Impact of Individual Budgets on Work and Financial Well-Being of Supported Employment Recipients With Serious Mental Illness.

OBJECTIVE: The authors sought to determine whether providing recipients of supported employment with individual budgets from which they could purchase employment-related goods and services would improve employment and financial outcomes. METHODS: Sixty study participants were recruited from an individual placement and support (IPS) program and randomly assigned (1:1) to receive IPS services only (N=32) or IPS services with a 12-month $950 flexible fund called a career account (N=28). Participants receiving IPS and a career account met with staff who helped them identify employment goals and create a budget for purchases directly tied to these goals. The primary outcome was competitive employment; secondary outcomes included job tenure, days worked, total earnings, and financial well-being. Outcomes were analyzed by using adjusted generalized linear models (GLMs) with binary logistic, negative binomial, and linear distributions. RESULTS: The proportion of participants who achieved competitive employment was largely similar for those in the career account+IPS group (54%) and in the IPS-only group (47%). However, the GLM analysis revealed that career account+IPS participants had significantly longer job tenure, more total days of employment, and higher total earnings than IPS-only participants. Feelings of financial well-being increased significantly among career account participants, whereas financial well-being declined among control participants. The amount of career account dollars participants spent was positively and significantly associated with longer job tenure, more days employed, and higher total earnings. CONCLUSIONS: Combining flexible funds with IPS-supported employment achieved some superior outcomes compared with IPS only. Further research is needed to assess the longer-term effects of this practice and its cost-effectiveness.

A Mixed-Methods Implementation Evaluation of Virtual Reality Job Interview Training in IPS Supported Employment.

OBJECTIVE: Employment rates among individuals with serious mental illness may be improved by engagement in the individual placement and support (IPS) model of supported employment. Results from a recent randomized controlled trial (RCT) indicate that virtual reality job interview training (VR-JIT) improves employment rates among individuals with serious mental illness who have been actively engaged in IPS for at least 90 days. This study reports on an initial implementation evaluation of VR-JIT during the RCT in a community mental health agency. METHODS: A sequential, complementary mixed-methods design included use of qualitative data to improve understanding of quantitative findings. Thirteen IPS staff trained to lead VR-JIT implementation completed VR-JIT acceptability, appropriateness, and feasibility surveys. Participants randomly assigned to IPS with VR-JIT completed acceptability (N=42) and usability (N=28) surveys after implementation. The authors also conducted five focus groups with IPS staff (N=11) and VR-JIT recipients (N=13) and semistructured interviews with IPS staff (N=9) and VR-JIT recipients (N=4), followed by an integrated analysis process. RESULTS: Quantitative results suggest that IPS staff found VR-JIT to be highly acceptable, appropriate for integration with IPS, and feasible for delivery. VR-JIT was highly acceptable to recipients. Qualitative results add important context to the quantitative findings, including benefits of VR-JIT for IPS staff as well as adaptations for delivering technology-based interventions to individuals with serious mental illness. CONCLUSIONS: These qualitative and quantitative findings are consistent with each other and were influenced by VR-JIT's adaptability and perceived benefits. Tailoring VR-JIT instruction and delivery to individuals with serious mental illness may help optimize VR-JIT implementation within IPS.

Psychometric properties of the mock interview rating scale for schizophrenia and other serious mental illnesses.

Background: Over the past 10 years, job interview training has emerged as an area of study among adults with schizophrenia and other serious mental illnesses who face significant challenges when navigating job interviews. The field of mental health services research has limited access to assessments of job interview skills with rigorously evaluated psychometric properties. Objective: We sought to evaluate the initial psychometric properties of a measure assessing job interview skills via role-play performance. Methods: As part of a randomized controlled trial, 90 adults with schizophrenia or other serious mental illnesses completed a job interview role-play assessment with eight items (and scored using anchors) called the mock interview rating scale (MIRS). A classical test theory analysis was conducted including confirmatory factor analyses, Rasch model analysis and calibration, and differential item functioning; along with inter-rater, internal consistency, and test-retest reliabilities. Pearson correlations were used to evaluate construct, convergent, divergent, criterion, and predictive validity by correlating the MIRS with demographic, clinical, cognitive, work history measures, and employment outcomes. Results: Our analyses resulted in the removal of a single item (sounding honest) and yielded a unidimensional total score measurement with support for its inter-rater reliability, internal consistency, and test-retest reliability. There was initial support for the construct, convergent, criterion, and predictive validities of the MIRS, as it correlated with measures of social competence, neurocognition, valuing job interview training, and employment outcomes. Meanwhile, the lack of correlations with race, physical health, and substance abuse lent support for divergent validity. Conclusion: This study presents initial evidence that the seven-item version of the MIRS has acceptable psychometric properties supporting its use to assess job interview skills reliably and validly among adults with schizophrenia and other serious mental illnesses. Clinical Trial Registration: NCT03049813.

An RCT of Virtual Reality Job Interview Training for Individuals With Serious Mental Illness in IPS Supported Employment.

OBJECTIVE: Virtual Reality Job Interview Training (VR-JIT) is a computerized interview simulator with efficacy at enhancing interview skills and employment outcomes. A randomized controlled trial assessed VR-JIT effectiveness for participants in individual placement and support (IPS), in which approximately 55% of individuals with serious mental illness obtain employment. METHODS: Ninety participants with serious mental illness were randomly assigned to IPS+VR-JIT (N=54) or IPS as usual (N=36), completing pretest-posttest assessments and an employment evaluation at 9 months. Intent-to-treat chi-square analysis, multivariable logistic regression, Cox proportional hazards models, and mixed-effects linear regressions were conducted. Fifty-one percent were IPS nonresponders (i.e., no employment within the first 90 days of IPS). RESULTS: IPS+VR-JIT participants did not have significantly higher employment rates, compared with IPS-as-usual participants (43% versus 28%). IPS nonresponders (N=46) in the IPS+VR-JIT group had greater odds of obtaining employment (odds ratio [OR]=5.82, p=0.014) and shorter time to employment (hazard ratio=2.70, p=0.044) compared with IPS nonresponders in the IPS-as-usual group. Intent-to-treat mixed-effects linear analyses indicated that IPS+VR-JIT, compared with IPS as usual, significantly improved interview skills (p=0.006), interview confidence (p=0.013), and interview anxiety (p=0.019). CONCLUSIONS: VR-JIT's potential benefits (increased employment in a shorter time) appeared to be specific to IPS nonresponders, whereas employment outcomes for recent IPS enrollees were not affected. VR-JIT could be a valuable resource for employment specialists to support IPS nonresponders, because 47% of participants engaged in mock interview training with their specialist. Future research should focus on evaluating the effectiveness and implementation of VR-JIT among IPS nonresponders.

Highlighting Cancer Cells with Halochromic Switches.

Halochromic coumarin-oxazine prefluorophores and targeting folate ligands can be connected covalently to the side chains of amphiphilic polymers. The resulting macromolecular constructs assemble into nanoparticles in aqueous environments. The prefluorophores do not produce any detectable fluorescence at neutral pH, but are converted into fluorophores with intense visible emission at acidic pH. Protonation opens the oxazine heterocycle to shift bathochromically the coumarin absorption and activate fluorescence with a brightness per nanoparticle approaching 5 × 105 M-1 cm-1. This value translates into a 170-fold enhancement relative to the isolated fluorophores dissolved in organic solvent. The folate ligands direct these multicomponent constructs into acidic intracellular compartments of folate-positive cells, where the prefluorophores switch to the corresponding fluorophores and produce fluorescence. The pH-induced activation of the signaling units ensures negligible background fluorescence from the extracellular matrix, which instead limits considerably the contrast accessible with model systems incorporating conventional nonactivatable fluorophores. Furthermore, no intracellular fluorescence can be detected when the very same measurements are performed with folate-negative cells. Nonetheless, control experiments demonstrate that the covalent connection of the prefluorophores to the polymer backbone of the amphiphilic constructs is essential to ensure selectivity. Model systems with prefluorophores noncovalently encapsulated cannot discriminate folate-positive from -negative cells. Thus, our structural design for the covalent integration of activatable signaling units and targeting ligands within the same nanostructured assembly together with the photophysical properties engineered into the emissive components offer the opportunity to highlight cancer cells selectively with high brightness and optimal contrast.

Bioimaging with Macromolecular Probes Incorporating Multiple BODIPY Fluorophores.

Seven macromolecular constructs incorporating multiple borondipyrromethene (BODIPY) fluorophores along a common poly(methacrylate) backbone with decyl and oligo(ethylene glycol) side chains were synthesized. The hydrophilic oligo(ethylene glycol) components impose solubility in aqueous environment on the overall assembly. The hydrophobic decyl chains effectively insulate the fluorophores from each other to prevent detrimental interchromophoric interactions and preserve their photophysical properties. As a result, the brightness of these multicomponent assemblies is approximately three times greater than that of a model BODIPY monomer. Such a high brightness level is maintained even after injection of the macromolecular probes in living nematodes, allowing their visualization with a significant improvement in signal-to-noise ratio, relative to the model monomer, and no cytotoxic or behavioral effects. The covalent scaffold of these macromolecular constructs also permits their subsequent conjugation to secondary antibodies. The covalent attachment of polymer and biomolecule does not hinder the targeting ability of the latter and the resulting bioconjugates can be exploited to stain the tubulin structure of model cells to enable their visualization with optimal signal-to-noise ratios. These results demonstrate that this particular structural design for the incorporation of multiple chromophores within the same covalent construct is a viable one to preserve the photophysical properties of the emissive species and enable the assembly of bioimaging probes with enhanced brightness.

Fluorescent Kinase Probes Enabling Identification and Dynamic Imaging of HER2(+) Cells.

The human epidermal growth factor receptor, EGFR/ERBB/HER, family of receptor tyrosine kinases is central to many signaling pathways and a validated chemotherapy target in multiple cancers. While EGFR/ERBB-targeted therapies, including monoclonal antibodies, e.g., trastuzumab, and small molecule kinase inhibitors, such as lapatinib, have been developed, rapid identification and classification of cancer cells is key to identifying the best treatment regime. We report ERBB2 (also HER2) targeting kinase probes that exhibit a "turn-on" emission response upon binding. These live cell compatible probes differentiate ERBB2(+) cells from low-level, ERBB2(-) cells by targeting the intracellular ATP-binding pocket of ERBB2 with therapeutic inhibitor-like specificity. Beyond kinase expression levels, probe signal is linked to the phosphotyrosine-correlated activation state of the ERBB2 population. Additionally, the rapid signaling capability of the probes can report changes in activation state in live cells providing a unique type of complementary information to immunohistochemical assays of receptor kinase populations.

Systematic review of barriers and facilitators to accessing and engaging with mental health care among at-risk young people.

INTRODUCTION: This study aims to review the literature on barriers and facilitators to accessing and engaging with mental health care among young people from potentially disadvantaged groups, including young people identified as Aboriginal or Torres Strait Islander (ATSI); culturally and linguistically diverse (CALD); lesbian, gay, bisexual, transgender, queer, or intersex (LGBTQI); homeless; substance using; and youth residing in rural or remote areas. METHODS: Fourteen databases were searched to identify qualitative and quantitative researches that examined barriers and/or facilitators to mental health care among the six groups of potentially disadvantaged young people. RESULTS: Out of 62 studies identified, 3 were conducted with ATSI young people, 1 with CALD young people, 4 with LGBTQI young people, 14 with homeless young people, 24 with substance-using young people, and 16 with young people residing in rural or remote areas. Findings generally confirmed barriers already established for all young people, but indicated that some may be heightened for young people in the six identified groups. Findings also pointed to both similarities and differences between these groups, suggesting that ATSI, CALD, LGBTQI, homeless, substance-using, and rural young people have some similar needs with respect to not only mental health care, but also other needs likely to reflect their individual circumstances. DISCUSSION: This systematic review highlights that young people from potentially disadvantaged groups have distinct needs that must be recognized to improve their experiences with mental health care. Future research of good methodological quality with young people is needed to increase accessibility of, and engagement with, mental health care.

One probe, two-channel imaging of nuclear and cytosolic compartments with orange and red emissive dyes.

Several new DNA-targeting probes that exhibit binding-induced 'turn on' fluorescence are presented. Two of the dyes, orange emissive 1, (E)-4-(4(-4-methylpiperazin-1-yl)phenyl)6-(4-(4-methylpi-perazin-1-yl)styryl)pyrimidin-2-ol), and red emissive 2, (E)-4-(4(-4-methyl-piperazin-1-yl)-phenyl)6-(4-(4-methylpiperazin-1-yl)styryl)-1,3-propanedionato-κO,κO']difluoroborane), are brightly fluorescent when bound to DNA, but are virtually non-fluorescent in aqueous solutions. Confocal fluorescence microscopy of live BT474, MCF7 and HEK293 cells demonstrates that both probes are cell permeable and rapidly accumulated intracellularly into cell nuclei and the cytosol. Taking advantage of their environmental sensitivity, these two pools of fluorophores are readily resolved into separate channels, and thus, a single dye allows two-color imaging of the nuclear and cytosolic compartments.

Binding-induced, turn-on fluorescence of the EGFR/ERBB kinase inhibitor, lapatinib.

We report the photophysical properties, binding-induced turn-on emission, and fluorescence imaging of the cellular uptake and distribution of lapatinib, an EGFR/ERBB inhibitor. Lapatinib, a type II, i.e. inactive state, inhibitor that targets the ATP binding pocket of the EGFR family of receptor tyrosine kinases. DFT calculations predict that the 6-furanylquinazoline core of lapatinib should exhibit an excited state with charge transfer character and an S0 to S1 transition energy of 3.4 eV. Absorption confirms an optical transition in the near UV to violet, while fluorescence spectroscopy shows that photoemission is highly sensitive to solvent polarity. The hydrophobicity of lapatinib leads to fluorescent aggregates in solution, however, binding to the lipid-carrier protein, BSA or to the kinase domain of ERBB2, produces spectroscopically distinct photoemission. Confocal fluorescence microscopy imaging of lapatinib uptake in ERBB2-overexpressing MCF7 and BT474 cells reveals pools of intracellular inhibitor with emission profiles consistent with aggregated lapatinib.

Turn-on, fluorescent nuclear stains with live cell compatibility.

DNA-binding, green and yellow fluorescent probes with excellent brightness and high on/off ratios are reported. The probes are membrane permeable, live-cell compatible, and optimally matched to 405 nm and 514 nm laser lines, making them attractive alternatives to UV-excited and blue emissive Hoechst 33342 and DAPI nuclear stains. Their electronic structure was investigated by optical spectroscopy supported by TD-DFT calculations. DNA binding is accompanied by 27- to 75-fold emission enhancements, and linear dichroism demonstrates that one dye is a groove binder while the other intercalates into DNA.

Fluorescent stilbazolium dyes as probes of the norepinephrine transporter: structural insights into substrate binding.

We report the synthesis, binding kinetics, optical spectroscopy and predicted binding modes of a series of sterically demanding, fluorescent norepinephrine transporter (NET) ligands. A series of bulky stilbazolium dyes, including six newly synthesized compounds, were evaluated to determine the effect of extending the molecular probes' 'heads' or 'tails'. Taking advantage of the dyes' characteristic 'turn-on' emission, the kinetic binding parameters, k(on) and k(off) were determined revealing that extension of the molecules' tails is well tolerated while expansion of the head is not. Additionally, a 'headfirst' orientation appears to be preferred over a 'tail-first' binding pose. Further details of the possible binding modes were obtained from the emission spectra of the bound probes. A small range of interplanar twist angles, approximately 35° to 60°, is predicted to produce the observed emission. Docking experiments and molecular modelling support the kinetic and spectroscopic data providing structural insights into substrate binding.

Effects of oat ß-glucan on the macrophage cytokine response to herpes simplex virus 1 infection in vitro.

Oat ß-glucan can counteract the increased risk for Herpes Simplex Virus 1 (HSV-1) infection in mice, the effects of which have, at least in part, been attributed to macrophages. However, the specific responses of macrophages to oat ß-glucan treatment in this model have yet to be elucidated. We examined the effects of varying doses of oat ß-glucan on the pro-inflammatory cytokine response in both peritoneal and lung macrophages with and without exposure to HSV-1 infection in vitro. Peritoneal and lung macrophages were obtained from mice and cultured with varying concentrations of oat ß-glucan (0 (control), 10, 100, and 1,000 µg) for 24 h and supernatants were collected. A standardized dose of HSV-1 was added for a second 24 h incubation period after which supernatants were again collected. Samples were analyzed for interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor α (TNF-α) using enzyme linked immunosorbent assay (ELISA). In most cases, oat ß-glucan resulted in a dose-dependent increase in pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) in lung and peritoneal macrophages with and without exposure to HSV-1 infection. When comparing across macrophage source, this response was greater for IL-1ß and IL-6 in peritoneal macrophages and for TNF-α in lung macrophages. This may be a mechanism for the decreased risk for HSV-1 infection following oat ß-glucan feedings in mice.

Probing the functional limits of the norepinephrine transporter with self-reporting, fluorescent stilbazolium dimers.

A series of stilbazolium dimers were synthesized and investigated as sterically demanding ligands targeting the norepinephrine transporter (NET). The environmentally sensitive fluorescence of the dyes enables their use as self-reporting ligands; binding to and displacement from NET can be monitored by fluorescence microscopy.

Fluorescent reporters of monoamine transporter distribution and function.

Serotonin is a monoamine serving as a chemical messenger in diverse brain regions, as well as in blood and various other organs. We synthesized six ethylamine functionalized fluorophores as fluorescent probes for serotonin. The one with best spectral properties and aqueous solubility, 6-amino-2-(2-aminoethyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione, was studied in detail both in vivo and in vitro. It was shown to act as a ligand for serotonin transporter (SERT) without acute cerebral or cardiovascular toxicity or adverse effects. Fluorescent serotonin analogs can be used for direct visualization of SERT distribution and activity in live tissue.

Luminescent charge-transfer complexes: tuning emission in binary fluorophore mixtures.

Charge-transfer (CT) complexes composed of a π-electron-poor naphthalene diimide (NDI) derivative combined with a series of π-electron-rich donors were investigated. Solutions of the CT complexes are nonemissive; however, solid-state complexes and aqueous suspensions display emission that is dependent on the energy of the HOMO of the electron donor. Crystallographic analysis of a pyrene-NDI complex reveals columnar packing and a high degree of frontier molecular orbital (FMO) overlap that likely contributes to the observed optical properties. The fluorescent CT particles are utilized as imaging agents; additional luminescent CT complexes may be realized by considering FMO energies and topologies.

Fluorescent neuroactive probes based on stilbazolium dyes.

A set of spectrally diverse stilbazolium dyes was identified in an uptake assay using cultured brainstem and cerebellum cells isolated from e19 chicks. Pretreatment of cells with indatraline, a monoamine reuptake inhibitor, allowed identification of dyes that may interact with monoamine transporters. Two structurally related, yet spectrally segregated, probes, (E)-1-methyl-4-[2-(2-naphthalenyl)ethenyl]-pyridinium iodide (NEP+, 3A) and (E)-4-[2-(6-hydroxy-2-naphthalenyl)ethenyl]-1-methyl-pyridinium iodide (HNEP+, 4A), were selected and further investigated using HEK-293 cells selectively expressing dopamine, norepinephrine or serotonin transporters. HNEP+ was selectively accumulated via catecholamine transporters, with the norepinephrine transporter (NET) giving the highest response; NEP+ was not transported, though possible binding was observed. The alternate modes of interaction enable the use of NEP+ and HNEP+ to image distinct cell populations in live brain tissue explants. The preference for HNEP+ accumulation via NET was confirmed by imaging uptake in the absence and presence of desipramine, a norepinephrine reuptake inhibitor.

Psychosocial risk factors for inconsistent condom use in young people with first episode psychosis.

There is evidence of high rates of unprotected sex among young people with first episode psychosis compared to their peers. Little research has explored factors associated with condom use in this population. The current study examined the association between previously identified psychosocial risk factors and condom use in young people with early psychosis and their peers. Sixty-seven sexually active young people with first episode psychosis and 48 sexually active control participants matched on a number of sociodemographic factors completed a self-report survey. Increased probability of inconsistent condom use was associated with clinical status, younger age, unemployment, and the absence of peer support for condom use. Psychological distress, self-esteem, social support, substance use, and impulsivity were not associated with condom use. The results suggest that sexual risk-reduction interventions for young people with psychosis should target peer norms, particularly among those who are younger and unemployed.

Reducing sexually-transmitted infection risk in young people with first-episode psychosis.

There is emerging evidence that young people with first-episode psychosis are at greater risk of sexually-transmitted infections (STI) than their peers. Theoretical constructs central to behavioural change theories, broadly defined as sexual health-related knowledge, attitudes, and beliefs, have guided most sexual risk-reduction interventions in other at-risk populations. The role of these constructs in the sexual risk behaviour of young people with early psychosis remains unknown. A convenience sample of 67 young people with first-episode psychosis and 48 healthy controls matched on a number of sociodemographic characteristics was recruited. Participants completed a survey assessing their sexual behaviour and sexual health-related knowledge, attitudes, and beliefs. Group differences and the role of these constructs in the condom-use behaviour of these young people were examined. Although some differences emerged, group similarities were prominent. Inconsistent condom use was predicted by clinical status, unemployment, and the absence of peer support for condom use. These results support previous findings that young people with psychosis have greater needs for STI prevention due to increased rates of unprotected sex. Risk-reduction interventions that target peer influence are important. Inquiry into a broader range of psychosocial factors could further our understanding of STI infection risk in early psychosis.

Sexual risk behaviour in young people with first episode psychosis.

AIM: Previous studies have consistently reported high rates of risky behaviour for sexually transmitted infections (STIs) amongst individuals with persistent psychosis. Whether such behaviours are evident from the first presentation or relate to a chronic illness course remains largely undetermined, with limited research conducted amongst young people with first episode psychosis. The aim of the current study was to compare engagement in sexual risk behaviour amongst young people with first episode psychosis with their peers. METHODS: Sixty-seven sexually active young people with first episode psychosis and 48 healthy control participants (aged 18-29 years) closely matched on sociodemographic characteristics completed a detailed questionnaire assessing a comprehensive range of sexual risk behaviours. RESULTS: There were few differences in the rates of sexual risk behaviour reported by the first episode sample and their peers. Compared with control participants, young people with first episode psychosis reported significantly more inconsistent condom use, less condom-related preparatory behaviour, more concern about HIV/STIs when sex was unprotected, less confidence discussing condom use and increased substance use by their last sexual partner. CONCLUSIONS: The sexual behaviour of young people with first episode psychosis appears similar to their peers. However, group differences, particularly increased frequency of unprotected sex amongst the first episode sample, suggest that those with psychosis are at increased STI risk and have distinct needs. The findings support the call for early intervention strategies that target reduction of sexual risk behaviour in the context of persistent mental illness.