Exploring the full range of N⋯I⋯X halogen-bonding interactions within a single compound using pressure.

The response of the trimethylammonium-iodinechloride and diiodide (TMA-ICl/I2) crystal structures have been examined under high pressure using neutron powder diffraction. TMA-ICl exhibits impressive pressure-driven electronic flexibility, where the N⋯I-Cl interactions progressively encompass all the distances represented in analogous structures recorded in the Cambridge Structural Database. Comparison with the TMA-I2 complex reveals that this flexibility is owed to the electronegativity of the chlorine atom which induces increased distortion of the iodine electron cloud. This structural flexibility may be influential in the future design of functional molecular materials.

HIV Risk and Interest in Preexposure Prophylaxis in Justice-Involved Persons.

Preexposure prophylaxis (PrEP) is underused in persons who use drugs and justice-involved persons. In an ongoing randomized controlled trial in 4 US locations comparing patient navigation versus mobile health unit on time to initiation of HIV medication or PrEP for justice-involved persons who use stimulants or opioids and who are at risk for or living with HIV, we assessed HIV risk factors, perceived HIV risk, and interest in PrEP. Participants without HIV (n = 195) were 77% men, 65% White, 23% Black, and 26% Hispanic; 73% reported a recent history of condomless sex, mainly with partners of unknown HIV status. Of 34% (67/195) reporting injection drug use, 43% reported sharing equipment. Despite risk factors, many persons reported their risk for acquiring HIV as low (47%) or no (43%) risk, although 51/93 (55%) with PrEP indications reported interest in PrEP. Justice-involved persons who use drugs underestimated their HIV risk and might benefit from increased PrEP education efforts.

Scales for participant Alliance with Recovery Coach (SPARC): initial development and pilot test.

Recovery coaches are individuals with lived experience with recovery from substance use disorder who typically engender a greater sense of trust than found with other types of healthcare providers. However, there currently are no validated tools that measure the connection between recovery coaches and their participants. The purpose of this study was to describe the initial development of the Scales for Participant Alliance with Recovery Coach (SPARC) to measure recovery coach connection or alliance, including initial psychometric analyses. Measurement development began with five scales of the Client Evaluation of Self Treatment (treatment participation, treatment satisfaction, rapport, peer support, and social support). Adapted items were pre-tested with focus groups (n = 8) to ensure they were meaningful and accurately reflected the domains (Study 1). After modifications, the SPARC has six scales (engagement, satisfaction, rapport, motivation and encouragement, role model and community linkage). The survey was piloted with 100 individuals (Study 2) age 18 or over who had met with a recovery coach within the last six months. Most study participants were male (60%) and white (87%) with less than two years in recovery. After removing two low performing items, the items for five of the domains had acceptable internal consistency. The items for the engagement domain had a slightly lower reliability. Findings suggest that items cover relevant recovery coach roles, are internally consistent within domains, and can be easily administered to individuals engaging in recovery coaching services. Additional research is needed with a larger, more heterogenous sample to further refine items.

The Effectiveness of the StaySafe Intervention Using a Paradigm for Predicting Missing Outcome Data.

Sample attrition is a confounding issue in the analysis of data collected in follow-up studies. The present study uses a regression procedure that includes a propensity score as a predictor in estimating imputed data. The utility of the procedure was addressed by comparing results from this augmented data with those from the original data. Data were from a randomized controlled study testing the utility of a tablet-based intervention designed to improve decision-making with respect to health risk behaviors. Outcomes included self-reported testing for HIV, STD, and hepatitis. Two samples were used (163 in community facilities and 348 in residential facilities). Seventy-eight in the community sample and 238 in the residential sample completed follow-up surveys. Propensity scores based on a stepwise logistic regression were used to make the calibration sample and the missing data sample as close as possible. Multilevel analysis was performed for each outcome and multiple imputation compared estimated mean differences for the augmented and original analyses. The model imputing missing data was effective for the three outcomes and increased power. Least square mean differences between augmented and original data appeared to be essentially the same for most of the outcomes. This protocol has been registered with https://www.clinicaltrials.gov/(NCT02777086).

Molecular annotation of G protein variants in a neurological disorder.

Heterotrimeric G proteins transduce extracellular chemical messages to generate appropriate intracellular responses. Point mutations in GNAO1, encoding the G protein αo subunit, have been implicated in a pathogenic condition characterized by seizures, movement disorders, intellectual disability, and developmental delay (GNAO1 disorder). However, the effects of these mutations on G protein structure and function are unclear. Here, we report the effects of 55 mutations on Gαo conformation, thermostability, nucleotide binding, and hydrolysis, as well as interaction with Gßγ subunits, receptors, and effectors. Our effort reveals four functionally distinct groups of mutants, including one group that sequesters receptors and another that sequesters Gßγ, both acting in a genetically dominant manner. These findings provide a more comprehensive understanding of disease-relevant mutations and reveal that GNAO1 disorder is likely composed of multiple mechanistically distinct disorders that will likely require multiple therapeutic strategies.

Decision-Making Styles as a Moderator on the Efficacy of the StaySafe Tablet Intervention.

Background: People with substance use disorders often differ in their decision-making styles. The present study addressed the impact of two decision-making styles (rational and dependent) on outcomes from a StaySafe tablet computer app intervention designed to improve decision-making around health risk behaviors and previously found to be effective for justice-involved people receiving treatment for a substance use disorder and under community supervision. Objectives: Participants were justice-involved residents in residential treatment. After completing a baseline survey, participants were randomly assigned to either complete the StaySafe app or to a standard procedure condition; and then asked to complete a post-intervention survey three months after baseline (this protocol has been registered with clinicaltrials.gov NCT02777086): 348 participants completed a baseline survey and 238 completed the post-test survey. Outcomes included measures of confidence and motivation around HIV knowledge and risks and getting tested. Multilevel analyses addressed the hypothesis that outcomes were related to decision-making style. Multiple imputation (MI) was used to address the effects of missing data. Results: StaySafe was more effective for those in the lower half of the decision-making dependent scale for HIV risks (HIV-Knowledge, Hepatitis testing, HIV Services testing, and Sex Risk, as well as motivation for treatment. The decision-making rational scale was less consistently related to HIV risk. Conclusions: The present study showed individuals with substance use disorders who differed in their decision-making styles reacted differently to the StaySafe intervention. Two scales, rational decision making, and dependent decision making are relevant to consider with respect to interventions targeting improving decision making among drug users.

Catalytic site mutations confer multiple states of G protein activation.

Heterotrimeric guanine nucleotide-binding proteins (G proteins) that function as molecular switches for cellular growth and metabolism are activated by GTP and inactivated by GTP hydrolysis. In uveal melanoma, a conserved glutamine residue critical for GTP hydrolysis in the G protein α subunit is often mutated in Gαq or Gα11 to either leucine or proline. In contrast, other glutamine mutations or mutations in other Gα subtypes are rare. To uncover the mechanism of the genetic selection and the functional role of this glutamine residue, we analyzed all possible substitutions of this residue in multiple Gα isoforms. Through cell-based measurements of activity, we showed that some mutants were further activated and inactivated by G protein-coupled receptors. Through biochemical, molecular dynamics, and nuclear magnetic resonance-based structural studies, we showed that the Gα mutants were functionally distinct and conformationally diverse, despite their shared inability to hydrolyze GTP. Thus, the catalytic glutamine residue contributes to functions beyond GTP hydrolysis, and these functions include subtype-specific, allosteric modulation of receptor-mediated subunit dissociation. We conclude that G proteins do not function as simple on-off switches. Rather, signaling emerges from an ensemble of active states, a subset of which are favored in disease and may be uniquely responsive to receptor-directed ligands.

Avoidance Self-Efficacy: Personal Indicators of Risky Sex and Substance Use among At-Risk Youth.

Adolescent substance use (SU) is associated with risky sex behavior and sexually transmitted infections and is a risk factor for subsequent risky sex decisions. Based on a sample of 1,580 youth in residential SU treatment, this study investigated how a static factor (race) and two dynamic personal factors (risk-taking, assertiveness) contributed to adolescents' perceived ability to avoid high-risk SU and sex behavior (avoidance self-efficacy). Results showed that race correlated with risk-taking and assertiveness, with White youth reporting higher ratings of assertiveness and risk-taking. Self-reported assertiveness and risk-taking also predicted SU and risky sex avoidance. This study underscores the importance of race and personal factors in relation to adolescents' confidence in avoiding high-risk situations.

Ab initio simulations of α- and ß-ammonium carbamate (NH4·NH2CO2), and the thermal expansivity of deuterated α-ammonium carbamate from 4.2 to 180†K by neutron powder diffraction.

Experimental and computational studies of ammonium carbamate have been carried out, with the objective of studying the elastic anisotropy of the framework manifested in (i) the thermal expansion and (ii) the compressibility; furthermore, the relative thermodynamic stability of the two known polymorphs has been evaluated computationally. Using high-resolution neutron powder diffraction data, the crystal structure of α-ammonium carbamate (ND4·ND2CO2) has been refined [space group Pbca, Z = 8, with a = 17.05189 (15), b = 6.43531 (7), c = 6.68093 (7) Šand V = 733.126 (9) Å3 at 4.2 K] and the thermal expansivity of α-ammonium carbamate has been measured over the temperature range 4.2-180 K. The expansivity shows a high degree of anisotropy, with the b axis most expandable. The ab initio computational studies were carried out on the α- and ß-polymorphs of ammonium carbamate using density functional theory. Fitting equations of state to the P(V) points of the simulations (run athermally) gave the following values: V0 = 744 (2) Å3 and bulk modulus K0 = 16.5 (4) GPa for the α-polymorph, and V0 = 713.6 (5) Å3 and K0 = 24.4 (4) GPa for the ß-polymorph. The simulations show good agreement with the thermoelastic behaviour of α-ammonium carbamate. Both phases show a high-degree of anisotropy; in particular, α-ammonium carbamate shows unusual compressive behaviour, being determined to have negative linear compressibility (NLC) along its a axis above 5 GPa. The thermodynamically stable phase at ambient pressure is the α-polymorph, with a calculated enthalpy difference with respect to the ß-polymorph of 0.399 kJ mol-1; a transition to the ß-polymorph could occur at ∼0.4 GPa.

Study protocol of a randomized controlled trial comparing two linkage models for HIV prevention and treatment in justice-involved persons.

BACKGROUND: Persons involved in the justice system are at high risk for HIV and drug overdose upon release to the community. This manuscript describes a randomized controlled trial of two evidence-based linkage interventions for provision of HIV prevention and treatment and substance use disorder (SUD) services in four high risk communities to assess which is more effective at addressing these needs upon reentry to the community from the justice system. METHODS: This is a 5-year hybrid type 1 effectiveness-implementation randomized controlled trial that compares two models (Patient Navigation [PN] or Mobile Health Unit [MHU] service delivery) of linking justice-involved individuals to the continuum of community-based HIV and SUD prevention and treatment service cascades of care. A total of 864 justice-involved individuals in four US communities with pre-arrest histories of opioid and/or stimulant use who are living with or at-risk of HIV will be randomized to receive either: (a) PN, wherein patient navigators will link study participants to community-based service providers; or (b) services delivered via an MHU, wherein study participants will be provided integrated HIV prevention/ treatment services and SUD services. The six-month post-release intervention will focus on access to pre-exposure prophylaxis (PrEP) for those without HIV and antiretroviral treatment (ART) for people living with HIV (PLH). Secondary outcomes will examine the continuum of PrEP and HIV care, including: HIV viral load, PrEP/ ART adherence; HIV risk behaviors; HCV testing and linkage to treatment; and sexually transmitted infection incidence and treatment. Additionally, opioid and other substance use disorder diagnoses, prescription, receipt, and retention on medication for opioid use disorder; opioid and stimulant use; and overdose will also be assessed. Primary implementation outcomes include feasibility, acceptability, sustainability, and costs required to implement and sustain the approaches as well as to scale-up in additional communities. DISCUSSION: Results from this project will help inform future methods of delivery of prevention, testing, and treatment of HIV, HCV, substance use disorders (particularly for opioids and stimulants), and sexually transmitted infections for justice-involved individuals in the community. TRIAL REGISTRATION: Clincialtrials.gov NCT05286879 March 18, 2022.

A psychometric reevaluation of the TCU criminal thinking scales (CTS).

In the United States, approximately 9 million people cycle in and out of jail and more than 600,000 people are released from prison each year. Unfortunately, the reentry process includes several barriers people must overcome (e.g., criminal thinking) to achieve adequate psychosocial functioning. As such, valid and reliable assessments that allow correctional staff to monitor clients' progress in treatment and test program effectiveness are paramount to reducing this major public safety concern. The TCU Criminal Thinking Scales (CTS) are a widely used assessment of criminal thinking in correctional settings. This study reevaluated the psychometric properties of the TCU CTS using Item Response Theory. Results showed the TCU CTS had good internal reliability and each scale loaded onto one factor. Item level analysis revealed most items adequately fit the model, generally measuring moderate levels of criminal thinking. Furthermore, several TCU CTS scales were negatively correlated with motivation for treatment and psychosocial functioning.

Existential isolation and well-being in justice-involved populations.

Much work in psychology has focused on feelings of social isolation and/or loneliness. Only recently have psychologists begun to explore the concept of existential isolation (EI). EI is the subjective sense that persons are alone in their experience and that others are unable to understand their perspective. EI thus occurs when people feel that they have a unique worldview unshared by others. Measured as either a state or trait, empirical studies have shown EI undermines life meaning and decreases well-being; people scoring high on EI report lower levels of need satisfaction, purpose in life, and meaningfulness and increased death-related concerns. There is also a positive correlation between EI and anxiety, depression, and suicidal ideation. The purpose of this perspective paper is to review literature on EI and discuss its relevance to people who have been involved with the justice system. Given their higher rates of substance use, mental health difficulties, and trauma, this traditionally underserved population is particularly susceptible to compromised well-being. We theorize that EI may impede the impact of therapeutic interventions in justice settings as more isolated individuals may feel disjointed from their counselors and peers, thereby decreasing levels of treatment engagement, participation, satisfaction, and perceived social support. Professionals may be able to mitigate issues related to EI by an enhanced focus on establishing authenticity within the therapist-client relationship (e.g., empathy, perspective taking, compassion), connecting with clients via I-sharing [i.e., matching on a shared experience(s)], and/or encouraging active participation in client's behavioral healthcare needs (e.g., self-reflection).

Analyses of the TCU Drug Screen 5: Using an Item Response Theory Model with a Sample of Juvenile Justice Youth.

It is important to identify substance use disorders among youth who enter the juvenile justice system using a validated screener, such as the Texas Christian University Drug Screen 5 (TCU DS 5), so that necessary services can be provided to youth in need of treatment. While the TCU DS 5 is a valid, evidence-based screener, the use of an Item Response Theory model may better differentiate between mild, moderate, and severe forms of substance use disorders. The current study analyzed the feasibility and incremental value gained in using an Item Response Theory model to compute drug use severity scores as compared to its current scoring methodology. Results showed that while Item Response Theory may not be worthwhile as the standard method of scoring, item level analyses revealed there are benefits to using Item Response Theory to determine which items on a screener are most suggestive of severe substance use problems.

Preventing opioid use among justice-involved youth as they transition to adulthood: leveraging safe adults (LeSA).

BACKGROUND: Juvenile justice (JJ) youth are at high risk of opioid and other substance use (SU), dysfunctional family/social relationships, and complex trauma. The purpose of the Leveraging Safe Adults (LeSA) Project is to examine the effectiveness of Trust-Based Relational Intervention® (TBRI®; leveraging family systems by providing emotional and instrumental guidance, support, and role modeling) in preventing opioid and other SU among youth after release from secure residential facilities. METHODS: An effectiveness-implementation Hybrid Type 1 design is used to test the effectiveness of TBRI for preventing non-medical use of opioids among JJ-youth (delayed-start at the site level; a randomized controlled trial at participant level) and to gain insight into facility-level barriers to TBRI implementation as part of JJ re-entry protocols. Recruitment includes two samples (effectiveness: 360 youth/caregiver dyads; implementation: 203 JJ staff) from nine sites in two states over 3 years. Participant eligibility includes 15 to 18-year-olds disposed to community supervision and receiving care in a secure JJ facility, without active suicide risk, and with one caregiver willing to participate. Effectiveness data come from (1) youth and caregiver self-report on background, SU, psychosocial functioning, and youth-caregiver relationships (Months 0, 3, 6, 12, and 18), youth monthly post-release check-ins, and caregiver report on youth psychological/behavioral symptoms, and (2) JJ facility records (e.g., recidivism, treatment utilization). Fidelity assessment includes post-session checklists and measures of TBRI strategy use. Collected four times over four years, implementation data include (1) JJ staff self-report on facility and staff characteristics, use of trauma-informed care and TBRI strategies, and (2) focus groups (line staff, leadership separately) on use of trauma-informed strategies, uptake of new interventions, and penetration, sustainment, and expansion of TBRI practices. DISCUSSION: The LeSA study is testing TBRI as a means to empower caregivers to help prevent opioid use and other SU among JJ-youth. TBRI's multiple components offer an opportunity for caregivers to supplement and extend gains during residential care. If effective and implemented successfully, the LeSA protocol will help expand the application of TBRI with a wider audience and provide guidance for implementing multi-component interventions in complex systems spanning multiple contexts. TRIAL REGISTRATION: ClinicalTrials.gov NCT04678960 ; registered November 11, 2020; https://clinicaltrials.gov/ct2/show/NCT04678960 .

An evaluation of StaySafe, a tablet app to improve health risk decision-making among people under community supervision.

BACKGROUND: A self-administered tablet app, StaySafe, helps people under community supervision to make better decisions regarding health risk behaviors, especially those linked to HIV, viral hepatitis, and other sexually transmitted infections. The multi-session StaySafe design uses an interactive, analytical schema called WORKIT that guides users through a series of steps, questions, and exercises aimed at promoting critical thinking about health risks associated with substance use and unprotected sex. Repetition of the WORKIT schema is designed to enhance procedural memory that can be rapidly accessed when individuals are faced with making decisions about risky behaviors. METHODS: A total of 511 participants under community supervision in community and residential treatment settings from three large Texas counties completed consent forms and baseline surveys, followed by randomization to one of two conditions: 12 weekly StaySafe sessions or standard practice (SP). The study also asked participants to complete a follow-up survey three months after baseline. Outcome measures included knowledge, confidence, and motivation (KCM) scales around HIV knowledge, avoiding risky sex, HIV services, and reducing health risks; decision-making; and reports of talking about issues such as making better decisions, avoiding HIV risks, and HIV prevention or treatment with others (probation officers, counselors, trusted friend or advisor, or family members). RESULTS: Participants in both community and residential settings voluntarily completed multiple StaySafe sessions, with those in the residential settings completing more sessions. When compared with SP participants, StaySafe participants showed greater improvement in the KCM measures-HIV knowledge, avoiding sex risks, HIV services, and risk reduction skills. In addition, greater improvements in the KCM measures as well as an increased likelihood to discuss issues with others were associated with completing more StaySafe sessions. CONCLUSION: These results suggest that the StaySafe app is a feasible and potentially effective tool for improving health risk reduction decision-making for individuals under community supervision.

Linking criminal justice-involved individuals to HIV, Hepatitis C, and opioid use disorder prevention and treatment services upon release to the community: Progress, gaps, and future directions.

Improving HIV and Hepatitis C Virus (HCV) management among people involved in the criminal justice (CJ) system who use drugs, in particular those with opioid use disorder (OUD), requires effective approaches to screening, linkage, and adherence to integrated prevention and treatment services across correctional and community agencies and providers. This manuscript reviews the literature to explore gaps in HIV, Hepatitis C, and OUD prevention, treatment, and delivery cascades of care for persons involved in the CJ system. Specifically, we compare two models of linkage to prevention and treatment services: Peer/Patient Navigation (PN) wherein the PN links CJ-involved individuals to community-based infectious disease (ID) and substance use prevention and treatment services, and Mobile Health Units (MHU) wherein individuals are linked to a MHU within their community that provides integrated ID and substance use prevention and treatment services. The most notable finding is a gap in the literature, with few to no comparisons of models linking individuals recently released from the CJ system to integrated HIV, Hepatitis C, and OUD prevention and treatment and other harm reduction services. Further, few published studies address the geographical distinctions that affect service implementation and their effects on these substance use, ID and harm reduction care cascades. This manuscript makes specific recommendations to fill this gap through a detailed evaluation of PN and MHU linkage models to co-located and integrated HIV, Hepatitis C, and OUD prevention and treatment services across different communities within the U.S.

The Role of Personality Functioning on Early Drop out in Outpatient Substance Misuse Treatment.

BACKGROUND: Treatment initiation is a major factor contributing to positive outcomes, but the supporting literature remains limited. It is difficult to draw conclusions regarding predictors of dropout, and there is a need to target clients' major early attrition vulnerabilities. Despite empirically validated models for assessing personality, little is known about its role in the treatment process. Studies that have been conducted in this area have focused mainly on stable personality traits and provide conflicting evidence. Aims: The aim of this study is to examine to what extent service users' personality functioning are potential determinants of early drop out. Methodology: A cross-sectional multi-site design examined the therapy process in a naturalistic setting in 5 outpatient preparation treatment centers with 210 service users. The current study adopts a contemporary dimensional-based framework, similar to the Alternative Model of Personality Disorder of the DSM-V and examines the role of characteristic adaptations (SIPP-118) on early drop out (CEST-Intake). Findings: From the broad spectrum of personality traits, only Depression remained significant predictor of drop out. Higher dysfunctional levels in Social Concordance [OR] = 1.85, Wald =19.87, p =.002, 95% CI [1.1, 1.9] as well as the facets Aggression Regulation, Respect and Purposefulness were also predictors of early drop out, while Treatment Readiness and Desire for Help accounted for a significant amount of variance. Conclusions: These findings extend our knowledge of the predictive role of characteristic adaptations in treatment and suggest it may be important to assess these individual differences early on and to design personalized-informed interventions.

A universal allosteric mechanism for G protein activation.

G proteins play a central role in signal transduction and pharmacology. Signaling is initiated by cell-surface receptors, which promote guanosine triphosphate (GTP) binding and dissociation of Gα from the Gßγ subunits. Structural studies have revealed the molecular basis of subunit association with receptors, RGS proteins, and downstream effectors. In contrast, the mechanism of subunit dissociation is poorly understood. We use cell signaling assays, molecular dynamics (MD) simulations, and biochemistry and structural analyses to identify a conserved network of amino acids that dictates subunit release. In the presence of the terminal phosphate of GTP, a glycine forms a polar network with an arginine and glutamate, putting torsional strain on the subunit binding interface. This "G-R-E motif" secures GTP and, through an allosteric link, discharges the Gßγ dimer. Replacement of network residues prevents subunit dissociation regardless of agonist or GTP binding. These findings reveal the molecular basis of the final committed step of G protein activation.

Justice community opioid innovation network (JCOIN): The TCU research hub.

Recognizing the current opioid crisis among justice-involved individuals and the need to intervene at the intersection of justice and community health, the JCOIN TCU hub study explores outcomes associated with a multi-level hybrid implementation approach. The study capitalizes on facilitated collaboration, training, and cross-system data sharing to leverage improvements in criminal justice (CJ) and community behavioral health (CBH) interagency collaboration. The goal is to improve local community public health and safety outcomes for reentering justice-involved individuals who have a history of (or are at risk for) using opioids. The study compares two implementation strategies: one (vertical) in which all units in a community are trained and begin the program simultaneously and another (horizontal) in which one lead-off unit in the community is trained as a prototype of the program, the prototype is tested and refined, and then the lead-off unit helps to train other units within the community. Specific aims are to 1) increase access to and retention in CBH and medications for opioid use disorder services; 2) improve outcomes associated with public health and safety; 3) compare two implementation strategies on systems-level outcomes designed to increase service initiation and receipt of implementation and services; and 4) examine the impact of these strategies on justice-involved individuals' outcomes. The study examines both implementation and implementation-effectiveness, seeking to answer the questions of which implementation strategy is most effective for rapid and sustainable uptake of evidence-based practices and for increasing service linkage and initiation, services retention, and improved opioid-related public health safety outcomes. The study uses a hybrid type 3 study design. The study's primary aim is to compare two implementation strategies and two interventions at two levels (client and system), with a secondary aim to assess client-level outcomes associated with the trial. The study design integrates 2 robust methodologies (stepped wedge and cluster randomized trial), and plans to include 18 research performance sites (communities) located in Texas, New Mexico, and Illinois. The study will contribute to the JCOIN network's effort to establish a national consortium of investigators examining promising strategies to enhance the capabilities and capacity of the justice system to more effectively address the opioid epidemic.