Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself

Respiratory Motion Correction in Dynamic PET with a Single Attenuation Map

In addition to static tracer uptake values used routinely in clinical facilities, PET imaging can provide useful information on tracer kinetics via the use of dynamic acquisitions where a set of time frames are acquired starting from the injection/inhalation of the radiotracer. In lung studies, kinetic parameters, estimated from compartmental modelling, are however affected by respiratory motion. When only one attenuation image is available, most existing motion compensation strategies are not appropriate for the initial short time frames, especially as the activity distribution changes rapidly over the early part of the dynamic acquisition. This work presents a preliminary study to handle respiratory motion using a two-step process that uses gated dynamic data as input. We first use joint reconstruction of activity and motion on the entire gated PET data to estimate deformation fields. This allows the subsequent reconstruction of each time frame separately with motion compensation. We present results comparing on one hand the compartment model fit residuals with and without respiratory motion compensation and on the other hand the diaphragm position in non-attenuation corrected images and from this method

Hypertonic saline reduces inflammation and enhances the resolution of oleic acid induced acute lung injury

<p>Abstract</p> <p>Background</p> <p>Hypertonic saline (HTS) reduces the severity of lung injury in ischemia-reperfusion, endotoxin-induced and ventilation-induced lung injury. However, the potential for HTS to modulate the resolution of lung injury is not known. We investigated the potential for hypertonic saline to modulate the evolution and resolution of oleic acid induced lung injury.</p> <p>Methods</p> <p>Adult male Sprague Dawley rats were used in all experiments. <b><it>Series 1 </it></b>examined the potential for HTS to reduce the severity of evolving oleic acid (OA) induced acute lung injury. Following intravenous OA administration, animals were randomized to receive isotonic (Control, n = 12) or hypertonic saline (HTS, n = 12), and the extent of lung injury assessed after 6 hours. <b><it>Series 2 </it></b>examined the potential for HTS to enhance the resolution of oleic acid (OA) induced acute lung injury. Following intravenous OA administration, animals were randomized to receive isotonic (Control, n = 6) or hypertonic saline (HTS, n = 6), and the extent of lung injury assessed after 6 hours.</p> <p>Results</p> <p>In <b><it>Series I</it></b>, HTS significantly reduced bronchoalveolar lavage (BAL) neutrophil count compared to Control [61.5 ± 9.08 versus 102.6 ± 11.89 × 10³ cells.ml^-1]. However, there were no between group differences with regard to: A-a O2 gradient [11.9 ± 0.5 vs. 12.0 ± 0.5 KPa]; arterial PO2; static lung compliance, or histologic injury. In contrast, in <b><it>Series 2</it></b>, hypertonic saline significantly reduced histologic injury and reduced BAL neutrophil count [24.5 ± 5.9 versus 46.8 ± 4.4 × 10³ cells.ml^-1], and interleukin-6 levels [681.9 ± 190.4 versus 1365.7 ± 246.8 pg.ml^-1].</p> <p>Conclusion</p> <p>These findings demonstrate, for the first time, the potential for HTS to reduce pulmonary inflammation and enhance the resolution of oleic acid induced lung injury.</p