Abnormal Structure of Fear Circuitry in Pediatric Post-Traumatic Stress Disorder

Structural brain studies of adult post-traumatic stress disorder (PTSD) show reduced gray matter volume (GMV) in fear regulatory areas including the ventromedial prefrontal cortex (vmPFC) and hippocampus. Surprisingly, neither finding has been reported in pediatric PTSD. One possibility is that they represent age-dependent effects that are not fully apparent until adulthood. In addition, lower-resolution MRI and image processing in prior studies may have limited detection of such differences. Here we examine fear circuitry GMV, including age-related differences, using higher-resolution MRI in pediatric PTSD vs healthy youth. In a cross-sectional design, 3 T anatomical brain MRI was acquired in 27 medication-free youth with PTSD and 27 healthy non-traumatized youth of comparable age, sex, and IQ. Voxel-based morphometry was used to compare GMV in a priori regions including the medial prefrontal cortex and amygdala/hippocampus. Compared with healthy youth, PTSD youth had reduced GMV but no age-related differences in anterior vmPFC (BA 10/11, Z=4.5), which inversely correlated with PTSD duration. In contrast, although there was no overall group difference in hippocampal volume, a group × age interaction (Z=3.6) was present in the right anterior hippocampus. Here, age positively predicted hippocampal volume in healthy youth but negatively predicted volume in PTSD youth. Within the PTSD group, re-experiencing symptoms inversely correlated with subgenual anterior cingulate cortex (sgACC, Z=3.7) and right anterior hippocampus (Z=3.5) GMV. Pediatric PTSD is associated with abnormal structure of the vmPFC and age-related differences in the hippocampus, regions important in the extinction and contextual gating of fear. Reduced anterior vmPFC volume may confer impaired recovery from illness, consistent with its role in the allocation of attentional resources. In contrast, individual differences in sgACC volume were associated with re-experiencing symptoms, consistent with the role of the sgACC in fear extinction. The negative relationship between age and hippocampal volume in youth with PTSD may suggest an ongoing neurotoxic process over development, which further contributes to illness expression. Future studies employing a longitudinal design would be merited to further explore these possibilities.     

Patient Health Literacy and Communication with Providers Among Women Living with HIV: A Mixed Methods Study

AIDS and Behavior - In this mixed-methods study, we examine the relationship between provider communication and patient health literacy on HIV continuum of care outcomes among women living with HIV...     

Magnetic field interactions between current consumer electronics and cardiac implantable electronic devices

Journal of Interventional Cardiac Electrophysiology - Ablation index (AI) is a radiofrequency lesion quality marker. The AI value that allows effective and safe pulmonary vein isolation (PVI) is...     

Binding of 125I-labelled thyrotrophin to transfected human thyrocytes (SGHTL-34 cells)

The binding of 125I-labelled bovine TSH to a human thyroid cell line (SGHTL-34) has been studied. Binding to hormonally responsive cells was time dependent, specific and reversible. Scatchard analysis of the binding data indicated the presence of a single binding site with high affinity (intrinsic dissociation constant (Kd) = 0.25 +/- 0.08 nmol/l; mean +/- S.E.M.; n = 4) and low capacity (maximum binding (Bmax) = 104 +/- 29 fmol/mg protein; mean +/- S.E.M.; n = 4). Hill plots confirmed the presence of a single site. Kinetic data demonstrated close agreement between the Kd and Bmax obtained from the competition data (Kd = 0.23 +/- 0.35 nmol/l; Bmax = 161 +/- 83 fmol/mg protein; n = 6).     

Risk of venous thromboembolism associated with the common hereditary haemochromatosis Hfe gene (C282Y) mutation

A high prevalence of a common mutation in the Hfe gene (C282Y) has recently been reported in patients with the factor V Leiden mutation and a history of thrombosis. The aim of this study was to estimate the relative risk of venous thromboembolism in a large case-control study. 56/481 patients (11.6%) and 57/497 controls (11.5%) were heterozygous for the C282Y allele giving an odds ratio of 1.02 (95%CI 0.69-1.51). 12/81 patients with the factor V Leiden mutation were heterozygous for the C282Y allele compared to 1/13 controls, odds ratio 2.09 (95%CI 0.25-17.6). An analysis of a further group of patients and controls selected for the factor V Leiden mutation did not indicate a higher prevalence of the C282Y allele in symptomatic patients, odds ratio 0.17 (95%CI 0.34-0.81). This study does not support the hypothesis that the C282Y allele is an additional risk factor for venous thrombosis in patients with the factor V Leiden mutation.     

Light chain 2 profile and activity of human ventricular myosin during dilated cardiomyopathy. Identification of a causal agent for impaired myocardial function.

BACKGROUND. A number of parameters reflecting the effects of idiopathic dilated cardiomyopathy (IDC) on the structure and function of myosin from the human myocardium were analyzed. METHODS AND RESULTS. The content of the regulatory light chain, LC2, was reduced in myopathic heart myosin in contrast to the controls in which it was present in stoichiometric amounts relative to the essential light chain, LC1. In IDC hearts, the absence or significant reduction in amount of LC2 was related to the presence of an active protease, which was isolated and purified about 130-fold. The protease exhibited a significant degree of specificity: It cleaved LC2 almost totally (but not the heavy chains) in human control heart myosin but only partially cleaved LC2 in canine heart or in rabbit skeletal muscle myosins. The protease was present at a very low level or was inactive in control heart tissue. When the LC1/LC2 molar ratio was calculated, it was found to be 1:1.0 in control heart myosin and remained constant in various samples analyzed, whereas in myopathic myosin from different individuals, this ratio varied from 1:0.1 to 1:0.69. The rates of ATP binding to control and myopathic myosins were similar, whereas the Vm of actin-activated ATPase of myopathic myosin was about 25% less than that of the control. However, ATP binding and its hydrolysis by control S1, i.e., the myosin head, were faster by a factor of 2 than that of the myopathic S1. In addition, control myosin synthetic thick filament length as well as turbidity in solution, measured by light scattering, were twice as large as those of the myopathic heart myosin. These effects induced by myopathy in both filament assembly and turbidity were reversed upon reassociation of IDC myosin with LC2. CONCLUSIONS. The changes in myosin structure and function were linked to a protease-mediated cleavage of LC2 in myosin; a possible role for the protease in the degenerative effects of idiopathic dilated cardiomyopathy is thus defined.     

Pulmonary vascular disease in neonates with transposition of the great arteries and intact ventricular septum.

BACKGROUND--Progressive pulmonary vascular disease in surgically unrepaired transposition of the great arteries with or without ventricular septal defect had been frequently described in the past. Occurrence of progressive pulmonary vascular disease has been reported even after atrial switch procedure done at three months of age. With the advent of neonatal surgical repair, this problem is virtually non-existent. There is a small subgroup of infants with transposition of the great arteries who show pulmonary vascular disease in the neonatal period that can adversely affect the surgical outcome. The clinico-pathological correlation in this group of patients was studied. OBSERVATIONS--Three patients, with transposition of the great arteries and intact ventricular septum, who showed histological evidence of pulmonary vascular disease in the neonatal period or early infancy are described. Two of these patients, continued to have poor systemic oxygenation despite adequate atrial communication. One patient had a close ductus arteriosus within the first two hours of birth while on prostaglandin E1 infusion. CONCLUSIONS--In the absence of left ventricular outflow tract obstruction, a poor response to atrial septostomy suggests pulmonary hypertension and pulmonary vascular disease. Antenatal constriction of the ductus arteriosus may contribute to such changes in pulmonary vasculature.