Peer Network Counseling Effects on Substance Use: an Individual Participant Data Meta-Analysis Integrating Three Randomized Controlled Trials.

The current study describes an individual participant data meta-analysis (IPDMA) testing the efficacy of a peer-network counseling (PNC) intervention for preventing substance use escalation in adolescents and young adults. PNC has shown efficacy in reducing substance use among adolescents and young adults across small-scale randomized controlled trials (RCTs). Identifying expected large-scale effects and moderators is an important next step in guiding use of PNC in practice. To this end, we combine three small-scale RCTs to test PNC intervention effects on substance use change in a combined sample of 421 adolescents and young adults (50% intervention, 55% female, 69% Black/African-American, M age [SD] = 17.3 [2.2] years). Our approach combines latent change score modeling in a structural equation modeling (SEM) framework with study-level fixed effects to obtain (a) a more generalizable PNC effect than we could obtain with each constituent sample and (b) greater power and precision for individual-level moderation of treatment effects. We found that although PNC main effects on substance use outcomes (past 30-day cannabis, alcohol, tobacco, and drug use) were not significant, PNC effects were moderated by individual-level pre-intervention substance use frequency. PNC more strongly reduced drug use at the 1-month follow-up and cannabis use at the 3-month follow-up among participants who showed higher baseline use of these substances. Implications of our approach and findings for prevention researchers are discussed.

Responsiveness to mHealth Intervention for Cannabis Use in Young Adults Predicts Improved Outcomes.

Mobile health (mHealth) interventions have proliferated rapidly in part because of their advantages in reducing consumer and provider burden, but less attention has been paid to participant responsiveness to mHealth programs and how this may affect outcomes. This study adds to that literature by examining whether participant responsiveness to a text messaging-delivered intervention was predictive of treatment outcomes over baseline levels of the outcome. We analyzed data from a pilot-randomized controlled trial of a text messaging-intervention to treat young adults with cannabis use disorder (treatment arm, N = 47), examining three indicators of responsiveness (two behavioral: treatment completion and booster message participation; and one subjective: perceived helpfulness of treatment) on abstinence from cannabis use and use-related problems measured at 3-month follow-up. With the exception of completion, the indicators were positively correlated with each other. Each of the indicators was predictive of better treatment outcomes above and beyond baseline risk. Treatment completion and booster participation-measured via technical data captured during intervention administration-appeared to be stronger predictors of improved outcomes than self-reported perceived helpfulness. Results suggest that behavioral and subjective responsiveness measures appear to be valid indicators of treatment response to mHealth interventions for substance use. Responsiveness measured via technical data captured during intervention administration may be a stronger and more efficient strategy for monitoring continued engagement. We discuss implications of these findings for deploying mHealth interventions at scale and monitoring responsiveness.

Recommendations for Identifying Valid Wear for Consumer-Level Wrist-Worn Activity Trackers and Acceptability of Extended Device Deployment in Children.

BACKGROUND: Self-reported physical activity is often inaccurate. Wearable devices utilizing multiple sensors are now widespread. The aim of this study was to determine acceptability of Fitbit Charge HR for children and their families, and to determine best practices for processing its objective data. METHODS: Data were collected via Fitbit Charge HR continuously over the course of 3 weeks. Questionnaires were given to each child and their parent/guardian to determine the perceived usability of the device. Patterns of data were evaluated and best practice inclusion criteria recommended. RESULTS: Best practices were established to extract, filter, and process data to evaluate device wear, r and establish minimum wear time to evaluate behavioral patterns. This resulted in usable data available from 137 (89%) of the sample. CONCLUSIONS: Activity trackers are highly acceptable in the target population and can provide objective data over longer periods of wear. Best practice inclusion protocols that reflect physical activity in youth are provided.

Reducing Risk for Adolescent Substance Misuse with Text-Delivered Counseling to Adolescents and Parents.

Background: Text-delivered prevention programs provide unique opportunities to deliver substance use prevention interventions to at-risk populations. Methods: A pilot randomized controlled trial was conducted to test the feasibility, acceptability, and preliminary efficacy of a 4-week, automated personalized text-messaging prevention program, designed to reduce risk factors and increase protective factors associated with adolescent substance use and misuse. Sixty-nine adolescents were recruited from a Federally Qualified Health Care clinic and randomized to a text-delivered intervention, or a wait-list control condition. Simultaneously, fifty-two parents of adolescent participants were enrolled into a parenting skills text-delivered intervention. Participants completed a baseline assessment and three follow-up surveys over three-months. Adolescent saliva specimens for drug testing were collected. Results: All intervention-allocated adolescents implemented at least one of the text-based counseling recommendations and 79% indicated that they found the texts helpful. Significant intervention effects were found on risk and protective factors for substance misuse. Adolescents in the intervention group reported reduced depression symptoms (d = -.63) and anxiety symptoms (d = -.57). Relative to controls, adolescents in the intervention group maintained a higher quality of parental relationship (d = .41) and parenting skills (d = .51), suggesting a prophylactic effect. Marginal decrease in the odds of positive drug tests were found for youth in intervention group (77.1% decrease, p = 0.07) but not with controls (54.3% decrease, p = 0.42,). Conclusions: Results provide preliminary evidence in the feasibility, acceptability, and efficacy of targeting risk and protective factors that are implicated in substance use via text-delivered interventions for high-risk populations.

Blood-Borne RNA Correlates with Disease Activity and IFN-Stimulated Gene Expression in Systemic Lupus Erythematosus.

The loss of tolerance and the presence of circulating autoantibodies directed against nuclear Ags is the hallmark of systemic lupus erythematosus (SLE). Many of these Ags are complexed with short, noncoding RNAs, such as U1 and Y1. The amount of U1 and Y1 RNA complexed with SLE patient Abs and immune complexes was measured in a cross-section of 228 SLE patients to evaluate the role of these RNA molecules within the known biochemical framework of SLE. The study revealed that SLE patients had significantly elevated levels of circulating U1 and/or Y1 RNA compared with healthy volunteers. In addition, the blood-borne RNA molecules were correlated with SLE disease activity and increased expression of IFN-inducible genes. To our knowledge, this study provides the first systematic examination of the role of circulating RNA in a large group of SLE patients and provides an important link with IFN dysregulation.

School, Friends, and Substance Use: Gender Differences on the Influence of Attitudes Toward School and Close Friend Networks on Cannabis Involvement.

The school environment is extremely salient in young adolescents' lives. Adolescents who have unfavorable attitudes toward school and teachers are at elevated risk for dropping out of school and engaging in behavioral health risks. Peer network health-a summation of the positive and negative behaviors in which one's close friend group engages-may be one way by which attitudes toward school exert influence on youth substance use. Utilizing a sample of 248 primarily African-American young urban adolescents, we tested a moderated mediation model to determine if the indirect effect of attitude to school on cannabis involvement through peer network health was conditioned on gender. Attitude toward school measured at baseline was the predictor (X), peer network health measured at 6 months was the mediator (M), cannabis involvement (including use, offers to use, and refusals to use) measured at 24 months was the outcome (Y), and gender was the moderator (W). Results indicated that negative attitudes toward school were indirectly associated with increased cannabis involvement through peer network health. This relationship was not moderated by gender. Adolescents in our sample with negative attitudes toward school were more likely to receive more offers to use cannabis and to use cannabis more frequently through the perceived health behaviors of their close friends. Implications from these results point to opportunities to leverage the dynamic associations among school experiences, friends, and cannabis involvement, such as offers and use.

Young Urban Adolescents' Activity Spaces, Close Peers, and the Risk of Cannabis Use: A Social-Spatial Longitudinal Analysis.

BACKGROUND: An understudied, yet important area of youth development research is the examination of how place affects critical psychosocial processes such as identity formation, problem solving, emotional regulation, and in particular with adolescents, belongingness, autonomy, social competency, and behavioral health. A growing spatially informed literature indicates that youth interact with meaningful places as environmental strategies, shaping developmental trajectories related to behavioral health. OBJECTIVES: The objective is to investigate the relationship between place preference and health behavior among adolescents, with a focus on substance use behavior, specifically, cannabis use. We theorize that cannabis use is associated with place preference for urban, city types of places, and that this particular place preference interacts with close peer network behaviors. METHODS: To understand the role of preferred locations, close peer relations, and mental health on cannabis use, 248 adolescents (ages 13 to 14) were studied longitudinally. Logistic regression models tested the moderating effects of peer network health (sum of close friends risk and protective behaviors) on selecting city locations (urban stress/neighborhoods) as preferred places, and subsequent cannabis use. RESULTS: Results indicated that peer network health moderated the effects of choosing city locations as favorite, increasing the odds of cannabis use more than eight-fold at 24 months. CONCLUSIONS: Favorite places located in city environments appear to interact with peer risk behaviors influencing the cannabis use of young urban adolescents, even after controlling for the influence of baseline cannabis use, neighborhood disorder the home neighborhood, age, gender, and mental health effects.

Chromatin-dependent binding of the S. cerevisiae HMGB protein Nhp6A affects nucleosome dynamics and transcription.

The Saccharomyces cerevisiae protein Nhp6A is a model for the abundant and multifunctional high-mobility group B (HMGB) family of chromatin-associated proteins. Nhp6A binds DNA in vitro without sequence specificity and bends DNA sharply, but its role in chromosome biology is poorly understood. We show by whole-genome chromatin immunoprecipitation (ChIP) and high-resolution whole-genome tiling arrays (ChIP-chip) that Nhp6A is localized to specific regions of chromosomes that include ∼23% of RNA polymerase II promoters. Nhp6A binding functions to stabilize nucleosomes, particularly at the transcription start site of these genes. Both genomic binding and transcript expression studies point to functionally related groups of genes that are bound specifically by Nhp6A and whose transcription is altered by the absence of Nhp6. Genomic analyses of Nhp6A mutants specifically defective in DNA bending reveal a critical role of DNA bending for stabilizing chromatin and coregulation of transcription but not for targeted binding by Nhp6A. We conclude that the chromatin environment, not DNA sequence recognition, localizes Nhp6A binding, and that Nhp6A stabilizes chromatin structure and coregulates transcription.

The Dynamic Role of Urban Neighborhood Effects in a Text-Messaging Adolescent Smoking Intervention.

INTRODUCTION: Neighborhood features such as the density of tobacco outlets relative to one's home and evaluations of safety of one's activity space (routine locations), are known to influence health behaviors. Understanding the time-varying nature of these aspects of the urban ecology provides unique insights into the dynamic interactions of individuals and their environments. METHODS: The present study tested the time-varying effects of tobacco outlets and perceived safety within a randomized controlled trial of an adolescent text-messaging smoking intervention. We used ecological momentary assessment data (EMA) from an automated text-messaging smoking cessation randomized trial with 197 primarily African American urban adolescents. We employed a time-varying effect model to estimate the effects of density of tobacco outlets within one-half mile of participants' home locations (time-invariant covariate) and evaluations of safety of their activity space (time-varying covariate) on momentary smoking over 6 months by treatment condition. The time-varying effect model approach models behavioral change and associations of coefficients expressed dynamically and graphically represented as smooth functions of time. RESULTS: Differences in trajectories of smoking between treatment conditions were apparent over the course of the study. During months 2 and 6, the association between tobacco outlet density and smoking was significantly stronger in the control condition, suggesting treatment dampens this association during these time periods. The intervention also significantly reduced the association of perceived safety and smoking among the treatment condition during months 3 through 6. CONCLUSIONS: Results support testing the time-varying effects of urban ecological features and perceptions of safety among adolescents in text-based smoking cessation interventions. IMPLICATIONS: This study makes a unique contribution towards understanding the time-varying effects of urban neighborhoods on adolescent tobacco use within the context of a text-delivered intervention. Helping to adjust the long-held conceptualization of intervention effects as a static outcome, to that of a dynamic, time-varying process, is an important contribution of this study. The ability to specify when behavioral change occurs within the context of a randomized control trial provides understanding into the time-varying treatment effects of text-based smoking intervention. For example, researchers can modify the intervention to have strategically timed booster sessions that align with when the odds of smoking begin to increase in order to provide more precise treatment. The current study results show that increasing support to participants during months 2 and 4 may help suppress smoking over the course of a 6-month intervention.

An interactive web application for the dissemination of human systems immunology data.

BACKGROUND: Systems immunology approaches have proven invaluable in translational research settings. The current rate at which large-scale datasets are generated presents unique challenges and opportunities. Mining aggregates of these datasets could accelerate the pace of discovery, but new solutions are needed to integrate the heterogeneous data types with the contextual information that is necessary for interpretation. In addition, enabling tools and technologies facilitating investigators' interaction with large-scale datasets must be developed in order to promote insight and foster knowledge discovery. METHODS: State of the art application programming was employed to develop an interactive web application for browsing and visualizing large and complex datasets. A collection of human immune transcriptome datasets were loaded alongside contextual information about the samples. RESULTS: We provide a resource enabling interactive query and navigation of transcriptome datasets relevant to human immunology research. Detailed information about studies and samples are displayed dynamically; if desired the associated data can be downloaded. Custom interactive visualizations of the data can be shared via email or social media. This application can be used to browse context-rich systems-scale data within and across systems immunology studies. This resource is publicly available online at [Gene Expression Browser Landing Page ( https://gxb.benaroyaresearch.org/dm3/landing.gsp )]. The source code is also available openly [Gene Expression Browser Source Code ( https://github.com/BenaroyaResearch/gxbrowser )]. CONCLUSIONS: We have developed a data browsing and visualization application capable of navigating increasingly large and complex datasets generated in the context of immunological studies. This intuitive tool ensures that, whether taken individually or as a whole, such datasets generated at great effort and expense remain interpretable and a ready source of insight for years to come.

Driving under the influence of prescription drugs used nonmedically: associations in a young adult sample.

BACKGROUND: Over the past 20 years, there has been a dramatic increase in the nonmedical use of prescription drugs (NMUPD). However, minimal attention has been given to driving under the influence of prescription drugs used nonmedically. METHODS: This study examines attitudes and characteristics that might be associated with driving while engaging in NMUPD. College students (N = 763) aged 18-25 years completed online surveys assessing demographic information, NMUPD, recreational use of other drugs, psychological variables, attitudes towards NMUPD and driving, and driving behavior. RESULTS: Overall, 28.0% of participants reported lifetime NMUPD; 12.2% reported ever driving while engaging in NMUPD; and 7.9% reported this behavior in the past 3 months. Participants who reported engaging in NMUPD while driving were significantly more likely to report the use of alcohol, marijuana, ecstasy, cocaine, methamphetamine, ketamine, GHB (γ-hydroxybutyric acid), rohypnol, and mephedrone. These participants also scored higher on measures of hopelessness, impulsivity, and sensation seeking. Individuals who engaged in NMUPD while driving also reported lower perceptions of the risks of this behavior and believed that NMUPD is more common in young adults. CONCLUSIONS: A significant percentage of college students engage in driving under the influence of prescription drugs. Public health interventions designed to increase driving safety may wish to focus attention on this type of drugged driving.

Development and Outcomes of a Text Messaging Tobacco Cessation Intervention With Urban Adolescents.

BACKGROUND: This paper describes the development of an urban adolescent text messaging tobacco cessation intervention and preliminary findings from a randomized, controlled trial. The authors successfully adapted a face-to-face intervention into a personalized, automated, and interactive 5-day texting protocol. METHODS: Respondent-driven sampling was used beginning at a community substance abuse facility. Seventy-two tobacco-dependent adolescents were randomized into an automated computer texting program that delivered either the experimental condition of 30 motivational interviewing- and social network counseling-based personalized messages or the attention control condition consisting of a texting program covering general (non-smoking-related) health habits. All teens were provided smartphones for the study and were assessed at baseline and at 1, 3, and 6 months post intervention. Analyses examined condition×time interactions. RESULTS: At 6 months, the experimental condition decreased the number of cigarettes smoked in the past 30 days, increased intentions not to smoke in the future, and increased peer social support compared with controls. Effect sizes were moderate to large. CONCLUSIONS: These findings are unique, as they target urban adolescents with a mobile health format and add to the growing literature on the efficacy of text-delivered interventions.

Mg²âº modulation of the single-channel properties of KCa3.1 in human erythroleukemia cells.

The activity of many ion channels is modulated by ions other than the ones they primarily conduct, with important consequences for cell signalling. In this study, we demonstrate that Mg(2+) inhibits the intermediate conductance calcium-activated potassium channel (KCa3.1) in human erythroleukemia cells via two distinct mechanisms. Firstly, intracellular Mg(2+) blocks this channel via a rapid, voltage-dependent mechanism that leads to a reduction of the channel's unitary current. We show that this block involves interactions which are well described by the Woodhull model. Secondly, we found that Mg(2+) reduces the open probability of the channel. By analysing the channel kinetics, we found that this reduction in open probability is at least partly due to a reduction in the rate of channel opening from the closed state, a finding that can be accounted for if Mg(2+) competes with Ca(2+) for the activation site. Consistent with this interpretation, we find that the decline in relative NPo observed in the presence of 5 mM Mg(2+) could be significantly reduced by increasing the free Ca(2+) concentration.

Peer attitudes effects on adolescent substance use: the moderating role of race and gender.

We examined the relationship between adolescents' perceptions of their close friends' attitudes about substance use, and their own use of cigarettes, alcohol, and marijuana. Using data from the 2010 National Survey on Drug Use and Health, a multistage area probability sample sponsored by the Substance Abuse and Mental Health Services Administration (n = 17,865), we tested the direct and moderating effects of subgroups of race and gender on perceptions of adolescents' close friends on past month substance use. Significant effects were found on peer attitudes influencing substance use for all race and gender subgroups. Close friends' attitudes of indifference were associated with increased substance use and disapproval associated with reduced use, controlling for age, income, family structure, and adolescents' own attitudes of risk of substance use. Significant moderating effects of peer attitudes on cigarette and marijuana use were found for both gender and race moderators. Conditional effects of the moderation by race were also examined for gender subgroups. The moderating effect of race on close friends' attitudes impacting cigarette and marijuana use was stronger in magnitude and significance for females compared to males. Female marijuana and cigarette use was more influenced by close friends' attitudes than males, and whites were more influenced by their close friends than Hispanics and blacks. White females are more susceptible to close friends' attitudes on cigarette use as compared to white males and youth of other races. Implications for socially oriented preventive interventions are discussed.

Young Adult Depression and Cannabis Use: Associations Before and After Recreational Legalization.

INTRODUCTION: The co-occurrence of depression with cannabis use worsens both mood and substance use disorder outcomes, with young adults particularly at risk of co-occurrence. This research investigates whether the association of state-level prevalence rates of young adult (age 18-25) depression and cannabis use in the U.S. changed following enactment of recreational (adult use) cannabis legalization between 2008 and 2019. METHODS: Annual, state prevalence data on past-year major depressive episode (hereafter, depression) and past-month cannabis use were extracted from the National Survey on Drug Use and Health (N=600 state-year observations). Moderated regression models tested whether the association of depression with cannabis use differed before versus after recreational legalization by comparing prevalence rates of depression and cannabis use in states that enacted recreational legalization to those that did not, while fixing state, year, and medical legalization effects. Data were accessed and analyzed in 2023. RESULTS: Prevalence rates of both depression and cannabis use increased throughout the study period. The positive statistical effect of depression on cannabis use more than doubled in magnitude after legalization (ß=0.564, 95% CI=0.291, 0.838) as compared to before (ß=0.229, 95% CI=0.049, 0.409), representing a significant change (ß=0.335, 95% CI=0.093, 0.577). CONCLUSIONS: These results suggest that the association between prevalence rates of young adult depression and cannabis use strengthened following recreational legalization in the U.S. This is potentially due to increases in cannabis accessibility and the acceptance of the health benefits of cannabis, which may enhance the use of cannabis as a coping mechanism among young adults with depression.

Treating young adult cannabis use disorder with text message-delivered peer network counseling.

BACKGROUND: Approximately 16.5% of U.S. young adults have a cannabis use disorder (CUD) and are at risk for negative outcomes. Treatment can reduce cannabis use, but young adults are less likely to seek help than older adults. Peer Network Counseling-txt (PNC-txt) is a brief, text-delivered, Motivational Interviewing-informed substance use intervention focusing on peer relations and activity spaces as mechanisms for behavioral change. PNC-txt has shown evidence of reducing tobacco and cannabis use with adolescents and young adults, but it has not been tested in the context of legal cannabis use. The current randomized controlled trial sought to expand the evidence regarding the context of PNC-txt effects, comparing one state in which cannabis is legal (Colorado) and one state in which it is not (Tennessee). We hypothesized that participants randomized to PNC-txt would show significant reductions in cannabis use compared to controls, with larger reductions for females and those in Colorado, and that peer relations and activity space would mediate effects. METHODS: One thousand, seventy eight 18-25 year olds (CO: 551; TN: 527) who met screening criteria for CUD and biologically-verified cannabis use were randomly assigned to PNC-txt or waitlist control condition. Every other day for 4 weeks, participants assigned to PNC-txt received pre-programmed text conversations, tailored via data from the baseline assessment. Self-report and biological indicators of cannabis use were measured at 1-, 3-, and 6-months. DISCUSSION: Data analysis is underway. Results will provide evidence regarding whether, and how, PNC-txt reduces cannabis use in young adults with CUD. TRIAL REGISTRATION: This trial was prospectively registered on September 28, 2020 with ClinicalTrials.gov (NCT04567394).

Voltage dependence of the Ca(2+)-activated K(+) channel K(Ca)3.1 in human erythroleukemia cells.

We have isolated a K(+)-selective, Ca(2+)-dependent whole cell current and single-channel correlate in the human erythroleukemia (HEL) cell line. The whole cell current was inhibited by the intermediate-conductance KCa3.1 inhibitors clotrimazole, TRAM-34, and charybdotoxin, unaffected by the small-conductance KCa2 family inhibitor apamin and the large-conductance KCa1.1 inhibitors paxilline and iberiotoxin, and augmented by NS309. The single-channel correlate of the whole cell current was blocked by TRAM-34 and clotrimazole, insensitive to paxilline, and augmented by NS309 and had a single-channel conductance in physiological K(+) gradients of ~9 pS. RT-PCR revealed that the KCa3.1 gene, but not the KCa1.1 gene, was expressed in HEL cells. The KCa3.1 current, isolated in HEL cells under whole cell patch-clamp conditions, displayed an activated current component during depolarizing voltage steps from hyperpolarized holding potentials and tail currents upon repolarization, consistent with voltage-dependent modulation. This activated current increased with increasing voltage steps above -40 mV and was sensitive to inhibition by clotrimazole, TRAM-34, and charybdotoxin and insensitive to apamin, paxilline, and iberiotoxin. In single-channel experiments, depolarization resulted in an increase in open channel probability (Po) of KCa3.1, with no increase in channel number. The voltage modulation of Po was an increasing monotonic function of voltage. In the absence of elevated Ca(2+), voltage was ineffective at inducing channel activity in whole cell and single-channel experiments. These data indicate that KCa3.1 in HEL cells displays a unique form of voltage dependence modulating Po.

Treating Young Adult Depression With Text-Delivered Cognitive Behavioral Therapy: A Pilot Randomized Clinical Trial.

Young adults (ages 18 to 25) in the U.S. suffer from the highest rates of past-year major depressive episode and are the least likely to receive treatment compared to other age groups. As such, we examined the feasibility, acceptability, and efficacy of a text-message delivered cognitive behavioral therapy: CBT-txt with young adults. The study was a 2-month pilot RCT to test a 4-week intervention for depression that contained 197 text messages (average 12 texts every other day). The sample, recruited via Facebook and Instagram, was 102 U.S. young adults who presented with at least moderate depressive symptomatology. Assessments occurred at baseline prior to randomization and at 1 and 2 months post enrollment. The primary outcome, severity of depressive symptoms, was assessed using the Beck Depression Inventory II. Feasibility benchmarks were met and participants reported high levels of engagement with and acceptability of the intervention. Logistic regression indicated that treatment participants were three times as likely to have minimal or mild depression symptoms at 2 months compared to waitlist control participants. Latent change score modeling found that the strongest significant treatment effect appeared at the 1-month follow-up period, particularly for participants who began with severe depressive symptoms. Mediation analysis revealed significant indirect treatment effects of increases in behavioral activation on reducing depressive symptoms, suggesting a mechanism of change. Limitations were that the sample was relatively small and consisted of primarily women. These results provide initial evidence for the feasibility, acceptability, and efficacy of a text-delivered treatment for young adult depression.

Testing Mechanisms of Change for Text Message-Delivered Cognitive Behavioral Therapy: Randomized Clinical Trial for Young Adult Depression.

BACKGROUND: Current psychiatric epidemiological evidence estimates that 17% of young adults (aged 18-25 years) experienced a major depressive episode in 2020, relative to 8.4% of all adults aged ≥26 years. Young adults with a major depressive episode in the past year are the least likely to receive treatment for depression compared with other age groups. OBJECTIVE: We conducted a randomized clinical trial following our initial 4-week SMS text message-delivered cognitive behavioral therapy (CBT-txt) for depression in young adults. We sought to test mechanisms of change for CBT-txt. METHODS: Based on participant feedback, outcome data, and the empirical literature, we increased the treatment dosage from 4-8 weeks and tested 3 mechanisms of change with 103 young adults in the United States. Participants were from 34 states, recruited from Facebook and Instagram and presenting with at least moderate depressive symptomatology. Web-based assessments occurred at baseline prior to randomization and at 1, 2, and 3 months after enrollment. The primary outcome, the severity of depressive symptoms, was assessed using the Beck Depression Inventory II. Behavioral activation, perseverative thinking, and cognitive distortions were measured as mechanisms of change. Participants were randomized to CBT-txt or a waitlist control condition. Those assigned to the CBT-txt intervention condition received 474 fully automated SMS text messages, delivered every other day over a 64-day period and averaging 14.8 (SD 2.4) SMS text messages per treatment day. Intervention texts are delivered via TextIt, a web-based automated SMS text messaging platform. RESULTS: Across all 3 months of the study, participants in the CBT-txt group showed significantly larger decreases in depressive symptoms than those in the control group (P<.001 at each follow-up), producing a medium-to-large effect size (Cohen d=0.76). Over half (25/47, 53%) of the treatment group moved into the "high-end functioning" category, representing no or minimal clinically significant depressive symptoms, compared with 15% (8/53) of the control condition. Mediation analysis showed that CBT-txt appeared to lead to greater increases in behavioral activation and greater decreases in cognitive distortions and perseverative thinking across the 3-month follow-up period, which were then associated with larger baseline to 3-month decreases in depression. The size of the indirect effects was substantial: 57%, 41%, and 50% of the CBT-txt effect on changes in depression were mediated by changes in behavioral activation, cognitive distortions, and perseverative thinking, respectively. Models including all 3 mediators simultaneously showed that 63% of the CBT-txt effect was mediated by the combined indirect effects. CONCLUSIONS: Results provide evidence for the efficacy of CBT-txt to reduce young adult depressive symptoms through hypothesized mechanisms. To the best of our knowledge, CBT-txt is unique in its SMS text message-delivered modality, the strong clinical evidence supporting efficacy and mechanisms of change. TRIAL REGISTRATION: ClinicalTrials.gov NCT05551702; https://clinicaltrials.gov/study/NCT05551702.

Constitutive expression of a Mg2+-inhibited K+ current and a TRPM7-like current in human erythroleukemia cells.

Whole cell patch-clamp experiments were undertaken to define the basal K(+) conductance(s) in human erythroleukemia cells and its contribution to the setting of resting membrane potential. Experiments revealed a non-voltage-activated, noninactivating K(+) current. The magnitude of the current recorded under whole cell conditions was inhibited by an increase in free intracellular Mg(2+) concentration. Activation or inactivation of the Mg(2+)-inhibited K(+) current (MIP) was paralleled by activation or inactivation of a Mg(2+)-inhibited TRPM7-like current displaying characteristics indistinguishable from those reported for molecularly identified TRPM7 current. The MIP and TRPM7 currents were inhibited by 5-lipoxygenase inhibitors. However, inhibition of the MIP current was temporally distinct from inhibition of TRPM7 current, allowing for isolation of the MIP current. Isolation of the MIP conductance revealed a current reversing near the K(+) equilibrium potential, indicative of a highly K(+)-selective conductance. Consistent with this finding, coactivation of the nonselective cation current TRPM7 and the MIP current following dialysis with nominally Mg(2+)-free pipette solution resulted in hyperpolarized whole cell reversal potentials, consistent with an important role for the MIP current in the setting of a negative resting membrane potential. The MIP and TRPM7-like conductances were constitutively expressed under in vivo conditions of intracellular Mg(2+), as judged by their initial detection and subsequent inactivation following dialysis with a pipette solution containing 5 mM free Mg(2+). The MIP current was blocked in a voltage-dependent fashion by extracellular Cs(+) and, to a lesser degree, by Ba(2+) and was blocked by extracellular La(3+) and 2-aminoethoxydiphenyl borate. MIP currents were unaffected by blockers of ATP-sensitive K(+) channels, human ether-à-go-go-related gene current, and intermediate-conductance Ca(2+)-activated K(+) channels. In addition, the MIP current displayed characteristics distinct from conventional inwardly rectifying K(+) channels. A similar current was detected in the leukemic cell line CHRF-288-11, consistent with this current being more generally expressed in cells of leukemic origin.