Identification of C-Terminal Binding Protein 1 as a Novel NMDA Receptor Interactor.

A new N-methyl D aspartate neurotransmitter receptor interacting protein has been identified by yeast two-hybrid screening of a mouse brain cDNA library. C-terminal binding protein 1 (CtBP1) was shown to associate with the intracellular C-terminal regions of the N-methyl D aspartate receptor subunits GluN2A and GluN2D but not with GluN1-1a cytoplasmic C-terminal region. In yeast mating assays using a series of GluN2A C-terminal truncations, it was demonstrated that the CtBP1 binding domain was localized to GluN2A 1157-1382. The GluN2A binding domain was identified to lie within the CtBP1 161-224 region. CtBP1 co-immunoprecipitated with assembled GluN1/GluN2A receptors expressed in mammalian cells and also, in detergent extracts of adult mouse brain. Co-expression of CtBP1 with GluN1/GluN2A resulted in a significant decrease in receptor cell surface expression. The family of C-terminal binding proteins function primarily as transcriptional co-repressors. However, they are also known to modulate intracellular membrane trafficking mechanisms. Thus the results reported herein describe a putative role for CtBP1 in the regulation of cell surface N-methyl D aspartate receptor expression.

Patient perceptions of treatment with medication treatment for opioid use disorder (MOUD) in the Vermont hub-and-spoke system.

In 2013, Vermont leaders implemented the "hub-and-spoke" (H & S) system to increase access to medication treatment for opioid use disorder (MOUD). "Hubs" are licensed specialty opioid treatment programs (OTPs) with the authority to dispense buprenorphine/naloxone and methadone. "Spokes" are primary care practices that provide office-based opioid treatment, primarily with buprenorphine/naloxone. This report describes the qualitative component of an evaluation of the H&S system, conducted in 2016. The qualitative data collection assessed patient perspectives about the positive and negative aspects of treatment in the H & S system. The data collected included 80 responses to five open-ended questions and 24 in-depth interviews. Five open-ended questions were completed with hub (n = 40) and spoke (n = 40) participants. In-depth qualitative interviews were conducted with different hub (n =12) and spoke (n =12) participants. Findings from both data collection approaches suggest positive perceptions about treatment overall by patients treated in both settings. Participants treated in spokes reported a positive treatment environment, minimal stigma, and few obstacles to treatment and a strong positive relationship with their prescriber. Hub patients valued the MOUD and expressed gratitude for having access to MOUD, but reported the treatment environment was somewhat challenging, with long lines and drug talk in the clinic, high staff turnover and "cookie cutter" treatment. There appear to be some differences in patient perceptions of MOUD treatment between patients treated in primary care settings and specialized OTP settings.

Surgery for the resolution of symptoms in malignant bowel obstruction in advanced gynaecological and gastrointestinal cancer.

BACKGROUND: This is an update of the original Cochrane review published in Issue 4, 2000. Intestinal obstruction commonly occurs in progressive advanced gynaecological and gastrointestinal cancers. Management of these patients is difficult due to the patients' deteriorating mobility and function (performance status), the lack of further chemotherapeutic options, and the high mortality and morbidity associated with palliative surgery. There are marked variations in clinical practice concerning surgery in these patients between different countries, gynaecological oncology units and general hospitals, as well as referral patterns from oncologists under whom these patients are often admitted. OBJECTIVES: To assess the efficacy of surgery for intestinal obstruction due to advanced gynaecological and gastrointestinal cancer. SEARCH METHODS: We searched the following databases for the original review in 2000 and again for this update in June 2015: CENTRAL (2015, Issue 6); MEDLINE (OVID June week 1 2015); and EMBASE (OVID week 24, 2015).We also searched relevant journals, bibliographic databases, conference proceedings, reference lists, grey literature and the world wide web for the original review in 2000; we also used personal contact. This searching of other resources yielded very few additional studies. The Cochrane Pain, Palliative and Supportive Care Review Group no longer routinely handsearch journals. For these reasons, we did not repeat the searching of other resources for the June 2015 update. SELECTION CRITERIA: As the review concentrates on the 'best evidence' available for the role of surgery in malignant bowel obstruction in known advanced gynaecological and gastrointestinal cancer we kept the inclusion criteria broad (including both prospective and retrospective studies) so as to include all studies relevant to the question. We sought published trials reporting on the effects of surgery for resolving symptoms in malignant bowel obstruction for adult patients with known advanced gynaecological and gastrointestinal cancer. DATA COLLECTION AND ANALYSIS: We used data extraction forms to collect data from the studies included in the review. Two review authors extracted the data independently to reduce error. Owing to concerns about the risk of bias we decided not to conduct a meta-analysis of data and we have presented a narrative description of the study results. We planned to resolve disagreements by discussion with the third review author. MAIN RESULTS: In total we have identified 43 studies examining 4265 participants. The original review included 938 patients from 25 studies. The updated search identified an additional 18 studies with a combined total of 3327 participants between 1997 and June 2015. The results of these studies did not change the conclusions of the original review.No firm conclusions can be drawn from the many retrospective case series so the role of surgery in malignant bowel obstruction remains controversial. Clinical resolution varies from 26.7% to over 68%, though it is often unclear how this is defined. Despite being an inadequate proxy for symptom resolution or quality of life, the ability to feed orally was a popular outcome measure, with success rates ranging from 30% to 100%. Rates of re-obstruction varied, ranging from 0% to 63%, though time to re-obstruction was often not included. Postoperative morbidity and mortality also varied widely, although again the definition of both of these surgical outcomes differed between many of the papers. There were no data available for quality of life. The reporting of adverse effects was variable and this has been described where available. Where discussed, surgical procedures varied considerably and outcomes were not reported by specific intervention. Using the 'Risk of bias' assessment tool, most included studies were at high risk of bias for most domains. AUTHORS' CONCLUSIONS: The role of surgery in malignant bowel obstruction needs careful evaluation, using validated outcome measures of symptom control and quality of life scores. Further information could include re-obstruction rates together with the morbidity associated with the various surgical procedures.Currently, bowel obstruction is managed empirically and there are marked variations in clinical practice by different units. In order to compare outcomes in malignant bowel obstruction, there needs to be a greater degree of standardisation of management.Since the last version of this review none of the new included studies have provided additional information to change the conclusions.

A demonstration project implementing extended-release naltrexone in Los Angeles County.

BACKGROUND: Extended-released naltrexone (XR-NTX) is a Food and Drug Administration (FDA)-approved medication associated with higher rates of abstinence, reduced cravings, and delayed relapse to use. However, there is a dearth of literature on real-world implementation of XR-NTX. The Los Angeles County Department of Public Health, in collaboration with UCLA Integrated Substance Abuse Programs, developed a demonstration project to increase access to XR-NTX. This article describes that project, along with data on the expansion of XR-NTX service delivery and patient uptake. METHODS: A secondary descriptive data analysis of demographics, substance use history, current substance use behaviors, health-related variables, and dosing records was conducted on 609 patients who received XR-NTX from Los Angeles County substance use disorder (SUD) treatment facilities from April 2010 through July 2013. A geographic information system approach mapped the distribution of XR-NTX-referring agencies across Los Angeles County. RESULTS: Of the 609 records analyzed, a majority of patients (64%) obtained more than 1 dose of XR-NTX. Most XR-NTX patients reported alcohol use disorder (71.9%; n = 438). Compared with the general Los Angeles County substance use disorder patients, XR-NTX recipients reported more severe substance use histories. Finally, XR-NTX was accessed by providers in 6 of the 8 Service Planning Areas of Los Angeles County. CONCLUSIONS: These findings reflect a higher XR-NTX cessation rate and a lower average number of doses, in contrast to similar demonstration projects in community settings with patients on parole or probation. However, this study shows that it is feasible to engage treatment providers in the use XR-NTX among their patients with alcohol or opioid use disorders. Several implications for future research and implementation are discussed.

APLP1 and APLP2, members of the APP family of proteins, behave similarly to APP in that they associate with NMDA receptors and enhance NMDA receptor surface expression.

The function of amyloid precursor protein (APP) is unknown, although the discovery that it contributes to the regulation of surface expression of N-methyl-D-aspartate (NMDA) receptors has afforded new insights into its functional significance. Since APP is a member of a gene family that contains two other members, amyloid precursor-like proteins 1 and 2 (APLP1 and APLP2), it is important to determine if the related APP proteins possess the same properties as APP with respect to their interactions with NMDA receptors. Following expression in mammalian cells, both APLP1 and APLP2 behaved similarly to APP in that they both co-immunoprecipitated with the two major NMDA receptor subtypes, GluN1/GluN2A and GluN1/GluN2B, via interaction with the obligatory GluN1 subunit. Immunoprecipitations from detergent extracts of adult mammalian brain showed co-immunoprecipitation of APLP1 and APLP2 with GluN2A- and GluN2B-containing NMDA receptors. Furthermore, similarly to APP, APLP1 and APLP2 both enhanced GluN1/GluN2A and GluN1/GluN2B cell surface expression. Thus, all the three members of the APP gene family behave similarly in that they each contribute to the regulation of cell surface NMDA receptor homoeostasis. Amyloid precursor protein (APP) has been shown to associate with N-methyl-d-aspartate (NMDA) receptors and to enhance their cell surface expression. Here, we show that the other members of the APP family, APLP1 and APLP2, behave similarly to APP in that they both associate with assembled NMDA receptors in the endoplasmic reticulum via their interaction with the NMDA receptor subunit, GluN1 and, they enhance receptor cell surface expression. Alternative scenarios are depicted since it is to be determined if respective associations are direct.

Homelessness, Discrimination, and Violent Victimization in Los Angeles County.

INTRODUCTION: People experiencing homelessness (PEH) are highly vulnerable to discrimination and violence, which impact physical and mental health. The study examines past-month discrimination and violence against PEH in Los Angeles County (LAC). METHODS: A total of 332 PEH in LAC were surveyed about their past-month experiences with discrimination, physical violence, and sexual violence from April-July 2023. Analyses were conducted in 2023. RESULTS: 31.8% of respondents reported experiencing discrimination daily and 53.9% reported it weekly, whereas rates of lifetime discrimination in studies of general populations of minoritized groups range between 13-60%. Nearly half of respondents who reported experiencing discrimination (49.6%) believed that their housing situation was the reason they were targeted. Victimization was also common, with 16.0% of participants experiencing physical violence and 7.5% experiencing sexual violence in the past 30 days. These rates of past-month victimization are high when compared to past-year physical violence (3.0%) and sexual violence (0.24%) among general populations in major U.S. cities. In multivariate regression analyses, discrimination was associated with being unsheltered in a vehicle (p<0.05) or outdoors (p<0.001), weekly illicit drug use (p<0.01), and psychological distress (p<0.001); violent victimization was associated with being sheltered (p<0.05) or unsheltered outdoors (p<0.001), physical health conditions (p<0.05), and psychological distress (p<0.01); and sexual victimization was associated with non-male gender (p<0.05) and being unsheltered outdoors (p<0.05). Discrimination and victimization outcomes were not associated with any race/ethnicity, sexual orientation, or time homeless characteristics. CONCLUSIONS: Study findings highlight the dangers of homelessness in the U.S., particularly for those who are unsheltered outdoors.

A scoping review of social determinants of health's impact on substance use disorders over the life course.

BACKGROUND: Substance use is a public crisis in the U.S. Substance use can be understood as a series of events in the life course, from initiation to mortality. Social Determinants of Health (SDoH) have increasingly been recognized as essential contributors to individuals' health. This scoping review aims to examine available evidence of SDoH impact on the life course of substance use disorder (SUD). METHODS: This study identified peer-reviewed articles that reported longitudinal studies with SDoH factors as independent variables and substance use and disorders as dependent variables from PubMed, Embase, and Web of Science. The reported associations between SDoH and substance use stages over the life course were narratively and graphically summarized. RESULTS: Among the 50 studies identified, ten revealed parental monitoring/support and early childhood education as protective factors, while negative peer influences and neighborhood instability were risk factors of substance use initiation. Nineteen articles reported factors associated with escalation in substance use, including unemployment, neighborhood vulnerability, negative peer influence, violence/trauma, and criminal justice system (CJS) involvement. Ten articles suggested that employment, social support, urban living, and low-barrier medication treatment facilitated treatment participation, while stigma and CJS involvement had negative impact on treatment trajectory. Social support and employment could foster progress in recovery and CJS involvement and unstable housing deterred recovery. Four studies suggested that unemployment, unstable housing, CJS involvement, and lack of social support were associated with overdose and mortality. CONCLUSIONS: This review underscores the influence of social networks and early life experiences on the life course of SUD. Future SDoH research should investigate overdose and mortality and the impact of broader upstream SDoH on SUD. Interventions addressing these social factors are needed to mitigate their detrimental effects on the trajectories of SUD over the life course.

Identification of N-methyl-D-aspartic acid (NMDA) receptor subtype-specific binding sites that mediate direct interactions with scaffold protein PSD-95.

N-methyl-D-aspartate (NMDA) neurotransmitter receptors and the postsynaptic density-95 (PSD-95) membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins are integral components of post-synaptic macromolecular signaling complexes that serve to propagate glutamate responses intracellularly. Classically, NMDA receptor NR2 subunits associate with PSD-95 MAGUKs via a conserved ES(E/D)V amino acid sequence located at their C termini. We previously challenged this dogma to demonstrate a second non-ES(E/D)V PSD-95-binding site in both NMDA receptor NR2A and NR2B subunits. Here, using a combination of co-immunoprecipitations from transfected mammalian cells, yeast two-hybrid interaction assays, and glutathione S-transferase (GST) pulldown assays, we show that NR2A subunits interact directly with PSD-95 via the C-terminal ESDV motif and additionally via an Src homology 3 domain-binding motif that associates with the Src homology 3 domain of PSD-95. Peptide inhibition of co-immunoprecipitations of NR2A and PSD-95 demonstrates that both the ESDV and non-ESDV sites are required for association in native brain tissue. Furthermore, we refine the non-ESDV site within NR2B to residues 1149-1157. These findings provide a molecular basis for the differential association of NMDA receptor subtypes with PSD-95 MAGUK scaffold proteins. These selective interactions may contribute to the organization, lateral mobility, and ultimately the function of NMDA receptor subtypes at synapses. Furthermore, they provide a more general molecular mechanism by which the scaffold, PSD-95, may discriminate between potential interacting partner proteins.

Neto1 associates with the NMDA receptor/amyloid precursor protein complex.

Neuropilin tolloid-like 1 (Neto1), is a CUB domain-containing transmembrane protein that was recently identified as a novel component of the NMDA receptor complex. Here, we have investigated the possible association of Neto1 with the amyloid precursor protein (APP)695/GluN1/GluN2A and APP695/GluN1/GluN2B NMDA receptor trafficking complexes that we have previously identified. Neto1(HA) was shown to co-immunoprecipitate with assembled NMDA receptors via GluN2A or GluN2B subunits; Neto1(HA) did not co-immunoprecipitate APP695(FLAG) . Co-immunoprecipitations from mammalian cells co-transfected with APP695(FLAG) , Neto1(HA) and GluN1/GluN2A or GluN1/GluN2B revealed that all four proteins co-exist within one macromolecular complex. Immunoprecipitations from native brain tissue similarly revealed the existence of a GluN1/GluN2A or GluN2B/APP/Neto1 complex. Neto1(HA) caused a reduction in the surface expression of both NMDA receptor subtypes, but had no effect on APP695(FLAG) - or PSD-95α(c-Myc) enhanced surface receptor expression. The Neto1 binding domain of GluN2A was mapped using GluN1/GluN2A chimeras and GluN2A truncation constructs. The extracellular GluN2A domain does not contribute to association with Neto1(HA) but deletion of the intracellular tail resulted in a loss of Neto-1(HA) co-immunoprecipitation which was paralleled by a loss of association between GluN2A and SAP102. Thus, Neto1 is concluded to be a component of APP/NMDA receptor trafficking complexes.

Polymorphic cis- and trans-regulation of human gene expression.

Expression levels of human genes vary extensively among individuals. This variation facilitates analyses of expression levels as quantitative phenotypes in genetic studies where the entire genome can be scanned for regulators without prior knowledge of the regulatory mechanisms, thus enabling the identification of unknown regulatory relationships. Here, we carried out such genetic analyses with a large sample size and identified cis- and trans-acting polymorphic regulators for about 1,000 human genes. We validated the cis-acting regulators by demonstrating differential allelic expression with sequencing of transcriptomes (RNA-Seq) and the trans-regulators by gene knockdown, metabolic assays, and chromosome conformation capture analysis. The majority of the regulators act in trans to the target (regulated) genes. Most of these trans-regulators were not known to play a role in gene expression regulation. The identification of these regulators enabled the characterization of polymorphic regulation of human gene expression at a resolution that was unattainable in the past.

An analysis of relapse prevention factors and their ability to predict sustained abstinence following treatment completion.

BACKGROUND & OBJECTIVES: This study assessed the role of 14 specific relapse-prevention activities and their underlying factors in maintaining abstinence among subjects (N = 302) completing outpatient treatment for stimulant dependence. METHODS: We examined what broader dimensions might subsume the 14 items constituting the Drug Avoidance Activities checklist (Farabee et al. J Subst Abuse Treat 2002;23:343-350), and how well these derived factors predicted concurrent drug use at baseline and again 3 and 12 months later. RESULTS: Although four factors were identified consistently for the three time points, only avoidance strategies had sufficient internal consistency to be retained for further analysis. Controlling for age, gender, and ethnicity, the avoidance subscale was a significant predictor of UA results at all time periods: a one-point increase in the avoidance strategies scale was associated with an 86% increase in odds of a negative UA at baseline (OR = 1.86, 95% CI = 1.37-2.53, p < .001), a 77% increase at 3-month follow-up (OR = 1.77, CI = 1.37-2.29, p < .001), and a 37% increase at 12-month follow-up (OR = 1.37, CI = 1.04-1.81, p = .026). CONCLUSIONS: Although correlations of individual items with UA results showed statistically significant (p < .05) results for 8 of 14 items at one or more observation points, avoidance-related behaviors showed the strongest associations with sustained abstinence.

Dynamic and specific interaction between synaptic NR2-NMDA receptor and PDZ proteins.

The relative content of NR2 subunits in the NMDA receptor confers specific signaling properties and plasticity to synapses. However, the mechanisms that dynamically govern the retention of synaptic NMDARs, in particular 2A-NMDARs, remain poorly understood. Here, we investigate the dynamic interaction between NR2 C termini and proteins containing PSD-95/Discs-large/ZO-1 homology (PDZ) scaffold proteins at the single molecule level by using high-resolution imaging. We report that a biomimetic divalent competing ligand, mimicking the last 15 amino acids of NR2A C terminus, specifically and efficiently disrupts the interaction between 2A-NMDARs, but not 2B-NMDARs, and PDZ proteins on the time scale of minutes. Furthermore, displacing 2A-NMDARs out of synapses lead to a compensatory increase in synaptic NR2B-NMDARs, providing functional evidence that the anchoring mechanism of 2A- or 2B-NMDARs is different. These data reveal an unexpected role of the NR2 subunit divalent arrangement in providing specific anchoring within synapses, highlighting the need to study such dynamic interactions in native conditions.

Toward Critically Analyzing Whiteness in Immigrant Health.

Assimilation theories dominate immigration scholarship to examine differential life chances, opportunities, and health of immigrants across three waves of immigrants in the United States. Assimilation theories are widely used in public health to explain the health status of immigrants despite the embedded White supremacist ideology while ignoring the role of whiteness. This article reviews and critiques assimilation theories to propose a critical analysis of whiteness in immigrant health scholarship. Critically analyzing whiteness in immigrant health studies allows us to recognize (a) the problematic framing of assimilation theories because of the theories' devotion to a White-European vision of upward mobility and a mainstream characterized as elite and White and (b) how a purportedly colorblind immigration law reinforces White supremacy through possessive investment in whiteness. To highlight whiteness in immigrant health, we examine the anti-immigration rhetoric and anti-immigrant policies and surveillance while providing implications for future research in the scholarship of immigrant health.

Perceptions of COVID-19 risk during the pandemic: perspectives from people seeking medication for opioid use disorder.

INTRODUCTION: The Coronavirus Disease 2019 (COVID-19) pandemic has had devastating consequences for persons with opioid use disorder (OUD). Yet, little is known about how people seeking treatment for OUD perceive the risks of COVID-19 and how their perception interplays with their health behaviours. METHODS: In-depth interviews were conducted from September 2021 to March 2022 with 32 patients seeking medication treatment for OUD (MOUD) in Southern California. All interviews were conducted virtually and lasted between one and two hours. Interviews were recorded and transcribed verbatim. Two qualitative researchers independently conducted a content analysis of the transcripts to identify themes. RESULTS: Three primary themes were identified: (1) perceptions and beliefs about COVID-19 susceptibility and severity; (2) perceptions of COVID-19 risk compared to substance use behaviours; and (3) vaccine hesitancy. Participants were mixed in their beliefs of susceptibility to contracting COVID-19 and the severity of the disease if contracted. Some participants reported taking precautions to mitigate their chances of acquiring COVID-19, and other participants reported that COVID was not a big concern as substance use took priority. For many of the participants, COVID-19 concerns were overshadowed by the risk of overdosing on substances and other risky substance use behaviour. Most of the participants (n = 23; 72%) had received at least one COVID-19 vaccine by the time of the interview, but over half (n = 19; 59%) expressed vaccine hesitancy. Vaccine hesitancy was driven by concerns about the unknown long-term side effects and potential interactions of the vaccine with MOUD. CONCLUSIONS: Our study provides insight into COVID-19 prevention measures as well as vaccination perceptions and hesitancy among people who received treatment for OUD.Key messagesParticipants expressed diverse perceptions of the seriousness of COVID-19, with some taking precautions to mitigate their chances of acquiring COVID-19 and others perceiving that the risk of contracting COVID-19 was less than the risk of overdosing.Substance use, social isolation, vaccine hesitancy and COVID-19 risk behaviours should be studied as co-occurring phenomena that have potentially overlapping relationships that can influence behaviours that impact health and well-being.

Utilization, measurement, and funding of recovery supports and services.

An environmental survey was conducted regarding substance abuse recovery supports and services (RSS) delivered across California, where these services are offered, and by whom. Inquiries were made regarding RSS measurement efforts, funding mechanisms, and technical assistance needs. A survey was disseminated to all 57 administrators of county alcohol and other drug or behavioral departments. Results indicate that 62% (23 of 37) of responding counties offer RSS. Overall, certified addiction counselors (CACs) were the staff most utilized to provide RSS, followed by peers, clinicians, and volunteers. Among recovery-community organizations (RCOs), peers, volunteers, and CACs were the most utilized staff. Sober living homes were the most prevalent type of RCO, followed by recovery centers, faith-based/recovery ministries, and recovery schools. Forty-five percent of counties reported funding RSS; 37.8% collect data. RSS may provide valuable support services for individuals recovering from alcohol/drug use; however, the field must further define RSS and develop measurement strategies to justify RSS funding.

The impact of COVID-19 on substance use disorder treatment in California: Service providers' perspectives.

BACKGROUND: The COVID-19 pandemic has had a profound impact on the U.S. health care system, including addiction treatment. The objective of this study is to describe the impact of COVID on the delivery of treatment for substance use disorders (SUDs) from the perspectives of service providers. METHODS: Between May and September 2020, 61 service providers from 16 SUD treatment sites in California participated in virtual focus groups that lasted about an hour. We recorded the discussions and transcribed them verbatim. Two qualitative analysts independently conducted content analysis to identify themes from the transcripts. RESULTS: At the beginning of the pandemic, service providers observed a slight decrease in patient admissions, followed by an uptick in patient flow due to increased mental health issues, alcohol use, and relapse. Many of the clinics adopted flexible service delivery modes, such as curbside dosing and extended take-home medication, to enable social distancing in clinic settings. Approximately half of the clinic encounters offered telemedicime, and a considerable proportion of patients preferred to use telephone-based services rather than video-based services. Internet instability and technical difficulties limited the use of telemedicine among their patients. CONCLUSION: COVID has been challenging for SUD treatment, but health care systems rapidly reacted with adjustments that may result in long-term changes in SUD service delivery. Telemedicine-based services have played a major role in ensuring uninterrupted patient care. Providers need organizational, technical, and logistical support to improve and sustain telemedicine services that increase access to quality care for their patients.

Sex under the influence of drugs or alcohol: common for men in substance abuse treatment and associated with high-risk sexual behavior.

Sex under the influence of drugs or alcohol is associated with high-risk sexual behavior. Heterosexual men (n = 505) in substance abuse treatment completed a computer-administered interview assessing sexual risk behaviors. Most men (73.3%) endorsed sex under the influence in the prior 90 days, and 39.1% endorsed sex under the influence during their most recent sexual event. Sex under the influence at the most recent event was more likely to involve anal intercourse, sex with a casual partner, and less condom use. Patients might benefit from interventions targeting sexual behavior and substance use as mutual triggers. (Am J Addict 2010;00:1-9).

Teaching condom use skills: practice is superior to observation.

Men exposed to a condom skills practice exercise were hypothesized to perform better on condom skills measures than those exposed only to a demonstration or to no intervention. As part of a larger National Institute on Drug Abuse (NIDA) Clinical Trials Network HIV Prevention protocol, men in substance abuse treatment were administered male and female condom use skills measures (MCUS, FCUS) at preintervention, 2 weeks, 3 months, and 6 months postintervention. The MCUS and FCUS scores were compared for 3 intervention exposure groups (demonstration only [DO, n = 149], demonstration plus practice [D+P; n = 112], attended no sessions [NS, n = 139]) across the 4 assessment time points using a mixed effects linear regression model. There is a statistically significant intervention group-by-time effect (P < .0001) for both the MCUS and FCUS. Post hoc, pairwise linear trends across time indicated that for both the MCUS and the FCUS, the D+P group is significantly superior to the DO group and the NS group.

Patient decision aid for medication treatment for opioid use disorder (PtDA-MOUD): Rationale, methodology, and preliminary results.

BACKGROUND AND AIMS: As treatment for opioid use disorder (OUD) expands within general healthcare settings such as primary care, mechanisms to facilitate decision-making processes are increasingly necessary. Decision aids have the capacity to bolster existing resources in diverse treatment settings by increasing knowledge of treatment options and facilitating shared decision making. The aim of this study is to develop and test a patient decision aid for medication treatment for opioid use disorder (PtDA-MOUD) that assists individuals with OUD in making informed decisions about treatment at the time of initial clinical visit. Use of the PtDA-MOUD will be further tested in diverse treatment settings within the California Hub and Spoke System developed under the SAMHSA State Targeted Response to the Opioid Crisis grants. METHODS: The PtDA-MOUD was iteratively developed with input from a scientific expert panel and both patient and provider focus groups, incorporating International Patient Decision Aid Standards. Thirty-six patients with OUD entering treatment pilot tested the PtDA and completed assessments, and results from clinical records were compared with matched controls who did not receive the PtDA. A clinical profile based on assessment data was created for use within the clinical visit. RESULTS: The developed decision aid provides information on MOUD and captures patient characteristics relevant to medication treatment decisions. Feedback indicated that the PtDA-MOUD was feasible to implement and useful. Though the small sample size limited the ability to detect significant differences (p > .05), a greater number of individuals who reviewed the PtDA (37%) were inducted on MOUD than controls (11%) and received MOUD for more days (M = 14.0, SD = 24.7) than controls (M = 8.4; SD = 22.5). Moreover, the difference in means for days receiving MOUD had an approximately medium effect size (r = 0.25). CONCLUSIONS: Patient perceptions of the decision aid were favorable and it showed promise as a tool in the OUD treatment process. Pilot testing results suggested preliminary positive effects on MOUD initiation. Future phases of this study will further investigate the usefulness of this tool. ClinicalTrials.govIdentifier:NCT03394261.

Amyloid precursor protein 695 associates with assembled NR2A- and NR2B-containing NMDA receptors to result in the enhancement of their cell surface delivery.

This is a study of the interaction between the two NMDA neurotransmitter receptor subtypes, NR1/NR2A and NR1/NR2B, and amyloid precursor protein (APP) 695, the major APP variant expressed in neurones. APP695 co-immunoprecipitated with assembled NR1-1a/NR2A and NR1-1a/NR2B NMDA receptors following expression in mammalian cells. Single NR1-1a, NR1-2a, NR1-4b(c-Myc), or NR2 subunit transfections revealed that co-association of APP695 with assembled NMDA receptors was mediated via the NR1 subunit; it was independent of the NR1 C1, C2, and C2' cassettes and, the use of an NR1-2a(c-Myc)-trafficking mutant suggested that interaction between the two proteins occurs in the endoplasmic reticulum. The use of antibodies directed against extracellular and intracellular NR2 subunit epitopes for immunoprecipitations suggested that APP/NMDA receptor association was mediated via N-terminal domains. Anti-APP antibodies immunoprecipitated NR1, NR2A, and NR2B immunoreactive bands from detergent extracts of mammalian brain; reciprocally, anti-NR1 or anti-NR2A antibodies co-immunoprecipitated APP immunoreactivity. Immune pellets from brain were sensitive to endoglycosidase H suggesting that, as for heterologous expression, APP and NMDA receptor association occurs in the endoplasmic reticulum. Co-expression of APP695 in mammalian cells resulted in enhanced cell surface expression of both NR1-1a/NR2A and NR1-1a/NR2B NMDA receptors with no increase in total subunit expression. These findings are further evidence for a role of APP in intracellular trafficking mechanisms. Further, they provide a link between two major brain proteins that have both been implicated in Alzheimer's disease.