Unhappy Triad: Infection with spp. and Associated with an Unusual Manifestation of Portal Vein Thrombosis.

Portal vein thrombosis (PVT) is a rare disease with an incidence of 0.7/100,000 inhabitants per year. Septic PVT (pylephlebitis) usually occurs secondary to infection in the anatomic region drained by the portal venous system.

Terrestrial Isopods Porcellio scaber and Oniscus asellus (Crustacea: Isopoda) Increase Bacterial Abundance and Modify Microbial Community Structure in Leaf Litter Microcosms: a Short-Term Decomposition Study.

Invasive terrestrial isopods are likely to have altered leaf litter decomposition processes in North American forests, but the mechanisms underlying these alterations and the degree to which they differ among isopod species are poorly characterized. Using mixed-deciduous leaf litter microcosms, we quantified the effects of two common, invasive isopods (Oniscus asellus and Porcellio scaber) on short-term leaf litter decomposition and microbial community structure and function. Microcosms containing ground litter and a microbial inoculant were exposed to one of the two isopod species or no isopods for 21 days.

Changes in brain arousal (EEG-vigilance) after therapeutic sleep deprivation in depressive patients and healthy controls.

Depressed patients frequently exhibit a hyperstable brain arousal regulation. According to the arousal regulation model of affective disorders, the antidepressant effect of therapeutic sleep deprivation could be achieved by counter-acting this dysregulation. We investigated the impact of partial sleep deprivation (PSD) on EEG-vigilance (an indicator of brain arousal regulation) in depressed patients (n = 27) and healthy controls (n = 16).

In vitro evaluation of the anti-estrogenic activity of hydroxyl substituted diphenylnaphthyl alkene ligands for the estrogen receptor.

There is still a need for additional scaffolds to further explore tissue selectivity and improving efficacy of selective estrogen receptor modulators (SERMs). A series of hydroxyl substituted diphenylnaphthyl alkene ligands for the two estrogen receptors are described that arose from an initial de novo designed diphenylnaphthyl propylene ligand 1. All compounds gave K(i)s under 10 nM when assayed in the presence of ERalpha.

Fuzzy clustering as a means of selecting representative conformers and molecular alignments.

This paper describes the first application of fuzzy c-means clustering for the selection of representatives from assemblies of conformations or alignments. In case of alignments, their quality is taken into account using a weighted c-means scheme, developed in this work. The performance of fuzzy cluster validity measures, such as compactness, partition function, and entropy, are studied on several examples, but the visual 3D representation of data points is shown to be most beneficial in determining the optimum number of clusters.

De novo design, synthesis, and evaluation of novel nonsteroidal phenanthrene ligands for the estrogen receptor.

Although there are many estrogen receptor antagonists with improved tissue selectivity profiles compared with tamoxifen, optimal tissue selectivity has not yet been demonstrated. As such there is still a need for additional diversity and new chemical scaffolds to allow for exploration of improved tissue selectivity. Here, we describe the discovery of a novel phenanthrene scaffold for estrogen receptor ligands utilizing a ligand based de novo design approach.

Synthesis and evaluation of a novel nonsteroidal-specific endothelial cell proliferation inhibitor.

The identification of agents with specific antiproliferative or cytostatic activity against endothelial cells has significant value for the treatment of pathologies associated with angiogenesis, including solid tumors. Here, we describe a novel substituted dibenzo[b,d]pyran-6-one scaffold, exemplified by structures 9a and 10, and report preliminary in vitro activity data indicating that this scaffold is a promising lead for the development of specific inhibitors of endothelial cell proliferation.

De novo design, synthesis and evaluation of a non-steroidal diphenylnaphthyl propylene ligand for the estrogen receptor.

There is still a strong need for additional diversity and new chemical scaffolds to allow for the exploration of improved tissue selectivity and finding better selective estrogen receptor modulators (SERMs). Using a de novo design technology a diphenylnaphthyl propylene scaffold, exemplified by (E)-9b, with ER antagonist activity has been generated. It was prepared by alkylating 1-[4-methoxyphenyl)-2-(4-(2-chloroethoxy)phenyl]-1-propanone under metal halogen exchange conditions with 1-iodo-6-methoxy-naphthalene.

Property distributions: differences between drugs, natural products, and molecules from combinatorial chemistry.

The differences between three different compound classes, natural products, molecules from combinatorial synthesis, and drug molecules, were investigated. The major structural differences between natural and combinatorial compounds originate mainly from properties introduced to make combinatorial synthesis more efficient. These include the number of chiral centers, the prevalence of aromatic rings, the introduction of complex ring systems, and the degree of the saturation of the molecule as well as the number and ratios of different heteroatoms.