Virtual Standardized Patients for Mental Health Education.

PURPOSE OF REVIEW: The training of psychiatrists and other mental health professionals requires education on a range of interpersonal, communication, and psychotherapy techniques. Classroom and workshop training must be augmented by experiential learning with feedback for skill implementation with fidelity. Virtual standardized patients (VSPs) are computerized conversational agents that can support experiential learning through standardized, consequence-free training environments at reduced costs. RECENT FINDINGS: Research on mental health VSPs is rife with feasibility and acceptability pilot studies across various training populations and settings. Users have generally reported positive reactions to training with VSPs, though frustrations with some VSP speech recognition or VSP response relevance has been reported. Several studies have demonstrated a promising transfer of clinical skills from VSP training to human standardized patients and randomized trials supporting improved skill relative to reading or academic study are encouraging. As technology improves and natural language processing and accurate computer response generation for broad ranging conversational topics emerges, the field would benefit from research on the characteristics of effective VSPs for a range of purposes and trainee populations. Well-designed randomized evaluations of VSPs relative to best practices in education are needed, particularly regarding the impact of VSPs on clinical practice among actual patients.

An investigation of the interactive effects of the capability for suicide and acute agitation on suicidality in a military sample.

BACKGROUND: According to the interpersonal theory of suicide (1, 2), the difficulties inherently associated with death by suicide deter many individuals from engaging in suicidal behavior. Consistent with the notion that suicide is fearsome, acute states of heightened arousal are commonly observed in individuals immediately prior to lethal and near-lethal suicidal behavior. We suggest that among individuals who possess elevated levels of the capability for suicide, the heightened state of arousal experienced during periods of acute agitation may facilitate suicidal behavior in part because it would provide the necessary energy to approach a potentially lethal stimulus. Among individuals who are low on capability, the arousal experienced during agitation may result in further avoidance. METHODS: In the present project we examine how acute agitation may interact with the capability for suicide to predict suicidality in a large military sample (n = 1,208) using hierarchical multiple regression. RESULTS: Results were in line with a priori hypotheses: among individuals high on capability, as agitation increases, suicidality increases whereas as agitation increases among individuals low on capability, suicidality decreases. Results held beyond the effects of thwarted belongingness, perceived burdensomeness, and suicidal cognitions. CONCLUSIONS: Beyond further substantiating the link between agitation and suicide, findings of the present study provide evidence for the construct validity of the acquired capability as well as offer initial evidence for moderating role of capability on the effect of agitation on suicide. Limitations of the current study highlight a need for future research that improves upon the techniques used in the present study. Implications for science and practice are discussed.

Site-saturation mutagenesis of position V117 in OXA-1 ß-lactamase: effect of side chain polarity on enzyme carboxylation and substrate turnover.

Class D ß-lactamases pose an emerging threat to the efficacy of ß-lactam therapy for bacterial infections. Class D enzymes differ mechanistically from other ß-lactamases by the presence of an active-site N-carboxylated lysine that serves as a general base to activate the serine nucleophile for attack. We have used site-saturation mutagenesis at position V117 in the class D ß-lactamase OXA-1 to investigate how alterations in the environment around N-carboxylated K70 affect the ability of that modified residue to carry out its normal function. Minimum inhibitory concentration analysis of the 20 position 117 variants demonstrates a clear pattern of charge and polarity effects on the level of ampicillin resistance imparted on Escherichia coli (E. coli). Substitutions that introduce a negative charge (D, E) at position 117 reduce resistance to near background levels, while the positively charged K and R residues maintain the highest resistance levels of all mutants. Treatment of the acidic variants with the fluorescent penicillin BOCILLIN FL followed by SDS-PAGE shows that they are active for acylation by substrate but deacylation-deficient. We used a novel fluorescence anisotropy assay to show that the specific charge and hydrogen-bonding potential of the residue at position 117 affect CO(2) binding to K70, which in turn correlates to deacylation activity. These conclusions are discussed in light of the mechanisms proposed for both class D ß-lactamases and BlaR ß-lactam sensor proteins and suggest a reason for the preponderance of asparagine at the V117-homologous position in the sensors.

EGFR ligands exhibit functional differences in models of paracrine and autocrine signaling.

Epidermal growth factor (EGF) family peptides are ligands for the EGF receptor (EGFR). Here, we elucidate functional differences among EGFR ligands and mechanisms underlying these distinctions. In 32D/EGFR myeloid and MCF10A breast cells, soluble amphiregulin (AR), transforming growth factor alpha (TGFα), neuregulin 2 beta, and epigen stimulate greater EGFR coupling to cell proliferation and DNA synthesis than do EGF, betacellulin, heparin-binding EGF-like growth factor, and epiregulin. EGF competitively antagonizes AR, indicating that its functional differences reflect dissimilar intrinsic activity at EGFR. EGF stimulates much greater phosphorylation of EGFR Tyr1045 than does AR. Moreover, the EGFR Y1045F mutation and z-cbl dominant-negative mutant of the c-cbl ubiquitin ligase potentiate the effect of EGF but not of AR. Both EGF and AR stimulate phosphorylation of EGFR Tyr992. However, the EGFR Y992F mutation and phospholipase C gamma inhibitor U73122 reduce the effect of AR much more than that of EGF. Expression of TGFα in 32D/EGFR cells causes greater EGFR coupling to cell proliferation than does expression of EGF. Moreover, expression of EGF in 32D/EGFR cells causes these cells to be largely refractory to stimulation with soluble EGF. Thus, EGFR ligands are functionally distinct in models of paracrine and autocrine signaling and EGFR coupling to biological responses may be specified by competition among functionally distinct EGFR ligands.