Patient distress was related to disease burden (standardized path coefficient=0.52) and patient social

relatedness (-0.32). Caregiver distress was related to caregiving burden (0.21) and caregiver social relatedness (-0.51). Caregiving burden was related to patient disease burden (0.43) and caregiver social relatedness (-0.37). Reciprocal pathways between patient and caregiver distress indicated that caregiver distress was influenced by patient distress (0.30) but not vice versa (0.12).

ConclusionsThese findings support the view that patients and caregivers constitute an interdependent relational system and interventions in this setting should take into account both interactions between patients and caregivers and the find more nature of their social relatedness. Copyright (c) 2013 John selleck inhibitor Wiley & Sons, Ltd.”
“Overwhelming evidence supports a central role for the amyloid beta-peptide (A beta) in the pathogenesis of Alzheimer’s disease (AD), and the proteases that produce A beta from its precursor protein APP are top targets for therapeutic intervention. Considerable effort has focused on targeting gamma-secretase, which generates the C-terminus of A beta; however, gamma-secretase inhibitors cause serious toxicities due to interference with the Notch signaling pathway. We have been working toward compounds that directly alter gamma-secretase activity to reduce A beta production without affecting the

proteolysis of Notch. Using purified enzyme and substrate, we have shown that gamma-secretase can be selectively inhibited in this way by naphthyl-substituted gamma-aminoketones and gamma-aminoalcohols. These early hits, however, suffered from chemical instability and/or poor potency. Iterative design, synthesis and evaluation have led to the discovery of Notch-sparing gamma-secretase inhibitors with substantially increased potencies

in biochemical and cellular assays. These compounds are of low molecular Selleckchem CX-6258 weight and are under evaluation for drug-like properties. The discovery and development of these compounds will be discussed.”
“The comorbid psychiatric disorders in patients with epilepsy have been neglected for a long time. And yet, epidemiological studies have demonstrated a relatively high prevalence of mood, anxiety, and attention deficit hyperactivity disorders. Furthermore, the relation between psychiatric disorders and epilepsy is complex, as illustrated by the relation between mood disorders and epilepsy. The aim of this article is to summarize the most relevant data oil the complex relation between mood disorders and epilepsy, which extends to anxiety disorders and which can be explained by the existence of common pathogenic mechanisms shared by these three conditions. The significance Of such a relation is not only theoretical, but has a marked impact on the response to pharmacological and surgical treatment of seizure disorders. (C) 2009 Elsevier Inc. All rights reserved.