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This study examined changes in Medicaid provider payments prior to and following approval for personal assistance services (PAS) among 471 PAS users compared to 295 nonusers who qualified for but did not use PAS, adjusting for differences between users and nonusers using propensity scores. PAS users showed a significantly greater increase in total monthly payments from pre- to post-PAS approval compared to nonusers (35% vs. -9) due to high average monthly payments for PAS ($1325). However, users showed a decrease in non-PAS payments compared to nonusers (1%-9% vs. -9%), with significant decreases in payments for both acute/rehabilitation hospitalizations and for nursing home/other long-term residential stays among users. While costly, savings in other areas may help reduce the net cost of PAS. [ABSTRACT FROM AUTHOR]

This study explores the capacity of individuals with severe mental illness to be employed in managerial or professional jobs and the correlates of their vocational success. Using purposive sampling techniques, we identified a national sample of 347 individuals for a mail survey who had succeeded in obtaining and retaining mid to upper level managerial or professional positions. The majority worked full-time and held their job for more than 2 years. Their vocational success was operationalized based on 4 employment outcomes: employment status (full-time vs. part-time), job tenure, occupational rank, and annual income. Key factors that contributed to respondents' vocational success were lesser severity of the illness as indicated by lack of lifetime receipt of disability benefits, capacity to manage one's own psychiatric condition, and higher education. Study findings point to the role of supported education and self-efficacy in promoting the employment outcomes among individuals with severe mental illnesses. [ABSTRACT FROM AUTHOR]

The principles of empowerment and demedicalization have been central to the formulations of rehabilitation and social service practices as well as case management, a core community support service provided to people with psychiatric disabilities. This study describes empowering and demedicalized practices in mental health case management. Semi-structured interviews were conducted with thirty leaders in the mental health consumer movement and five professionals. Twentyfive categories of such practices were developed and are presented. Findings have implications for both the nature of the interaction between case manager and client and for program structures, activities, and missions. [ABSTRACT FROM AUTHOR]

Objective: This study identifies patterns and correlates of disclosure among professionals and managers with serious psychiatric conditions.Design: A national mail survey of such respondents was conducted.Results: A large proportion (87%) of study participants reported having disclosed their mental illness. About half of the disclosers reported unfavorable circumstances leading to disclosure while one third disclosed when they felt comfortable. Most frequently, respondents disclosed to supervisors; one third made their disability known when applying for the job. About half of the respondents had no regrets about disclosing. Multivariate analysis showed that correlates with the occurrence, timing, and choice of disclosure converge around constructs related to job confidence, empowerment, and recovery. We also describe those who chose not to disclose.Conclusion: Higher rates than previously reported and better experiences with disclosure were evident and may be related to this population's greater recovery as well as to occupational factors. [ABSTRACT FROM AUTHOR]

Semi-structured interviews were conducted with nine Individual Placement and Support (IPS) employment specialists who expanded and enhanced the IPS model for the youngest of working age youth with mental health conditions (ages 16-21). Semi-structured interviews were conducted with 100% of the providers delivering IPS-based career services for high school aged youth during an exploratory pilot. Content coding was applied to interview transcripts. Findings reflect the complexities of providing career services to high school age youth, suggesting components needed for effective services. These components include: provision of supports that help youth complete high school and negotiate the transition to college, coaching and skill development to improve executive functioning for work and school, coping skills coaching for mental health symptoms, flexible engagement strategies that assure youth self-determination of goals, longer range career and goal planning, and close collaboration with families., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: The authors conducted a systematic review of studies evaluating vocational interventions for young people with psychiatric conditions to determine the extent to which services were adapted for young people and whether services promoted gains in postsecondary education and employment., Methods: Five databases (PubMed, PsycINFO, Web of Science, Academic Search Premier, and ERIC) were searched. Sources eligible for inclusion were controlled studies published between 2000 and mid-2020 that evaluated a vocational intervention and examined postsecondary educational or employment outcomes for youths or young adults (ages 14-35 years) with psychiatric conditions., Results: Ten studies met the inclusion criteria. Several of the studies evaluated services that were adapted for young people, including through the incorporation of educational supports. The most consistent finding was that services based on the individual placement and support (IPS) model improved employment outcomes more effectively than did comparison approaches and treatment as usual. Fewer studies assessed educational outcomes, and they yielded mixed results; however, recent findings from a controlled trial indicate that an enhanced IPS intervention that included well-specified supported education and skills training led to significantly superior outcomes in both education and employment., Conclusions: These results provide support for the efficacy of IPS-based services to improve employment outcomes among young people with psychiatric conditions and suggest that adapting IPS to include comprehensive educational supports and skills training may be important for efforts to improve postsecondary educational outcomes. Additional well-controlled intervention studies that examine educational and longer-term outcomes should further inform the development and delivery of vocational services for this population.

Background: Understanding consumer service preferences is important for recovery-oriented care., Aims: To test the influence of perceived service needs on importance attached to treatment for alcohol, drug, mental health, and physical health problems and identify the influence of service needs and preferences on service use., Methods: Formerly homeless dually diagnosed Veterans in supported housing were surveyed in three waves for 1 year, with measures of treatment interests, health problems, social support, clinician-assessed risk of housing loss, and sociodemographics. Multiple regression analysis was used to identify independent influences on preferences in each wave. Different health services at the VA were distinguished in administrative records and baseline predictors for services used throughout the project were identified with multiple regression analysis., Results: Self-assessed problem severity was associated with the importance of treatment for alcohol, drug, mental health, and physical health problems. Social support also had some association with treatment interest for alcohol abuse, as did baseline clinician risk rating at the project's end. Preferences, but not perceived problem severity, predicted the use of the corresponding health services., Conclusions: The health beliefs model of service interests was supported, but more integrated service delivery models may be needed to strengthen the association of health needs with service use.

Objective: Few existing instruments measure recovery-oriented organizational climate and culture. This study developed, psychometrically assessed, and validated an instrument to measure recovery climate and culture., Methods: Organizational theory and an evidence-based conceptualization of mental health recovery guided instrument development. Items from existing instruments were reviewed and adapted, and new items were developed as needed. All items were rated by recovery experts. A 35-item instrument was pilot-tested and administered to a national sample of mental health staff in U.S. Department of Veterans Affairs Psychosocial Rehabilitation and Recovery Centers (PRRCs). Analysis entailed an exploratory factor analysis (EFA) and inter-item reliability and scale correlation assessment. Blinded site visits to four PRRCs were performed to validate the instrument., Results: The EFA determined a seven-factor solution for the data. The factors identified were staff expectations, values, leadership, rewards, policies, education and training, and quality improvement. Seven items did not meet retention criteria and were dropped from the final instrument. The instrument exhibited good internal consistency (Cronbach's α=0.81; subscales, α=0.84-0.88). Scale correlations were between 0.16 and 0.61, well below the threshold (α=0.9) for indicating overlapping constructs. Site visitors validated the instrument by correctly identifying high-scoring and low-scoring centers., Conclusions: These findings provide a psychometrically tested and validated instrument for measuring recovery climate and culture in mental health programs. This instrument can be used in evaluation of mental health services to determine the extent to which programs possess the organizational precursors that drive recovery-oriented service delivery.

Objectives: This study tested the impacts of peer specialists on housing stability, substance abuse, and mental health status for previously homeless Veterans with cooccurring mental health issues and substance abuse., Methods: Veterans living in the US Housing and Urban Development-Veterans Administration Supported Housing (HUD-VASH) program were randomized to peer specialist services that worked independently from HUD-VASH case managers (ie, not part of a case manager/peer specialist dyad) and to treatment as usual that included case management services. Peer specialist services were community-based, using a structured curriculum for recovery with up to 40 weekly sessions. Standardized self-report measures were collected at 3 timepoints. The intent-to-treat analysis tested treatment effects using a generalized additive mixed-effects model that allows for different nonlinear relationships between outcomes and time for treatment and control groups. A secondary analysis was conducted for Veterans who received services from peer specialists that were adherent to the intervention protocol., Results: Treated Veterans did not spend more days in housing compared with control Veterans during any part of the study at the 95% level of confidence. Veterans assigned to protocol adherent peer specialists showed greater housing stability between about 400 and 800 days postbaseline. Neither analysis detected significant effects for the behavioral health measures., Conclusions: Some impact of peer specialist services was found for housing stability but not for behavioral health problems. Future studies may need more sensitive measures for early steps in recovery and may need longer time frames to effectively impact this highly challenged population.

Objective: A site visit protocol was developed to assess recovery promotion in the organizational climate and culture of programs for veterans with serious mental illnesses., Method: The protocol was pilot-tested in 4 programs: 2 that had scored high on the pilot version of a staff survey measure of program-level recovery promotion and 2 that had scored low. Two-person teams conducted onsite visits and assigned global and organizational domain ratings. Interrater agreement was assessed by examining adjacent agreement and computing weighted kappa., Results: The on-site protocol had good interrater agreement and discriminated between sites that scored high and low on the staff survey., Conclusions and Implications for Practice: This site visit protocol and procedure shows promise for evaluating recovery promotion in milieu-based programs. After further refinement of this tool, adaptations could be developed for accreditation protocols or for program self-assessment and quality improvement efforts. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Although peer specialists play an increasing role in mental health service delivery, little is known about the best program structures for maximizing effective service delivery. This study reports on qualitative data from a larger study on peer specialists working with veterans in a Veterans Affairs homelessness program who were dually diagnosed with substance abuse and mental health concerns. Peer specialists were trained to deliver a recovery support program that is carried out weekly over 9 months and includes 20 structured sessions using a workbook and 20 unstructured, individually planned sessions. A sample of 20 veterans who were in the program were interviewed, along with 8 case managers and 3 peer specialists involved with the program. Interview transcripts were coded for 3 elements of program structure: time, content, and delivery. Results show that the program structure allowed flexibility for individual needs and that the workbook sessions were useful. Veterans ascribed value to the peer specialist delivering the content, compared to working alone on the material. Deliberate use of unstructured time with the peer specialist was seen as reducing isolation, increasing community integration, and encouraging recovery activities. The weekly, dependable nature of the program was seen as highly positive, whereas the 9-month duration was seen as too short. All groups interviewed expressed satisfaction with the program, although the case managers reported some reservations related to supervision and boundaries. Results suggest that, compared to completely structured or unstructured approaches that are common for peer specialist services, a middle level of structure for peer specialist programs could be a useful alternative. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

This study examined careers services provided to young adults with serious mental health conditions. Based on an internet survey and key informant telephone interview of 31 programs nominated for delivering innovative practices for young adults, the state of the field for career services was described. Most programs offered supported education and supported employment along with mental health services. Detailed and written planning was a key feature. Programs emphasized working closely with families, inter-agency collaboration, and use of normative community resources. Programs provided direct skills training for school and work and other life skills. Largely, existing models are being applied. However, providers described unique adaptations including greater flexibility in service delivery, attending to the turbulence and developmental changes characteristic of this age group, use of social media, and a heightened willingness to meet young people where "they are at" both literally and figuratively.

A randomized controlled pilot of supported education services was conducted with 33 Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn (OEF, OIF, OND, respectively) veterans with posttraumatic stress disorder (PTSD) who had higher education goals. Veteran peers delivered supported education services to an intervention group; for the control group, peers provided "matched attention" of generalized support without supporting educational goals. The intervention was based on a manualized veteran-centric program of supported education using principles of supported employment for individuals living with mental illness and components of civilian models of supported education. The attrition rate was high, with 30% lost to services between the baseline screening and the first peer session, although this drop-out rate is comparable to other rehabilitation studies. Despite a small sample and a matched attention control that could have diluted possible effects, significant positive differences were found, with the intervention group spending greater amounts of time on educational activities than did the control group. Effect sizes for the impact of the intervention were large between Time 1 and Time 2, and moderately large between Time 2 and Time 3. PTSD-symptom severity and recovery attitudes did not predict the impact of the supported education intervention. Implementation of the veteran supported education program using veteran peers appears feasible, although assertive outreach may be necessary to recruit and engage veterans with PTSD. Findings suggest that supported education services can have a measurable effect on time spent attaining an educational goal. Future studies will need to be longitudinal, as well as attend to the attrition issue and capture the impact on other education outcomes, such as successful program completion. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

This review assessed the concordance of the literature on recovery with the definition and components of recovery developed by the Substance Abuse and Mental Health Services Administration (SAMHSA). Each SAMHSA identified recovery component was first explicated with synonyms and keywords and made mutually exclusive by authors. Inter-rater reliability was established on the coding of the presence of 17 recovery components and dimensions in 67 literature reviews on the recovery concept in mental health. The review indicated that concordance varied across SAMHSA components. The components of recovery with greatest concordance were: individualized/person centered, empowerment, purpose, and hope.

Background: Approximately 600,000 persons are released from prison annually in the United States. Relatively few receive sufficient re-entry services and are at risk for unemployment, homelessness, poverty, substance abuse relapse and recidivism. Persons leaving prison who have a mental illness and/or a substance use disorder are particularly challenged. This project aims to create a peer mentor program to extend the reach and effectiveness of reentry services provided by the Department of Veterans' Affairs (VA). We will implement a peer support for reentry veterans sequentially in two states. Our outcome measures are 1) fidelity of the intervention, 2) linkage to VA health care and, 3) continued engagement in health care. The aims for this project are as follows: (1) Conduct contextual analysis to identify VA and community reentry resources, and describe how reentry veterans use them. (2) Implement peer-support, in one state, to link reentry veterans to Veterans' Health Administration (VHA) primary care, mental health, and SUD services. (3) Port the peer-support intervention to another, geographically, and contextually different state., Design: This intervention involves a 2-state sequential implementation study (Massachusetts, followed by Pennsylvania) using a Facilitation Implementation strategy. We will conduct formative and summative analyses, including assessment of fidelity, and a matched comparison group to evaluate the intervention's outcomes of veteran linkage and engagement in VHA health care (using health care utilization measures). The study proceeds in 3 phases., Discussion: We anticipate that a peer support program will be effective at improving the reentry process for veterans, particularly in linking them to health, mental health, and SUD services and helping them to stay engaged in those services. It will fill a gap by providing veterans with access to a trusted individual, who understands their experience as a veteran and who has experienced justice involvement. The outputs from this project, including training materials, peer guidebooks, and implementation strategies can be adapted by other states and regions that wish to enhance services for veterans (or other populations) leaving incarceration. A larger cluster-randomized implementation-effectiveness study is planned., Trial Registration: This protocol is registered with clinicaltrials.gov on November 4, 2016 and was assigned the number NCT02964897 .

Objective: Veterans Affairs (VA) is expanding peer support. Research is limited on Veterans' perspective on benefits from peer services. We describe homeless Veteran perceptions of value and examine characteristics associated with benefit., Method: From a sample of Veterans in a multisite randomized control trial, we studied addition of peers in VA Primary Care and homeless-oriented primary care clinics. We used qualitative methods to study the perceptions of peer services among a subsample of homeless Veterans. Quantitative methods were used to validate findings in both samples., Results: Sixty-five percent of the subsample and 83% of the full sample benefited from a peer mentor. Participants who benefited had more peer visits and minutes of intervention (p<.05), were more likely to be minority, and were less likely to have posttraumatic stress disorder., Conclusion: The majority of Veteran participants in this study benefited from receiving peer mentor intervention. African American Veterans were more likely to benefit and Veterans with PTSD were less likely to benefit. Client endorsement of the peer's role influenced outcomes., (© 2016 Wiley Periodicals, Inc.)

Objectives: Patterns and predictors of engagement in peer support services were examined among 50 previously homeless veterans with co-occurring mental health conditions and substance use histories receiving services from the Veterans Health Administration supported housing program., Method: Veteran peer specialists were trained to deliver sessions focusing on mental health and substance use recovery to veterans for an intended 1-hr weekly contact over 9 months. Trajectories of peer engagement over the study's duration are summarized. A mixed-effects log-linear model of the rate of peer engagement is tested with three sets of covariates representing characteristics of the veterans. These sets were demographics, mental health and substance use status, and indicators of community participation and support., Results: Data indicate that veterans engaged with peers about once per month rather than the intended once per week. However, frequency of contacts varied greatly. The best predictor of engagement was time, with most contacts occurring within the first 6 months. No other veteran characteristic was a statistically significant predictor of engagement. Older veterans tended to have higher rates of engagement with peer supporters., Conclusions and Implications for Practice: Planners of peer support services could consider yardsticks of monthly services up to 6 months. Peer support services need a flexible strategy with varying levels of intensity according to need. Peer support services will need to be tailored to better engage younger veterans. Future research should consider other sources of variation in engagement with peer support such as characteristics of the peer supporters and service content and setting. (PsycINFO Database Record, ((c) 2016 APA, all rights reserved).)

Effective services are needed to assist young people with serious mental health conditions to successfully transition to employment or education, especially among those with intensive adolescent mental health service utilization. To meet these needs, the Individual Placement and Support (IPS) model of supported employment was adapted and its feasibility was tested in a psychiatric treatment program for early-emerging adults. Participants were 17-20 years old (mean age = 18.5 years). Most were African American, under the custody of the state, with a primary mood disorder diagnosis. Adaptations to IPS included adding the following: near age peer mentors, a supported education component, and a career development focus. This open trial feasibility study tracked the model's development, recruitment, and retention and tracked vocational and educational outcomes for 12 months. Model refinement resulted in the development of a separate educational specialist position, greater integration of the peer mentor with the vocational team, and further specification of the role of peer mentor. There was an 80% retention rate in the feasibility evaluation. Of the 35 participants, 49% started a job and/or enrolled in an education program over the 12-month period.

College students' need for mental health care has increased dramatically, leaving campus counseling and mental health centers struggling to meet the demand. This has led to the investigation and development of extra-center, population-based interventions. Student-to-student support programs are but one example. Students themselves are a plentiful, often-untapped resource that extends the reach of mental health services on campus. Student-to-student programs capitalize on students' natural inclination to assist their peers. A brief review of the prevalence and effects of mental disorders in the college population is provided, followed by a broad overview of the range of peer-to-peer programs that can be available on college campuses. Two innovative programs are highlighted: (1) a hospital- and community-based program, the College Mental Health Program (CMHP) at McLean Hospital, and 2) the Student Support Network (SSN) at Worcester Polytechnic Institute. The subsequent section reviews the literature on peer-to-peer programs for students with serious and persistent mental illness for which there is a small but generally positive body of research. This lack of an empirical basis in college mental health leads the authors to argue for development of broad practice-research networks.

Zinc is essential for all bacteria, but excess amounts of the metal can have toxic effects. To address this, bacteria have developed tightly regulated zinc uptake systems, such as the ZnuABC zinc transporter which is regulated by the Fur-like zinc uptake regulator (Zur). In Pseudomonas aeruginosa, a Zur protein has yet to be identified experimentally, however, sequence alignment revealed that the zinc-responsive transcriptional regulator Np20, encoded by np20 (PA5499), shares high sequence identity with Zur found in other bacteria. In this study, we set out to determine whether Np20 was functioning as Zur in P. aeruginosa. Using RT-PCR, we determined that np20 (hereafter known as zur) formed a polycistronic operon with znuC and znuB. Mutant strains, lacking the putative znuA, znuB, or znuC genes were found to grow poorly in zinc deplete conditions as compared to wild-type strain PAO1. Intracellular zinc concentrations in strain PAO-Zur (Δzur) were found to be higher than those for strain PAO1, further implicating the zur as the zinc uptake regulator. Reporter gene fusions and real time RT-PCR revealed that transcription of znuA was repressed in a zinc-dependent manner in strain PAO1, however zinc-dependent transcriptional repression was alleviated in strain PAO-Zur, suggesting that the P. aeruginosa Zur homolog (ZurPA) directly regulates expression of znuA. Electrophoretic mobility shift assays also revealed that recombinant ZurPA specifically binds to the promoter region of znuA and does not bind in the presence of the zinc chelator N,N',N-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN). Taken together, these data support the notion that Np20 is the P. aeruginosa Zur, which regulates the transcription of the genes encoding the high affinity ZnuABC zinc transport system.

Objective: The purpose of this study was to construct and validate an instrument that measures practitioners' competence to promote the recovery among individuals with psychiatric disabilities from the perspective of the person served. Items were developed based upon input from individuals served and practitioners as well as the extant literature on recovery. "Recovery-promoting competence" was conceptualized as a set of practitioner capabilities that promote the recovery process and enhance the working alliance., Method: A scale was developed using a two-stage process that initially identified specific recovery-promoting competencies and then tested candidate items measuring those competencies. Item Response Theory and Classical Test Theory approaches were used to validate the instrument and assess its psychometric properties with a national sample of 382 individuals with psychiatric disabilities., Results: Analyses revealed two distinct sets of recovery-promoting competencies: (a) competencies that enhance clients' recovery, and (b) competencies that build and maintain a strong therapeutic or working alliance. The first set further differentiated into subcompetencies-enhancing clients' hopefulness, empowerment, and self-acceptance. The instrument had high internal consistency and acceptable stability over time, convergent, criterion, and known groups' validity., Conclusions and Implications for Practice: This scale is a tool for assessing mental health and rehabilitation practitioners' competencies from the perspective of the individual served which can be used both in research and program evaluation of agencies serving individuals with psychiatric disabilities., (PsycINFO Database Record (c) 2013 APA, all rights reserved)

Purpose: The influx of young adult veterans with mental health challenges from recent wars combined with newly expanded veteran education benefits has highlighted the need for a supported education service within the Veterans Administration. However, it is unknown how such a service should be designed to best respond to these needs. This study undertook a qualitative needs assessment for education supports among veterans with post-9/11 service with self-reported PTSD symptoms., Methods: Focus groups were held with 31 veterans, 54% of whom were under age 30. Transcripts were analyzed and interpreted using a thematic approach and a Participatory Action Research team., Results: Findings indicate a need for age relevant services that assist with: education planning and access, counseling for the G.I. Bill, accommodations for PTSD symptoms, community and family re-integration, and outreach and support., Conclusions and Implications for Practice: The veterans recommended that supported education be integrated with the delivery of mental health services, that services have varied intensity, and there be linkages between colleges and the Veterans Health Administration.

Objectives: The purpose of this study was to empirically validate a set of conceptually derived recovery-promoting competencies from the perspectives of mental health consumers, consumer-providers and providers., Methods: A national sample of 603 consumers, 153 consumer-providers and 239 providers completed an anonymous survey via the Internet. The survey evaluated respondents' perceptions about a set of 37 competencies hypothesized to enhance clients' hope and empowerment and inquired about interactions with providers that enhanced clients' recovery process. We used descriptive statistics and ranking to establish the relevance of each competency and generalized linear models and post-hoc tests to examine differences in the consumers', consumer-providers' and providers' assessments of these competencies., Results: Analyses confirmed the recovery relevance of several competencies and their relative importance within each group of study participants. They also revealed that while most competencies tended to have universal significance, others depended more strongly on the client's preferences. Finally, differences in the perceptions of consumers, consumer-providers and providers about the recovery relevance of these competencies were established., Conclusions and Implications for Practice: The study highlighted the crucial role practitioners play in enhancing recovery from serious mental illnesses through specific strategies and attitudes that acknowledge clients' personhood and foster their hopefulness, empowerment and illness management. It informed the development of a new instrument measuring providers' recovery-promoting competence and provides guidelines for sharpening the recovery focus of a wide range of mental health and rehabilitation services.

Objective: This study examines the outcomes of a statewide implementation of Intensive Psychiatric Rehabilitation (IPR) for improving residential and employment status and earnings among individuals with severe mental illnesses and also examines its implementation with respect to mental health service utilization and costs., Methods: This study employs a pre-post design with participants acting as their own controls for rehabilitation outcomes (residential status, vocational outcomes and earnings) comparing those who "completed" or had a sufficiently intense dose of IPR (one year) to those who dropped out early (before six months of service) and those who dropped out later in service (6-12 months). A separate analysis was conducted examining the relationship of IPR to other mental service use and costs using a quasi-experimental design that contrasted IPR completers with a control group matched via propensity scores., Results: The results suggested significant improvement in residential status, employment status and gross monthly earnings for IPR completers relative to other groups. IPR completers also tended to use more mental health services or have more shallow decreases in use and cost of services relative to matched controls., Conclusions and Implications for Practice: Gains in rehabilitation outcomes can be expected for those who engage in and complete IPR services, but IPR cannot be expected to result in reduced overall mental health service use and costs. Rather, IPR may improve service access or perhaps ameliorate any containment effect of managed care on service use.

Many bacteria utilize acyl-homoserine lactones as cell to cell signals that can regulate the expression of numerous genes. Structural differences in acyl-homoserine lactones produced by different bacteria, such as acyl side chain length and the presence or absence of an oxy group, make many of the commonly used detection bioassays impractical for broad range detection. Here we present a simple, broad range acyl-homoserine lactone detection bioassay that can be used to detect a wide range of these chemical signals. A plasmid (pEAL01) was constructed and transformed into Pseudomonas aeruginosa strain QSC105 to allow for detection of a broad range of acyl-homoserine lactones through induction of a lasB'-lacZ transcriptional fusion. Monitoring beta-galactosidase activity from this bioassay showed that P. aeruginosa strain QSC105 (pEAL01) could detect the presence of eight acyl-homoserine lactones tested at physiological concentrations. This novel strain could also detect acyl-homoserine lactones from the extracts of four different bacteria that produce different acyl-homoserine lactones signals. These data indicate that strain QSC105 (pEAL01) can be used to detect a wide variety of acyl-homoserine lactones by a simple beta-galactosidase assay and this bioassay could be a useful and inexpensive tool to quickly identify the presence of these signal molecules.

Pseudomonas aeruginosa is an opportunistic pathogen that causes both acute and chronic infections in immunocompromised individuals. This gram-negative bacterium produces a battery of virulence factors that allow it to infect and survive in many different hostile environments. The control of many of these virulence factors falls under the influence of one of three P. aeruginosa cell-to-cell signaling systems. The focus of this study, the quinolone signaling system, functions through the Pseudomonas quinolone signal (PQS), previously identified as 2-heptyl-3-hydroxy-4-quinolone. This signal binds to and activates the LysR-type transcriptional regulator PqsR (also known as MvfR), which in turn induces the expression of the pqsABCDE operon. The first four genes of this operon are required for PQS synthesis, but the fifth gene, pqsE, is not. The function of the pqsE gene is not known, but it is required for the production of multiple PQS-controlled virulence factors and for virulence in multiple models of infection. In this report, we show that PqsE can activate PQS-controlled genes in the absence of PqsR and PQS. Our data also suggest that the regulatory activity of PqsE requires RhlR and indicate that a pqsE mutant can be complemented for pyocyanin production by a large excess of exogenous N-butyryl homoserine lactone (C4-HSL). Finally, we show that PqsE enhances the ability of Escherichia coli expressing RhlR to respond to C4-HSL. Overall, our data lead us to conclude that PqsE functions as a regulator that is independent of PqsR and PQS but dependent on the rhl quorum-sensing system.

Pasteurella multocida exhibits nonspecific susceptibility to nonpolar antimicrobial agents such as triclosan, despite possessing an ultrastructurally typical gram-negative cell envelope. Capsulated and noncapsulated cell surface variants were examined to investigate the role outer membrane permeability plays in triclosan susceptibility. Test strains were unable to initiate growth in the presence of bile salts and were susceptible to triclosan with minimal inhibitory concentrations (MICs) ranging from 0.06 to 0.25 microg/ml. Disk agar diffusion bioassays revealed triclosan susceptibility to be dose dependent and all strains were susceptible to the hydrophobic antibiotics novobiocin, rifamycin SV, and chloramphenicol. Triclosan minimal bactericidal concentrations were greater than MICs, thereby suggesting that dose dependency reflected both bacteriostatic and bactericidal effects. Total and viable cell density growth kinetic determinations revealed a triclosan concentration of 2.0 microg/ml resulted in loss of batch culture viability within 4-24 h. Concentrations of 0.02 and 0.2 microg/ml exerted either a bacteriostatic or bactericidal effect depending on the strain. Uptake of the hydrophobic probe 1-N-phenylnaphthylamine was greater in P. multocida strains than refractory control organisms Pseudomonas aeruginosa and Escherichia coli thereby suggesting the presence of phospholipid bilayer regions in the outer membrane. Because triclosan inhibits a conserved enoyl-ACP reductase necessary for bacterial fatty acid biosynthesis, these data support the notion that extreme susceptibility in P. multocida is due to the general inability of the outer membrane to exclude nonpolar compounds. Moreover, susceptibility is independent of the presence of capsular material and the biocide is bactericidal in a concentration dependent manner.

Pseudomonas aeruginosa is intrinsically resistant to the hydrophobic biocide triclosan, and yet it can be sensitized to low concentrations by permeabilization of the outer membrane using compound 48/80. A selective plating assay revealed that compound 48/80-permeabilized YM64, a triclosan-recognizing efflux pump-deficient variant, was unable to initiate growth on a medium containing triclosan. Macrobroth dilution assay data revealed that treatment with compound 48/80 synergistically decreased minimal inhibitory concentrations of the hydrophobic antibacterial agents rifamycin SV and chloramphenicol for all cell envelope variant strains examined. A low concentration of triclosan exerted a transient bactericidal effect on permeabilized wild-type strain PAO1, after which exponential growth resumed within 4 h. Permeabilized strain YM64 was unable to overcome the inhibition; yet, both strains remained susceptible to chloramphenicol for as long as 6 h, thereby suggesting that the outer membrane remained permeable to nonpolar compounds. These data support the notion that the transitory nature of compound 48/80 sensitization to triclosan in P. aeruginosa does not involve obviation of the hydrophobic diffusion pathway through the outer membrane. The inability of strain YM64 to overcome the synergistic effect of compound 48/80 and triclosan strongly suggests that triclosan-recognizing efflux pumps are involved in maintaining viability in wild-type cells whose outer membranes are otherwise compromised.

The present study was undertaken to investigate the possibility that outer cell envelope impermeability might be involved in the intrinsic resistance of Pseudomonas aeruginosa to low levels of the hydrophobic biocide triclosan. Macrobroth dilution and batch cultural turbidimetric assays were employed to assess the ability of compounds that render the Gram-negative outer membrane permeable to non-polar molecules to sensitise cell envelope variants to triclosan. Pseudomonas aeruginosa strains possessing highly refractory (PAO1) and atypically permeable (Z61) outer cell envelopes as well as a PAO1 derivative lacking four multidrug efflux pumps (YM64) were examined. Whilst the triclosan minimal inhibitory concentrations (MICs) differed dramatically for both PAO1 and Z61, significant decreases were seen for both strains in the presence of the outer membrane permeabiliser polymyxin B-nonapeptide. Strain YM64 was as resistant to triclosan as strain PAO1. Turbidimetric assessments of batch cultural growth kinetics revealed that the three chemically unrelated outer membrane permeabilisers polymyxin B-nonapeptide, compound 48/80 and ethylenediaminetetraacetate (EDTA) sensitised all strains to a sub-MIC concentration of triclosan (2.0 microg/mL). These data support the notion that the outer membrane exclusionary properties of P. aeruginosa for non-polar molecules confer intrinsic resistance to low concentrations of triclosan such as might be expected to occur in environmental residues. Moreover, a role for outer cell envelope impermeability is suggested for resistance to high triclosan concentrations in vitro.

This article describes a model for integrating psychiatric rehabilitation services in a managed behavioral health care structure. Psychiatric rehabilitation and managed care are two distinct developments in the provision of mental health services that have proceeded independently though they can have compatible methods and outcomes. Descriptive detail is provided about a state initiative in Iowa to provide psychiatric rehabilitation services to those with serious mental illness through the state-contracted managed behavioral health care corporation. The article describes factors leading to the program's implementation, service delivery structures, reimbursements, personnel requirements, and performance indicators. Evidence for supporting this innovation is provided through a case-controlled outcomes study of mental health service units used and their costs for participants and matched controls.

In the last several years, state mental health authorities throughout the United States have assigned a high priority to the funding, development, and operation of case management programs. Although the concept of case management has been in existence for over a decade, there is still confusion regarding the definition of case management and the identification of alternative case management approaches. Recognizing this confusion, the Center for Psychiatric Rehabilitation undertook a comprehensive study to determine the state of case management practice today. This article reports on the results of a national survey of case management programs and describes the characteristics of the programs themselves, the case managers, the clients they serve, and the systems within which they operate. Implications of these findings for a definition of case management are discussed.

We have investigated the role of biochemical markers in breast and lung cancer but have found that currently available tests have little role in management. In breast cancer, for example, we have found that the most sensitive method for routine screening for metastases is by using chest x-ray and clinical examination, liver function tests, and carcinoembryonic antigen measurements. We are now examining other methods for detecting metastases using immunocytochemistry in cytological preparations of bone marrow and attempting to raise monoclonal antibodies to breast cancer cells. In lung cancer, the major effort has been directed towards characterisation of large-molecular-weight ectopic hormones, particularly calcitonin.

The production of corticotrophin releasing factor (CRF) activity by human tumour cells in monolayer culture was investigated. The secretion of CRF activity by a bronchial carcinoid cell line was demonstrated using a rat pituitary cell monolayer system. The long-term production (5 years) of CRF activity suggested the synthesis and secretion of active factors by the tumour cells. The CRF activity was concentrated from medium previously exposed to the tumour cells using batchwise extraction on columns packed with ODS. When these extracts were fractionated by analytical high pressure liquid chromatography, the CRF activity was resolved into two molecular forms.

A method of estimating doses from multiple dilutions of an unknown sample in radioimmunoassay is described. It uses a computer program to minimise the root mean square error about a standard curve. The confidence limits of the estimates were evaluated from the sum of squares error as a function of dose. An attached subroutine reported and suppressed points in the data set that showed unexpectedly large errors of fit. The program agreed well with an alternative point-by-point evaluation for most practical data but also responded robustly to errors at the limits of the assay curve. By studying patterns of point rejection, it is possible to build up information about the relation between the standard curve parameters and those in the unknown sets. The method is illustrated by studies of laboratory-based materials and by an assay of alphafetoprotein in samples of body fluids.

Many patients with advanced non-thyroid malignancies have elevated plasma immunoreactive calcitonin concentrations. Breast and bronchial carcinomas contain immunoreactive calcitonin and an epidermoid bronchial carcinoma has been shown to produce immunoreactive calcitonin in vitro. We have established monolayer cultures of breast carcinomas and eight out of fifteen consecutive carcinomas released immunoreactive calcitonin; some released HCG (human chorionic gonadotrophin) or CEA (carcinoembryonic antigen). In addition, a primary human breast carcinoma has been shown to release and contain calcitonin after being passaged in 'nude' mice over 1 year. Chromatography of extracts and culture media of a bronchical carcinoma demonstrated that, in contrast with the other tumours, it secreted a form or forms of calcitonin having size, charge and immunological differences when compared to calcitonin M. Preliminary evaluation of plasma immunoreactive calcitonin estimations in patients with breast carcinoma showed that twenty-three out of twenty-eight patients with metastatic disease had elevated plasma calcitonin concentrations, whereas only one out of thirteen with localized disease had high levels.

Immunohistochemical localisation of keratin was assessed on 45 diagnostic specimens of small cell carcinoma of the lung in patients who subsequently received combination chemotherapy. Nine out of 45 (20%) contained keratin immunoreactive cells. Six of these achieved a complete response to treatment compared to 12 of the tumours which did not show positive staining for keratin. For 2 patients the tumours were shown to contain nests of keratin immunoreactive cells. Both of these are alive and free of disease more than 5 yr after the initial diagnosis. The results indicate that the presence of keratin immunoreactive cells may not directly equate with squamous differentiation and therefore not constitute an adverse prognostic factor in terms of response to chemotherapy.

We have studied growth hormone production in a patient with a bronchial carcinoid and acromegaly. The absence of growth hormone from the carcinoid tumour was demonstrated by extraction, cell culture and immunoperosidase techniques. Using a linked perfusion culture system, effluent from the bronchial carcinoid tumour culture stimulated a rapid release of growth hormone from a rat pituitary monolayer. This is the first time evidence of growth hormone releasing activity by a bronchial carcinoid has been demonstrated in a production.

A total of 37 human bronchial carcinomas (15 small cell, 10 squamous, six large cell and six adenocarcinomas) have been successfully heterotransplanted into immune-suppressed mice. Monolayer tissue cultures have been established from 23 of the xenograft lines. After contact with tumour cells, supernatant culture medium was analysed by radioimmunoassay for adrenocorticotrophin (ACTH), calcitonin, human chorionic gonadotropin beta subunit (beta HCG) and carcinoembryonic antigen (CEA). Calcitonin production was associated with three (13%) xenograft lines (two small cell, one adenocarcinoma). beta HCG was found in three (13%) lines (one small cell, two large cell anaplastic). CEA was produced in 13 (56.5%) lines (seven small cell, two squamous, one large cell, three adenocarcinomas). ACTH was present in 18 (78.2%) lines (11 small cell, two squamous, two large cell, three adenocarcinomas), but evidence indicates that this hormone is not in all cases produced and secreted by the tumour.

The nature of corticotrophin releasing factor (CRF) activity secreted by a human bronchial carcinoid cell line was investigated. The CRF activity in incubation media exposed to bronchial tumour cells was concentrated by preparative high pressure liquid chromatography (HPLC). Analytical HPLC resolved the CRF activity into several different forms. The incorporation of [3H]leucine and other [3H]amino acids into materials which co-eluted with CRF activity when fractionated by analytical HPLC suggested that the bronchial carcinoid cells were secreting peptide CRF(s). The most abundant radioactive material was shown to have a molecular weight of 12 000 by sodium dodecyl sulphate gel electrophoresis. This radioactive fraction also stimulated ACTH secretion by rat pituitary cell cultures in a dose-responsive manner.

Studies on the high-molecular-weight immunoreactive calcitonin produced ectopically in culture by an epidermoid bronchial carcinoma cell line are reported. In cell-exposed medium, the principal component has a molecular weight of 40000 and molecules of mol.wts. 13000 and 10000 also occur. Only a trace amount of material co-eluting with 35000-mol.wt. human calcitonin is detectable. None of the calcitonins show cross-reactivity with anti-corticotropin serum. The 40000-mol.wt. immunoreactive calcitonin is readily proteolysed to the 13000- and 10000-mol.wt. components, but the 10000-mol.wt. component behaves as a comparatively stable 'core' molecule. By using immunoprecipitation and high-pressure liquid chromatography (h.p.l.c.), it is possible to prepare radiochemically homogeneous 10000-mol.wt. immunoreactive calcitonin from cells grown in the presence of individual 35S- or 3H-labelled amino acids. Peptide mapping of enzymic digests of this material by h.p.l.c. shows that it contains peptides in common with synthetic human calcitonin.

The human epidermoid bronchial carcinoma (BEN) cell line has been shown to have specific membrane binding sites for calcitonin and to secrete high-molecular-weight forms (ranging from 40000 to 10000) of immunoreactive calcitonin. Synthetic salmon and human calcitonins and a thyroid extract of porcine calcitonin have been shown to displace 125I-labelled salmon calcitonin from the receptors in a dose-related fashion. The binding to these receptors of calcitonins derived from the BEN cell line and a medullary thyroid carcinoma with molecular weights ranging from 28000 to 3500 (both separated by gel-filtration chromatography) has been investigated. Neither major peaks of BEN-cell-line calcitonin showed receptor binding activity. Only one form of medullary thyroid carcinoma calcitonin, that which co-eluted with synthetic calcitonin monomer on gel-filtration chromatography, caused any significant displacement of labelled hormone from the receptors.

Monolayer tissue culture has been used as a system in which to study aspects of ectopic hormone secretion. Of a series of twenty-four human bronchial carcinomas, nineteen were successfully established in culture and the supernatant medium from each tested for peptide hormones by radioimmunoassay. Six tumours were found to produce adrenocorticotrophin (ACTH), four to release calcitonin (CT) and one to release both of these hormones. No growth hormone or insulin was detected throughout the series. Net in vitro synthesis of both ACTH and CT was demonstrated by recovery of more hormone during culture than was originally contained in the explanted tumour tissue. The production of hormone by four out of six proliferative cultures established, and its persistence through many subculture passages, confirms ectopic hormone production as a stable heritable characteristic of some lung tumours. The ability of hormone-producing bronchial tumour cells to respond to factors known to influence hormone output from normal endocrine cells was tested. ACTH release was stimulated in one tumour by Pitressin and CT in another by gastrin. In addition, the release of CT from the same tumour cell line was shown to be inhibited by the accumulation of high external concentrations of CT as has been reported for normal C-cells.

The posterior pituitary gland is considered to be a source of a corticotrophin releasing factor(s) distinct from vasopressin. In this study, the corticotrophin releasing activity of a commercial posterior pituitary extract (Pitressin) and synthetic vasopressin were compared, using a perfused rat pituitary monolayer system. Pitressin was shown to have approximately twice the releasing activity than could be accounted for by its vasopressin content. Fractionation of the posterior pituitary extract, using high pressure liquid chromatography, showed it to contain active material co-eluting with synthetic vasopressin, and at least three other corticotrophin releasing factors. The releasing activity of the most active of these factors was investigated and was found to stimulate ACTH release in a dose-related manner.