Predictors of physical activity among rural adults following cardiac rehabilitation.

Purpose/objective: Cardiac rehabilitation aims to reduce the likelihood of recurrent cardiac events through physical activity (PA) and education. There is limited understanding about the predictors of physical activity behavior in rural adults beyond rehabilitation. This study explored predictors of regular physical activity in rural adults, 6-12 months post cardiac rehabilitation.

Central pontine myelinolysis secondary to hyperglycaemia.

Central pontine myelinolysis is characterised by focal osmotic demyelination within the pons. Its clinical presentation varies, but may include acute paralysis, dysarthria and dysphagia. The cause is traditionally associated with overzealous correction of hyponatraemia in patients who are malnourished, alcoholic or chronically ill.

Gliomatosis cerebri type 1 with extensive involvement of the spinal cord and BRAF V600E mutation.

Gliomatosis cerebri (GC) is a rare neoplasm in which there is a diffuse cerebral infiltration by malignant glial cells with relative conservation of the underlying structures. A 67-year-old lady was admitted complaining of balance problems, troubled breathing, stuttered speech, decreased mobility, progressive ataxia and also some mild cognitive problems. MRI demonstrated ill defined T2 hyperintensity with mild mass effect mainly involving the brain stem and cerebellar hemispheres, with minor signal abnormalities extending supratentorially along the corticospinal tracts.

Clinical experience with oral lacosamide as adjunctive therapy in adult patients with uncontrolled epilepsy: a multicentre study in epilepsy clinics in the United Kingdom (UK).

Introduction: Lacosamide (LCS) is a new antiepileptic drug (AED) licensed in the European Union (EU) and United States (US) in 2008.

Aims: To evaluate the efficacy and tolerability of add-on LCS in an out-patient epilepsy clinic setting to obtain useful information for everyday practice.

Methods: We pooled data retrospectively from the case note of patients with refractory epilepsy in whom LCS had been prescribed in 19 hospitals across the United Kingdom.

Methods for evaluation of positive allosteric modulators of glutamate AMPA receptors.

Hypofunctioning of glutamate synaptic transmission in the central nervous system (CNS) has been proposed as a factor that may contribute to cognitive deficits associated with various neurological and psychiatric disorders. Positive allosteric modulation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) subtype of glutamate receptors has been proposed as a novel therapeutic approach, because these receptors mediate the majority of rapid excitatory neurotransmission and are intimately involved in long-term changes in synaptic plasticity thought to underlie mnemonic processing. By definition, positive allosteric modulators do not affect AMPA receptor activity alone but can markedly enhance ion flux through the ion channel pore in the presence of bound agonist.

Molecular determinants responsible for differences in desensitization kinetics of AMPA receptor splice variants.

Flip (i) and flop (o) alternatively spliced variants of the four glutamate AMPA receptor subunits (GluR1-4) are differentially expressed in the CNS and can display distinct rates of desensitization that contribute to the heterogeneity of native AMPA receptor-dependent synaptic responses. In the present study, we initially compared the kinetics of desensitization in response to fast application of glutamate (1 mm) for the eight different homomeric recombinant human AMPA receptors (hGluR1-4i and o) heterologously expressed in mammalian cells. Consistent with previous reports on recombinant rat AMPA receptors, the time constants of desensitization between human GluR1i and GluR1o receptors were the same, whereas the flip isoforms for GluR2-4 receptors exhibited significantly slower rates of desensitization compared with the flop isoforms.

Multiple molecular determinants for allosteric modulation of alternatively spliced AMPA receptors.

Positive allosteric regulation of glutamate AMPA receptors involves conformational changes that can attenuate receptor desensitization and enhance ion flux through the channel pore. Many allosteric modulators (e.g.

A single residue contributes sensitivity to allosteric modulation of AMPA receptors by LY395153.

Previous studies have shown that a single point mutation (S(750)Q) in the splice variant region of rat Glu(1) subunits can eliminate positive allosteric modulation by cyclothiazide. The present study investigated the effects of mutating the equivalent residue (S(776)Q) in the human Glu(4) subunit on the activity and binding of a novel AMPA receptor potentiator, LY395153 (N-2-(4-benzamidophenylpropyl-2-propanesulfonamide)). The mutation markedly attenuated, but did not eliminate, potentiation by LY395153 and cyclothiazide.

LY404187: a novel positive allosteric modulator of AMPA receptors.

LY404187 is a selective, potent and centrally active positive allosteric modulator of AMPA receptors. LY404187 preferentially acts at recombinant human homomeric GluR2 and GluR4 versus GluR1 and GluR3 AMPA receptors. In addition, LY404187 potentiates the flip splice variant of these AMPA receptors to a greater degree than the flop splice variant.