Hippocampal BOLD response during category learning predicts subsequent performance on transfer generalization

To test a prediction of our previous computational model of cortico‐hippocampal interaction (Gluck and Myers [1993, 2001]) for characterizing individual differences in category learning, we studied young healthy subjects using an fMRI‐adapted category‐learning task that has two phases, an initial phase in which associations are learned through trial‐and‐error feedback followed by a generalization phase in which previously learned rules can be applied to novel associations (Myers et al. [2003]). As expected by our model, we found a negative correlation between learning‐related hippocampal responses and accuracy during transfer, demonstrating that hippocampal adaptation during learning is associated with better behavioral scores during transfer generalization. In addition, we found an inverse relationship between Blood Oxygenation Level Dependent (BOLD) activity in the striatum and that in the hippocampal formation and the orbitofrontal cortex during the initial learning phase. Conversely, activity in the dorsolateral prefrontal cortex, orbitofrontal cortex and parietal lobes dominated over that of the hippocampal formation during the generalization phase. These findings provide evidence in support of theories of the neural substrates of category learning which argue that the hippocampal region plays a critical role during learning for appropriately encoding and representing newly learned information so that that this learning can be successfully applied and generalized to subsequent novel task demands. Hum Brain Mapp 35:3122–3131, 2014. © 2013 Wiley Periodicals, Inc .     

Human renalase: a review of its biology,function, and implications for hypertension

Renalase is a novel flavoprotein, highly expressed in kidney and heart, which metabolizes catecholamines and catecholamine-like substances via a superoxide (O2^–)-dependent mechanism using nicotinamide adenine dinucleotide (NADH) as a cofactor. Its mechanism of action is distinct from that of monoaminooxidases A and B, because it oxidizes catecholamines (epinephrine>>L-DOPA>dopamine = norepinephrine) to aminochrome, and the reaction rate increases ～4- to 6-fold in presence of NADH. Tissue and plasma renalase levels are decreased in animal models of chronic kidney disease, and renalase deficiency is associated with increased blood pressure and elevated circulating catecholamines. Renalase plasma levels, measured by enzyme-linked immunosorbent assay, are reported to be ～ 5-fold higher in patients with end-stage renal disease than in normal control subjects. They were also increased in kidney and heart transplant recipients, and inversely correlated with estimated glomerular filtration rate. Renalase has potential therapeutic applications. Experimental models demonstrate that the chronic administration of renalase decreases ambulatory blood pressure and prevents the development of cardiac hypertrophy in rats, and that its acute administration decreases ischemic acute kidney injury in mice. Here we provide a detailed review of renalase biology including its mechanism of action, secretion into blood, interaction with the renal dopamine and epinephrine system, and early studies evaluating its association with outcomes related to hypertension and target-organ injury.     

C-reactive protein,platelets, and patent ductus arteriosus

The association between inflammation, platelets, and patent ductus arteriosus (PDA) has not been studied so far. The purpose of this study was to evaluate whether C-reactive protein (CRP) is related to low platelet count and PDA. This was a retrospective study of 88 infants with a birth weight ≤1500 g and a gestational age ≤30 weeks. Platelet count, CRP, and an echocardiogram were assessed in all infants. The subjects were matched by sex, gestational age, and birth weight. Differences were compared using the χ², t-test, or Mann–Whitney U-test, as appropriate. Significant variables were entered into a logistic regression model. The association between CRP and platelets was evaluated by correlation and regression analysis. Platelet count (167 000 vs. 213 000 µl^?1, p = 0.015) was lower and the CRP (0.45 vs. 0.20 mg/dl, p = 0.002) was higher, and the platelet count correlated inversely with CRP (r = ?0.145, p = 0.049) in the infants with vs. without PDA. Only CRP was independently associated with PDA in a logistic regression model (OR 64.1, 95% confidence interval 1.4–2941, p = 0.033).     

Sensitization and pain

Migraine is often accompanied with signs of increased intracranial and extracranial mechanical sensitivities. The prevailing view today is that migraine headache is a neurovascular disorder with intracranial origin and involvement of meningeal blood vessels and their pain nerve fibers. Allodynia, defined as perception of pain following not painful stimulation, is a common clinical feature in various pain syndromes, and as part of migraine pain, it can be considered an indicator of trigeminal neural network sensitization. The cutaneous allodynia that accompanies the migraine headache in a large percentage of patients may be considered the clinical expression of central nervous system sensitization and is characterized by pain provoked by stimulation of the skin that would ordinarily not produce pain. An altered codification process of sensory impulses in the brainstem, in particular by the nucleus caudalis trigeminalis, may justify the temporal aspects and symptoms in the course of migraine attack.