Search

Virtual behavioral health (VBH) services are used frequently to address the high demand for behavioral health (BH) services in the military. Few studies have investigated the relationship between the use of VBH services and BH outcomes or preferences for the use of VBH technologies. In this article, we evaluated BH interviews conducted via video teleconferencing (VTC) or face-to-face in terms of BH symptoms, satisfaction rates, stigma, barriers to care, and preferences for future use of BH care. Soldiers (n = 307) from the headquarters element of an operational unit were surveyed 4 months following a 12-month deployment to Iraq. There were no significant differences in satisfaction rates based on interview modality, but significantly more soldiers preferred face-to-face interviews over VTC interviews in the future. Soldiers who preferred face-to-face interviews also reported higher levels of anxiety and depression symptoms than those who preferred VTC interviews. No significant age differences were found in terms of interview modality satisfaction or preference. Soldiers with greater deployment experience were more likely to report that they would not like using VTC if seeking BH care in the future than soldiers with less deployment experience. These findings highlight the importance of promoting choice in type of BH interview modality. [ABSTRACT FROM AUTHOR]

Calcium binding to the regulatory domain of cardiac troponin C (cNTnC) causes a conformational change that exposes a hydrophobic surface to which troponin I (cTnI) binds, prompting a series of protein-protein interactions that culminate in muscle contraction. A number of cTnC variants that alter the Ca(2+) sensitivity of the thin filament have been linked to disease. Tikunova and Davis engineered a series of cNTnC mutations that altered Ca(2+) binding properties and studied the effects on the Ca(2+) sensitivity of the thin filament and contraction [Tikunova, S. B., and Davis, J. P. (2004) J. Biol. Chem. 279, 35341-35352]. One of the mutations they engineered, the L48Q variant, resulted in a pronounced increase in the cNTnC Ca(2+) binding affinity and Ca(2+) sensitivity of cardiac muscle force development. In this work, we sought structural and mechanistic explanations for the increased Ca(2+) sensitivity of contraction for the L48Q cNTnC variant, using an array of biophysical techniques. We found that the L48Q mutation enhanced binding of both Ca(2+) and cTnI to cTnC. Nuclear magnetic resonance chemical shift and relaxation data provided evidence that the cNTnC hydrophobic core is more exposed with the L48Q variant. Molecular dynamics simulations suggest that the mutation disrupts a network of crucial hydrophobic interactions so that the closed form of cNTnC is destabilized. The findings emphasize the importance of cNTnC's conformation in the regulation of contraction and suggest that mutations in cNTnC that alter myofilament Ca(2+) sensitivity can do so by modulating Ca(2+) and cTnI binding.

The unique biophysical properties of tryptophan residues have been exploited for decades to monitor protein structure and dynamics using a variety of spectroscopic techniques, such as fluorescence and nuclear magnetic resonance (NMR). We recently designed a tryptophan mutant in the regulatory N-domain of cardiac troponin C (F77W-cNTnC) to study the domain orientation of troponin C in muscle fibers using solid-state NMR. In our previous study, we determined the NMR structure of calcium-saturated mutant F77W-V82A-cNTnC in the presence of 19% 2,2,2-trifluoroethanol (TFE). TFE is a widely used cosolvent in the biophysical characterization of the solution structures of peptides and proteins. It is generally assumed that the structures are unchanged in the presence of cosolvents at relatively low concentrations, and this has been verified for TFE at the level of the overall secondary and tertiary structure for several calcium regulatory proteins. Here, we present the NMR solution structure of the calcium saturated F77W-cNTnC in presence of its biological binding partner troponin I peptide (cTnI(144-163)) and in the absence of TFE. We have also characterized a panel of six F77W-cNTnC structures in the presence and absence TFE, cTnI(144-163), and the extra mutation V82A, and used (19)F NMR to characterize the effect of TFE on the F77(5fW) analog. Our results show that although TFE did not perturb the overall protein structure, TFE did induce a change in the orientation of the indole ring of the buried tryptophan side chain from the anticipated position based upon homology with other proteins, highlighting the potential dangers of the use of cosolvents.

To determine whether alterations in adrenocortical function occur early in the development of inflammatory joint disease, we examined patients with new onset synovitis (<1 yr) prior to treatment with corticosteroids or other disease-modifying antirheumatic drugs. Thirty-two patients with new onset synovitis, including 15 fitting criteria for rheumatoid arthritis (RA), taking no medications, were referred for study by local rheumatologists; 32 age- and sex-matched healthy individuals were recruited as controls. Patients and controls had blood drawn under identical conditions between 0900 and 1100 h. Plasma ACTH, cortisol, dehydroepiandrosterone (DHEA), DHEA sulfate, free and total testosterone, erythrocyte sedimentation rate, C-reactive protein, and rheumatoid factor were measured. Compared with controls, patients had higher inflammatory indices (erythrocyte sedimentation rate, C-reactive protein) and lower basal morning levels of free testosterone (lower in males age > or =45 yr), but similar levels of ACTH, cortisol, DHEA, DHEA sulfate, and total testosterone. In addition, the positive correlations between ACTH-cortisol, ACTH-DHEA, and cortisol-DHEA, observed in the normal controls, were weakened or abolished in the patients (both total and RA subset). No positive relations between inflammatory indices and ACTH or cortisol were noted, yet an inverse correlation between these indices and DHEA and testosterone was observed. Moreover, a steeper age-associated decline in DHEA was observed in our cross-sectional sample of patients with new onset synovitis. We conclude that patients with synovitis (including those fitting criteria for RA) have adrenocortical hormone alterations within a year of disease onset. Paradoxically, these patients have no positive relation between indices of inflammation and ACTH or cortisol, but rather serum androgen levels are inversely correlated with these indices. In addition, the relations between ACTH, the classic stimulus of cortisol and adrenal androgens, and these hormones are weakened or abolished, whereas the negative relation between age and zona reticularis function is steeper than that of controls.

Adenosine (ADO) exerts potent anti-inflammatory and immunosuppressive effects. In this paper we address the possibility that these effects are partly mediated by inhibition of the secretion of IL-12, a proinflammatory cytokine and a major inducer of Th1 responses. We demonstrate that 5'-N-ethylcarboxamidoadenosine (NECA), a nonspecific ADO analogue, and 2-p-(2-carbonyl-ethyl)phenylethylamino-5'-N-ethylcarboxamidoadenos ine (CGS-21680), a specific A2a receptor agonist, dose-dependently inhibited, in whole blood ex vivo and monocyte cultures, the production of human IL-12 induced by LPS and Stapholococcus aureus Cowan strain 1. However, the A1 receptor agonist 2-Chloro-N6-cyclopentyladenosine and the A3 receptor agonists N6-Benzyl-NECA and 1-deoxy-1-[6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-N-methyl-be ta-d -ribofuranuronamide expressed only weak inhibitory effects. On the other hand, NECA and CGS-21680 dose-dependently potentiated the production of IL-10. The differential effect of these drugs on monocyte IL-12 and IL-10 production implies that these effects are mediated by A2a receptor signaling rather than by intracellular toxicity of ADO analogue's metabolites. Moreover, CGS-21680 inhibited IL-12 production independently of endogenous IL-10 induction, because anti-IL-10 Abs failed to prevent its effect. The selective A2a antagonist 8-(3-Chlorostyryl) caffeine prevented the inhibitory effect of CGS-21680 on IL-12 production. The phosphodiesterase inhibitor Ro 20-1724 dose-dependently potentiated the inhibitory effect of CGS-21680 and, furthermore, Rp-cAMPS, a protein kinase A inhibitor, reversed the inhibitory effect of CGS-21680, implicating a cAMP/protein kinase A pathway in its action. Thus, ligand activation of A2a receptors simultaneously inhibits IL-12 and stimulates IL-10 production by human monocytes. Through this mechanism, ADO released in excess during inflammatory and ischemic conditions, or tissue injury, may contribute to selective suppression of Th1 responses and cellular immunity.

We postulated that changes in the cell surface display of molecules that facilitate cell-cell and cell-matrix adhesions may reflect the changing immunosurveillance capacity of blood monocytes during progression of human immunodeficiency virus (HIV) infections. In Centers for Disease Control (CDC) stage A patients, whose monocytes' ability to phagocytose bacteria and generate reactive oxygen intermediates is often increased, the frequency of monocytes expressing CD49d, HLA-DP, HLA-DQ, and an activation epitope of CD11a/CD18 was increased and monocyte transendothelial migration was unimpaired. In CDC stage B/C patients, whose monocytes' ability to phagocytose bacteria and migrate across confluent endothelial monolayers was diminished, surface expression of CD49e and CD62L and the percentage of monocytes expressing CD18, CD11a, CD29, CD49e, CD54, CD58, CD31, and HLA-I were significantly decreased. Incubating normal donor monocytes with immune complexes in vitro reproduced the phenotypic and functional abnormalities seen in stage B/C patients. By contrast, in vitro stimulation with subcellular particulates released by apoptotic lymphocytes reproduced changes seen in stage A patients' monocytes. Although circulating monocytes appear to be activated at all stages, these data suggest that the high levels of circulating immune complexes, found predominantly in the later stages of HIV infection, may be particularly instrumental in reducing the monocyte's capacity to maintain surveillance against infection.