Explore the vast range of titles available.

mGluR2 receptors are widely expressed in limbic brain regions associated with memory, including the hippocampal formation, retrosplenial and frontal cortices, as well as subcortical regions including the mammillary bodies. mGluR2/3 agonists have been proposed as potential therapeutics for neurological and psychiatric disorders, however, there is still little known about the role of these receptors in cognitive processes, including memory consolidation. To address this, we assessed the effect of the mGluR2/3 agonist, eglumetad, on spatial memory consolidation in both mice and rats. Using the novel place preference paradigm, we found that post-sample injections of eglumetad impaired subsequent spatial discrimination when tested 6 h later. Using the immediate early gene c- fos as a marker of neural activity, we showed that eglumetad injections reduced activity in a network of limbic brain regions including the hippocampus and mammillary bodies. To determine whether the systemic effects could be replicated with more targeted manipulations, we performed post-sample infusions of the mGluR2/3 agonist 2 R ,4 R -APDC into the mammillary bodies. This impaired novelty discrimination on a place preference task and an object-in-place task, again highlighting the role of mGluR2/3 transmission in memory consolidation and demonstrating the crucial involvement of the mammillary bodies in post-encoding processing of spatial information.

Current indications for pulmonary valve replacement (PVR) in repaired tetralogy of Fallot (rTOF) rely on cardiovascular magnetic resonance (CMR) image-based indices but are inconsistently applied, lead to mixed outcomes, and remain debated. This study aimed to test the hypothesis that specific markers of biventricular shape may discriminate differences between rTOF patients who did and did not require subsequent PVR better than standard imaging indices. In this cross-sectional retrospective study, biventricular shape models were customized to CMR images from 84 rTOF patients. A statistical atlas of end-diastolic shape was constructed using principal component analysis. Multivariate regression was used to quantify shape mode and imaging index associations with subsequent intervention status (PVR, n = 48 vs. No-PVR, n = 36), while accounting for confounders. Clustering analysis was used to test the ability of the most significant shape modes and imaging indices to discriminate PVR status as evaluated by a Matthews correlation coefficient (MCC). Geometric strain analysis was also conducted to assess shape mode associations with systolic function. PVR status correlated significantly with shape modes associated with right ventricular (RV) apical dilation and left ventricular (LV) dilation ( p  < 0.01), RV basal bulging and LV conicity ( p  < 0.05), and pulmonary valve dilation ( p  < 0.01). PVR status also correlated significantly with RV ejection fraction ( p  < 0.05) and correlated marginally with LV end-systolic volume index ( p  < 0.07). Shape modes discriminated subsequent PVR better than standard imaging indices (MCC = 0.49 and MCC = 0.28, respectively) and were significantly associated with RV and LV radial systolic strain. Biventricular shape modes discriminated differences between patients who did and did not require subsequent PVR better than standard imaging indices in current use. These regional features of cardiac morphology may provide insight into adaptive vs. maladaptive types of structural remodeling and point toward an improved quantitative, patient-specific assessment tool for clinical use.

Background Relationships between right ventricular (RV) and left ventricular (LV) shape and function may be useful in determining optimal timing for pulmonary valve replacement in patients with repaired tetralogy of Fallot (rTOF). However, these are multivariate and difficult to quantify. We aimed to quantify variations in biventricular shape associated with pulmonary regurgitant volume (PRV) in rTOF using a biventricular atlas. Methods In this cross-sectional retrospective study, a biventricular shape model was customized to cardiovascular magnetic resonance (CMR) images from 88 rTOF patients (median age 16, inter-quartile range 11.8–24.3 years). Morphometric scores quantifying biventricular shape at end-diastole and end-systole were computed using principal component analysis. Multivariate linear regression was used to quantify biventricular shape associations with PRV, corrected for age, sex, height, and weight. Regional associations were confirmed by univariate correlations with distances and angles computed from the models, as well as global systolic strains computed from changes in arc length from end-diastole to end-systole. Results PRV was significantly associated with 5 biventricular morphometric scores, independent of covariates, and accounted for 12.3% of total shape variation (p < 0.05). Increasing PRV was associated with RV dilation and basal bulging, in conjunction with decreased LV septal-lateral dimension (LV flattening) and systolic septal motion towards the RV (all p < 0.05). Increased global RV radial, longitudinal, circumferential and LV radial systolic strains were significantly associated with increased PRV (all p < 0.05). Conclusion A biventricular atlas of rTOF patients quantified multivariate relationships between left–right ventricular morphometry and wall motion with pulmonary regurgitation. Regional RV dilation, LV reduction, LV septal-lateral flattening and increased RV strain were all associated with increased pulmonary regurgitant volume. Morphometric scores provide simple metrics linking mechanisms for structural and functional alteration with important clinical indices.

Background Electrocardiograms (ECGs) in athletes commonly reveal findings related to physiologic adaptations to exercise, that may be difficult to discern from true underlying cardiovascular abnormalities. North American and European societies have published consensus statements for normal, borderline, and abnormal ECG findings for athletes, but these criteria are not based on established correlation with disease states. Additionally, data comparing ECG findings in athletes to non-athlete control subjects are lacking. Our objective was to compare the ECGs of collegiate athletes and non-athlete controls using Z-scores for digital ECG variables to better identify significant differences between the groups and to evaluate the ECG variables in athletes falling outside the normal range. Methods Values for 102 digital ECG variables on 7206 subjects aged 17–22 years, including 672 athletes, from Hawaii Pacific Health, University of Hawaii, and Rady Children’s Hospital San Diego were obtained through retrospective review. Age and sex-specific Z-scores for ECG variables were derived from normal subjects and used to assess the range of values for specific ECG variables in young athletes. Athletes with abnormal ECGs were referred to cardiology consultation and/or echocardiogram. Results Athletes had slower heart rate, longer PR interval, more rightward QRS axis, longer QRS duration but shorter QTc duration, larger amplitude and area of T waves, prevalent R’ waves in V1, and higher values of variables traditionally associated with left ventricular hypertrophy (LVH): amplitudes of S waves (leads V1-V2), Q waves (V6, III) and R waves (II, V5, V6). Z-scores of these ECG variables in 558 (83%) of the athletes fell within − 2.5 and 2.5 range derived from the normal population dataset, and 60 (8.9%) athletes had a Z-score outside the − 3 to 3 range. While 191 (28.4%) athletes met traditional voltage criteria for diagnosis of LVH on ECG, only 53 athletes (7.9%) had Z-scores outside the range of -2.5 to 2.5 for both S amplitude in leads V1-V2 and R amplitude in leads V5-6. Only one athlete was diagnosed with hypertrophic cardiomyopathy with a Z-score of R wave in V6 of 2.34 and T wave in V6 of -5.94. Conclusion The use of Z-scores derived from a normal population may provide more precise screening to define cardiac abnormalities in young athletes and reduce unnecessary secondary testing, restrictions and concern. Key Points • Athletes had slower heart rate, longer PR interval, greater QRS axis, longer QRS duration, shorter QTc interval, higher peak amplitude of S waves in leads V1 and V2, Q waves in leads III and V6, R waves in leads II, V5, and V6 compared to control subjects. • However, most of the athletes had ECG variable Z-scores within range of -2.5 and 2.5 (83%) and − 3 and 3 (91.1%), all of which had no identified cardiac pathologies. • ECG assessment in athletes utilizing Z-scores derived from normal subjects may guide clinical decision making regarding secondary screening.

Heart rate is commonly used in pediatric early warning scores. Age-related changes in the anatomy and physiology of infants and children produce normal ranges for electrocardiogram features that differ from adults and vary with age. Bradycardia is defined as a heart rate below the lowest normal value for age. Pediatric bradycardia most commonly manifests as sinus bradycardia, junctional bradycardia, or atrioventricular block. As a result of several different etiologies, it may occur in an entirely structurally normal heart or in association with concomitant congenital heart disease. Genetic variants in multiple genes have been described to date in the pathogenesis of inherited sinus node dysfunction or progressive cardiac conduction disorders. Management and eventual prognosis of bradycardia in the young are entirely dependent upon the underlying cause. Reasons to intervene for bradycardia are the association of related symptoms and/or the downstream risk of heart failure or pause-dependent tachyarrhythmia. The simplest aspect of severe bradycardia management is reflected in the Pediatric and Advanced Life Support (PALS) guidelines. Conclusion : Early diagnosis and appropriate management are critical in many cases in order to prevent sudden death, and this review critically assesses our current practice for evaluation and management of bradycardia in neonates and children. What is Known: • Bradycardia is defined as a heart rate below the lowest normal value for age. Age related changes in the anatomy and physiology of infants and children produce normal ranges for electrocardiogram features that differ from adults and vary with age. • Pediatric bradycardia most commonly manifests as sinus bradycardia, junctional bradycardia, or atrioventricular block. What is New: • Management and eventual prognosis of bradycardia in the young are entirely dependent upon the underlying cause. Bradycardia may occur in a structurally normal heart or in association with congenital heart disease. Genetic variants in multiple genes have been described. • Reasons to intervene for bradycardia are the association of related symptoms and/or the downstream risk of heart failure or pause-dependent tachyarrhythmia. Early diagnosis and appropriate management are critical in order to prevent sudden death.

Congenital long QT syndrome (LQTS) is characterized by QT prolongation with predisposition to life-threatening arrhythmia. There have been sporadic reports of LQTS coexisting with more common forms of congenital heart disease (CHD). However, the diagnosis of LQTS when CHD is present may be confounded by several common variables including postoperative electromechanical factors predisposing to ventricular arrhythmia, intrinsic, and postoperative QRS abnormalities. This report documents a single-center experience with patients who have both genetically confirmed LQTS and CHD to examine their modes of presentation and factors associated with making the diagnosis of LQTS in this patient population, as well as potential confounding variables that may mask or delay both LQTS diagnosis and initiation of therapy. A retrospective review was performed of subjects with confirmed LQTS and associated CHD from 1999 to January 2017. Genetic analysis was performed predominantly using commercially available panel testing. A chart review included detailed analysis of electrocardiograms, 24-hour 3-lead rhythm monitors and exercise stress test tracings as well as the genetic test reports. QT intervals were measured using Bazett's formula. Eleven patients were identified. Four patients had LQTS type 1, 6 had LQTS type 2, and 1 had a disease-associated mutation in KCNQ1 and a variant of unknown significance in KCNH2 gene. Two patients had positive cascade screening. Arrhythmia presentations of the LQTS were at both extremes of the cohort age range (in-utero and midchildhood age). There was a seeming overrepresentation of conotruncal anomalies and/or arch anomalies, with 7 of the 11 patients. In conclusion, the diagnosis of LQTS may be challenging in the setting of CHD (a prolonged ST segment may be helpful), and high index of suspicion is required. The overall incidence of LQTS in CHD appears extremely rare, but the diagnosis and true incidence may be masked by confounding electrocardiogrpahic findings and other variables common in CHD.

Tachycardia-induced cardiomyopathy (TIC) is a treatable cause of heart failure in children, but there is little information as to which clinical variables best discriminate TIC from other forms of cardiomyopathy. TIC cases with dilated cardiomyopathy (DC) from 16 participating centers were identified and compared with controls with other forms of DC. Presenting clinical, echocardiographic, and electrocardiographic characteristics were collected. Heart rate (HR) percentile was defined as HR/median HR for age, and PR index as the PR/RR interval. P-wave morphology (PWM) was defined as possible sinus or nonsinus based on a predefined algorithm. Eighty TIC cases and 135 controls were identified. Cases demonstrated lower LV end-diastolic diameter and LV end-systolic diameter than DC controls (4.3 vs 6.5, p <0.001; 7.4 vs 10.9, p <0.001) and were less likely to receive inotropic medication at presentation (p <0.001 for both). Multivariable logistic regression identified HR percentile (OR 2.1 per 10% increase, CI 1.3 to 4.6; p = 0.014), PR index (OR 1.2, CI 1.1 to 1.4; p = 0.004), and nonsinus PWM (OR 104.9, CI 15.2 to 1,659.8; p <0.001) as predictive of TIC status. A risk score using HR percentile >130%, PR index >30%, and nonsinus PWM was associated with a sensitivity of 100% and specificity of 87% for the diagnosis of TIC. Model training and validation area under the curves were similar at 0.97 and 0.94, respectively. In conclusion, pediatric TIC may be accurately discriminated from other forms of DC using simple electrocardiographic parameters. This may allow for rapid diagnosis and early treatment of this condition.

Background:  Neuronal plasticity is thought to underlie learning and memory formation. The density of dendritic spines in the CA1 region of the hippocampus has been repeatedly linked to mnemonic processes. Both the number and spatial location of the spines, in terms of proximity to nearest neighbour, have been implicated in memory formation. To examine how spatial training impacts synaptic structure in the hippocampus, Lister-Hooded rats were trained on a hippocampal-dependent spatial task in the radial-arm maze.  Methods:  One group of rats were trained on a hippocampal-dependent spatial task in the radial arm maze. Two further control groups were included: a yoked group which received the same sensorimotor stimulation in the radial-maze but without a memory load, and home-cage controls. At the end of behavioural training, the brains underwent Golgi staining. Spines on CA1 pyramidal neuron dendrites were imaged and quantitatively assessed to provide measures of density and distance from nearest neighbour.  Results: There was no difference across behavioural groups either in terms of spine density or in the clustering of dendritic spines. Conclusions:  Spatial learning is not always accompanied by changes in either the density or clustering of dendritic spines on the basal arbour of CA1 pyramidal neurons when assessed using Golgi imaging.

Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease. Infants diagnosed with TOF require surgical interventions to survive into adulthood. However, as a result of postoperative structural malformations and long-term ventricular remodeling, further interventions are often required later in life. To help identify those at risk of disease progression, serial cardiac magnetic resonance (CMR) imaging is used to monitor these patients. However, most of the detailed information on cardiac shape and biomechanics contained in these large four-dimensional (4D) data sets goes unused in clinical practice for lack of efficient and comprehensive quantitative analysis tools. While current global metrics of cardiac size and function, such as indexed ventricular mass and volumes, can identify patients at risk of further complications, they are not adequate to explain the underlying mechanisms causing the postoperative malfunctions, and help cardiologists plan optimal personalized treatments. We are proposing a novel approach that uses 4D ventricular shape models derived from CMR imaging exams to generate statistical atlases of ventricular shape and finite-element models of ventricular biomechanics to identify specific features of cardiac shape and biomechanical properties that explain variations in ventricular function. This study has the potential to discover novel biomarkers that precede adverse ventricular remodeling and dysfunction.

Reduced exercise capacity is nearly universal among Fontan patients. Although many factors have emerged as possible contributors, the degree to which each impacts the overall hemodynamics is largely unknown. Computational modeling provides a means to test hypotheses of causes of exercise intolerance via precisely controlled virtual experiments and measurements. We quantified the physiological impacts of commonly encountered, clinically relevant dysfunctions introduced to the exercising Fontan system via a previously developed lumped-parameter model of Fontan exercise. Elevated pulmonary arterial pressure was observed in all cases of dysfunction, correlated with lowered cardiac output (CO), and often mediated by elevated atrial pressure. Pulmonary vascular resistance was not the most significant factor affecting exercise performance as measured by CO. In the absence of other dysfunctions, atrioventricular valve insufficiency alone had significant physiological impact, especially under exercise demands. The impact of isolated dysfunctions can be linearly summed to approximate the combined impact of several dysfunctions occurring in the same system. A single dominant cause of exercise intolerance was not identified, though several hypothesized dysfunctions each led to variable decreases in performance. Computational predictions of performance improvement associated with various interventions should be weighed against procedural risks and potential complications, contributing to improvements in routine patient management protocol.