Motor development in children with congenital cardiac diseases compared to their healthy peers

Their perceptual and motor experiences determine the physical and motor development of children, and impact also on their emotional, psychosocial, and cognitive development. Our aim, therefore, was to evaluate motor development in children with congenitally malformed hearts compared to their healthy peers. We compared 194 children, with a mean age of 10.0 years, and standard deviation of 2.7 years, representing the entire spectrum of congenital cardiac disease, to a control group of 455 healthy children, having a mean age 9.6 years, with standard deviation of 2.17 years. The bodily coordination test for children was used to examine motor development. Of the children with congenitally malformed hearts, 26.8% showed moderate, and 31.9% had severe disturbances of motor development, compared to 16.5% and 5.5% of the control group, the p-value for these differences being less than 0.001. The mean motor quotient adjusted for age and gender was lower in the children with congenitally malformed hearts than in their healthy peers, at 79.6, with standard deviation of 18.9 as opposed to 96.6, with standard deviation of 15, this difference having a p-value of less than 0.001. Depending on the presence, and/or the degree, of residual sequels, the children with congenitally malformed hearts were divided into two subgroups, with either no or mild residual sequels, or with significant sequels. The mean motor quotient was lower in those with significant residual sequels, at 75, with standard deviation of 19.3, as opposed to 83, with standard deviation of 17.9, the p-value for this difference being less than 0.01. In both subgroups, the mean motor quotient was lower, with a p-value of less than 0.01, than in the control group. Our findings show that children with congenitally malformed hearts have deficits in their motor development, these being found in the presence of no or mild sequels, as well as with significant residual sequels. Parental overprotection may contribute to these findings.     

Inflammatory pseudotumor of the lung following invasive aspergillosis in a patient with chronic graft-vs.-host disease

Inflammatory myofibroblastic tumor (IMT) is an uncommon cause of solitary or multifocal lung nodules and can also be rarely found in various other extrapulmonary sites. Although this pseudotumor is benign, it can be locally very aggressive. The pathogenesis of IMT remains unclear; autoimmune or infectious origins have been hypothesized, so far. Here, we report a case of inflammatory pseudotumor of the lung secondary to invasive pulmonary aspergillosis in a patient with chronic graft-vs.-host disease. The 42-year-old patient presented with coughing and hemoptysis as major clinical signs 1 yr after successful HLA-identical stem cell transplantation. Aspergillus fumigatus was cultured from the bronchoscopic lavage, but intensive antifungal treatment could only initially improve the clinical situation. Diagnostic re-evaluation by open-chest biopsy surprisingly revealed an inflammatory pseudotumor responsible for clinical and radiographical deterioration. Both clinical and radiographical signs resolved under long-term steroids and secondary antifungal prophylaxis.     

Working memory and fear conditioning

Previous studies of associative learning implicate higher-level cognitive processes in some forms of classical conditioning. An ongoing debate is concerned with the extent to which attention and awareness are necessary for trace but not delay eye-blink conditioning [Clark, R. E. & Squire, L. R. (1998) Science 280, 77-81; Lovibond, P. F. & Shanks, D. (2002) J. Exp. Psychol. Anim. Behav. Processes 28, 38-42]. In trace conditioning, a short interval is interposed between the termination of the conditioned stimulus (CS) and the onset of the unconditioned stimulus (US). In delay conditioning, the CS and US overlap. We here investigate the extent to which human classical fear conditioning depends on working memory. Subjects had to carry out an n-back task, requiring tracking an item 1 or 2 back in a sequentially presented list of numbers, while simultaneously being tested for their ability to associate auditory cues with shocks under a variety of conditions (single-cue versus differential; delay versus trace; no task versus 0-, 1-, and 2-back). Differential delay conditioning proved to be more resilient than differential trace conditioning but does show a reduction due to task interference similar in slope to that found in trace conditioning. Explicit knowledge of the stimulus contingency facilitates but does not guarantee trace conditioning. Only the single-cue delay protocol shows conditioning during the more difficult working memory task. Our findings suggest that the larger the cognitive demands on the system, the less likely conditioning occurs. A postexperimental questionnaire showed a positive correlation between conditioning and awareness for differential trace conditioning extinction.     

Determinants of mortality in patients with type 2 diabetes: a review

We aimed to review and summarize the evidence from accomplished trials analyzing factors influencing mortality in patients with T2DM and to provide some recommendations for targets and treatment in the European region. The following databases were searched for relevant trials: PubMed and the Cochrane Library. Of 3.806 citations, 134 trials met our inclusion criteria. Results: The reduction in lifetime for 65 + ?years-old patients having less than 10 years T2DM amounts to 1.8 years. Having T2DM for more than 10 years lifetime will be reduced by 2.7 years. However, the lifetime shortening factor of T2DM will even be stronger for 40 + ?years-old patients at onset. Males will lose 11.6 years of life and 18.6 QUALYs. T2DM among females will reduce life by 14 QUALYs by 22 years. From a statistical point of view, the highest mortality rate will occur in an over 55-years-old European smoking and non-compliant diabetic woman with alcohol abuse living in a rural area with a low level of education and a low socio-economic status. Furthermore, other co-morbidities such as cardiovascular diseases, gout, and depression affect mortality. Additionally, mortality will increase with a BMI over 35 and also with a BMI under 20–25. This refers to the obesity paradox indicating a higher mortality rate among normal weight patients with T2DM compared to overweight patients with T2DM. HbA1c-levels between 6.5 % and 7 % are associated with the lowest impact on mortality.     

Structural insights into the antigenicity of myelin oligodendrocyte glycoprotein

Multiple sclerosis is a chronic disease of the central nervous system (CNS) characterized by inflammation, demyelination, and axonal loss. The immunopathogenesis of demyelination in multiple sclerosis involves an autoantibody response to myelin oligodendrocyte glycoprotein (MOG), a type I transmembrane protein located at the surface of CNS myelin. Here we present the crystal structures of the extracellular domain of MOG (MOGIgd) at 1.45-A resolution and the complex of MOGIgd with the antigen-binding fragment (Fab) of the MOG-specific demyelinating monoclonal antibody 8-18C5 at 3.0-A resolution. MOGIgd adopts an IgV like fold with the A'GFCC'C" sheet harboring a cavity similar to the one used by the costimulatory molecule B7-2 to bind its ligand CTLA4. The antibody 8-18C5 binds to three loops located at the membrane-distal side of MOG with a surprisingly dominant contribution made by MOG residues 101-108 containing a strained loop that forms the upper edge of the putative ligand binding site. The sequence R101DHSYQEE108 is unique for MOG, whereas large parts of the remaining sequence are conserved in potentially tolerogenic MOG homologues expressed outside the immuno-privileged environment of the CNS. Strikingly, the only sequence identical to DHSYQEE was found in a Chlamydia trachomatis protein of unknown function, raising the possibility that Chlamydia infections may play a role in the MOG-specific autoimmune response in man. Our data provide the structural basis for the development of diagnostic and therapeutic strategies targeting the pathogenic autoantibody response to MOG.     

A Novel Angiographic Quantification of Aortic Regurgitation After TAVR Provides an Accurate Estimation of Regurgitation Fraction Derived From Cardiac Magnetic Resonance Imaging

Objectives

This study sought to compare a new quantitative angiographic technique to cardiac magnetic resonance-derived regurgitation fraction (CMR-RF) for the quantification of prosthetic valve regurgitation (PVR) after transcatheter aortic valve replacement (TAVR).