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Matthew E Sprong,1,2 Heaven Hollender,3 Bob Blankenberger,2 Stuart Rumrill,4 Yu-Sheng Lee,5 Travis Bland,2 Jeremiah Bailey,6 Kenneth Weber,1 James Gilbert,1 Ken Kriz,2 Frank D Buono7 1Edward Hines Jr. VA Medical Center, Hines, IL, USA; 2University of Illinois Springfield, School of Public Management and Policy, Springfield, IL, USA; 3Indiana University - Indianapolis, School of Health & Human Services, Indianapolis, IN, USA; 4Univerity of Illinois Urbana-Champaign, Department of Kinesiology and Community Health, Champaign, IL, USA; 5University of Illinois Springfield, School of Integrated Sciences, Sustainability, and Public Health, Springfield, IL, USA; 6Florida Agricultural and Mechanical University, Department of Sociology and Criminal Justice, Tallahassee, FL, USA; 7Yale School of Medicine, New Haven, CT, USACorrespondence: Matthew E Sprong, Email mspro2@uis.eduIntroduction: Veterans diagnosed with mental health and/or substance use disorders (SUD) often face significant barriers to employment and reintegration into civilian society. In the current study, we investigated whether how the VA healthcare system for mental health and/or SUD treatment predicted program enrollment into vocational rehabilitation, simultaneous mental health and/or SUD treatment while enrolled in vocational rehabilitation predicted employment at discharge, and mental health and/or SUD treatment continues and employment remain 60-days-post-vocational-rehabilitation discharge.Methods: An outcome-based, summative program evaluation design to measure quality assurance of vocational rehabilitation services provided to 402 veteran patients enrolled in a VA healthcare located within the Great Lakes Health Care System – Veterans Integrated Services Network.Results: Multivariable logistic regression analyses showed psychological empowerment (confidence in one’s ability to work or find work) is a significant factor determining whether a veteran is enrolled in the vocational rehabilitation program, prior mental health treatment (yes/no) and frequency of mental health treatment did not predict program enrollment, and frequency of SUD VA system treatment 60 days prior did not predict program enrollment. Other findings showed that simultaneous mental health and/or SUD treatment while enrolled in vocational rehabilitation did not predict employment at discharge, and employment at discharge did not predict continued mental health and/or SUD treatment post-discharge from vocational rehabilitation. However, veterans with both SUD and mental health and continued mental health treatment were less likely to be employed.Conclusion: Utilization of real-world program evaluation data from an actual VHA vocational rehabilitation program enhances the study’s ecological validity, offering practical implications for policymakers and practitioners in the field. The findings support the importance of veterans enrolling in mental health and/or SUD treatment simultaneously while enrolled in vocational rehabilitation services, as integrating vocational rehabilitation with mental health and SUD treatment services can lead to improved vocational and health outcomes for veterans (eg, development of targeted interventions to support veterans’ successful reintegration into the workforce and society).Keywords: substance use disorders, mental health, veterans affairs, health administration, veterans, vocational rehabilitation, treatment access

HIV-1 reverse transcriptase is one of the most attractive targets for the treatment of AIDS. However, the rapid emergence of drug-resistant strains and unsatisfactory drug-like properties seriously limit the clinical application of HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). Here we show that a series of piperazine sulfonyl-bearing diarylpyrimidine-based NNRTIs were designed to improve the potency against wild-type and NNRTI-resistant strains by enhancing backbone-binding interactions. Among them, compound 18b1 demonstrates single-digit nanomolar potency against the wild-type and five mutant HIV-1 strains, which is significantly better than the approved drug etravirine. The co-crystal structure analysis and molecular dynamics simulation studies were conducted to explain the broad-spectrum inhibitory activity of 18b1 against reverse transcriptase variants. Besides, compound 18b1 demonstrates improved water solubility, cytochrome P450 liability, and other pharmacokinetic properties compared to the currently approved diarylpyrimidine (DAPY) NNRTIs. Therefore, we consider compound 18b1 a potential lead compound worthy of further study., (© 2023. The Author(s).)

Human immunodeficiency virus type I (HIV-1) is a retrovirus that infects cells of the host's immune system leading to acquired immunodeficiency syndrome and potentially death. Although treatments are available to prevent its progression, HIV-1 remains a major burden on health resources worldwide. Continued emergence of drug-resistance mutations drives the need for novel drugs that can inhibit HIV-1 replication through new pathways. The viral protein reverse transcriptase (RT) plays a fundamental role in the HIV-1 replication cycle, and multiple approved medications target this enzyme. In this study, fragment-based drug discovery was used to optimize a previously identified hit fragment (compound B-1 ), which bound RT at a novel site. Three series of compounds were synthesized and evaluated for their HIV-1 RT binding and inhibition. These series were designed to investigate different vectors around the initial hit in an attempt to improve inhibitory activity against RT. Our results show that the 4-position of the core scaffold is important for binding of the fragment to RT, and a lead compound with a cyclopropyl substitution was selected and further investigated. Requirements for binding to the NNRTI-binding pocket (NNIBP) and a novel adjacent site were investigated, with lead compound 27 -a minimal but efficient NNRTI-offering a starting site for the development of novel dual NNIBP-Adjacent site inhibitors.

Background: Most people with multiple sclerosis (MS) are employed at the time of their diagnosis; however, due to the unpredictable nature of MS, most exit the workforce shortly thereafter. A plethora of research has examined factors that negatively affect employment outcomes for people with MS. However, little is known about how hope, a modifiable positive psychology factor, affects employment., Objective: This study examined the role of hope and its association with employment outcomes for people with MS., Methods: Two-hundred and fifty-five adults with MS (mean ± SD age, 45.45 years ± 10.28) completed surveys about their MS, employment, disability-related stress, and hope. A three-step hierarchical logistic regression was conducted to examine the extent to which hope explains the variance in employment, over and above demographic and disability related covariates., Results: The final model explained 28% of the variance in employment, suggesting that the model was able to distinguish people with MS who were employed versus those who were unemployed. Higher levels of hope were associated with an increased probability of being employed (OR = 4.65; 95% CI [1.98, 10.92])., Conclusion: This study supports that hope is associated with favorable employment outcomes for people with MS. Persons with MS may benefit from working with rehabilitation professionals to enhance their hope, and this study provides a foundation for the development of hope-based interventions to improve employment outcomes among this population.

Background: Apathy remains a common and problematic neuropsychiatric feature associated with Parkinson's disease resulting in reductions in health-related quality of life, and effective treatments remain elusive. Meaning in life (MIL) has been implicated in a variety of positive health outcomes, and this study assesses the relationship between apathy and MIL while hoping to identify a potential new interventional target., Methods: A cross-sectional sample of 237 PwPD completed surveys to evaluate MIL and a variety of non-motor symptoms (NMS), and a hierarchical regression analysis was conducted to evaluate relationships of interest., Results: Correlational analysis indicated the presence of meaning in life was statistically negatively and moderately to strongly correlated with apathy (r = - 0.60, p < .001). Hierarchical regression analysis results showed that presence of meaning in life explained a total of 48% of variance in apathy. More specifically, the presence of meaning in life (β = - 0.43, p < .001) was associated with apathy after controlling for sociodemographic and other potentially confounding variables., Conclusions: This study demonstrates the significant negative relationship between MIL and apathy. Considering the lack of effective treatments for apathy, which is one of the most disabling symptoms affecting PwPD, identifying a potential target for intervention is exciting. MIL has the potential to offer clinicians a novel intervention to provide a much-needed treatment option to improve both apathy and HRQoL., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: Social effectiveness is key to success in the labor market. For decades, social motivation has been empirically studied as both a presumed cause and consequence of social effectiveness. Yet, few direct measures of social motivation exist, and even fewer have been validated with a disability population. This study provides the measurement structure and psychometric properties of a newly created measure of social motivation tested with a general disability population., Research Design: Participants included 1,013 US adults with disabilities. Exploratory factor analysis (EFA) and Confirmatory Factor Analysis (CFA) were implemented to validate the measure., Results: Results of the EFA suggest that a reduced 26-item inventory exhibits a 5-factor structure in a general population of people with disabilities. These results were confirmed with the CFA. Concurrent validity analysis revealed that most factors were significantly associated with relevant psychosocial variables in the expected directions., Conclusions: The Social Motivation Inventory provides a useful tool for enhancing understanding of social motivation in rehabilitation psychology and rehabilitation counseling research and practice. (PsycInfo Database Record (c) 2021 APA, all rights reserved).