Spatial working memory (WM; i.e., "scratchpad" memory) is constantly updated to guide behavior based on representational knowledge of spatial position. It is maintained by spatially tuned, recurrent excitation within networks of prefrontal cortical (PFC) neurons, evident during delay periods in WM tasks. Stimulation of postsynaptic alpha2A adrenoceptors (alpha2A-ARs) is critical for WM. We report that alpha2A-AR stimulation strengthens WM through inhibition of cAMP, closing Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channels and strengthening the functional connectivity of PFC networks. Ultrastructurally, HCN channels and alpha2A-ARs were colocalized in dendritic spines in PFC. In electrophysiological studies, either alpha2A-AR stimulation, cAMP inhibition or HCN channel blockade enhanced spatially tuned delay-related firing of PFC neurons. Conversely, delay-related network firing collapsed under conditions of excessive cAMP. In behavioral studies, either blockade or knockdown of HCN1 channels in PFC improved WM performance. These data reveal a powerful mechanism for rapidly altering the strength of WM networks in PFC.

Background: Methylphenidate (MPH) is the classic treatment for Attention Deficit Hyperactivity Disorder (ADHD), yet the mechanisms underlying its therapeutic actions remain unclear. Recent studies have identified an oral, MPH dose regimen which when given to rats produces drug plasma levels similar to those measured in humans. The current study examined the effects of these low, orally-administered doses of MPH in rats performing a delayed alternation task dependent on prefrontal cortex (PFC), a brain region that is dysfunctional in ADHD, and is highly sensitive to levels of catecholamines. The receptor mechanisms underlying the enhancing effects of MPH were explored by challenging the MPH response with the noradrenergic α2 adrenoceptor antagonist, idazoxan, and the dopamine D1 antagonist, SCH23390.

Ten patients who suffered iatrogenic injury to a vertebral artery during anterior cervical decompression were reviewed to assess the mechanisms of injury, their operative management, and the subsequent outcome. All had been undergoing a partial vertebral body resection for spondylitic radiculopathy or myelopathy (4), tumour (2), ossification of the posterior longitudinal ligament (1), nonunion of a fracture (2), or osteomyelitis (1). The use of an air drill had been responsible for most injuries. The final control of haemorrhage had been by tamponade (3), direct exposure and electrocoagulation (1), transosseous suture (2), open suture (1), or open placement of a haemostatic clip (3). Five patients had postoperative neurological deficits, but most of them resolved. We found direct arterial exposure and control to be safe, quick and reliable. Careful use of the air drill, particularly in pathologically weakened bone, as in infection or tumour, is essential. Arterial injury is best avoided by a thorough knowledge of the anatomical relationships of the artery, the spinal canal, and the vertebral body.

With the technical assistance of Anne Dudley T HE DETERMINATION of the level of circulating endogenous heparin is important, since heparin may normally function to keep the blood in a fluid state, and it also probably plays a major role in the clearing of alimentary lipemia from the bloodstream. Unfortunately, methods for the extraction of native heparin are not only difficult and tedious, but the end-product includes other mucopolysaccharides that interfere with assays based upon metachromatic technics.' On the other hand, coagulation tests, such as the protamine titration and toluidine blue procedures, are not an index of the amount of heparin but rather indicators of the equilibrium between the systems of factors favoring or inhibiting blood clotting.2 A relatively simple procedures based upon thrombin neutralization is available, but it is only discriminating enough to disclose marked increases in heparin levels. There are excellent methods4 for measuring the levels of injected, free heparin, but these do not afford information about the quantity of endogenous plasma heparin, which. with rare exceptions, is always protein-bound.These various difficulties, and the failure to appreciate them, have led to marked discrepancies in the results reported in studies of circulating heparin. Some responsible investigators4 imply that heparin is not normally present in human plasma, whereas others5 have reported very high levels. It

The ability to de novo synthesize purines has been associated with the intracellular survival of multiple bacterial pathogens. Uropathogenic Escherichia coli (UPEC), the predominant cause of urinary tract infections, undergoes a transient intracellular lifestyle during which bacteria clonally expand into multicellular bacterial communities within the cytoplasm of bladder epithelial cells. Here, we characterized the contribution of the conserved de novo purine biosynthesis-associated locus cvpA-purF to UPEC pathogenesis. Deletion of cvpA-purF, or of purF alone, abolished de novo purine biosynthesis but did not impact bacterial adherence properties in vitro or in the bladder lumen. However, upon internalization by bladder epithelial cells, UPEC deficient in de novo purine biosynthesis was unable to expand into intracytoplasmic bacterial communities over time, unless it was extrachromosomally complemented. These findings indicate that UPEC is deprived of purine nucleotides within the intracellular niche and relies on de novo purine synthesis to meet this metabolic requirement.

In children with neuropathic bladder the cystatin C estimated glomerular filtration rate is a better screening test for early renal insufficiency that is not detected by creatinine based rate calculations. To our knowledge it remains to be determined whether the cystatin C estimated glomerular filtration rate can ultimately improve the clinical outcome in this population.

Experienced pediatric urologists demonstrate variability during interpretation of videourodynamic tracings. Subjectivity of assessment of electromyographic activity and detrusor overactivity was confirmed in this expanded study. Future work to improve the reliability of videourodynamic interpretation would improve the quality of clinical care and the quality of multi-institutional studies that use urodynamic data points as outcomes.

Faculty interpretations of urodynamic tracings showed only moderate agreement despite a close working relationship and similar training at a single institution. Variability in interpretation can strongly impact patient treatment. Therefore, further work is needed to standardize the reporting and interpretation of urodynamic studies to optimize patient care.