Effort test failure: toward a predictive model.

Predictors of effort test failure were examined in an archival sample of 555 traumatically brain-injured (TBI) adults. Logistic regression models were used to examine whether compensation-seeking, injury-related, psychological, demographic, and cultural factors predicted effort test failure (ETF). ETF was significantly associated with compensation-seeking (OR = 3.51, 95% CI [1.25, 9.79]), low education (OR:. 83 [.74, . 94]), self-reported mood disorder (OR: 5.53 [3.10, 9.85]), exaggerated displays of behavior (OR: 5.84 [2.15, 15.84]), psychotic illness (OR: 12.86 [3.21, 51.44]), being foreign-born (OR: 5.10 [2.35, 11.06]), having sustained a workplace accident (OR: 4.60 [2.40, 8.81]), and mild traumatic brain injury severity compared with very severe traumatic brain injury severity (OR: 0.37 [0.13, 0.995]). ETF was associated with a broader range of statistical predictors than has previously been identified and the relative importance of psychological and behavioral predictors of ETF was evident in the logistic regression model. Variables that might potentially extend the model of ETF are identified for future research efforts.

Seleno-auranofin (Et3PAuSe-tagl): synthesis, spectroscopic (EXAFS, 197Au Mössbauer, 31P, 1H, 13C, and 77Se NMR, ESI-MS) characterization, biological activity, and rapid serum albumin-induced triethylphosphine oxide generation.

Seleno-auranofin (SeAF), an analogue of auranofin (AF), the orally active antiarthritic gold drug in clinical use, was synthesized and has been characterized by an array of physical techniques and biological assays. The Mössbauer and extended X-ray absorption fine structure (EXAFS) parameters of the solid compound demonstrate a linear P-Au-Se coordination environment at a gold(I) center, analogous to the structure of auranofin. The (31)P, (13)C, and (1)H NMR spectra of SeAF in chloroform solution closely resemble those of auranofin. The (77)Se spectrum consists of a singlet at 481 ppm, consistent with a metal-bound selenolate ligand. The absence of (2)J(PSe) coupling in the (31)P and (77)Se spectra may arise from dynamic processes occurring in solution or because the (2)J(PSe) coupling constants are smaller than the observed bandwidths. Electrospray ionization mass spectrometry (ESI-MS) spectra of SeAF in 50:50 methanol-water exhibited strong signals for [(Et(3)P)(2)Au](+), [(Et(3)PAu)(2)-mu-Se-tagl](+), and [Au(Se-tagl)(2)](-), which arise from ligand scrambling reactions. Three assays of the anti-inflammatory activity of SeAF allowed comparison to AF. SeAF exhibited comparable activity in the topically administered murine arachadonic acid-induced and phorbol ester-induced anti-inflammatory assays but was inactive in the orally administered carrageenan-induced assay in rats. However, in vivo serum gold levels were comparable in the rat, suggesting that differences between the in vivo metabolism of the two compounds, leading to differences in transport to the inflamed site, may account for the differential activity in the carrageenan-induced assay. Reactions of serum albumin, the principal transport protein of gold in the serum, demonstrated formation of AlbSAuPEt(3) at cysteine 34 and provided evidence for facile reduction of disulfide bonds at cysteine 34 and very rapid formation of Et(3)P=O, a known metabolite of auranofin.

Preliminary water quality assessment of Spunky Bottoms restored wetland.

The approximately 1200-acre "Spunky Bottoms" wetland in Southern Illinois has been undergoing restoration to conditions prior to levying of the Illinois River and draining of adjacent floodplain for intensive agriculture (circa 1900). As part of a long-term water quality impact assessment of this restoration project, baseline water quality monitoring was conducted soon after restoration began. During this baseline/preliminary assessment, water samples were taken every 2-4 weeks from 10 sampling wells and seven surface water sites throughout the wetlands area for a period of 18 months. Measured parameters include nutrients (nitrate (NO3-) and phosphate (PO4(3-)), cations and anions (SO4(2-), Cl-, Na+, K+, Mg2+, Ca2+) commonly found in surface and well water, trace metals (Al, Cd, Cu, Fe, Mn, Ni, Pb, Se, Zn), total dissolved solids (TDS), pH, and trace organics (triazine herbicides and their metabolites). In general, highest concentrations of ions were found in the southwest and northeast perimeter of the wetland area for both surface and ground water samples. Primarily low concentrations of heavy metals and organic compounds were found throughout the wetland sampling area. Distribution of NO3--N suggests that this restored wetland, even at its infant age, may still contribute to biogeochemical (particularly N) element cycling. Continued monitoring and further research is necessary to determine long-term specific contribution of restored wetland to biogeochemical cycles.

Glutathionato-S-Gold(III) complexes formed as intermediates in the reduction of auricyanide by glutathione.

The reduction of auricyanide ([Au(CN)(4)](-), a potential gold(III) metabolite of antiarthritic gold(I) compounds), by glutathione (G(-)SH, an anionic biological reductant) proceeds through two intermediates (I(230) and I(290)) which have previously been identified by their UV-vis spectra, but not isolated. Negative-ion electrospray ionization-mass spectroscopy (ESI-MS) has unambiguously identified them as [Au(CN)(3)(SG)](2-) and [Au(CN)(2)(SG)(2)](3-), respectively, and allowed their formation and decay to be monitored. The spectra also confirm that the products are aurocyanide ([Au(CN)(2)](-), a known metabolite of chrysotherapy agents) and oxidized glutathione (GSSG(2-)). The reactions are dependent on the presence or absence of buffering agents and the pH of the reaction media. The reaction can be driven to the first intermediate by using an excess of auricyanide or by running the reaction at low pH which prevents further reaction. At neutral pH and/or with excess of glutathione present, the reaction proceeds to the second intermediate, which is then reduced to aurocyanide. The monoanions, [Au(CN)(3)(SGH)](-) at m/z=581.2 and [Au(CN)(2)(SGH)(2)](-) at m/z=861.5 generate more intense signals than their respective dianions, [Au(CN)(3)(SG)](2-) at m/2=290.2 and [Au(CN)(2)(SG)(SGH)](2-)m/2=430.9, respectively, whereas the trianion [Au(CN)(2)(SG)(2)](3-) (m/3=281.2) was not observed. These studies demonstrate the value of ESI-MS methods for characterizing reactions of metallopharmaceuticals under biomimetic conditions and suggest that they will be useful for other systems which give strong ESI-MS signals.

Proton-linked bi- and tri-metallic gold cyanide complexes observed by ESI-MS spectrometry.

Electrospray ionization spectra of potential cyanide-containing gold-drug metabolites revealed additional, weak, unanticipated peaks at approximately twice the mass of the gold(I) and gold(III) cyanide complexes. The exact masses correspond to proton-linked bimetallic complexes, [H[Au(CN)(m)](2)](-), (m=2,4). Further investigation revealed a total of 12 examples, including trimetallic complexes, [H(2)[Au(CN)(m)](3)](-); mixed species with two complexes, [H[Au(CN)(2)][Au(CN)(4)]](-); and thiolato species, [H[(RS)Au(CN)(3)](2)](-). trans-[AuX(2)(CN)(2)Cl(2)](-) and trans-[AuX(2)(CN)(2)Br(2)](-) generated (35)Cl/(37)Cl and (79)Br/(81)Br isotopic patterns for the protonated bi- and tri-metallic analogues which were in good agreement with the presence of four or six halide ligands, respectively. Concentration-dependent studies demonstrated that the signals are independent of the solution concentrations of mono-metallic precursors, suggesting formation in the gas phase during or following droplet desolvation.

Molecular characterization of the copper transport system in Staphylococcus aureus.

The Staphylococcus aureus copA gene codes for a putative copper-translocating P-type ATPase and the downstream copZ gene codes for a copper chaperone. Genome database analyses demonstrate that these copper transport genes are highly conserved in S. aureus. The expression of copA and copZ was inducible by copper and to some extent by ferric and lead ions. A mutant strain containing a partially deleted copA gene was more sensitive than the parent strain to copper, ferric and lead ions. The copper-sensitive phenotype was due to the accumulation of intracellular copper and thus the copA product is involved in the export of copper ions. The metal-sensitive phenotype of the mutant was complemented in trans by a 2.7 kbp DNA containing copA. We have cloned and overexpressed the metal-binding domains of CopA and CopZ and have shown by site-directed mutagenesis that the cysteine residues in the CXXC metal-binding motif in CopA are involved in copper binding and thus play an important role in copper transport in S. aureus.