular dysplasia? Arrhythmogenic right ventricular dysplasia (say: “uh-rith-mo-jen-ic right ven-trick- ...

  20. Abnormal human sex chromosome constitutions

    SciTech Connect

    1993-12-31

    Chapter 22, discusses abnormal human sex chromosome constitution. Aneuploidy of X chromosomes with a female phenotype, sex chromosome aneuploidy with a male phenotype, and various abnormalities in X chromosome behavior are described. 31 refs., 2 figs.

  1. Anger and ventricular arrhythmias

    PubMed Central

    Lampert, Rachel

    2011-01-01

    Purpose of review Although anecdotal evidence has long suggested links between emotion and ventricular arrhythmia, more recent studies have prospectively demonstrated the arrhythmogenic effects of anger, as well as mechanisms underlying these effects. Recent findings Epidemiological studies reveal that psychological stress increases sudden death, as well as arrhythmias, in patients with implantable cardioverter-defibrillators, in populations during emotionally devastating disasters such as earthquake or war. Diary-based studies confirm that anger and other negative emotions can trigger potentially lethal ventricular arrhythmias. Anger alters electrophysiological properties of the myocardium, including T-wave alternans, a measure of heterogeneity of repolarization, suggesting one mechanistic link between emotion and arrhythmia. Pilot studies of behavioral interventions have shown promise in decreasing arrhythmias in patients with implantable cardioverter-defibrillators. Summary Anger and other strong emotions can trigger polymorphic, potentially life-threatening ventricular arrhythmias in vulnerable patients. Through autonomic changes including increased sympathetic activity and vagal withdrawal, anger leads to increases in heterogeneity of repolarization as measured by T-wave alternans, known to be associated with arrhythmogenesis, as well as increasing inducibility of arrhythmia. Further delineation of mechanisms linking anger and arrhythmia, and of approaches to decrease the detrimental effects of anger and other negative emotions on arrhythmogenesis, are important areas of future investigation. PMID:19864944

  2. Two-dimensional echocardiographic features of right ventricular infarction

    SciTech Connect

    D'Arcy, B.; Nanda, N.C.

    1982-01-01

    Real-time, two-dimensional echocardiographic studies were performed in 10 patients with acute myocardial infarction who had clinical features suggestive of right ventricular involvement. All patients showed right ventricular wall motion abnormalities. In the four-chamber view, seven patients showed akinesis of the entire right ventricular diaphragmatic wall and three showed akinesis of segments of the diaphragmatic wall. Segmental dyskinetic areas involving the right ventricular free wall were identified in four patients. One patient showed a large right ventricular apical aneurysm. Other echocardiographic features included enlargement of the right ventricle in eight cases, paradoxical ventricular septal motion in seven cases, tricuspid incompetence in eight cases, dilation of the stomach in four cases and localized pericardial effusion in two cases. Right ventricular infarction was confirmed by radionuclide methods in seven patients, at surgery in one patient and at autopsy in two patients.

  3. The α4β2 nicotinic acetylcholine receptor modulates autism-like behavioral and motor abnormalities in pentylenetetrazol-kindled mice.

    PubMed

    Takechi, Kenshi; Suemaru, Katsuya; Kiyoi, Takeshi; Tanaka, Akihiro; Araki, Hiroaki

    2016-03-15

    Epilepsy is associated with several psychiatric disorders, including cognitive impairment, autism and attention deficit/hyperactivity disorder (ADHD). However, the psychopathology of epilepsy is frequently unrecognized and untreated in patients. In the present study, we investigated the effects of ABT-418, a neuronal nicotinic acetylcholine receptor agonist, on pentylenetetrazol (PTZ)-kindled mice with behavioral and motor abnormalities. PTZ-kindled mice displayed impaired motor coordination (in the rotarod test), anxiety (in the elevated plus maze test) and social approach impairment (in the three-chamber social test) compared with control mice. ABT-418 treatment (0.05mg/kg, intraperitoneally) alleviated these behavioral abnormalities in PTZ-kindled mice. Immunolabeling of tissue sections demonstrated that expression of the α4 nicotinic acetylcholine receptor subunit in the medial habenula was similar in control and PTZ-kindled mice. However, expression was significantly decreased in the piriform cortex in PTZ-kindled mice. In addition, we examined the expression of the synaptic adhesion molecule neuroligin 3 (NLG3). NLG3 expression in the piriform cortex was significantly higher in PTZ-kindled mice compared with control mice. Collectively, our findings suggest that ADHD-like or autistic-like behavioral abnormalities associated with epilepsy are closely related to the downregulation of the α4 nicotinic receptor and the upregulation of NLG3 in the piriform cortex. In summary, this study indicates that ABT-418 might have therapeutic potential for attentional impairment in epileptic patients with psychiatric disorders such as autism and ADHD. PMID:26868186

  4. [Drug-induced ventricular tachycardia].

    PubMed

    Fauchier, J P; Fauchier, L; Babuty, D; Breuillac, J C; Cosnay, P; Rouesnel, P

    1993-05-01

    Certain drugs can induce ventricular tachycardia (VT) by creating reentry, ventricular after potentials or exaggerating the slope of phase 4. These may or may not be symptomatic, sustained or non-sustained and have variable ECG appearances: monomorphic or polymorphic, bidirectional, torsades de pointes. They risk degenerating into ventricular flutter of fibrillation and have been held responsible for the increased mortality observed unexpectedly in some long-term treatments. The drugs responsible are mainly those used in cardiology, probably due to predisposing circumstances (cardiomegaly, cardiac failure, previous severe ventricular arrhythmias, therapeutic associations, metabolic abnormalities). These include primarily the antiarrhythmic drugs (IA, IC, sotalol and bepridil), digitalis, sympathomimetics and phosphodiesterase inhibitors. These complications may be toxic or idiosyncratic, in patients with or without cardiac disease, and may also occur with other drugs: vasodilators and anti-anginal drugs (lidoflazine, vincamine, fenoxedil), psychotropic agents (phenothiazine and imipramine), antimitotics, antimalarials (chloroquine) or antibiotics (erythromycin, pentamidine). The prognosis is severe and the treatment is often difficult which makes prevention, helped by repeated surface ECG (or Holter monitoring), very important with careful assessment of patients at risk. PMID:8267504

  5. Abnormal Eu behavior at formation of H2O- and Cl-bearing fluids during degassing of granite magmas

    NASA Astrophysics Data System (ADS)

    Lukanin, Oleg

    2010-05-01

    melt. The abnormal behavior of Eu shows itself the stronger, the lower fO2and, accordingly, the more fraction of Eu2+is present in melt. The work is supported of the Geosciences Department of the Russian Academy of Science (the program 2- 2010) and RFBR (grant 08-05-00022). References [1] Reed M.J., Candela Ph.A., Piccoli Ph.M. Contrib. Mineral. Petrol. 2000. V. 140. P. 251-262. [2] Lukanin O.A., Dernov-Pegarev V.F. Vestnik Otd. Nauk Zemle RAN, No 1(25)'2007 URL: http://www.scgis.ru/russian/cp1251/h_dgggms/1-2007/informbul-1_2007/term-30e.pdf [3] Drake M.J. Geochim. Cosmochim. Acta. 1975. V. 39. P. 55-64. [4] Wilke M. Behrens H. Contrib. Mineral. Petrol. 1999. V. 137. P. 102-114. [5] Lukanin O.A. Vestnik Otd. Nauk o Zemle RAN, No 1(26)'2008. URL: http://www.scgis.ru/russian/cp1251/h_dgggms/1-2008/informbul-1_2008/magm-20e.pdf [6] Lukanin O.A., Dernov-Pegarev V.F. Geochemistry International, 2010 (in press)

  6. Sequential Notch activation regulates ventricular chamber development

    PubMed Central

    D'Amato, Gaetano; Luxán, Guillermo; del Monte-Nieto, Gonzalo; Martínez-Poveda, Beatriz; Torroja, Carlos; Walter, Wencke; Bochter, Matthew S.; Benedito, Rui; Cole, Susan; Martinez, Fernando; Hadjantonakis, Anna-Katerina; Uemura, Akiyoshi; Jiménez-Borreguero, Luis J.; de la Pompa, José Luis

    2016-01-01

    Ventricular chambers are essential for the rhythmic contraction and relaxation occurring in every heartbeat throughout life. Congenital abnormalities in ventricular chamber formation cause severe human heart defects. How the early trabecular meshwork of myocardial fibres forms and subsequently develops into mature chambers is poorly understood. We show that Notch signalling first connects chamber endocardium and myocardium to sustain trabeculation, and later coordinates ventricular patterning and compaction with coronary vessel development to generate the mature chamber, through a temporal sequence of ligand signalling determined by the glycosyltransferase manic fringe (MFng). Early endocardial expression of MFng promotes Dll4–Notch1 signalling, which induces trabeculation in the developing ventricle. Ventricular maturation and compaction require MFng and Dll4 downregulation in the endocardium, which allows myocardial Jag1 and Jag2 signalling to Notch1 in this tissue. Perturbation of this signalling equilibrium severely disrupts heart chamber formation. Our results open a new research avenue into the pathogenesis of cardiomyopathies. PMID:26641715

  7. Abnormal social behavior, hyperactivity, impaired remote spatial memory, and increased D1-mediated dopaminergic signaling in neuronal nitric oxide synthase knockout mice

    PubMed Central

    Tanda, Koichi; Nishi, Akinori; Matsuo, Naoki; Nakanishi, Kazuo; Yamasaki, Nobuyuki; Sugimoto, Tohru; Toyama, Keiko; Takao, Keizo; Miyakawa, Tsuyoshi

    2009-01-01

    Background Neuronal nitric oxide synthase (nNOS) is involved in the regulation of a diverse population of intracellular messenger systems in the brain. In humans, abnormal NOS/nitric oxide metabolism is suggested to contribute to the pathogenesis and pathophysiology of some neuropsychiatric disorders, such as schizophrenia and bipolar disorder. Mice with targeted disruption of the nNOS gene exhibit abnormal behaviors. Here, we subjected nNOS knockout (KO) mice to a battery of behavioral tests to further investigate the role of nNOS in neuropsychiatric functions. We also examined the role of nNOS in dopamine/DARPP-32 signaling in striatal slices from nNOS KO mice and the effects of the administration of a dopamine D1 receptor agonist on behavior in nNOS KO mice. Results nNOS KO mice showed hyperlocomotor activity in a novel environment, increased social interaction in their home cage, decreased depression-related behavior, and impaired spatial memory retention. In striatal slices from nNOS KO mice, the effects of a dopamine D1 receptor agonist, SKF81297, on the phosphorylation of DARPP-32 and AMPA receptor subunit GluR1 at protein kinase A sites were enhanced. Consistent with the biochemical results, intraperitoneal injection of a low dose of SKF81297 significantly decreased prepulse inhibition in nNOS KO mice, but not in wild-type mice. Conclusion These findings indicate that nNOS KO upregulates dopamine D1 receptor signaling, and induces abnormal social behavior, hyperactivity and impaired remote spatial memory. nNOS KO mice may serve as a unique animal model of psychiatric disorders. PMID:19538708

  8. Exercise thallium testing in ventricular preexcitation

    SciTech Connect

    Archer, S.; Gornick, C.; Grund, F.; Shafer, R.; Weir, E.K.

    1987-05-01

    Ventricular preexcitation, as seen in Wolff-Parkinson-White syndrome, results in a high frequency of positive exercise electrocardiographic responses. Why this occurs is unknown but is not believed to reflect myocardial ischemia. Exercise thallium testing is often used for noninvasive assessment of coronary artery disease in patients with conditions known to result in false-positive electrocardiographic responses. To assess the effects of ventricular preexcitation on exercise thallium testing, 8 men (aged 42 +/- 4 years) with this finding were studied. No subject had signs or symptoms of coronary artery disease. Subjects exercised on a bicycle ergometer to a double product of 26,000 +/- 2,000 (+/- standard error of mean). All but one of the subjects had at least 1 mm of ST-segment depression. Tests were terminated because of fatigue or dyspnea and no patient had chest pain. Thallium test results were abnormal in 5 patients, 2 of whom had stress defects as well as abnormally delayed thallium washout. One of these subjects had normal coronary arteries on angiography with a negative ergonovine challenge, and both had normal exercise radionuclide ventriculographic studies. Delayed thallium washout was noted in 3 of the subjects with ventricular preexcitation and normal stress images. This study suggests that exercise thallium testing is frequently abnormal in subjects with ventricular preexcitation. Ventricular preexcitation may cause dyssynergy of ventricular activation, which could alter myocardial thallium handling, much as occurs with left bundle branch block. Exercise radionuclide ventriculography may be a better test for noninvasive assessment of coronary artery disease in patients with ventricular preexcitation.

  9. ENU-mutagenesis mice with a non-synonymous mutation in Grin1 exhibit abnormal anxiety-like behaviors, impaired fear memory, and decreased acoustic startle response

    PubMed Central

    2013-01-01

    Background The Grin1 (glutamate receptor, ionotropic, NMDA1) gene expresses a subunit of N-methyl-D-aspartate (NMDA) receptors that is considered to play an important role in excitatory neurotransmission, synaptic plasticity, and brain development. Grin1 is a candidate susceptibility gene for neuropsychiatric disorders, including schizophrenia, bipolar disorder, and attention deficit/hyperactivity disorder (ADHD). In our previous study, we examined an N-ethyl-N-nitrosourea (ENU)-generated mutant mouse strain (Grin1Rgsc174/Grin1+) that has a non-synonymous mutation in Grin1. These mutant mice showed hyperactivity, increased novelty-seeking to objects, and abnormal social interactions. Therefore, Grin1Rgsc174/Grin1+ mice may serve as a potential animal model of neuropsychiatric disorders. However, other behavioral characteristics related to these disorders, such as working memory function and sensorimotor gating, have not been fully explored in these mutant mice. In this study, to further investigate the behavioral phenotypes of Grin1Rgsc174/Grin1+ mice, we subjected them to a comprehensive battery of behavioral tests. Results There was no significant difference in nociception between Grin1Rgsc174/Grin1+ and wild-type mice. The mutants did not display any abnormalities in the Porsolt forced swim and tail suspension tests. We confirmed the previous observations that the locomotor activity of these mutant mice increased in the open field and home cage activity tests. They displayed abnormal anxiety-like behaviors in the light/dark transition and the elevated plus maze tests. Both contextual and cued fear memory were severely deficient in the fear conditioning test. The mutant mice exhibited slightly impaired working memory in the eight-arm radial maze test. The startle amplitude was markedly decreased in Grin1Rgsc174/Grin1+ mice, whereas no significant differences between genotypes were detected in the prepulse inhibition (PPI) test. The mutant mice showed no obvious

  10. Theory of mind mediates the prospective relationship between abnormal social brain network morphology and chronic behavior problems after pediatric traumatic brain injury.

    PubMed

    Ryan, Nicholas P; Catroppa, Cathy; Beare, Richard; Silk, Timothy J; Crossley, Louise; Beauchamp, Miriam H; Yeates, Keith Owen; Anderson, Vicki A

    2016-04-01

    Childhood and adolescence coincide with rapid maturation and synaptic reorganization of distributed neural networks that underlie complex cognitive-affective behaviors. These regions, referred to collectively as the 'social brain network' (SBN) are commonly vulnerable to disruption from pediatric traumatic brain injury (TBI); however, the mechanisms that link morphological changes in the SBN to behavior problems in this population remain unclear. In 98 children and adolescents with mild to severe TBI, we acquired 3D T1-weighted MRIs at 2-8 weeks post-injury. For comparison, 33 typically developing controls of similar age, sex and education were scanned. All participants were assessed on measures of Theory of Mind (ToM) at 6 months post-injury and parents provided ratings of behavior problems at 24-months post-injury. Severe TBI was associated with volumetric reductions in the overall SBN package, as well as regional gray matter structural change in multiple component regions of the SBN. When compared with TD controls and children with milder injuries, the severe TBI group had significantly poorer ToM, which was associated with more frequent behavior problems and abnormal SBN morphology. Mediation analysis indicated that impaired theory of mind mediated the prospective relationship between abnormal SBN morphology and more frequent chronic behavior problems. Our findings suggest that sub-acute alterations in SBN morphology indirectly contribute to long-term behavior problems via their influence on ToM. Volumetric change in the SBN and its putative hub regions may represent useful imaging biomarkers for prediction of post-acute social cognitive impairment, which may in turn elevate risk for chronic behavior problems. PMID:26796967

  11. Meiotic abnormalities

    SciTech Connect

    1993-12-31

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

  12. Cause and Consequence: Mitochondrial Dysfunction Initiates and Propagates Neuronal Dysfunction, Neuronal Death and Behavioral Abnormalities in Age Associated Neurodegenerative Diseases

    PubMed Central

    Gibson, Gary E.; Starkov, Anatoly; Blass, John P.; Ratan, Rajiv R.; Beal, M. Flint

    2009-01-01

    SUMMARY Age-related neurodegenerative diseases are associated with mild impairment of oxidative metabolism and accumulation of abnormal proteins. Within the cell, the mitochondria appears to be a dominant site for initiation and propagation of disease processes. Shifts in metabolism in response to mild metabolic perturbations may decrease the threshold for irreversible injury in response to ordinarily sub lethal metabolic insults. Mild impairment of metabolism accrue from and lead to increased reactive oxygen species (ROS). Increased ROS change cell signaling via post transcriptional and transcriptional changes. The cause and consequences of mild impairment of mitochondrial metabolism is one focus of this review. Many experiments in tissues from humans support the notion that oxidative modification of the α-ketoglutarate dehydrogenase complex (KGDHC) compromises neuronal energy metabolism and enhance ROS production in Alzheimer’s Disease (AD). These data suggest that cognitive decline in AD derives from the selective tricarboxylic acid (TCA) cycle abnormalities. By contrast in Huntington’s Disease (HD), a movement disorder with cognitive features distinct form AD, complex II + III abnormalities may dominate. These distinct mitochondrial abnormalities culminate in oxidative stress, energy dysfunction, and aberrant homeostasis of cytosolic calcium. Cytosolic calcium, elevations even only transiently, leads to hyperactivity of a number of enzymes. One calcium activated enzyme with demonstrated pathophysiological import in HD and AD is transglutaminase (TGase). TGase is a cross linking enzymes that can modulate transcrption, inactivate metabolic enzymes, and cause aggregation of critical proteins. Recent data indicate that TGase can silence expression of genes involved in compensating for metabolic stress. Altogether, our results suggest that increasing KGDHC via inhibition of TGase or via a host of other strategies to be described would be effective therapeutic

  13. Right ventricular infarction: identification by hemodynamic measurements before and after volume loading and correlation with noninvasive techniques

    SciTech Connect

    Dell'Italia, L.J.; Starling, M.R.; Crawford, M.H.; Boros, B.L.; Chaudhuri, T.K.; O'Rourke, R.A.

    1984-11-01

    To evaluate the potential occurrence of right ventricular infarction, 53 patients with acute inferior transmural myocardial infarction were studied within 36 hours of symptoms by right heart catheterization, equilibrium radionuclide angiography and two-dimensional echocardiography. Technetium-99m pyrophosphate myocardial scintigraphy was performed 3 days after the onset of symptoms. The hemodynamic standard for right ventricular infarction was defined as both a right atrial pressure of 10 mm Hg or more and a right atrial/pulmonary artery wedge pressure ratio of 0.8 or more. Eight (15%) of the 53 patients had hemodynamic measurements at rest characteristic of right ventricular infarction, and 6 (11%) additional patients met these criteria after volume loading. Nineteen (37%) of the 51 patients who had radionuclide angiography had right ventricular dysfunction manifested by both a reduced right ventricular ejection fraction (less than 40%) and right ventricular regional wall motion abnormalities (akinesia or dyskinesia). An abnormal radionuclide angiogram was observed in 12 of 13 patients with hemodynamic measurements indicating right ventricular infarction. In 12 patients with an abnormal radionuclide angiographic study, right ventricular ejection fraction improved 6 to 12 weeks after infarction. Twenty-two (49%) of the 45 patients with adequate two-dimensional echocardiograms had a right ventricular regional wall motion abnormality. An abnormal two-dimensional echocardiogram was seen in 9 of 11 patients with hemodynamic measurements characteristic of right ventricular infarction. Technetium-99m pyrophosphate scintigraphy was positive for right ventricular infarction in 3 of 12 patients who had hemodynamic measurements indicating right ventricular infarction.

  14. Recurrent reciprocal 1q21.1 deletions and duplications associated with microcephaly or macrocephaly and developmental and behavioral abnormalities.

    PubMed

    Brunetti-Pierri, Nicola; Berg, Jonathan S; Scaglia, Fernando; Belmont, John; Bacino, Carlos A; Sahoo, Trilochan; Lalani, Seema R; Graham, Brett; Lee, Brendan; Shinawi, Marwan; Shen, Joseph; Kang, Sung-Hae L; Pursley, Amber; Lotze, Timothy; Kennedy, Gail; Lansky-Shafer, Susan; Weaver, Christine; Roeder, Elizabeth R; Grebe, Theresa A; Arnold, Georgianne L; Hutchison, Terry; Reimschisel, Tyler; Amato, Stephen; Geragthy, Michael T; Innis, Jeffrey W; Obersztyn, Ewa; Nowakowska, Beata; Rosengren, Sally S; Bader, Patricia I; Grange, Dorothy K; Naqvi, Sayed; Garnica, Adolfo D; Bernes, Saunder M; Fong, Chin-To; Summers, Anne; Walters, W David; Lupski, James R; Stankiewicz, Pawel; Cheung, Sau Wai; Patel, Ankita

    2008-12-01

    Chromosome region 1q21.1 contains extensive and complex low-copy repeats, and copy number variants (CNVs) in this region have recently been reported in association with congenital heart defects, developmental delay, schizophrenia and related psychoses. We describe 21 probands with the 1q21.1 microdeletion and 15 probands with the 1q21.1 microduplication. These CNVs were inherited in most of the cases in which parental studies were available. Consistent and statistically significant features of microcephaly and macrocephaly were found in individuals with microdeletion and microduplication, respectively. Notably, a paralog of the HYDIN gene located on 16q22.2 and implicated in autosomal recessive hydrocephalus was inserted into the 1q21.1 region during the evolution of Homo sapiens; we found this locus to be deleted or duplicated in the individuals we studied, making it a probable candidate for the head size abnormalities observed. We propose that recurrent reciprocal microdeletions and microduplications within 1q21.1 represent previously unknown genomic disorders characterized by abnormal head size along with a spectrum of developmental delay, neuropsychiatric abnormalities, dysmorphic features and congenital anomalies. These phenotypes are subject to incomplete penetrance and variable expressivity. PMID:19029900

  15. Idiopathic left ventricular apical hypoplasia.

    PubMed

    Raza, Ali; Waleed, Mohammad; Balerdi, Matthew; Bragadeesh, Thanjavur; Clark, Andrew L

    2014-01-01

    A 46-year-old man was found to have an abnormal ECG taken during a routine health and blood pressure check. His only symptom was non-specific central chest discomfort, unrelated to exertion. His ECG showed sinus rhythm, a normal axis and poor R wave progression across the chest leads and lateral T wave flattening. An echocardiogram showed a dilated left ventricle with a thin and hypokinetic septum bulging to the right. The apex was 'not well seen' but also appeared thin and hypokinetic. The right heart and valves were normal. The patient was further investigated for left ventricular hypoplasia. PMID:24585345

  16. Abnormal chromosome behavior during meiosis in the allotetraploid of Carassius auratus red var. (♀) × Megalobrama amblycephala (♂)

    PubMed Central

    2014-01-01

    Background Allopolyploids generally undergo bivalent pairing at meiosis because only homologous chromosomes pair up. On the other hand, several studies have documented abnormal chromosome behavior during mitosis and meiosis in allopolyploids plants leading to the production of gametes with complete paternal or maternal chromosomes. Polyploidy is relatively rare in animals compared with plants; thus, chromosome behavior at meiosis in the allopolyploid animals is poorly understood. Results Tetraploid hybrids (abbreviated as 4nRB) (4n = 148, RRBB) of Carassius auratus red var. (abbreviated as RCC) (2n = 100, RR) (♀) × Megalobrama amblycephala (abbreviated as BSB) (2n = 48, BB) (♂) generated gametes of different size. To test the genetic composition of these gametes, the gynogenetic offspring and backcross progenies of 4nRB were produced, and their genetic composition were examined by chromosome analysis and FISH. Our results suggest that 4nRB can produce several types of gametes with different genetic compositions, including allotetraploid (RRBB), autotriploid (RRR), autodiploid (RR), and haploid (R) gametes. Conclusions This study provides direct evidence of abnormal chromosome behavior during meiosis in an allotetraploid fish. PMID:25178799

  17. Craniofacial Abnormalities

    MedlinePlus

    ... of the skull and face. Craniofacial abnormalities are birth defects of the face or head. Some, like cleft ... palate, are among the most common of all birth defects. Others are very rare. Most of them affect ...

  18. Walking abnormalities

    MedlinePlus

    ... include: Arthritis of the leg or foot joints Conversion disorder (a psychological disorder) Foot problems (such as a ... injuries. For an abnormal gait that occurs with conversion disorder, counseling and support from family members are strongly ...

  19. Congenital Abnormalities

    MedlinePlus

    ... serious health problems (e.g. Down syndrome ). Single-Gene Abnormalities Sometimes the chromosomes are normal in number, ... blood flow to the fetus impair fetal growth. Alcohol consumption and certain drugs during pregnancy significantly increase ...

  20. Chromosome Abnormalities

    MedlinePlus

    ... decade, newer techniques have been developed that allow scientists and doctors to screen for chromosomal abnormalities without using a microscope. These newer methods compare the patient's DNA to a normal DNA ...

  1. Nail abnormalities

    MedlinePlus

    Nail abnormalities are problems with the color, shape, texture, or thickness of the fingernails or toenails. ... Fungus or yeast cause changes in the color, texture, and shape of the nails. Bacterial infection may ...

  2. Flow behavior within the 12-cc Penn State pulsatile pediatric ventricular assist device: an experimental study of the initial design.

    PubMed

    Manning, Keefe B; Wivholm, Brandon D; Yang, Ning; Fontaine, Arnold A; Deutsch, Steven

    2008-06-01

    Planar particle image velocimetry was used to explore the flow behavior of the newly designed 12-cc Penn State pneumatic pediatric assist pump. Wall shear maps complemented the velocity data. Bjork-Shiley Monostrut 17-mm mechanical heart valves were used in the inlet and outlet ports. In comparison with larger Penn State pumps, the 12-cc device is not only smaller but has reduced valve effective orifice areas and more highly angled valve ports. In contrast to results from the larger pumps, the flow field was highly three dimensional during early diastole with poorer penetration by the valve inlet jet. This led to a later start to a "wall washing" rotational pattern. A significant separation region, never before observed, was created upstream of the outlet valve leaflet during late diastole--effectively reducing the area and increasing the pressure drop through the valve. Wall shear maps suggest that regions of low shear might persist throughout the cycle at the bottom of the pump on the outlet side. An attempt to improve the flow field characteristics by exploring different valves, valve orientations and inlet valve angles, systolic/diastolic flow timing, and perhaps a larger outlet valve was planned. PMID:18422800

  3. Ventricular Aneurysm Following Myocardial Infarction

    PubMed Central

    Walters, M. B.

    1966-01-01

    Cineradiographic examination appears to be the best method for the study of cardiac pulsations. Fifty consecutive patients, who had sustained transmural myocardial infarction at least six months previously, were studied by this technique. Thirty-six had some abnormality of pulsation and eight had dynamic ventricular aneurysm. Six of the eight had suffered severe infarct. Functional recovery in those with aneurysm was not as complete as in the rest of the group. Two made a poor functional recovery, two a fair recovery, and four a moderately good recovery. Clinically, there were no systemic emboli in the patients with dynamic aneurysms. Five of the 50 had persistent ST-segment elevation and “coving” of the T waves; three of these patients had aneurysms. There was no good correlation between the electrocardiographic site of the infarct and the site of the abnormal pulsation. ImagesFig. 1 PMID:5928534

  4. A BDNF loop-domain mimetic acutely reverses spontaneous apneas and respiratory abnormalities during behavioral arousal in a mouse model of Rett syndrome

    PubMed Central

    Kron, Miriam; Lang, Min; Adams, Ian T.; Sceniak, Michael; Longo, Frank; Katz, David M.

    2014-01-01

    Reduced levels of brain-derived neurotrophic factor (BDNF) are thought to contribute to the pathophysiology of Rett syndrome (RTT), a severe neurodevelopmental disorder caused by loss-of-function mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2). In Mecp2 mutant mice, BDNF deficits have been associated with breathing abnormalities, a core feature of RTT, as well as with synaptic hyperexcitability within the brainstem respiratory network. Application of BDNF can reverse hyperexcitability in acute brainstem slices from Mecp2-null mice, suggesting that therapies targeting BDNF or its receptor, TrkB, could be effective at acute reversal of respiratory abnormalities in RTT. Therefore, we examined the ability of LM22A-4, a small-molecule BDNF loop-domain mimetic and TrkB partial agonist, to modulate synaptic excitability within respiratory cell groups in the brainstem nucleus tractus solitarius (nTS) and to acutely reverse abnormalities in breathing at rest and during behavioral arousal in Mecp2 mutants. Patch-clamp recordings in Mecp2-null brainstem slices demonstrated that LM22A-4 decreases excitability at primary afferent synapses in the nTS by reducing the amplitude of evoked excitatory postsynaptic currents and the frequency of spontaneous and miniature excitatory postsynaptic currents. In vivo, acute treatment of Mecp2-null and -heterozygous mutants with LM22A-4 completely eliminated spontaneous apneas in resting animals, without sedation. Moreover, we demonstrate that respiratory dysregulation during behavioral arousal, a feature of human RTT, is also reversed in Mecp2 mutants by acute treatment with LM22A-4. Together, these data support the hypothesis that reduced BDNF signaling and respiratory dysfunction in RTT are linked, and establish the proof-of-concept that treatment with a small-molecule structural mimetic of a BDNF loop domain and a TrkB partial agonist can acutely reverse abnormal breathing at rest and in response to behavioral arousal

  5. Arrhythmogenic right ventricular cardiomyopathy/dysplasia.

    PubMed

    Thiene, Gaetano; Corrado, Domenico; Basso, Cristina

    2007-01-01

    Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a heart muscle disease clinically characterized by life-threatening ventricular arrhythmias. Its prevalence has been estimated to vary from 1:2,500 to 1:5,000. ARVC/D is a major cause of sudden death in the young and athletes. The pathology consists of a genetically determined dystrophy of the right ventricular myocardium with fibro-fatty replacement to such an extent that it leads to right ventricular aneurysms. The clinical picture may include: a subclinical phase without symptoms and with ventricular fibrillation being the first presentation; an electrical disorder with palpitations and syncope, due to tachyarrhythmias of right ventricular origin; right ventricular or biventricular pump failure, so severe as to require transplantation. The causative genes encode proteins of mechanical cell junctions (plakoglobin, plakophilin, desmoglein, desmocollin, desmoplakin) and account for intercalated disk remodeling. Familiar occurrence with an autosomal dominant pattern of inheritance and variable penetrance has been proven. Recessive variants associated with palmoplantar keratoderma and woolly hair have been also reported. Clinical diagnosis may be achieved by demonstrating functional and structural alterations of the right ventricle, depolarization and repolarization abnormalities, arrhythmias with the left bundle branch block morphology and fibro-fatty replacement through endomyocardial biopsy. Two dimensional echo, angiography and magnetic resonance are the imaging tools for visualizing structural-functional abnormalities. Electroanatomic mapping is able to detect areas of low voltage corresponding to myocardial atrophy with fibro-fatty replacement. The main differential diagnoses are idiopathic right ventricular outflow tract tachycardia, myocarditis, dialted cardiomyopathy and sarcoidosis. Only palliative therapy is available and consists of antiarrhythmic drugs, catheter ablation and

  6. Genetic damage and the expression of behavioral abnormalities in the progeny of male rats exposed to ionizing radiation

    SciTech Connect

    Lowery, M.C.

    1987-01-01

    To determine the possible genetic nature of behavioral anomalies, an identifiable genetic endpoint, inherited chromosome translocations in the offspring, was selected to evaluate the relationship to behavior. Young adult male Fischer 344 rats were exposed to 50-300 rads of ionizing radiation. Two weeks following their irradiation, the males were mated with four virgin females for one week. During this time, fertilizing sperm were derived from post-meiotic spermatids, the stage of the spermatogenic cycle most sensitive to the mutagenic effects of radiation. Behavioral analyses of the resulting 390 offspring consisted of both motor reflex and motor coordination measurements as well as learning and retention parameters. Significant differences in performance were seen in several of the motor reflex measurements in progeny of males exposed to some of the higher doses of irradiation. A similar phenomenon was observed in the performance of a single learned behavior.

  7. Chronic exposure to environmentally-relevant concentrations of fluoxetine (Prozac) decreases survival, increases abnormal behaviors, and delays predator escape responses in guppies.

    PubMed

    Pelli, Marco; Connaughton, Victoria P

    2015-11-01

    This study evaluates the impact of fluoxetine, an antidepressant drug and common pollutant in aquatic environments, on growth, survival, and behavior in juvenile guppies and on predator escape responses in adult guppies (Poecilia reticulata). In juveniles, the effects of acute (4d) and chronic (35d) exposure on growth and survival were examined, and behavioral changes were noted throughout the chronic experiment. In adults, escape responses to a mock predator during chronic (28d) fluoxetine exposure were videotaped to determine the overall speed of response in treated vs. control fish. The effects of fish gender and the presence of a group/school on escape responses were also determined. Our results show that acute exposure to nominal concentrations of 0.03 and 0.5μg/L, levels within the environment, did not adversely impact juvenile guppy survival. However, chronic exposure significantly reduced weight, length, and belly width/girth measurements compared to controls. Chronic exposure also resulted in abnormal swimming behavior and reduced survival in juveniles. In adults, fluoxetine exposure significantly delayed predator escape responses in both males and females. Escape responses were also reduced when adults were tested either individually or in a group, with significantly more delayed responses seen in individually tested fish. Taken together, these findings suggest that fluoxetine can impact guppy populations, during both juvenile and adult stages, with chronic exposure resulting in decreased survival and growth and altered behavioral responses. PMID:26126230

  8. Unusual Manifestation of Graves' Disease: Ventricular Fibrillation

    PubMed Central

    Kobayashi, Hiroki; Haketa, Akira; Abe, Masanori; Tahira, Kazunobu; Hatanaka, Yoshinari; Tanaka, Sho; Ueno, Takahiro; Soma, Masayoshi

    2015-01-01

    Background It is well known that thyrotoxicosis causes rhythm disorders including sinus tachycardia, atrial fibrillation, and atrial flutter. Atrial fibrillation is the most common arrhythmia in thyrotoxicosis, occurring in 5-15% of patients over 60 years of age, whereas ventricular arrhythmia is an unusual manifestation. Case Report An 18-year-old Japanese woman was admitted to our emergency department because of loss of consciousness caused by ventricular fibrillation. She had been diagnosed with Graves' disease only 5 days earlier and had no other past medical history. Blood examination showed no obvious abnormality except thyrotoxicosis, and coronary angiography revealed patent coronary arteries. She was diagnosed with thyroid storm due to Graves' disease and is currently healthy during outpatient follow-up. Conclusion This case highlights that thyrotoxicosis can, albeit extremely rarely, cause ventricular fibrillation even in the absence of hypokalemia or underlying cardiovascular disease. PMID:26558239

  9. Alzheimer Disease in a Mouse Model: MR Imaging–guided Focused Ultrasound Targeted to the Hippocampus Opens the Blood-Brain Barrier and Improves Pathologic Abnormalities and Behavior

    PubMed Central

    Dubey, Sonam; Yeung, Sharon; Hough, Olivia; Eterman, Naomi; Aubert, Isabelle; Hynynen, Kullervo

    2014-01-01

    Purpose To validate whether repeated magnetic resonance (MR) imaging–guided focused ultrasound treatments targeted to the hippocampus, a brain structure relevant for Alzheimer disease (ADAlzheimer disease), could modulate pathologic abnormalities, plasticity, and behavior in a mouse model. Materials and Methods All animal procedures were approved by the Animal Care Committee and are in accordance with the Canadian Council on Animal Care. Seven-month-old transgenic (TgCRND8) (Tg) mice and their nontransgenic (non-Tg) littermates were entered in the study. Mice were treated weekly with MR imaging–guided focused ultrasound in the bilateral hippocampus (1.68 MHz, 10-msec bursts, 1-Hz burst repetition frequency, 120-second total duration). After 1 month, spatial memory was tested in the Y maze with the novel arm prior to sacrifice and immunohistochemical analysis. The data were compared by using unpaired t tests and analysis of variance with Tukey post hoc analysis. Results Untreated Tg mice spent 61% less time than untreated non-Tg mice exploring the novel arm of the Y maze because of spatial memory impairments (P < .05). Following MR imaging–guided focused ultrasound, Tg mice spent 99% more time exploring the novel arm, performing as well as their non-Tg littermates. Changes in behavior were correlated with a reduction of the number and size of amyloid plaques in the MR imaging–guided focused ultrasound–treated animals (P < .01). Further, after MR imaging–guided focused ultrasound treatment, there was a 250% increase in the number of newborn neurons in the hippocampus (P < .01). The newborn neurons had longer dendrites and more arborization after MR imaging–guided focused ultrasound, as well (P < .01). Conclusion Repeated MR imaging–guided focused ultrasound treatments led to spatial memory improvement in a Tg mouse model of ADAlzheimer disease. The behavior changes may be mediated by decreased amyloid pathologic abnormalities and increased neuronal

  10. Variability in Post-Error Behavioral Adjustment Is Associated with Functional Abnormalities in the Temporal Cortex in Children with ADHD

    ERIC Educational Resources Information Center

    Spinelli, Simona; Vasa, Roma A.; Joel, Suresh; Nelson, Tess E.; Pekar, James J.; Mostofsky, Stewart H.

    2011-01-01

    Background: Error processing is reflected, behaviorally, by slower reaction times (RT) on trials immediately following an error (post-error). Children with attention-deficit hyperactivity disorder (ADHD) fail to show RT slowing and demonstrate increased intra-subject variability (ISV) on post-error trials. The neural correlates of these behavioral…

  11. Chromosomal Abnormalities and Schizophrenia

    PubMed Central

    BASSETT, ANNE S.; CHOW, EVA W.C.; WEKSBERG, ROSANNA

    2011-01-01

    Schizophrenia is a common and serious psychiatric illness with strong evidence for genetic causation, but no specific loci yet identified. Chromosomal abnormalities associated with schizophrenia may help to understand the genetic complexity of the illness. This paper reviews the evidence for associations between chromosomal abnormalities and schizophrenia and related disorders. The results indicate that 22q11.2 microdeletions detected by fluorescence in-situ hybridization (FISH) are significantly associated with schizophrenia. Sex chromosome abnormalities seem to be increased in schizophrenia but insufficient data are available to indicate whether schizophrenia or related disorders are increased in patients with sex chromosome aneuploidies. Other reports of chromosomal abnormalities associated with schizophrenia have the potential to be important adjuncts to linkage studies in gene localization. Advances in molecular cytogenetic techniques (i.e., FISH) have produced significant increases in rates of identified abnormalities in schizophrenia, particularly in patients with very early age at onset, learning difficulties or mental retardation, or dysmorphic features. The results emphasize the importance of considering behavioral phenotypes, including adult onset psychiatric illnesses, in genetic syndromes and the need for clinicians to actively consider identifying chromosomal abnormalities and genetic syndromes in selected psychiatric patients. PMID:10813803

  12. Abnormal Pre-Attentive Arousal in Young Children with Autism Spectrum Disorder Contributes to Their Atypical Auditory Behavior: An ERP Study

    PubMed Central

    Stroganova, Tatiana A.; Kozunov, Vladimir V.; Posikera, Irina N.; Galuta, Ilia A.; Gratchev, Vitaliy V.; Orekhova, Elena V.

    2013-01-01

    Auditory sensory modulation difficulties and problems with automatic re-orienting to sound are well documented in autism spectrum disorders (ASD). Abnormal preattentive arousal processes may contribute to these deficits. In this study, we investigated components of the cortical auditory evoked potential (CAEP) reflecting preattentive arousal in children with ASD and typically developing (TD) children aged 3-8 years. Pairs of clicks (‘S1’ and ‘S2’) separated by a 1 sec S1-S2 interstimulus interval (ISI) and much longer (8-10 sec) S1-S1 ISIs were presented monaurally to either the left or right ear. In TD children, the P50, P100 and N1c CAEP components were strongly influenced by temporal novelty of clicks and were much greater in response to the S1 than the S2 click. Irrespective of the stimulation side, the ‘tangential’ P100 component was rightward lateralized in TD children, whereas the ‘radial’ N1c component had higher amplitude contralaterally to the stimulated ear. Compared to the TD children, children with ASD demonstrated 1) reduced amplitude of the P100 component under the condition of temporal novelty (S1) and 2) an attenuated P100 repetition suppression effect. The abnormalities were lateralized and depended on the presentation side. They were evident in the case of the left but not the right ear stimulation. The P100 abnormalities in ASD correlated with the degree of developmental delay and with the severity of auditory sensory modulation difficulties observed in early life. The results suggest that some rightward-lateralized brain networks that are crucially important for arousal and attention re-orienting are compromised in children with ASD and that this deficit contributes to sensory modulation difficulties and possibly even other behavioral deficits in ASD. PMID:23935931

  13. Abnormal pre-attentive arousal in young children with autism spectrum disorder contributes to their atypical auditory behavior: an ERP study.

    PubMed

    Stroganova, Tatiana A; Kozunov, Vladimir V; Posikera, Irina N; Galuta, Ilia A; Gratchev, Vitaliy V; Orekhova, Elena V

    2013-01-01

    Auditory sensory modulation difficulties and problems with automatic re-orienting to sound are well documented in autism spectrum disorders (ASD). Abnormal preattentive arousal processes may contribute to these deficits. In this study, we investigated components of the cortical auditory evoked potential (CAEP) reflecting preattentive arousal in children with ASD and typically developing (TD) children aged 3-8 years. Pairs of clicks ('S1' and 'S2') separated by a 1 sec S1-S2 interstimulus interval (ISI) and much longer (8-10 sec) S1-S1 ISIs were presented monaurally to either the left or right ear. In TD children, the P50, P100 and N1c CAEP components were strongly influenced by temporal novelty of clicks and were much greater in response to the S1 than the S2 click. Irrespective of the stimulation side, the 'tangential' P100 component was rightward lateralized in TD children, whereas the 'radial' N1c component had higher amplitude contralaterally to the stimulated ear. Compared to the TD children, children with ASD demonstrated 1) reduced amplitude of the P100 component under the condition of temporal novelty (S1) and 2) an attenuated P100 repetition suppression effect. The abnormalities were lateralized and depended on the presentation side. They were evident in the case of the left but not the right ear stimulation. The P100 abnormalities in ASD correlated with the degree of developmental delay and with the severity of auditory sensory modulation difficulties observed in early life. The results suggest that some rightward-lateralized brain networks that are crucially important for arousal and attention re-orienting are compromised in children with ASD and that this deficit contributes to sensory modulation difficulties and possibly even other behavioral deficits in ASD. PMID:23935931

  14. Mice that lack the C-terminal region of Reelin exhibit behavioral abnormalities related to neuropsychiatric disorders.

    PubMed

    Sakai, Kaori; Shoji, Hirotaka; Kohno, Takao; Miyakawa, Tsuyoshi; Hattori, Mitsuharu

    2016-01-01

    The secreted glycoprotein Reelin is believed to play critical roles in the pathogenesis of several neuropsychiatric disorders. The highly basic C-terminal region (CTR) of Reelin is necessary for efficient activation of its downstream signaling, and the brain structure of knock-in mice that lack the CTR (ΔC-KI mice) is impaired. Here, we performed a comprehensive behavioral test battery on ΔC-KI mice, in order to evaluate the effects of partial loss-of-function of Reelin on brain functions. The ΔC-KI mice were hyperactive and exhibited reduced anxiety-like and social behaviors. The working memory in ΔC-KI mice was impaired in a T-maze test. There was little difference in spatial reference memory, depression-like behavior, prepulse inhibition, or fear memory between ΔC-KI and wild-type mice. These results suggest that CTR-dependent Reelin functions are required for some specific normal brain functions and that ΔC-KI mice recapitulate some aspects of neuropsychiatric disorders, such as schizophrenia, bipolar disorder, and autism spectrum disorder. PMID:27346785

  15. Mice that lack the C-terminal region of Reelin exhibit behavioral abnormalities related to neuropsychiatric disorders

    PubMed Central

    Sakai, Kaori; Shoji, Hirotaka; Kohno, Takao; Miyakawa, Tsuyoshi; Hattori, Mitsuharu

    2016-01-01

    The secreted glycoprotein Reelin is believed to play critical roles in the pathogenesis of several neuropsychiatric disorders. The highly basic C-terminal region (CTR) of Reelin is necessary for efficient activation of its downstream signaling, and the brain structure of knock-in mice that lack the CTR (ΔC-KI mice) is impaired. Here, we performed a comprehensive behavioral test battery on ΔC-KI mice, in order to evaluate the effects of partial loss-of-function of Reelin on brain functions. The ΔC-KI mice were hyperactive and exhibited reduced anxiety-like and social behaviors. The working memory in ΔC-KI mice was impaired in a T-maze test. There was little difference in spatial reference memory, depression-like behavior, prepulse inhibition, or fear memory between ΔC-KI and wild-type mice. These results suggest that CTR-dependent Reelin functions are required for some specific normal brain functions and that ΔC-KI mice recapitulate some aspects of neuropsychiatric disorders, such as schizophrenia, bipolar disorder, and autism spectrum disorder. PMID:27346785

  16. Left Ventricular Relative Wall Thickness Versus Left Ventricular Mass Index in Non-Cardioembolic Stroke Patients

    PubMed Central

    Hashem, M-Sherif; Kalashyan, Hayrapet; Choy, Jonathan; Chiew, Soon K.; Shawki, Abdel-Hakim; Dawood, Ahmed H.; Becher, Harald

    2015-01-01

    Abstract In non-cardioembolic stroke patients, the cardiac manifestations of high blood pressure are of particular interest. Emerging data suggest that echocardiographically determined left ventricular hypertrophy is independently associated with risk of ischemic stroke. The primary objective of this study was to evaluate the frequency of different patterns of left ventricular (LV) remodeling and hypertrophy in a group of consecutive patients admitted with non-cardioembolic stroke or transient ischemic attack (TIA). In particular, we were interested in how often the relative wall thickness (RWT) was abnormal in patients with normal LV mass index (LVMI). As both abnormal RWT and LVMI indicate altered LV remodeling, the secondary objective of this research was to study whether a significant number of patients would be missing the diagnosis of LV remodeling if the RWT is not measured. All patients were referred within 48 hours after a stroke or a TIA for a clinically indicated transthoracic echocardiogram. The echocardiographic findings of consecutive patients with non-cardioembolic stroke or TIA were analyzed. All necessary measurements were performed in 368 patients, who were enrolled in the study. Mean age was 63.7 ± 12.5 years, 64.4% men. Concentric remodeling carried the highest frequency, 49.2%, followed by concentric hypertrophy, 30.7%, normal pattern, 15.5%, and eccentric hypertrophy, 4.1%. The frequency of abnormal left ventricular RWT (80.4%) was significantly higher than that of abnormal LVMI (35.3%), (McNemar P < 0.05). In this group of non-cardioembolic stroke patients, abnormal LV remodeling as assessed by relative wall thickness is very frequent. As RWT was often found without increased LV mass, the abnormal left ventricular geometry may be missed if RWT is not measured or reported. PMID:25997067

  17. Are there gender-specific pathways from early adolescence psychological distress symptoms toward the development of substance use and abnormal eating behavior?

    PubMed

    Beato-Fernández, Luis; Rodríguez-Cano, Teresa; Pelayo-Delgado, Esther; Calaf, Myralys

    2007-02-01

    The aim of the present longitudinal community study was to test whether psychological distress at 13 years of age predicted reported substance use problems in boys and abnormal eating behavior in girls 2 years later. The sample consisted of 500 male and 576 female students. The use of substances was evaluated using a semi-structured interview, psychological distress with the General Health Questionnaire (GHQ) and eating psychopathology with the Eating Attitudes Test (EAT-40), and the Bulimic Investigatory Test Edinburgh (BITE). Controlling the effect of initial substance use problems, psychological distress predicted later reported substance use problems in males. Girls with an initial score above the cut-off point on the GHQ were two times more likely to be at risk of having an eating disorder 2 years later. Therefore, psychological distress might take different developmental pathways in males and females, leading toward eating problems in the latter versus substance use in the former. PMID:17001526

  18. Prenatal and Early Postnatal Exposure to Cigarette Smoke Decreases BDNF/TrkB Signaling and Increases Abnormal Behaviors Later in Life

    PubMed Central

    Xiao, Lan; Kish, Vincent L.; Benders, Katherine M.

    2016-01-01

    Background: Cigarette smoke exposure during prenatal and early postnatal periods increases the incidence of a variety of abnormal behaviors later in life. The purpose of this study was to identify the possible critical period of susceptibility to cigarette smoke exposure and evaluate the possibe effects of cigarette smoke during early life on brain-derived neurotrophic factor/neurotrophic tyrosine kinase receptor B signaling in the brain. Methods: Three different age of imprinting control region mice were exposed to cigarette smoke or filtered air for 10 consecutive days beginning on either gestational day 7 by maternal exposure, or postnatal days 2 or 21 by direct inhalation. A series of behavioral profiles and neurotrophins in brain were measured 24 hours after mice received acute restraint stress for 1 hour on postnatal day 59. Results: Cigarette smoke exposure in gestational day 7 and postnatal day 2 produced depression-like behaviors as evidenced by significantly increased immobility in both tail suspension and forced-swim test. Increased entry latencies, but not ambulation in the open field test, were also observed in the gestational day 7 and postnatal day 2 cigarette smoke exposure groups. Genetic analysis showed that gestational day 7 cigarette smoke exposure significantly altered mRNA level of brain-derived neurotrophic factor/tyrosine kinase receptor B in the hippocampus. However, behavioral profiles and brain-derived neurotrophic factor/tyrosine kinase receptor B signaling were not significantly changed in PND21 cigarette smoke exposure group compared with FA group. Conclusions: These results suggest that a critical period of susceptibility to cigarette smoke exposure exists in the prenatal and early postnatal period, which results a downregulation in brain-derived neurotrophic factor/tyrosine kinase receptor B signaling in the hippocampus and enhances depression-like behaviors later in life. PMID:26503133

  19. Percutaneous left ventricular restoration.

    PubMed

    Ige, Mobolaji; Al-Kindi, Sadeer G; Attizzani, Guilherme; Costa, Marco; Oliveira, Guilherme H

    2015-04-01

    The ventricular partitioning device known as Parachute is the first and only percutaneously implantable device aimed at restoration of normal left ventricular geometry in humans. Since its conception, this technology has undergone extensive animal and human testing, with proved feasibility and safety, and is currently being studied in a pivotal randomized clinical trial. This article discusses ventricular remodeling and therapies attempted in the past, details the components of the ventricular partitioning device, describes the implanting technique, and reviews the most current experience of this device in humans. PMID:25834974

  20. Behavioral Abnormalities in a Mouse Model of Chronic Toxoplasmosis Are Associated with MAG1 Antibody Levels and Cyst Burden

    PubMed Central

    Xiao, Jianchun; Li, Ye; Prandovszky, Emese; Kannan, Geetha; Viscidi, Raphael P.; Pletnikov, Mikhail V.; Yolken, Robert H.

    2016-01-01

    There is marked variation in the human response to Toxoplasma gondii infection. Epidemiological studies indicate associations between strain virulence and severity of toxoplasmosis. Animal studies on the pathogenic effect of chronic infection focused on relatively avirulent strains (e.g. type II) because they can easily establish latent infections in mice, defined by the presence of bradyzoite-containing cysts. To provide insight into virulent strain-related severity of human toxoplasmosis, we established a chronic model of the virulent type I strain using outbred mice. We found that type I-exposed mice displayed variable outcomes ranging from aborted to severe infections. According to antibody profiles, we found that most of mice generated antibodies against T. gondii organism but varied greatly in the production of antibodies against matrix antigen MAG1. There was a strong correlation between MAG1 antibody level and brain cyst burden in chronically infected mice (r = 0.82, p = 0.0021). We found that mice with high MAG1 antibody level displayed lower weight, behavioral changes, altered levels of gene expression and immune activation. The most striking change in behavior we discovered was a blunted response to amphetamine-trigged locomotor activity. The extent of most changes was directly correlated with levels of MAG1 antibody. These changes were not found in mice with less cyst burden or mice that were acutely but not chronically infected. Our finding highlights the critical role of cyst burden in a range of disease severity during chronic infection, the predictive value of MAG1 antibody level to brain cyst burden and to changes in behavior or other pathology in chronically infected mice. Our finding may have important implications for understanding the heterogeneous effects of T. gondii infections in human. PMID:27124472

  1. Behavioral Abnormalities in a Mouse Model of Chronic Toxoplasmosis Are Associated with MAG1 Antibody Levels and Cyst Burden.

    PubMed

    Xiao, Jianchun; Li, Ye; Prandovszky, Emese; Kannan, Geetha; Viscidi, Raphael P; Pletnikov, Mikhail V; Yolken, Robert H

    2016-04-01

    There is marked variation in the human response to Toxoplasma gondii infection. Epidemiological studies indicate associations between strain virulence and severity of toxoplasmosis. Animal studies on the pathogenic effect of chronic infection focused on relatively avirulent strains (e.g. type II) because they can easily establish latent infections in mice, defined by the presence of bradyzoite-containing cysts. To provide insight into virulent strain-related severity of human toxoplasmosis, we established a chronic model of the virulent type I strain using outbred mice. We found that type I-exposed mice displayed variable outcomes ranging from aborted to severe infections. According to antibody profiles, we found that most of mice generated antibodies against T. gondii organism but varied greatly in the production of antibodies against matrix antigen MAG1. There was a strong correlation between MAG1 antibody level and brain cyst burden in chronically infected mice (r = 0.82, p = 0.0021). We found that mice with high MAG1 antibody level displayed lower weight, behavioral changes, altered levels of gene expression and immune activation. The most striking change in behavior we discovered was a blunted response to amphetamine-trigged locomotor activity. The extent of most changes was directly correlated with levels of MAG1 antibody. These changes were not found in mice with less cyst burden or mice that were acutely but not chronically infected. Our finding highlights the critical role of cyst burden in a range of disease severity during chronic infection, the predictive value of MAG1 antibody level to brain cyst burden and to changes in behavior or other pathology in chronically infected mice. Our finding may have important implications for understanding the heterogeneous effects of T. gondii infections in human. PMID:27124472

  2. Hierarchical representation and machine learning from faulty jet engine behavioral examples to detect real time abnormal conditions

    NASA Technical Reports Server (NTRS)

    Gupta, U. K.; Ali, M.

    1988-01-01

    The theoretical basis and operation of LEBEX, a machine-learning system for jet-engine performance monitoring, are described. The behavior of the engine is modeled in terms of four parameters (the rotational speeds of the high- and low-speed sections and the exhaust and combustion temperatures), and parameter variations indicating malfunction are transformed into structural representations involving instances and events. LEBEX extracts descriptors from a set of training data on normal and faulty engines, represents them hierarchically in a knowledge base, and uses them to diagnose and predict faults on a real-time basis. Diagrams of the system architecture and printouts of typical results are shown.

  3. Deletion in the N-terminal half of olfactomedin 1 modifies its interaction with synaptic proteins and causes brain dystrophy and abnormal behavior in mice.

    PubMed

    Nakaya, Naoki; Sultana, Afia; Munasinghe, Jeeva; Cheng, Aiwu; Mattson, Mark P; Tomarev, Stanislav I

    2013-12-01

    Olfactomedin 1 (Olfm1) is a secreted glycoprotein that is preferentially expressed in neuronal tissues. Here we show that deletion of exons 4 and 5 from the Olfm1 gene, which encodes a 52 amino acid long region in the N-terminal part of the protein, increased neonatal death and reduced body weight of surviving homozygous mice. Magnetic resonance imaging analyses revealed reduced brain volume and attenuated size of white matter tracts such as the anterior commissure, corpus callosum, and optic nerve. Adult Olfm1 mutant mice demonstrated abnormal behavior in several tests including reduced marble digging, elevated plus maze test, nesting activity and latency on balance beam tests as compared with their wild-type littermates. The olfactory system was both structurally and functionally disturbed by the mutation in the Olfm1 gene as shown by functional magnetic resonance imaging analysis and a smell test. Deficiencies of the olfactory system may contribute to the neonatal death and loss of body weight of Olfm1 mutant. Shotgun proteomics revealed 59 candidate proteins that co-precipitated with wild-type or mutant Olfm1 proteins in postnatal day 1 brain. Olfm1-binding targets included GluR2, Cav2.1, teneurin-4 and Kidins220. Modified interaction of Olfm1 with binding targets led to an increase in intracellular Ca(2+) concentration and activation of ERK1/2, MEK1 and CaMKII in the hippocampus and olfactory bulb of Olfm1 mutant mice compared with their wild-type littermates. Excessive activation of the CaMKII and Ras-ERK pathways in the Olfm1 mutant olfactory bulb and hippocampus by elevated intracellular calcium may contribute to the abnormal behavior and olfactory activity of Olfm1 mutant mice. PMID:24095980

  4. Deletion in the N-terminal Half of Olfactomedin 1 Modifies Its Interaction with Synaptic Proteins and Causes Brain Dystrophy and Abnormal Behavior in Mice

    PubMed Central

    Nakaya, Naoki; Sultana, Afia; Munasinghe, Jeeva; Cheng, Aiwu; Mattson, Mark P.; Tomarev, Stanislav I.

    2013-01-01

    Olfactomedin 1 (Olfm1) is a secreted glycoprotein that is preferentially expressed in neuronal tissues. Here we show that deletion of exons 4 and 5 from the Olfm1 gene, which encodes a 52 amino acid long region in the N-terminal part of the protein, increased neonatal death and reduced body weight of surviving homozygous mice. Magnetic resonance imaging analyses revealed reduced brain volume and attenuated size of white matter tracts such as the anterior commissure, corpus callosum, and optic nerve. Adult Olfm1 mutant mice demonstrated abnormal behavior in several tests including reduced marble digging, elevated plus maze test, nesting activity and latency on balance beam tests as compared with their wild-type littermates. The olfactory system was both structurally and functionally disturbed by the mutation in the Olfm1 gene as shown by functional magnetic resonance imaging analysis and a smell test. Deficiencies of the olfactory system may contribute to the neonatal death and loss of body weight of Olfm1 mutant. Shotgun proteomics revealed 59 candidate proteins that co-precipitated with wild-type or mutant Olfm1 proteins in postnatal day 1 brain. Olfm1-binding targets included GluR2, Cav2.1, Teneurin-4 and Kidins220. Modified interaction of Olfm1 with binding targets led to an increase in intracellular Ca2+ concentration and activation of ERK1/2, MEK1 and CaMKII in the hippocampus and olfactory bulb of Olfm1 mutant mice compared with their wild-type littermates. Excessive activation of the CaMKII and Ras-ERK pathways in the Olfm1 mutant olfactory bulb and hippocampus by elevated intracellular calcium may contribute to the abnormal behavior and olfactory activity of Olfm1 mutant mice. PMID:24095980

  5. Sleep and Sex: What Can Go Wrong? A Review of the Literature on Sleep Related Disorders and Abnormal Sexual Behaviors and Experiences

    PubMed Central

    Schenck, Carlos H.; Arnulf, Isabelle; Mahowald, Mark W.

    2007-01-01

    Study Objectives: To formulate the first classification of sleep related disorders and abnormal sexual behaviors and experiences. Design: A computerized literature search was conducted, and other sources, such as textbooks, were searched. Results: Many categories of sleep related disorders were represented in the classification: parasomnias (confusional arousals/sleepwalking, with or without obstructive sleep apnea; REM sleep behavior disorder); sleep related seizures; Kleine-Levin syndrome (KLS); severe chronic insomnia; restless legs syndrome; narcolepsy; sleep exacerbation of persistent sexual arousal syndrome; sleep related painful erections; sleep related dissociative disorders; nocturnal psychotic disorders; miscellaneous states. Kleine-Levin syndrome (78 cases) and parasomnias (31 cases) were most frequently reported. Parasomnias and sleep related seizures had overlapping and divergent clinical features. Thirty-one cases of parasomnias (25 males; mean age, 32 years) and 7 cases of sleep related seizures (4 males; mean age, 38 years) were identified. A full range of sleep related sexual behaviors with self and/or bed partners or others were reported, including masturbation, sexual vocalizations, fondling, sexual intercourse with climax, sexual assault/rape, ictal sexual hyperarousal, ictal orgasm, and ictal automatism. Adverse physical and/or psychosocial effects from the sleepsex were present in all parasomnia and sleep related seizure cases, but pleasurable effects were reported by 5 bed partners and by 3 patients with sleep related seizures. Forensic consequences were common, occurring in 35.5% (11/31) of parasomnia cases, with most (9/11) involving minors. All parasomnias cases reported amnesia for the sleepsex, in contrast to 28.6% (2/7) of sleep related seizure cases. Polysomnography (without penile tumescence monitoring), performed in 26 of 31 parasomnia cases, documented sexual moaning from slow wave sleep in 3 cases and sexual intercourse during

  6. Abnormal Osmotic Avoidance Behavior in C. elegans Is Associated with Increased Hypertonic Stress Resistance and Improved Proteostasis

    PubMed Central

    Lee, Elaine C.; Kim, Heejung; Ditano, Jennifer; Manion, Dacie; King, Benjamin L.; Strange, Kevin

    2016-01-01

    Protein function is controlled by the cellular proteostasis network. Proteostasis is energetically costly and those costs must be balanced with the energy needs of other physiological functions. Hypertonic stress causes widespread protein damage in C. elegans. Suppression and management of protein damage is essential for optimal survival under hypertonic conditions. ASH chemosensory neurons allow C. elegans to detect and avoid strongly hypertonic environments. We demonstrate that mutations in osm-9 and osm-12 that disrupt ASH mediated hypertonic avoidance behavior or genetic ablation of ASH neurons are associated with enhanced survival during hypertonic stress. Improved survival is not due to altered systemic volume homeostasis or organic osmolyte accumulation. Instead, we find that osm-9(ok1677) mutant and osm-9(RNAi) worms exhibit reductions in hypertonicity induced protein damage in non-neuronal cells suggesting that enhanced proteostasis capacity may account for improved hypertonic stress resistance in worms with defects in osmotic avoidance behavior. RNA-seq analysis revealed that genes that play roles in managing protein damage are upregulated in osm-9(ok1677) worms. Our findings are consistent with a growing body of work demonstrating that intercellular communication between neuronal and non-neuronal cells plays a critical role in integrating cellular stress resistance with other organismal physiological demands and associated energy costs. PMID:27111894

  7. Cardiac abnormalities in end stage renal failure and anaemia.

    PubMed Central

    Morris, K P; Skinner, J R; Wren, C; Hunter, S; Coulthard, M G

    1993-01-01

    Thirteen anaemic children on dialysis were assessed to determine the incidence of cardiac changes in end stage renal failure. Nine children had an increased cardiothoracic ratio on radiography. The electrocardiogram was abnormal in every case but no child had left ventricular hypertrophy as assessed by voltage criteria. However, left ventricular hypertrophy, often gross, was found on echocardiography in 12 children and affected the interventricular septum disproportionately. Cardiac index was increased in 10 patients as a result of an increased left ventricular stroke volume rather than heart rate. Left ventricular hypertrophy was significantly greater in those on treatment for hypertension and in those with the highest cardiac index. Abnormal diastolic ventricular function was found in 6/11 children. Children with end stage renal failure have significant cardiac abnormalities that are likely to contribute to the high cardiovascular mortality in this group. Anaemia and hypertension, or its treatment, probably contribute to these changes. Voltage criteria on electrocardiogram are of no value in detecting left ventricular hypertrophy. Echocardiography must be performed, with the results corrected for age and surface area, in order to detect and follow these abnormalities. Images PMID:8323332

  8. Abnormal Brain Iron Metabolism in Irp2 Deficient Mice Is Associated with Mild Neurological and Behavioral Impairments

    PubMed Central

    Zumbrennen-Bullough, Kimberly B.; Becker, Lore; Garrett, Lillian; Hölter, Sabine M.; Calzada-Wack, Julia; Mossbrugger, Ilona; Quintanilla-Fend, Leticia; Racz, Ildiko; Rathkolb, Birgit; Klopstock, Thomas; Wurst, Wolfgang; Zimmer, Andreas; Wolf, Eckhard; Fuchs, Helmut; Gailus-Durner, Valerie; de Angelis, Martin Hrabě; Romney, Steven J.; Leibold, Elizabeth A.

    2014-01-01

    Iron Regulatory Protein 2 (Irp2, Ireb2) is a central regulator of cellular iron homeostasis in vertebrates. Two global knockout mouse models have been generated to explore the role of Irp2 in regulating iron metabolism. While both mouse models show that loss of Irp2 results in microcytic anemia and altered body iron distribution, discrepant results have drawn into question the role of Irp2 in regulating brain iron metabolism. One model shows that aged Irp2 deficient mice develop adult-onset progressive neurodegeneration that is associated with axonal degeneration and loss of Purkinje cells in the central nervous system. These mice show iron deposition in white matter tracts and oligodendrocyte soma throughout the brain. A contrasting model of global Irp2 deficiency shows no overt or pathological signs of neurodegeneration or brain iron accumulation, and display only mild motor coordination and balance deficits when challenged by specific tests. Explanations for conflicting findings in the severity of the clinical phenotype, brain iron accumulation and neuronal degeneration remain unclear. Here, we describe an additional mouse model of global Irp2 deficiency. Our aged Irp2−/− mice show marked iron deposition in white matter and in oligodendrocytes while iron content is significantly reduced in neurons. Ferritin and transferrin receptor 1 (TfR1, Tfrc), expression are increased and decreased, respectively, in the brain from Irp2−/− mice. These mice show impairments in locomotion, exploration, motor coordination/balance and nociception when assessed by neurological and behavioral tests, but lack overt signs of neurodegenerative disease. Ultrastructural studies of specific brain regions show no evidence of neurodegeneration. Our data suggest that Irp2 deficiency dysregulates brain iron metabolism causing cellular dysfunction that ultimately leads to mild neurological, behavioral and nociceptive impairments. PMID:24896637

  9. Long-term recovery from hippocampal-related behavioral and biochemical abnormalities induced by noise exposure during brain development. Evaluation of auditory pathway integrity.

    PubMed

    Uran, S L; Gómez-Casati, M E; Guelman, L R

    2014-10-01

    Sound is an important part of man's contact with the environment and has served as critical means for survival throughout his evolution. As a result of exposure to noise, physiological functions such as those involving structures of the auditory and non-auditory systems might be damaged. We have previously reported that noise-exposed developing rats elicited hippocampal-related histological, biochemical and behavioral changes. However, no data about the time lapse of these changes were reported. Moreover, measurements of auditory pathway function were not performed in exposed animals. Therefore, with the present work, we aim to test the onset and the persistence of the different extra-auditory abnormalities observed in noise-exposed rats and to evaluate auditory pathway integrity. Male Wistar rats of 15 days were exposed to moderate noise levels (95-97 dB SPL, 2 h a day) during one day (acute noise exposure, ANE) or during 15 days (sub-acute noise exposure, SANE). Hippocampal biochemical determinations as well as short (ST) and long term (LT) behavioral assessments were performed. In addition, histological and functional evaluations of the auditory pathway were carried out in exposed animals. Our results show that hippocampal-related behavioral and biochemical changes (impairments in habituation, recognition and associative memories as well as distortion of anxiety-related behavior, decreases in reactive oxygen species (ROS) levels and increases in antioxidant enzymes activities) induced by noise exposure were almost completely restored by PND 90. In addition, auditory evaluation shows that increased cochlear thresholds observed in exposed rats were re-established at PND 90, although with a remarkable supra-threshold amplitude reduction. These data suggest that noise-induced hippocampal and auditory-related alterations are mostly transient and that the effects of noise on the hippocampus might be, at least in part, mediated by the damage on the auditory pathway

  10. Early Behavioral Abnormalities and Perinatal Alterations of PTEN/AKT Pathway in Valproic Acid Autism Model Mice

    PubMed Central

    Yang, Eun-Jeong; Ahn, Sangzin; Lee, Kihwan; Mahmood, Usman; Kim, Hye-Sun

    2016-01-01

    Exposure to valproic acid (VPA) during pregnancy has been linked with increased incidence of autism, and has repeatedly been demonstrated as a useful autism mouse model. We examined the early behavioral and anatomical changes as well as molecular changes in mice prenatally exposed to VPA (VPA mice). In this study, we first showed that VPA mice showed developmental delays as assessed with self-righting, eye opening tests and impaired social recognition. In addition, we provide the first evidence that primary cultured neurons from VPA-treated embryos present an increase in dendritic spines, compared with those from control mice. Mutations in phosphatase and tensin homolog (PTEN) gene are also known to be associated with autism, and mice with PTEN knockout show autistic characteristics. Protein expression of PTEN was decreased and the ratio of p-AKT/AKT was increased in the cerebral cortex and the hippocampus, and a distinctive anatomical change in the CA1 region of the hippocampus was observed. Taken together, our study suggests that prenatal exposure to VPA induces developmental delays and neuroanatomical changes via the reduction of PTEN level and these changes were detectable in the early days of life. PMID:27071011

  11. Transplantation of melanocytes obtained from the skin ameliorates apomorphine-induced abnormal behavior in rodent hemi-parkinsonian models.

    PubMed

    Asanuma, Masato; Miyazaki, Ikuko; Diaz-Corrales, Francisco J; Higashi, Youichirou; Namba, Masayoshi; Ogawa, Norio

    2013-01-01

    Tyrosinase, which catalyzes both the hydroxylation of tyrosine and consequent oxidation of L-DOPA to form melanin in melanocytes, is also expressed in the brain, and oxidizes L-DOPA and dopamine. Replacement of dopamine synthesis by tyrosinase was reported in tyrosine hydroxylase null mice. To examine the potential benefits of autograft cell transplantation for patients with Parkinson's disease, tyrosinase-producing cells including melanocytes, were transplanted into the striatum of hemi-parkinsonian model rats or mice lesioned with 6-hydroxydopamine. Marked improvement in apomorphine-induced rotation was noted at day 40 after intrastriatal melanoma cell transplantation. Transplantation of tyrosinase cDNA-transfected hepatoma cells, which constitutively produce L-DOPA, resulted in marked amelioration of the asymmetric apomorphine-induced rotation in hemi-parkinsonian mice and the effect was present up to 2 months. Moreover, parkinsonian mice transplanted with melanocytes from the back skin of black newborn mice, but not from albino mice, showed marked improvement in the apomorphine-induced rotation behavior up to 3 months after the transplantation. Dopamine-positive signals were seen around the surviving transplants in these experiments. Taken together with previous studies showing dopamine synthesis and metabolism by tyrosinase, these results highlight therapeutic potential of intrastriatal autograft cell transplantation of melanocytes in patients with Parkinson's disease. PMID:23776585

  12. Surface IgM expression and function are associated with clinical behavior, genetic abnormalities, and DNA methylation in CLL.

    PubMed

    D'Avola, Annalisa; Drennan, Samantha; Tracy, Ian; Henderson, Isla; Chiecchio, Laura; Larrayoz, Marta; Rose-Zerilli, Matthew; Strefford, Jonathan; Plass, Christoph; Johnson, Peter W; Steele, Andrew J; Packham, Graham; Stevenson, Freda K; Oakes, Christopher C; Forconi, Francesco

    2016-08-11

    Chronic lymphocytic leukemia (CLL) with unmutated (U-CLL) or mutated (M-CLL) immunoglobulin gene heavy-chain variable region (IGHV) displays different states of anergy, indicated by reduced surface immunoglobulin M (sIgM) levels and signaling, consequent to chronic (super)antigen exposure. The subsets also differ in the incidence of high-risk genetic aberrations and in DNA methylation profile, preserved from the maturational status of the original cell. We focused on sIgM expression and function, measured as intracellular Ca(2+) mobilization following stimulation, and probed correlations with clinical outcome. The relationship with genetic features and maturation status defined by DNA methylation of an 18-gene panel signature was then investigated. sIgM levels/signaling were higher and less variable in U-CLL than in M-CLL and correlated with disease progression between and within U-CLL and M-CLL. In U-CLL, increased levels/signaling associated with +12, del(17p) or NOTCH1 mutations. In M-CLL, there were fewer genetic lesions, although the methylation maturation status, generally higher than in U-CLL, varied and was increased in cases with lower sIgM levels/signaling. These features revealed heterogeneity in M-CLL and U-CLL with clear clinical correlations. Multivariate analyses with phenotype, genetic lesions, or DNA methylation maturation status identified high sIgM levels as a new potential independent factor for disease progression. Multiple influences on sIgM include the cell of origin, the clonal history of antigen encounter in vivo, and genetic damage. This simple marker compiles these different factors into an indicator worthy of further investigations for prediction of clinical behavior, particularly within the heterogeneous M-CLL subset. PMID:27301861

  13. The duplication 17p13.3 phenotype: analysis of 21 families delineates developmental, behavioral and brain abnormalities, and rare variant phenotypes.

    PubMed

    Curry, Cynthia J; Rosenfeld, Jill A; Grant, Erica; Gripp, Karen W; Anderson, Carol; Aylsworth, Arthur S; Saad, Taha Ben; Chizhikov, Victor V; Dybose, Giedre; Fagerberg, Christina; Falco, Michelle; Fels, Christina; Fichera, Marco; Graakjaer, Jesper; Greco, Donatella; Hair, Jennifer; Hopkins, Elizabeth; Huggins, Marlene; Ladda, Roger; Li, Chumei; Moeschler, John; Nowaczyk, Malgorzata J M; Ozmore, Jillian R; Reitano, Santina; Romano, Corrado; Roos, Laura; Schnur, Rhonda E; Sell, Susan; Suwannarat, Pim; Svaneby, Dea; Szybowska, Marta; Tarnopolsky, Mark; Tervo, Raymond; Tsai, Anne Chun-Hui; Tucker, Megan; Vallee, Stephanie; Wheeler, Ferrin C; Zand, Dina J; Barkovich, A James; Aradhya, Swaroop; Shaffer, Lisa G; Dobyns, William B

    2013-08-01

    Chromosome 17p13.3 is a gene rich region that when deleted is associated with the well-known Miller-Dieker syndrome. A recently described duplication syndrome involving this region has been associated with intellectual impairment, autism and occasional brain MRI abnormalities. We report 34 additional patients from 21 families to further delineate the clinical, neurological, behavioral, and brain imaging findings. We found a highly diverse phenotype with inter- and intrafamilial variability, especially in cognitive development. The most specific phenotype occurred in individuals with large duplications that include both the YWHAE and LIS1 genes. These patients had a relatively distinct facial phenotype and frequent structural brain abnormalities involving the corpus callosum, cerebellar vermis, and cranial base. Autism spectrum disorders were seen in a third of duplication probands, most commonly in those with duplications of YWHAE and flanking genes such as CRK. The typical neurobehavioral phenotype was usually seen in those with the larger duplications. We did not confirm the association of early overgrowth with involvement of YWHAE and CRK, or growth failure with duplications of LIS1. Older patients were often overweight. Three variant phenotypes included cleft lip/palate (CLP), split hand/foot with long bone deficiency (SHFLD), and a connective tissue phenotype resembling Marfan syndrome. The duplications in patients with clefts appear to disrupt ABR, while the SHFLD phenotype was associated with duplication of BHLHA9 as noted in two recent reports. The connective tissue phenotype did not have a convincing critical region. Our experience with this large cohort expands knowledge of this diverse duplication syndrome. PMID:23813913

  14. Effects of carvedilol on left ventricular function, mass, and scintigraphic findings in isolated left ventricular non-compaction

    PubMed Central

    Toyono, M; Kondo, C; Nakajima, Y; Nakazawa, M; Momma, K; Kusakabe, K

    2001-01-01

    A four month old infant with isolated left ventricular non-compaction was treated with carvedilol. Haemodynamic studies and various types of imaging—including echocardiography, radiographic angiography, magnetic resonance imaging, and single photon emission computed tomography with 201Tl, 123I-β-methyliodophenylpentadecanoic acid (BMIPP), and 123I-metaiodobenzylguanidine (MIBG)—were performed before and 14 months after treatment. Left ventricular ejection fraction increased from 30% to 57%, and left ventricular end diastolic volume, end systolic volume, and end diastolic pressure showed striking reductions during treatment. Left ventricular mass decreased to about two thirds of the baseline value after treatment. Per cent wall thickening increased after carvedilol in the segments corresponding to non-compacted myocardium. A mismatch between 201Tl and BMIPP uptake in the area of non-compaction observed before carvedilol disappeared after treatment. Impaired sympathetic neuronal function shown by MIBG recovered after treatment. Thus carvedilol had beneficial effects on left ventricular function, hypertrophy, and both metabolic and adrenergic abnormalities in isolated left ventricular non-compaction.


Keywords: isolated left ventricular non-compaction; carvedilol; cardiac sympathetic nerve; ventricular remodelling PMID:11410581

  15. Lack of parvalbumin in mice leads to behavioral deficits relevant to all human autism core symptoms and related neural morphofunctional abnormalities

    PubMed Central

    Wöhr, M; Orduz, D; Gregory, P; Moreno, H; Khan, U; Vörckel, K J; Wolfer, D P; Welzl, H; Gall, D; Schiffmann, S N; Schwaller, B

    2015-01-01

    Gene mutations and gene copy number variants are associated with autism spectrum disorders (ASDs). Affected gene products are often part of signaling networks implicated in synapse formation and/or function leading to alterations in the excitation/inhibition (E/I) balance. Although the network of parvalbumin (PV)-expressing interneurons has gained particular attention in ASD, little is known on PV's putative role with respect to ASD. Genetic mouse models represent powerful translational tools for studying the role of genetic and neurobiological factors underlying ASD. Here, we report that PV knockout mice (PV−/−) display behavioral phenotypes with relevance to all three core symptoms present in human ASD patients: abnormal reciprocal social interactions, impairments in communication and repetitive and stereotyped patterns of behavior. PV-depleted mice also showed several signs of ASD-associated comorbidities, such as reduced pain sensitivity and startle responses yet increased seizure susceptibility, whereas no evidence for behavioral phenotypes with relevance to anxiety, depression and schizophrenia was obtained. Reduced social interactions and communication were also observed in heterozygous (PV+/−) mice characterized by lower PV expression levels, indicating that merely a decrease in PV levels might be sufficient to elicit core ASD-like deficits. Structural magnetic resonance imaging measurements in PV−/− and PV+/− mice further revealed ASD-associated developmental neuroanatomical changes, including transient cortical hypertrophy and cerebellar hypoplasia. Electrophysiological experiments finally demonstrated that the E/I balance in these mice is altered by modification of both inhibitory and excitatory synaptic transmission. On the basis of the reported changes in PV expression patterns in several, mostly genetic rodent models of ASD, we propose that in these models downregulation of PV might represent one of the points of convergence, thus

  16. Lack of parvalbumin in mice leads to behavioral deficits relevant to all human autism core symptoms and related neural morphofunctional abnormalities.

    PubMed

    Wöhr, M; Orduz, D; Gregory, P; Moreno, H; Khan, U; Vörckel, K J; Wolfer, D P; Welzl, H; Gall, D; Schiffmann, S N; Schwaller, B

    2015-01-01

    Gene mutations and gene copy number variants are associated with autism spectrum disorders (ASDs). Affected gene products are often part of signaling networks implicated in synapse formation and/or function leading to alterations in the excitation/inhibition (E/I) balance. Although the network of parvalbumin (PV)-expressing interneurons has gained particular attention in ASD, little is known on PV's putative role with respect to ASD. Genetic mouse models represent powerful translational tools for studying the role of genetic and neurobiological factors underlying ASD. Here, we report that PV knockout mice (PV(-/-)) display behavioral phenotypes with relevance to all three core symptoms present in human ASD patients: abnormal reciprocal social interactions, impairments in communication and repetitive and stereotyped patterns of behavior. PV-depleted mice also showed several signs of ASD-associated comorbidities, such as reduced pain sensitivity and startle responses yet increased seizure susceptibility, whereas no evidence for behavioral phenotypes with relevance to anxiety, depression and schizophrenia was obtained. Reduced social interactions and communication were also observed in heterozygous (PV(+/-)) mice characterized by lower PV expression levels, indicating that merely a decrease in PV levels might be sufficient to elicit core ASD-like deficits. Structural magnetic resonance imaging measurements in PV(-/-) and PV(+/-) mice further revealed ASD-associated developmental neuroanatomical changes, including transient cortical hypertrophy and cerebellar hypoplasia. Electrophysiological experiments finally demonstrated that the E/I balance in these mice is altered by modification of both inhibitory and excitatory synaptic transmission. On the basis of the reported changes in PV expression patterns in several, mostly genetic rodent models of ASD, we propose that in these models downregulation of PV might represent one of the points of convergence, thus providing a

  17. [Treatment of ventricular tachycardia].

    PubMed

    Iturralde Torres, P

    2001-01-01

    Evaluation and management of postinfarct ventricular tachycardia has changed dramatically in the past two decades. The introduction of the implantable cardioverter defibrillator has played a major role in this change, alternating both, the purpose of the patients evaluation and treatment options. Episodes of sustained ventricular tachycardia can occur in a variety of clinical settings; the most common of which is the patient who has suffered a myocardial infarction. In this paper, I explore the causes and effects of some of these changes and review current strategies, specially the radiofrequency catheter ablation, for the management of the patient with postinfarct ventricular tachycardia. PMID:11565352

  18. Attentive, Affective, and Adaptive Behavior in the Cat: Sensory deprivation of the forebrain by lesions in the brain stem results in striking behavioral abnormalities.

    PubMed

    Sprague, J M; Chambers, W W; Stellar, E

    1961-01-20

    Lesions of the lateral portion of the upper midbrain, involving medial, lateral, spinal, and trigeminal lemnisci primarily, result in a consistent syndrome of symptoms in the cat. (i) There is a marked sensory deficit, characterized mainly by sensory inattention and poor localization in the tactile, proprioceptive, auditory, gustatory, and nociceptive modalities, where direct pathways are interrupted. Similar defectsappear in vision and olfaction where no known direct or primary paths are interrupted. (ii) These cats are characterized by a lack of affect, showing little or no defensive and aggressive reaction to noxious and aversive situations and no response to pleasurable stimulation or solicitation of affection or petting. The animals are mute, lack facial expression, and show minimal autonomic responses. (iii) They show a hyperexploratory activity characterized by incessant, stereotyped wandering, sniffing, and visual searching, as though hallucinating. This behavior appears to be centrally directed and is very difficult to interrupt with environmental stimuli. (iv) They also demonstrate exaggerated oral activities: they snap in response to tactile stimulation of the lips, seizing and swallowing small objects even if inedible; they overeat; they hold objects too large to swallow (a mouse, a catnip ball) firmly clamped in the mouth for long periods of time; they mount and seize other animals (rat, cat, dog, monkey) by the back or the neck; they lick and chew the hair and skin of the back or tail incessantly when confined in a cage. In interpreting these results we emphasize the view that the syndrome is due chiefly to the extensive, specific, sensory deprivation produced by interruption of the lemnisci at the rostral midbrain. The relation of these findings to the effects of sensory isolation in man and animals, to the effects of midbrain lesions and neodecortication, to parietal lobe syndrome in primates, and to the behavior of autistic children is discussed

  19. Arrhythmogenic right ventricular cardiomyopathy, clinical manifestations, and diagnosis.

    PubMed

    Haugaa, Kristina H; Haland, Trine F; Leren, Ida S; Saberniak, Jørg; Edvardsen, Thor

    2016-07-01

    This review aims to give an update on the pathogenesis, clinical manifestations, and diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC). Arrhythmogenic right ventricular cardiomyopathy is mainly an autosomal dominant inherited disease linked to mutations in genes encoding desmosomes or desmosome-related proteins. Classic symptoms include palpitations, cardiac syncope, and aborted cardiac arrest due to ventricular arrhythmias. Heart failure may develop in later stages. Diagnosis is based on the presence of major and minor criteria from the Task Force Criteria revised in 2010 (TFC 2010), which includes evaluation of findings from six different diagnostic categories. Based on this, patients are classified as having possible, borderline, or definite ARVC. Imaging is important in ARVC diagnosis, including both echocardiography and cardiac magnetic resonance imaging for detecting structural and functional abnormalities, but importantly these findings may occur after electrical alterations and ventricular arrhythmias. Electrocardiograms (ECGs) and signal-averaged ECGs are analysed for depolarization and repolarization abnormalities, including T-wave inversions as the most common ECG alteration. Ventricular arrhythmias are common in ARVC and are considered a major diagnostic criterion if originating from the RV inferior wall or apex. Family history of ARVC and detection of an ARVC-related mutation are included in the TFC 2010 and emphasize the importance of family screening. Electrophysiological studies are not included in the diagnostic criteria, but may be important for differential diagnosis including RV outflow tract tachycardia. Further differential diagnoses include sarcoidosis, congenital abnormalities, myocarditis, pulmonary hypertension, dilated cardiomyopathy, and athletic cardiac adaptation, which may mimic ARVC. PMID:26498164

  20. Left ventricular restoration devices.

    PubMed

    Oliveira, Guilherme H; Al-Kindi, Sadeer G; Bezerra, Hiram G; Costa, Marco A

    2014-04-01

    Left ventricular (LV) remodeling results in continuous cardiac chamber enlargement and contractile dysfunction, perpetuating the syndrome of heart failure. With current exhaustion of the neurohormonal medical paradigm, surgical and device-based therapies have been increasingly investigated as a way to restore LV chamber architecture and function. Left ventricular restoration has been attempted with surgical procedures, such as partial left ventriculectomy, surgical ventricular restoration with or without revascularization, and devices, such as the Acorn CorCap, the Paracor HeartNet, and the Myocor Myosplint. Whereas all these techniques require surgical access, with or without cardiopulmonary bypass, a newer ventricular partitioning device (VPD) called Parachute, can be delivered percutaneously through the aortic valve. Designed to achieve LV restoration from within the ventricle, this VPD partitions the LV by isolating aneurysmal from normal myocardium thereby diminishing the functioning cavity. This review aims to critically appraise the above methods, with particular attention to device-based therapies. PMID:24574107

  1. Cardiac ventricular aneurysm

    PubMed Central

    Harley, Hugh R. S.

    1969-01-01

    A case of successful excision of a ventricular aneurysm due to myocardial infarction is presented. The aetiology, incidence, pathogenesis, pathology, clinical features, and diagnosis of the condition are discussed. An account is given of the haemodynamic upset caused by aneurysms of the ventricle. The prognosis of untreated aneurysms is discussed. Although there is difference of opinion, it is concluded that a ventricular aneurysm adversely affects the prognosis after myocardial infarction. The indications for, and the mortality and results of, resection of ventricular aneurysms are discussed. The conclusion is drawn that persistent cardiac failure and angina can be relieved and the risk of systemic embolism reduced by the excision of expansile ventricular aneurysms of a fibrous nature. It is possible that excision may also reduce the incidence of subsequent acute myocardial infarction. Images PMID:5821618

  2. 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.

  3. Mapping of Regional Myocardial Strain and Work During Ventricular Pacing

    PubMed Central

    Prinzen, Frits W.; Hunter, William C.; Wyman, Bradley T.; McVeigh, Elliot R.

    2007-01-01

    OBJECTIVES The purpose of this study was to determine the spatial distribution of myocardial function (myofiber shortening and work) within the left ventricular (LV) wall during ventricular pacing. BACKGROUND Asynchronous electrical activation, as induced by ventricular pacing, causes various abnormalities in LV function, perfusion and structure. These derangements may be caused by abnormalities in regional contraction patterns. However, insight into these patterns during pacing is as yet limited. METHODS In seven anesthetized dogs, high spatial and temporal resolution magnetic resonance-tagged images were acquired in three orthogonal planes. Three-dimensional deformation data and LV cavity pressure and volume were used to determine midwall circumferential strain and external and total mechanical work at 192 sites around the left ventricle. RESULTS During ventricular pacing, systolic fiber strain and external work were approximately zero in regions near the pacing site, and gradually increased to more than twice the normal value in the most remote regions. Total mechanical work, normalized to the value during right atrial pacing, was 38 ± 13% (right ventricular apex [RVapex] pacing) and 61 ± 23% (left ventricular base [LVbase] pacing) close to the pacing site, and 125 ± 48% and 171 ± 60% in remote regions, respectively (p < 0.05 between RVapex and LVbase pacing). The number of regions with reduced work was significantly larger during RVapex than during LVbase pacing. This was associated with a reduction of global LV pump function during RVapex pacing. CONCLUSIONS Ventricular pacing causes a threefold difference in myofiber work within the LV wall. This difference appears large enough to regard local myocardial function as an important determinant for abnormalities in perfusion, metabolism, structure and pump function during asynchronous electrical activation. Pacing at sites that cause more synchronous activation may limit the occurrence of such derangements

  4. [First degree atrio-ventricular block in acute thyrotoxicosis].

    PubMed

    Vilches, Antonio R; Lerman, Jorge

    2004-01-01

    Thyrotoxicosis may present with a variety of cardiovascular symptoms. Sinus tachycardia is the most frequently encountered electrocardiographic abnormality and conduction disturbances are extremely uncommon. We present a case of first degree atrio-ventricular block in a patient with newly diagnosed hyperthyroidism and discuss the underlying pathophysiological mechanisms and the clinical implications from the internist's standpoint. PMID:15034958

  5. Arrhythmogenic right ventricular cardiomyopathy: contribution of different electrocardiographic techniques.

    PubMed

    Moreira, Davide; Delgado, Anne; Marmelo, Bruno; Correia, Emanuel; Gama, Pedro; Pipa, João; Nunes, Luís; Santos, Oliveira

    2014-04-01

    Arrhythmogenic right ventricular cardiomyopathy, also known as arrhythmogenic right ventricular dysplasia, is a condition in which myocardium is replaced by fibrous or fibrofatty tissue, predominantly in the right ventricle. It is clinically characterized by potentially lethal ventricular arrhythmias, and is a leading cause of sudden cardiac death. Its prevalence is not known exactly but is estimated at approximately 1:5000 in the adult population. Diagnosis can be on the basis of structural and functional alterations of the right ventricle, electrocardiographic abnormalities (including depolarization and repolarization alterations and ventricular arrhythmias) and family history. Diagnostic criteria facilitate the recognition and interpretation of non-specific clinical features of this disease. The authors present a case in which the diagnosis of arrhythmogenic right ventricular cardiomyopathy was prompted by the suspicion of right ventricular disease on transthoracic echocardiography. This was confirmed by detection of epsilon waves on analysis of the ECG, which generally go unnoticed but in this case were the key to the diagnosis. Their presence was also shown by non-conventional ECG techniques such as modified Fontaine ECG. The course of the disease culminated in the occurrence of ventricular tachycardia, which prompted placement of an implantable cardioverter-defibrillator. PMID:24780127

  6. Echocardiographic evaluation of systolic left-ventricular function in infants with critical aortic stenosis before and after aortic valvotomy.

    PubMed

    Hofstetter, R; Zeike, B; Messmer, B J; von Bernuth, G

    1990-08-01

    Infants with critical aortic stenosis may have global or regional left ventricular contraction abnormalities. In order to evaluate the clinical significance of these contraction abnormalities, we examined the systolic left ventricular function before and after aortic valvotomy in 16 infants operated on between 1980 and 1987. Left ventricular free wall and septal motion were studied by cross sectional echocardiography using the apical 4-chamber view. Enddiastolic and endsystolic left ventricular frames were digitized. The relative systolic reduction of the total left ventricular area (reflecting ejection fraction) as well as of 5 left ventricular sectors (reflecting regional wall motion) was calculated and compared to previously established normal values. Before valvotomy, 8 infants had normal and the other 8 impaired left ventricular systolic wall motion. These latter infants showed hypokinesia of the apex and/or the posterolateral left ventricular wall resulting in a decreased systolic reduction of the total left ventricular area. Four of these infants had evidence of myocardial infarction on intraoperative inspection. Early after operation, the systolic reduction of the total left ventricular area was normal in all infants, and the left ventricular apex and poster-lateral wall were either normo- or hyperkinetic. Follow-up studies of all infants more than 10 months and of 7 infants more than 3 years after operation showed that the left ventricular systolic wall motion remained normal in all, irrespective of whether it was normal or abnormal preoperatively. This study suggests that left ventricular contraction abnormalities in infants with critical aortic stenosis may be reversible and thus do not constitute a contraindication against aortic valvotomy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2237884

  7. Detection of Structural Abnormalities Using Neural Nets

    NASA Technical Reports Server (NTRS)

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

    1996-01-01

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

  8. Left ventricular function in chronic aortic regurgitation

    SciTech Connect

    Iskandrian, A.S.; Hakki, A.H.; Manno, B.; Amenta, A.; Kane, S.A.

    1983-06-01

    Left ventricular performance was determined in 42 patients with moderate or severe aortic regurgitation during upright exercise by measuring left ventricular ejection fraction and volume with radionuclide ventriculography. Classification of the patients according to exercise tolerance showed that patients with normal exercise tolerance (greater than or equal to 7.0 minutes) had a significantly higher ejection fraction at rest (probability (p) . 0.02) and during exercise (p . 0.0002), higher cardiac index at exercise (p . 0.0008) and lower exercise end-systolic volume (p . 0.01) than did patients with limited exercise tolerance. Similar significant differences were noted in younger patients compared with older patients in ejection fraction at rest and exercise (both p . 0.001) and cardiac index at rest (p . 0.03) and exercise (p . 0.0005). The end-diastolic volume decreased during exercise in 60% of the patients. The patients with a decrease in volume were significantly younger and had better exercise tolerance and a larger end-diastolic volume at rest than did patients who showed an increase in volume. The mean corrected left ventricular end-diastolic radius/wall thickness ratio was significantly greater in patients with abnormal than in those with normal exercise reserve (mean +/- standard deviation 476 +/- 146 versus 377 +/- 92 mm Hg, p less than 0.05). Thus, in patients with chronic aortic regurgitation: 1) left ventricular systolic function during exercise was related to age, exercise tolerance and corrected left ventricular end-diastolic radius/wall thickness ratio, and 2) the end-diastolic volume decreased during exercise, especially in younger patients and patients with normal exercise tolerance or a large volume at rest.

  9. Alterations in local thyroid hormone signaling in the hippocampus of the SAMP8 mouse at younger ages: association with delayed myelination and behavioral abnormalities.

    PubMed

    Sawano, Erika; Negishi, Takayuki; Aoki, Tomoyuki; Murakami, Masami; Tashiro, Tomoko

    2013-03-01

    The senescence-accelerated mouse (SAM) strains were established through selective inbreeding of the AKR/J strain based on phenotypic variations of aging and consist of senescence-prone (SAMP) and senescence-resistant (SAMR) strains. Among them, SAMP8 is considered as a model of neurodegeneration displaying age-associated learning and memory impairment and altered emotional status. Because adult hypothyroidism is one of the common causes of cognitive impairment and various psychiatric disorders, we examined the possible involvement of thyroid hormone (TH) signaling in the pathological aging of SAMP8 using the senescence-resistant SAMR1 as control. Although plasma TH levels were similar in both strains, a significant decrease in type 2 deiodinase (D2) gene expression was observed in the SAMP8 hippocampus from 1 to 8 months of age, which led to a 35-50% reductions at the protein level and 20% reduction of its enzyme activity at 1, 3, and 5 months. D2 is responsible for local conversion of thyroxine into transcriptionally active 3,5,3'-triiodothyronine (T3), so the results suggest a reduction in T3 level in the SAMP8 hippocampus. Attenuation of local TH signaling was confirmed by downregulation of TH-dependent genes and by immunohistochemical demonstration of delayed and reduced accumulation of myelin basic protein, the expression of which is highly dependent on TH. Furthermore, we found that hyperactivity and reduced anxiety were not age-associated but were characteristic of young SAMP8 before they start showing impairments in learning and memory. Early alterations in local TH signaling may thus underlie behavioral abnormalities as well as the pathological aging of SAMP8. PMID:23224839

  10. Noncompaction of the Ventricular Myocardium and Polycystic Kidney Disease: A Case Report.

    PubMed

    Fukino, Keiko; Ishiwata, Junpei; Shinohara, Hiroki; Oshima, Tsukasa; Kozaki, Tsunashi; Ikutomi, Masayasu; Amaki, Toshihiro; Nakamura, Fumitaka

    2016-06-01

    Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common hereditary disorders, characterized by the formation of multiple cysts in the kidneys and other organs, as well as noncystic manifestations such as cerebral aneurysm. The most common cardiovascular disorders associated with ADPKD include valvular abnormalities and aortic aneurysm. An association between ADPKD and impaired left ventricular function has occasionally been reported. We describe a 74-year-old woman with ADPKD and exertional dyspnea. Impaired left ventricular function resulting from noncompaction of the ventricular myocardium (NVM) and secondary left ventricular aneurysm were diagnosed. Cardiac sarcoidosis and ischemic heart disease were ruled out. Myocardial ischemia resulting from NVM was the presumptive cause of the ventricular aneurysm. To our knowledge, this is the first report of concurrent isolated NVM and left ventricular aneurysm in a patient with ADPKD. ADPKD and various cardiomyopathies, including NVM, are all reported to involve mutations of sarcomere genes, suggesting a possible link between the conditions. PMID:26873255

  11. Echocardiographic features of impaired left ventricular diastolic function in Chagas's heart disease.

    PubMed Central

    Combellas, I; Puigbo, J J; Acquatella, H; Tortoledo, F; Gomez, J R

    1985-01-01

    To study left ventricular diastolic function in Chagas's disease, simultaneous echocardiograms, phonocardiograms, and apexcardiograms were recorded in 20 asymptomatic patients with positive Chagas's serology and no signs of heart disease (group 1), 12 with Chagas's heart disease and symptoms of ventricular arrhythmia but no heart failure (group 2), 20 normal subjects (group 3), and 12 patients with left ventricular hypertrophy (group 4). The recordings were digitised to determine left ventricular isovolumic relaxation time and the rate and duration of left ventricular cavity dimension increase and wall thinning. In groups 1 and 2 (a) aortic valve closure (A2) and mitral valve opening were significantly delayed relative to minimum dimension and were associated with prolonged isovolumic relaxation, (b) left ventricular cavity size was abnormally increased during isovolumic relaxation and abnormally reduced during isovolumic contraction, and (c) peak rate of posterior wall thinning and dimension increase were significantly reduced and duration of posterior wall thinning was significantly prolonged; both of these abnormalities occurred at the onset of diastolic filling. These abnormalities were more pronounced in group 2 and were accompanied by an increase in the height of the apexcardiogram "a" wave, an indication of pronounced atrial systole secondary to end diastolic filling impairment due to reduced left ventricular distensibility. Group 4, which had an established pattern of diastolic abnormalities, showed changes similar to those in group 2; however, the delay in aortic valve closure (A2) and in mitral valve opening and the degree of dimension change were greater in the latter group. Thus early isovolumic relaxation and left ventricular abnormalities were pronounced in the patients with Chagas's heart disease and may precede systolic compromise, which may become apparent in later stages of the disease. The digitised method is valuable in the early detection of

  12. Electrocardiographic abnormalities and cardiac arrhythmias in chronic obstructive pulmonary disease.

    PubMed

    Goudis, Christos A; Konstantinidis, Athanasios K; Ntalas, Ioannis V; Korantzopoulos, Panagiotis

    2015-11-15

    Chronic obstructive pulmonary disease (COPD) is independently associated with an increased burden of cardiovascular disease. Besides coronary artery disease (CAD) and congestive heart failure (CHF), specific electrocardiographic (ECG) abnormalities and cardiac arrhythmias seem to have a significant impact on cardiovascular prognosis of COPD patients. Disturbances of heart rhythm include premature atrial contractions (PACs), premature ventricular contractions (PVCs), atrial fibrillation (AF), atrial flutter (AFL), multifocal atrial tachycardia (MAT), and ventricular tachycardia (VT). Of note, the identification of ECG abnormalities and the evaluation of the arrhythmic risk may have significant implications in the management and outcome of patients with COPD. This article provides a concise overview of the available data regarding ECG abnormalities and arrhythmias in these patients, including an elaborated description of the underlying arrhythmogenic mechanisms. The clinical impact and prognostic significance of ECG abnormalities and arrhythmias in COPD as well as the appropriate antiarrhythmic therapy and interventions in this setting are also discussed. PMID:26218181

  13. Mild carbon monoxide poisoning impairs left ventricular diastolic function

    PubMed Central

    Çiftçi, Özgür; Günday, Murat; Çalışkan, Mustafa; Güllü, Hakan; Doğan, Rafi; Güven, Aytekin; Müderrisoğlu, Haldun

    2013-01-01

    Rationale: Carbon monoxide (CO) poisoning is associated with direct cardiovascular toxicity. In mild CO poisoning in which cardiovascular life support is not required, the effects of CO on left and right ventricular functions are unknown in patients without cardiac failure. Objectives: Echocardiography was used to determine whether or not mild CO poisoning impairs ventricular function. Twenty otherwise healthy patients with CO poisoning and 20 age- and gender-matched controls were studied. Echocardiographic examinations were performed at the time of admission and 1 week after poisoning. Results: The impairment observed in the left and right ventricular diastolic function at the time of admission was greater than the impairment 1 week after poisoning. Mild CO poisoning did not have a significant effect on systolic function. Carboxyhemoglobin levels were positively correlated with left ventricular diastolic dysfunction, whereas the levels were not correlated with right ventricular diastolic function. Conclusions: In CO intoxication, the development of left and right ventricular diastolic dysfunction precedes systolic abnormality. Patients with mild CO poisoning do not manifest cardiovascular symptoms; however, it should be borne in mind that most of these patients have myocardial involvement. PMID:24082611

  14. Ablation of Ventricular Tachycardia in Patients with Ischemic Cardiomyopathy.

    PubMed

    Garabelli, Paul; Stavrakis, Stavros; Po, Sunny S

    2016-03-01

    Ventricular tachycardias (VTs) occurring after prior myocardial infarction are usually caused by reentrant circuits formed by surviving myocardial bundles. Although part of the reentrant circuits may be located in the midmyocardium or epicardium, most of the VTs can be safely and successfully ablated by endocardial ablation targeting the late potentials/local abnormal ventricular activation, which are surrogates for the surviving myocardial bundles. A combination of activation, substrate, pace, and entrainment mapping, as well as the use of contact force catheters, further improves ablation success and safety. PMID:26920180

  15. Daily oral intake of theanine prevents the decline of 5-bromo-2'-deoxyuridine incorporation in hippocampal dentate gyrus with concomitant alleviation of behavioral abnormalities in adult mice with severe traumatic stress.

    PubMed

    Takarada, Takeshi; Nakamichi, Noritaka; Kakuda, Takami; Nakazato, Ryota; Kokubo, Hiroshi; Ikeno, Shinsuke; Nakamura, Saki; Hinoi, Eiichi; Yoneda, Yukio

    2015-03-01

    Posttraumatic stress disorder is a long-lasting psychiatric disease with the consequence of hippocampal atrophy in humans exposed to severe fatal stress. We demonstrated a positive correlation between the transient decline of 5-bromo-2'-deoxyuridine (BrdU) incorporation in the hippocampal dentate gyrus (DG) and long-lasting behavioral abnormalities in mice with traumatic stress. Here, we investigated pharmacological properties of theanine on the declined BrdU incorporation and abnormal behaviors in mice with traumatic stress. Prior daily oral administration of theanine at 50-500 mg/kg for 5 days significantly prevented the decline of BrdU incorporation, while theanine significantly prevented the decline in the DG even when administered for 5 days after stress. Consecutive daily administration of theanine significantly inhibited the prolonged immobility in mice with stress in forced swimming test seen 14 days later. Although traumatic stress significantly increased spontaneous locomotor activity over 30 min even when determined 14 days later, the increased total locomotion was significantly ameliorated following the administration of theanine at 50 mg/kg for 14 days after stress. These results suggest that theanine alleviates behavioral abnormalities together with prevention of the transient decline of BrdU incorporation in the hippocampal DG in adult mice with severe traumatic stress. PMID:25837925

  16. X-linked Christianson syndrome: heterozygous female Slc9a6 knockout mice develop mosaic neuropathological changes and related behavioral abnormalities.

    PubMed

    Sikora, Jakub; Leddy, Jennifer; Gulinello, Maria; Walkley, Steven U

    2016-01-01

    Christianson syndrome (CS) is an X-linked neurodevelopmental and neurological disorder characterized in males by core symptoms that include non-verbal status, intellectual disability, epilepsy, truncal ataxia, postnatal microcephaly and hyperkinesis. CS is caused by mutations in the SLC9A6 gene, which encodes a multipass transmembrane sodium (potassium)-hydrogen exchanger 6 (NHE6) protein, functional in early recycling endosomes. The extent and variability of the CS phenotype in female heterozygotes, who presumably express the wild-type and mutant SLC9A6 alleles mosaically as a result of X-chromosome inactivation (XCI), have not yet been systematically characterized. Slc9a6 knockout mice (Slc9a6 KO) were generated by insertion of the bacterial lacZ/β-galactosidase (β-Gal) reporter into exon 6 of the X-linked gene. Mutant Slc9a6 KO male mice have been shown to develop late endosomal/lysosomal dysfunction associated with glycolipid accumulation in selected neuronal populations and patterned degeneration of Purkinje cells (PCs). In heterozygous female Slc9a6 KO mice, β-Gal serves as a transcriptional/XCI reporter and thus facilitates testing of effects of mosaic expression of the mutant allele on penetrance of the abnormal phenotype. Using β-Gal, we demonstrated mosaic expression of the mutant Slc9a6 allele and mosaically distributed lysosomal glycolipid accumulation and PC pathology in the brains of heterozygous Slc9a6 KO female mice. At the behavioral level, we showed that heterozygous female mice suffer from visuospatial memory and motor coordination deficits similar to but less severe than those observed in X-chromosome hemizygous mutant males. Our studies in heterozygous Slc9a6 KO female mice provide important clues for understanding the likely phenotypic range of Christianson syndrome among females heterozygous for SLC9A6 mutations and might improve diagnostic practice and genetic counseling by helping to characterize this presumably underappreciated patient

  17. X-linked Christianson syndrome: heterozygous female Slc9a6 knockout mice develop mosaic neuropathological changes and related behavioral abnormalities

    PubMed Central

    Sikora, Jakub; Leddy, Jennifer; Gulinello, Maria; Walkley, Steven U.

    2016-01-01

    ABSTRACT Christianson syndrome (CS) is an X-linked neurodevelopmental and neurological disorder characterized in males by core symptoms that include non-verbal status, intellectual disability, epilepsy, truncal ataxia, postnatal microcephaly and hyperkinesis. CS is caused by mutations in the SLC9A6 gene, which encodes a multipass transmembrane sodium (potassium)-hydrogen exchanger 6 (NHE6) protein, functional in early recycling endosomes. The extent and variability of the CS phenotype in female heterozygotes, who presumably express the wild-type and mutant SLC9A6 alleles mosaically as a result of X-chromosome inactivation (XCI), have not yet been systematically characterized. Slc9a6 knockout mice (Slc9a6 KO) were generated by insertion of the bacterial lacZ/β-galactosidase (β-Gal) reporter into exon 6 of the X-linked gene. Mutant Slc9a6 KO male mice have been shown to develop late endosomal/lysosomal dysfunction associated with glycolipid accumulation in selected neuronal populations and patterned degeneration of Purkinje cells (PCs). In heterozygous female Slc9a6 KO mice, β-Gal serves as a transcriptional/XCI reporter and thus facilitates testing of effects of mosaic expression of the mutant allele on penetrance of the abnormal phenotype. Using β-Gal, we demonstrated mosaic expression of the mutant Slc9a6 allele and mosaically distributed lysosomal glycolipid accumulation and PC pathology in the brains of heterozygous Slc9a6 KO female mice. At the behavioral level, we showed that heterozygous female mice suffer from visuospatial memory and motor coordination deficits similar to but less severe than those observed in X-chromosome hemizygous mutant males. Our studies in heterozygous Slc9a6 KO female mice provide important clues for understanding the likely phenotypic range of Christianson syndrome among females heterozygous for SLC9A6 mutations and might improve diagnostic practice and genetic counseling by helping to characterize this presumably

  18. Right Ventricular Myxoma.

    PubMed

    Vadivelmurugan, S; Senthamarai; Sakthimohan; Janarthanan; Balanayagam; Anand, Vijay; Venkateswaran, K J; Ramkumar; Selvaraj

    2015-10-01

    We report a case of 30 year female who presented with complaints of intermittent chest pain and breathlessness for 8 months, Diagnosed to have right ventricular mass protruding into main pulmonary artery during each systole. The mass was completely excised. Histopathological examination showed myxoma. PMID:27608701

  19. Management of arrhythmogenic right ventricular cardiomyopathy.

    PubMed

    Silvano, Maria; Mastella, Giulio; Zorzi, Alessandro; Migliore, Federico; Pilichou, Kalliopi; Bauce, Barbara; Rigato, Ilaria; Perazzolo Marra, Martina; Iliceto, Sabino; Thiene, Gaetano; Basso, Cristina; Corrado, Domenico

    2016-08-01

    Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically determined heart muscle disorder, predisposing to sudden cardiac death (SCD), particularly in young patients and athletes. Pathological features include loss of myocytes and fibrofatty replacement of right ventricular myocardium; a biventricular involvement is often observed. The diagnosis of ARVC (prevalence 1:5.000 in the general population) does not rely on a single gold standard test but is achieved using a scoring system, proposed in 2010 by an International Task Force, which encompasses familial and genetic factors, ECG abnormalities, arrhythmias, and structural/functional ventricular alterations. The main goal of treatment is the prevention of SCD. Implantable cardioverter defibrillator (ICD) is the only proven "lifesaving" therapy; however, it is associated with a significant morbidity due to device-related complications and inappropriate ICD interventions. Other treatment options such as life style changes, antiarrhythmic drugs, beta-blockers and catheter ablation may reduce the arrhythmic burden and alleviate symptoms, without evident impact on prevention of SCD. Selection of patient candidates to ICD implantation is the most challenging issue in the clinical management of ARVC. This article reviews the current perspective on management of ARVC, focusing on clinical manifestations, diagnostic criteria, risk stratification and therapeutic strategies of affected patients. PMID:27186923

  20. Left Ventricular Assist Devices

    PubMed Central

    2004-01-01

    Executive Summary Objective The objective of this health technology policy assessment was to determine the effectiveness and cost-effectiveness of using implantable ventricular assist devices in the treatment of end-stage heart failure. Heart Failure Heart failure is a complex syndrome that impairs the ability of the heart to maintain adequate blood circulation, resulting in multiorgan abnormalities and, eventually, death. In the period of 1994 to 1997, 38,702 individuals in Ontario had a first hospital admission for heart failure. Despite reported improvement in survival, the five-year mortality rate for heart failure is about 50%. For patients with end-stage heart failure that does not respond to medical therapy, surgical treatment or traditional circulatory assist devices, heart transplantation (in appropriate patients) is the only treatment that provides significant patient benefit. Heart Transplant in Ontario With a shortage in the supply of donor hearts, patients are waiting longer for a heart transplant and may die before a donor heart is available. From 1999 to 2003, 55 to 74 people received a heart transplant in Ontario each year. Another 12 to 21 people died while waiting for a suitable donor heart. Of these, 1 to 5 deaths occurred in people under 18 years old. The rate-limiting factor in heart transplant is the supply of donor hearts. Without an increase in available donor hearts, attempts at prolonging the life of some patients on the transplant wait list could have a harmful effect on other patients that are being pushed down the waiting list (knock on effect). LVAD Technology Ventricular assist devices [VADs] have been developed to provide circulatory assistance to patients with end-stage heart failure. These are small pumps that usually assist the damaged left ventricle [LVADs] and may be situated within the body (intracorporeal] or outside the body [extracorporeal). Some of these devices were designed for use in the right ventricle [RVAD] or both

  1. Ventricular Tachycardias: Characteristics and Management.

    PubMed

    Baldzizhar, Aksana; Manuylova, Ekaterina; Marchenko, Roman; Kryvalap, Yury; Carey, Mary G

    2016-09-01

    Ventricular tachycardias include ventricular tachycardia, ventricular fibrillation, and torsades de pointes; although these rhythms may be benign and asymptomatic, others may be life threatening and lead to increased morbidity and mortality. To optimize patient outcomes, ventricular tachycardias need to be rapidly diagnosed and managed, and often the electrocardiogram (ECG) is the first and only manifestation of a cardiac defect. Understanding of the initial electrocardiographic pattern and subsequent changes can lead to early intervention and an improved outcome. This article describes mechanisms, ECG characteristics, and management of ventricular tachycardias. PMID:27484660

  2. Noninvasive mapping of ventricular arrhythmias.

    PubMed

    Shah, Ashok J; Lim, Han S; Yamashita, Seigo; Zellerhoff, Stephan; Berte, Benjamin; Mahida, Saagar; Hooks, Darren; Aljefairi, Nora; Derval, Nicolas; Denis, Arnaud; Sacher, Frédéric; Jais, Pierre; Dubois, Rémi; Hocini, Meleze; Haissaguerre, Michel

    2015-03-01

    Several decades of research has led to the development of a 252-lead electrocardiogram-based three-dimensional imaging modality to refine noninvasive diagnosis and improve the management of heart rhythm disorders. This article reviews the clinical potential of this noninvasive mapping technique in identifying the sources of electrical disorders and guiding the catheter ablation of ventricular arrhythmias (premature ventricular beats and ventricular tachycardia). The article also briefly refers to the noninvasive electrical imaging of the arrhythmogenic ventricular substrate based on the electrophysiologic characteristics of postinfarction ventricular myocardium. PMID:25784026

  3. Ectopia cordis with a double outlet right ventricle, large ventricular septal defect, malposed great arteries and left ventricular hypoplasia.

    PubMed

    Malik, Rabiya; Zilberman, Mark V; Tang, Liwen; Miller, Susan; Pandian, Natesa G

    2015-03-01

    Ectopia cordis, defined as partial or complete displacement of the heart outside of the thoracic cavity, is a rare congenital malformation. If not surgically corrected during the early years of life, ectopia cordis can prove to be a fatal abnormality. However, due to the presence of multiple intracardiac and extracardiac malformations, a corrective surgery might not always be successful. The pathology of ectopia cordis with a double outlet right ventricle, large ventricular septal defect, malposed great arteries and left ventricular hypoplasia is discussed, highlighting the complexities involved in such a rare disorder. PMID:25409882

  4. Relation of magnetocardiographic arrhythmia risk parameters to delayed ventricular conduction in postinfarction ventricular tachycardia.

    PubMed

    Korhonen, Petri; Pesola, Katja; Järvinen, Antero; Mäkijärvi, Markku; Katila, Toivo; Toivonen, Lauri

    2002-09-01

    Time-domain late field and intra-QRS fragmentation parameters in magnetocardiography (MCG) identify patients prone to VT after myocardial infarction. This study investigated if they are related to slow ventricular conduction and affected by arrhythmia surgery. Twenty-two patients with old myocardial infarction undergoing map-guided subendocardial resection to treat sustained VT were included. Bipolar electrograms were recorded during operation using an epicardial jacket and endocardial balloon electrode array. The time from the QRS onset to the end of local ventricular excitation in each electrogram was measured during sinus rhythm. Multi-channel MCG was recorded before and after operation and filtered QRS duration (QRSd), root mean square amplitude of the magnetic field strength during the last 40 ms of the QRS complex (RMS40), duration of the low amplitude signal < 300 fT (LAS300), fragmentation index M (M), and fragmentation score S (S) were determined. All patients had one or two VT foci localized and resected. MCG parameters correlated with time to the latest end of ventricular excitation; r = 0.45 for QRSd (P = 0.035), r = 0.64 for M (P = 0.001), and r = 0.73 for S (P < 0.001). The correlations were even better in patients with anterior infarction (e.g., r = 0.87 for QRSd, P < 0.001; r = 0.91 for M, P < 0.001). The operation reduced the abnormalities in MCG parameters and 20 of the 21 patients tested postoperatively became noninducible. MCG parameters indicating postinfarction arrhythmia propensity are related to delayed ventricular conduction. Abolition of the arrhythmia substrate reverses the abnormality of these parameters. PMID:12380770

  5. Left Ventricular Non-compaction with Multiple Ventricular Septal Defects

    PubMed Central

    Moorthy, Nagaraja; Jain, Sandeep; Neyaz, Zafar; Kumar, Sunil; Goel, Pravin K.

    2015-01-01

    Left ventricular non-compaction (LVNC) is a congenital cardiomyopathy characterized by deep ventricular trabeculations thought to be due to an arrest of myocardial morphogenesis. Integration of various cardiac imaging modalities such as echocardiography, cardiac computed tomography and cardiac magnetic resonance imaging help in the diagnosis of this rare clinical entity. We describe a child with rare variant of LVNC with predominant involvement of interventricular septum resulting in multiple ventricular septal defects. PMID:27326350

  6. The effects of intraventricular gradients on left ventricular ejection dynamics.

    PubMed

    Murgo, J P; Alter, B R; Dorethy, J F; Altobelli, S A; Craig, W E; McGranahan, G M

    1983-11-01

    The generation of abnormal gradients between the apical cavity and the subaortic valvular region of the left ventricle in patients with hypertrophic cardiomyopathy (HCM) has traditionally been equated to a dynamic obstruction to left ventricular outflow. To examine this concept in more detail, left ventricular ejection dynamics were studied during cardiac catheterization in 30 patients with HCM and 29 patients with no evidence of cardiovascular disease. Using multisensor catheterization techniques, ascending aortic flow velocity and micromanometer left ventricular and aortic pressures were simultaneously recorded during rest (n = 47). Dynamic left ventricular emptying was also analyzed with frame-by-frame angiography (n = 46). The temporal distribution of left ventricular outflow was independently derived from both flow velocity and angiographic techniques. The HCM patients were subdivided into three groups: I, intraventricular gradients at rest (n = 9); II, intraventricular gradients only with provocation (n = 12); III, no intraventricular gradients despite provocation (n = 9). Expressed as a precentage of the available systolic ejection period (%SEP), the time required for ejection of the total stroke volume was (mean +/- 1 S.D.): Group I, 69 +/- 17% (flow), 64 +/- 6% (angio); Group II, 63 +/- 14% (flow), 65 +/- 6% (angio); Group III, 61 +/- 16% (flow), 62 +/- 4% (angio); control group, 90 +/- 5% (flow) 86 +/- 10% (angio). No significant difference was observed between any of the three HCM subgroups, but, compared with the control group, ejection was completed much earlier in systole independent of the presence or absence of intraventricular gradients. The presence of coexisting mitral regurgitation in 12 of the HCM patients did not alter these results. This study demonstrates that 'outflow obstruction', as traditionally defined by the presence of an abnormal intraventricular pressure gradient and systolic anterior motion of the mitral valve, does not impede left

  7. Ventricular tachycardia from intracardiac hematoma in the setting of blunt thoracic trauma.

    PubMed

    Solhpour, Amirreza; Ananaba-Ekeruo, Ijeoma; Memon, Nada B; Kantharia, Bharat K

    2014-01-01

    In the victims of motor vehicle accidents, unrecognized myocardial injuries may pose diagnostic and therapeutic challenges. Herein, we present a case of a 17-year-old man who developed multiple ventricular premature complexes and nonsustained ventricular tachycardia in the setting of blunt chest trauma from a motor vehicle accident. We discuss significance of the electrocardiographic abnormalities in making an accurate diagnosis of cardiac hematoma and its management. PMID:24581106

  8. Mitral Subvalvular Aneurysm in a Patient with Chagas Disease and Recurrent Episodes of Ventricular Tachycardia

    PubMed Central

    Grillo, Tereza Augusta; Athayde, Guilherme Rafael S.; Belfort, Ana Flávia L.; Miranda, Reynaldo C.; Beaton, Andrea Z.; Nascimento, Bruno R.

    2015-01-01

    Subvalvular left ventricular aneurysm is a rare disease of obscure origin suggesting unique causes such as congenital, traumatic, and inflammatory or infectious diseases. Its mortality is closely related to heart failure, mitral insufficiency, thromboembolic phenomena, and cardiac arrhythmias. Although association with coronary artery disease is not described, the compression of epicardial vessels by the aneurysm may lead to ischemic manifestations. We report here a case of mitral subvalvular left ventricular aneurysm of probable chagasic origin, in a patient with normal left ventricular function evolving with repeated episodes of monomorphic ventricular tachycardia, despite noninducible electrophysiological testing and the use of optimal medical treatment, including amiodarone. The indication for implantable cardioverter-defibrillator in patients with Chagas cardiomyopathy and segmental wall motion abnormalities but without global systolic dysfunction remains unclear in literature, even in the presence of complex ventricular arrhythmias. A brief review of the literature on morphological features, diagnosis, prognosis, and treatment will be also discussed. PMID:26634158

  9. Cardiac Sympathetic Nerve Sprouting and Susceptibility to Ventricular Arrhythmias after Myocardial Infarction.

    PubMed

    Li, Chang-Yi; Li, Yi-Gang

    2015-01-01

    Ventricular arrhythmogenesis is thought to be a common cause of sudden cardiac death following myocardial infarction (MI). Nerve remodeling as a result of MI is known to be an important genesis of life-threatening arrhythmias. It is hypothesized that neural modulation might serve as a therapeutic option of malignant arrhythmias. In fact, left stellectomy or β-blocker therapy is shown to be effective in the prevention of ventricular tachyarrhythmias (VT), ventricular fibrillation (VF), and sudden cardiac death (SCD) after MI both in patients and in animal models. Results from decades of research already evidenced a positive relationship between abnormal nerve density and ventricular arrhythmias after MI. In this review, we summarized the molecular mechanisms involved in cardiac sympathetic rejuvenation and mechanisms related to sympathetic hyperinnervation and arrhythmogenesis after MI and analyzed the potential therapeutic implications of nerve sprouting modification for ventricular arrhythmias and SCD control. PMID:26793403

  10. Cardiac Sympathetic Nerve Sprouting and Susceptibility to Ventricular Arrhythmias after Myocardial Infarction

    PubMed Central

    Li, Chang-Yi; Li, Yi-Gang

    2015-01-01

    Ventricular arrhythmogenesis is thought to be a common cause of sudden cardiac death following myocardial infarction (MI). Nerve remodeling as a result of MI is known to be an important genesis of life-threatening arrhythmias. It is hypothesized that neural modulation might serve as a therapeutic option of malignant arrhythmias. In fact, left stellectomy or β-blocker therapy is shown to be effective in the prevention of ventricular tachyarrhythmias (VT), ventricular fibrillation (VF), and sudden cardiac death (SCD) after MI both in patients and in animal models. Results from decades of research already evidenced a positive relationship between abnormal nerve density and ventricular arrhythmias after MI. In this review, we summarized the molecular mechanisms involved in cardiac sympathetic rejuvenation and mechanisms related to sympathetic hyperinnervation and arrhythmogenesis after MI and analyzed the potential therapeutic implications of nerve sprouting modification for ventricular arrhythmias and SCD control. PMID:26793403

  11. Nonischemic Left Ventricular Scar as a Substrate of Life-Threatening Ventricular Arrhythmias and Sudden Cardiac Death in Competitive Athletes

    PubMed Central

    Zorzi, Alessandro; Perazzolo Marra, Martina; Rigato, Ilaria; De Lazzari, Manuel; Susana, Angela; Niero, Alice; Pilichou, Kalliopi; Migliore, Federico; Rizzo, Stefania; Giorgi, Benedetta; De Conti, Giorgio; Sarto, Patrizio; Serratosa, Luis; Patrizi, Giampiero; De Maria, Elia; Pelliccia, Antonio; Basso, Cristina; Schiavon, Maurizio; Bauce, Barbara; Iliceto, Sabino; Thiene, Gaetano

    2016-01-01

    Background— The clinical profile and arrhythmic outcome of competitive athletes with isolated nonischemic left ventricular (LV) scar as evidenced by contrast-enhanced cardiac magnetic resonance remain to be elucidated. Methods and Results— We compared 35 athletes (80% men, age: 14–48 years) with ventricular arrhythmias and isolated LV subepicardial/midmyocardial late gadolinium enhancement (LGE) on contrast-enhanced cardiac magnetic resonance (group A) with 38 athletes with ventricular arrhythmias and no LGE (group B) and 40 healthy control athletes (group C). A stria LGE pattern with subepicardial/midmyocardial distribution, mostly involving the lateral LV wall, was found in 27 (77%) of group A versus 0 controls (group C; P<0.001), whereas a spotty pattern of LGE localized at the junction of the right ventricle to the septum was respectively observed in 11 (31%) versus 10 (25%; P=0.52). All athletes with stria pattern showed ventricular arrhythmias with a predominant right bundle branch block morphology, 13 of 27 (48%) showed ECG repolarization abnormalities, and 5 of 27 (19%) showed echocardiographic hypokinesis of the lateral LV wall. The majority of athletes with no or spotty LGE pattern had ventricular arrhythmias with a predominant left bundle branch block morphology and no ECG or echocardiographic abnormalities. During a follow-up of 38±25 months, 6 of 27 (22%) athletes with stria pattern experienced malignant arrhythmic events such as appropriate implantable cardiac defibrillator shock (n=4), sustained ventricular tachycardia (n=1), or sudden death (n=1), compared with none of athletes with no or LGE spotty pattern and controls. Conclusions— Isolated nonischemic LV LGE with a stria pattern may be associated with life-threatening arrhythmias and sudden death in the athlete. Because of its subepicardial/midmyocardial location, LV scar is often not detected by echocardiography. PMID:27390211

  12. Fat in the ventricular septum

    PubMed Central

    Donaldson, Erin E.; Ko, Jong Mi; Kuiper, Johannes J.; Chamogeorgakis, Themistokles

    2014-01-01

    Described herein is a 68-year-old man who underwent cardiac transplantation for severe chronic heart failure resulting from ischemic cardiomyopathy. Examination of the excised heart showed not only extensive left ventricular scarring but also a huge collection of adipose tissue in the subepicardial region and surprisingly also in the ventricular septum. The finding of fat in the ventricular septum is extremely rare and prompted this report. PMID:24982572

  13. Ventricular dysfunction in children with obstructive sleep apnea: radionuclide assessment

    SciTech Connect

    Tal, A.; Leiberman, A.; Margulis, G.; Sofer, S.

    1988-01-01

    Ventricular function was evaluated using radionuclide ventriculography in 27 children with oropharyngeal obstruction and clinical features of obstructive sleep apnea. Their mean age was 3.5 years (9 months to 7.5 years). Conventional clinical assessment did not detect cardiac involvement in 25 of 27 children; however, reduced right ventricular ejection fraction (less than 35%) was found in 10 (37%) patients (mean: 19.5 +/- 2.3% SE, range: 8-28%). In 18 patients wall motion abnormality was detected. In 11 children in whom radionuclide ventriculography was performed before and after adenotonsillectomy, right ventricular ejection fraction rose from 24.4 +/- 3.6% to 46.7 +/- 3.4% (P less than 0.005), and in all cases wall motion showed a definite improvement. In five children, left ventricular ejection fraction rose greater than 10% after removal of oropharyngeal obstruction. It is concluded that right ventricular function may be compromised in children with obstructive sleep apnea secondary to adenotonsillar hypertrophy, even before clinical signs of cardiac involvement are present.

  14. Ventricular arrhythmias in congestive heart failure: clinical significance and management.

    PubMed Central

    Khoshnevis, G R; Massumi, A

    1999-01-01

    The benefit of defibrillator therapy has been well established for patients with LV dysfunction (ejection fraction less than 35%), coronary artery disease, NSVT, and inducible and nonsuppressible ventricular tachycardia. Implantable cardioverter-defibrillator therapy is also indicated for all CHF patients in NYHA functional classes I, II, and III who present with aborted sudden cardiac death, or ventricular fibrillation, or hemodynamically unstable ventricular tachycardia--and also in patients with syncope with no documented ventricular tachycardia but with inducible ventricular tachycardia at electrophysiology study. The ongoing MADIT II trial was designed to evaluate the benefit of prophylactic ICD implantation in these patients (ejection fraction less than 30%, coronary artery disease, and NSVT) without prior risk stratification by PES. The CABG Patch trial concluded that prophylactic placement of an ICD during coronary artery bypass grafting in patients with low ejection fraction and abnormal SAECG is not justifiable. Except for the indications described above, ICD implantation has not been proved to be beneficial as primary or secondary therapy. Until more data are available, patients should be encouraged to enroll in the ongoing clinical trials. PMID:10217470

  15. In normal aging ventricular system never attains pathological values of Evans' index.

    PubMed

    Missori, Paolo; Rughetti, Aurelia; Peschillo, Simone; Gualdi, Gianfranco; Di Biasi, Claudio; Nofroni, Italo; Marinelli, Lucio; Fattapposta, Francesco; Currà, Antonio

    2016-03-15

    Ventricular enlargement in normal aging frequently forces the radiological diagnosis of hydrocephalus, but the reliability of Evans' index as a radiological marker of abnormal ventricular enlargement (values > 0.30) during aging is not assessed. Here we analyze ventricular size during aging and the reliability of Evans' index as a radiological marker of abnormal ventricular enlargement. We calculated Evans' index in the axial Computed Tomography scans of 1221 consecutive individuals (aged 45-101 years) from an emergency department. Stratified analysis of one-year cohorts showed that the mean Evans' index value per class was invariably < 0.30. Roughly one out five Computed Tomography scans was associated with Evans' index values > 0.30 and Evans' index values increased with age. The risk of having an Evans' index value > 0.30 increased by 7.8% per year of age (p < 0.001) and males were at 83.9% greater risk than females (p < 0.001). Overall, this study shows that normal aging enlarges the ventricular system, but never causes abnormal ventricular enlargement. Evans' index values > 0.30 should reflect an underlying neurological condition in every individual. PMID:26919252

  16. In normal aging ventricular system never attains pathological values of Evans' index

    PubMed Central

    Missori, Paolo; Rughetti, Aurelia; Peschillo, Simone; Gualdi, Gianfranco; Di Biasi, Claudio; Nofroni, Italo; Marinelli, Lucio; Fattapposta, Francesco; Currà, Antonio

    2016-01-01

    Ventricular enlargement in normal aging frequently forces the radiological diagnosis of hydrocephalus, but the reliability of Evans' index as a radiological marker of abnormal ventricular enlargement (values > 0.30) during aging is not assessed. Here we analyze ventricular size during aging and the reliability of Evans' index as a radiological marker of abnormal ventricular enlargement. We calculated Evans' index in the axial Computed Tomography scans of 1221 consecutive individuals (aged 45-101 years) from an emergency department. Stratified analysis of one-year cohorts showed that the mean Evans' index value per class was invariably < 0.30. Roughly one out five Computed Tomography scans was associated with Evans' index values > 0.30 and Evans' index values increased with age. The risk of having an Evans' index value > 0.30 increased by 7.8% per year of age (p < 0.001) and males were at 83.9% greater risk than females (p < 0.001). Overall, this study shows that normal aging enlarges the ventricular system, but never causes abnormal ventricular enlargement. Evans' index values > 0.30 should reflect an underlying neurological condition in every individual. PMID:26919252

  17. Abnormal Head Position

    MedlinePlus

    ... cause. Can a longstanding head turn lead to any permanent problems? Yes, a significant abnormal head posture could cause permanent ... occipitocervical synostosis and unilateral hearing loss. Are there any ... postures? Yes. Abnormal head postures can usually be improved depending ...

  18. Urine - abnormal color

    MedlinePlus

    ... straw-yellow. Abnormally colored urine may be cloudy, dark, or blood-colored. Causes Abnormal urine color may ... red blood cells, or mucus in the urine. Dark brown but clear urine is a sign of ...

  19. Is There a Relationship between Restricted, Repetitive, Stereotyped Behaviors and Interests and Abnormal Sensory Response in Children with Autism Spectrum Disorders?

    ERIC Educational Resources Information Center

    Gabriels, Robin L.; Agnew, John A.; Miller, Lucy Jane; Gralla, Jane; Pan, Zhaoxing; Goldson, Edward; Ledbetter, James C.; Dinkins, Juliet P.; Hooks, Elizabeth

    2008-01-01

    This study examined the relation between restricted, repetitive, and stereotyped behaviors and interests (RBs) and sensory responses in a group of 70 children and adolescents diagnosed with an autism spectrum disorder (ASD). Caregivers completed the Repetitive Behavior Scale-Revised (RBS-R) and the Sensory Profile. Controlling for IQ and age,…

  20. In utero and Lactational Exposure to Acetamiprid Induces Abnormalities in Socio-Sexual and Anxiety-Related Behaviors of Male Mice.

    PubMed

    Sano, Kazuhiro; Isobe, Tomohiko; Yang, Jiaxin; Win-Shwe, Tin-Tin; Yoshikane, Mitsuha; Nakayama, Shoji F; Kawashima, Takaharu; Suzuki, Go; Hashimoto, Shunji; Nohara, Keiko; Tohyama, Chiharu; Maekawa, Fumihiko

    2016-01-01

    Neonicotinoids, a widely used group of pesticides designed to selectively bind to insect nicotinic acetylcholine receptors, were considered relatively safe for mammalian species. However, they have been found to activate vertebrate nicotinic acetylcholine receptors and could be toxic to the mammalian brain. In the present study, we evaluated the developmental neurotoxicity of acetamiprid (ACE), one of the most widely used neonicotinoids, in C57BL/6J mice whose mothers were administered ACE via gavage at doses of either 0 mg/kg (control group), 1.0 mg/kg (low-dose group), or 10.0 mg/kg (high-dose group) from gestational day 6 to lactation day 21. The results of a battery of behavior tests for socio-sexual and anxiety-related behaviors, the numbers of vasopressin-immunoreactive cells in the paraventricular nucleus of the hypothalamus, and testosterone levels were used as endpoints. In addition, behavioral flexibility in mice was assessed in a group-housed environment using the IntelliCage, a fully automated mouse behavioral analysis system. In adult male mice exposed to ACE at both low and high doses, a significant reduction of anxiety level was found in the light-dark transition test. Males in the low-dose group also showed a significant increase in sexual and aggressive behaviors. In contrast, neither the anxiety levels nor the sexual behaviors of females were altered. No reductions in the testosterone level, the number of vasopressin-immunoreactive cells, or behavioral flexibility were detected in either sex. These results suggest the possibility that in utero and lactational ACE exposure interferes with the development of the neural circuits required for executing socio-sexual and anxiety-related behaviors in male mice specifically. PMID:27375407

  1. In utero and Lactational Exposure to Acetamiprid Induces Abnormalities in Socio-Sexual and Anxiety-Related Behaviors of Male Mice

    PubMed Central

    Sano, Kazuhiro; Isobe, Tomohiko; Yang, Jiaxin; Win-Shwe, Tin-Tin; Yoshikane, Mitsuha; Nakayama, Shoji F.; Kawashima, Takaharu; Suzuki, Go; Hashimoto, Shunji; Nohara, Keiko; Tohyama, Chiharu; Maekawa, Fumihiko

    2016-01-01

    Neonicotinoids, a widely used group of pesticides designed to selectively bind to insect nicotinic acetylcholine receptors, were considered relatively safe for mammalian species. However, they have been found to activate vertebrate nicotinic acetylcholine receptors and could be toxic to the mammalian brain. In the present study, we evaluated the developmental neurotoxicity of acetamiprid (ACE), one of the most widely used neonicotinoids, in C57BL/6J mice whose mothers were administered ACE via gavage at doses of either 0 mg/kg (control group), 1.0 mg/kg (low-dose group), or 10.0 mg/kg (high-dose group) from gestational day 6 to lactation day 21. The results of a battery of behavior tests for socio-sexual and anxiety-related behaviors, the numbers of vasopressin-immunoreactive cells in the paraventricular nucleus of the hypothalamus, and testosterone levels were used as endpoints. In addition, behavioral flexibility in mice was assessed in a group-housed environment using the IntelliCage, a fully automated mouse behavioral analysis system. In adult male mice exposed to ACE at both low and high doses, a significant reduction of anxiety level was found in the light-dark transition test. Males in the low-dose group also showed a significant increase in sexual and aggressive behaviors. In contrast, neither the anxiety levels nor the sexual behaviors of females were altered. No reductions in the testosterone level, the number of vasopressin-immunoreactive cells, or behavioral flexibility were detected in either sex. These results suggest the possibility that in utero and lactational ACE exposure interferes with the development of the neural circuits required for executing socio-sexual and anxiety-related behaviors in male mice specifically. PMID:27375407

  2. Ventricular Septal Defect

    MedlinePlus

    ... Cardiac Rhythm Disturbances Thoracic Aortic Aneurysm Pediatric and Congenital Heart Disease Heart abnormalities that are present at birth in ... common, accounting for 20% to 30% of all congenital heart defects. The US Centers for Disease Control and Prevention (CDC) estimates that 42 out ...

  3. Right ventricular failure after left ventricular assist device implantation: the need for an implantable right ventricular assist device.

    PubMed

    Furukawa, Kojiro; Motomura, Tadashi; Nosé, Yukihiko

    2005-05-01

    Right ventricular failure after implantation of a left ventricular assist device is an unremitting problem. Consideration of portal circulation is important for reversing liver dysfunction and preventing multiple organ failure after left ventricular assist device implantation. To achieve these objectives, it is imperative to maintain the central venous pressure as low as possible. A more positive application of right ventricular assistance is recommended. Implantable pulsatile left ventricular assist devices cannot be used as a right ventricular assist device because of their structure and device size. To improve future prospects, it is necessary to develop an implantable right ventricular assist device based on a rotary blood pump. PMID:15854212

  4. Electrical injury causing ventricular arrhythmias.

    PubMed Central

    Jensen, P J; Thomsen, P E; Bagger, J P; Nørgaard, A; Baandrup, U

    1987-01-01

    Dangerous or long lasting ventricular arrhythmias developed in three patients who had sustained an electrical injury in which current passed through the thorax. In all three cases there was a delay of 8-12 hours between the injury and the onset of symptoms. The ventricular arrhythmias were severe and long lasting. In two of the three patients, ventricular tachycardia or ventricular fibrillation or both occurred and in one patient ventricular parasystole developed. No enzymatic evidence of myocardial necrosis was found but the results of an endomyocardial biopsy carried out in two of the three patients showed focal myocardial fibrosis and increased numbers of Na, K-pumps. The two patients with ventricular tachycardia became symptom free after appropriate antiarrhythmic treatment and in the third patient ventricular parasystole disappeared spontaneously within two years. Patients sustaining electrical injury in which current passes through the thorax should be monitored electrocardiographically for at least 24 hours, and patients with unexpected arrhythmias should be questioned about previous electrical injury. Images Fig 2 PMID:3566986

  5. Epicardial ventricular tachycardia.

    PubMed

    Garan, Hasan

    2013-12-01

    In ventricular tachycardia (VT) arising in the myocardial tissue, the site of origin may be the endocardium, mid-myocardium or epicardium. The incidence of epicardial origin varies with the underlying heart disease, and is probably not more than 20% in ischemic heart disease and higher in non-ischemic cardiomyopathies. Percutaneous subxiphoid access to the pericardial space has enabled a non-surgical approach to catheter mapping and ablation of epicardial VT. Several algorithms are available for electrocardiographic recognition of epicardial origin. Idiopathic epicardial VTs are rare but may be curable by catheter ablation. The electrophysiologic principles guiding the mapping and ablation of epicardial VTs are similar to those used for endocardial VTs, but the biophysics of energy delivery may be different. Complications of the epicardial approach are also different from those of endocardial ablation, and specific precautions have to be taken to protect the coronary arteries and phrenic nerves and to avoid pericardial tamponade. PMID:24351953

  6. Tooth - abnormal shape

    MedlinePlus

    Hutchinson incisors; Abnormal tooth shape; Peg teeth; Mulberry teeth; Conical teeth ... from many different conditions. Specific diseases can affect tooth shape, tooth color, time of appearance, or absence ...

  7. Tooth - abnormal shape

    MedlinePlus

    Hutchinson incisors; Abnormal tooth shape; Peg teeth; Mulberry teeth; Conical teeth ... The appearance of normal teeth varies, especially the molars. ... conditions. Specific diseases can affect tooth shape, tooth ...

  8. Arrhythmogenic right ventricular cardiomyopathy in a weimaraner

    PubMed Central

    Eason, Bryan D.; Leach, Stacey B.; Kuroki, Keiichi

    2015-01-01

    Arrhythmogenic right ventricular cardiomyopathy (ARVC) was diagnosed postmortem in a weimaraner dog. Syncope, ventricular arrhythmias, and sudden death in this patient combined with the histopathological fatty tissue infiltration affecting the right ventricular myocardium are consistent with previous reports of ARVC in non-boxer dogs. Arrhythmogenic right ventricular cardiomyopathy has not been previously reported in weimaraners. PMID:26483577

  9. Abnormal behavior of threshold voltage shift in bias-stressed a-Si:H thin film transistor under extremely high intensity illumination.

    PubMed

    Han, Sang Youn; Park, Kyung Tea; Kim, Cheolkyu; Jeon, Sanghyun; Yang, Sung-Hoon; Kong, Hyang-Shik

    2015-07-22

    We report on the unusual behavior of threshold voltage turnaround in a hydrogenated amorphous silicon (a-Si:H) thin film transistor (TFT) when biased under extremely high intensity illumination. The threshold voltage shift changes from negative to positive gate bias direction after ∼30 min of bias stress even when the negative gate bias stress is applied under high intensity illumination (>400 000 Cd/cm(2)), which has not been observed in low intensity (∼6000 Cd/cm(2)). This behavior is more pronounced in a low work function gate metal structure (Al: 4.1-4.3 eV), compared to the high work function of Cu (4.5-5.1 eV). Also this is mainly observed in shorter wavelength of high photon energy illumination. However, this behavior is effectively prohibited by embedding the high energy band gap (∼8.6 eV) of SiOx in the gate insulator layer. These imply that this behavior could be originated from the injection of electrons from gate electrode, transported and trapped in the electron trap sites of the SiNx/a-Si:H interface, which causes the shift of threshold voltage toward positive gate bias direction. The results reported here can be applicable to the large-sized outdoor displays which are usually exposed to the extremely high intensity illumination. PMID:26132513

  10. Pilot randomized trial demonstrating reversal of obesity-related abnormalities in reward system responsivity to food cues with a behavioral intervention

    PubMed Central

    Deckersbach, T; Das, S K; Urban, L E; Salinardi, T; Batra, P; Rodman, A M; Arulpragasam, A R; Dougherty, D D; Roberts, S B

    2014-01-01

    Objectives: Obesity is associated with hyperactivation of the reward system for high-calorie (HC) versus low-calorie (LC) food cues, which encourages unhealthy food selection and overeating. However, the extent to which this hyperactivation can be reversed is uncertain, and to date there has been no demonstration of changes by behavioral intervention. Subjects and methods: We used functional magnetic resonance imaging to measure changes in activation of the striatum for food images at baseline and 6 months in a pilot study of 13 overweight or obese adults randomized to a control group or a novel weight-loss intervention. Results: Compared to controls, intervention participants achieved significant weight loss (−6.3±1.0 kg versus +2.1±1.1 kg, P<0.001) and had increased activation for LC food images with a composition consistent with that recommended in the behavioral intervention at 6 months versus baseline in the right ventral putamen (P=0.04), decreased activation for HC images of typically consumed foods in the left dorsal putamen (P=0.01). There was also a large significant shift in relative activation favoring LC versus HC foods in both regions (P<0.04). Conclusions: This study provides the first demonstration of a positive shift in activation of the reward system toward healthy versus unhealthy food cues in a behavioral intervention, suggesting new avenues to enhance behavioral treatments of obesity. PMID:25177910