Protein S-palmitoylation enhances profibrotic signaling in response to cadmium.

Cadmium (Cd) is a naturally occurring, toxic environmental metal found in foods. Humans do not have an efficient mechanism for Cd elimination; thus, Cd burden in humans increases with age. Cell and mouse studies show that Cd burden from low environmental levels of exposure impacts lung cell metabolism, proliferation signaling and cell growth as part of disease-promoting profibrotic responses in the lungs. Prior integrative analysis of metabolomics and transcriptomics identified the zDHHC11 transcript as a central functional hub in response to Cd dose. zDHHC11 encodes a protein S-palmitoyltransferase, but no evidence is available for effects of Cd on protein S-palmitoylation. In the present research, we studied palmitoylation changes in response to Cd and found increased protein S-palmitoylation in human lung fibroblasts that was inhibited by 2-bromopalmitate (2-BP), an irreversible palmitoyltransferase inhibitor. Mass spectrometry-based proteomics showed palmitoylation of proteins involved in divalent metal transport and in fibrotic signaling. Mechanistic studies showed that 2-BP inhibited palmitoylation of divalent metal ion transporter ZIP14 and also inhibited cellular Cd uptake. Transcription analyses showed that Cd stimulated transforming growth factor (TGF)-ß1 and ß3 expression within 8 h and lung fibrotic markers α-smooth muscle actin, matrix metalloproteinase-2, and collagen 1α1 gene expression and that these effects were blocked by 2-BP. Because 2-BP also blocked palmitoylation of proteins controlled by TGFß1, these results show that palmitoylation impacts Cd-dependent fibrotic signaling both by enhancing cellular Cd accumulation and by supporting post-translational processing of TGFß1-dependent proteins.

Low-dose vanadium pentoxide perturbed lung metabolism associated with inflammation and fibrosis signaling in male animal and in vitro models.

Vanadium is available as a dietary supplement and also is known to be toxic if inhaled, yet little information is available concerning the effects of vanadium on mammalian metabolism when concentrations found in food and water. Vanadium pentoxide (V+5) is representative of the most common dietary and environmental exposures, and prior research shows that low-dose V+5 exposure causes oxidative stress measured by glutathione oxidation and protein S-glutathionylation. We examined the metabolic impact of V+5 at relevant dietary and environmental doses (0.01, 0.1, and 1 ppm for 24 h) in human lung fibroblasts (HLFs) and male C57BL/6J mice (0.02, 0.2, and 2 ppm in drinking water for 7 mo). Untargeted metabolomics using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) showed that V+5 induced significant metabolic perturbations in both HLF cells and mouse lungs. We noted 30% of the significantly altered pathways in HLF cells, including pyrimidines and aminosugars, fatty acids, mitochondrial and redox pathways, showed similar dose-dependent patterns in mouse lung tissues. Alterations in lipid metabolism included leukotrienes and prostaglandins involved in inflammatory signaling, which have been associated with the pathogenesis of idiopathic pulmonary fibrosis (IPF) and other disease processes. Elevated hydroxyproline levels and excessive collagen deposition were also present in lungs from V+5-treated mice. Taken together, these results show that oxidative stress from environmental V+5, ingested at low levels, could alter metabolism to contribute to common human lung diseases.NEW & NOTEWORTHY We used relevant dietary and environmental doses of Vanadium pentoxide (V+5) to examine its metabolic impact in vitro and in vivo. Using liquid chromatography-high-resolution mass spectrometry (LC-HRMS), we found significant metabolic perturbations, with similar dose-dependent patterns observed in human lung fibroblasts and male mouse lungs. Alterations in lipid metabolism included inflammatory signaling, elevated hydroxyproline levels, and excessive collagen deposition were present in V+5-treated lungs. Our findings suggest that low levels of V+5 could trigger pulmonary fibrotic signaling.

Metabolomics of V2O5 nanoparticles and V2O5 nanofibers in human airway epithelial BEAS-2B cells.

Vanadium is a toxic metal listed by the IARC as possibly carcinogenic to humans. Manufactured nanosize vanadium pentoxide (V2O5) materials are used in a wide range of industrial sectors and recently have been developed as nanomedicine for cancer therapeutics, yet limited information is available to evaluate relevant nanotoxicity. In this study we used high-resolution metabolomics to assess effects of two V2O5 nanomaterials, nanoparticles and nanofibers, at exposure levels (0.01, 0.1, and 1 ppm) that did not cause cell death (i.e., non-cytotoxic) in a human airway epithelial cell line, BEAS-2B. As prepared, V2O5 nanofiber exhibited a fibrous morphology, with a width approximately 63 ± 12 nm and length in average 420 ± 70 nm; whereas, V2O5 nanoparticles showed a typical particle morphology with a size 36 ± 2 nm. Both V2O5 nanoparticles and nanofibers had dose-response effects on aminosugar, amino acid, fatty acid, carnitine, niacin and nucleotide metabolism. Differential effects of the particles and fibers included dibasic acid, glycosphingolipid and glycerophospholipid pathway associations with V2O5 nanoparticles, and cholesterol and sialic acid metabolism associations with V2O5 nanofibers. Examination by transmission electron microscopy provided evidence for mitochondrial stress and increased lysosome fusion by both nanomaterials, and these data were supported by effects on mitochondrial membrane potential and lysosomal activity. The results showed that non-cytotoxic exposures to V2O5 nanomaterials impact major metabolic pathways previously associated with human lung diseases and suggest that toxico-metabolomics may be useful to evaluate health risks from V2O5 nanomaterials.

Identification of Species by Combining Molecular and Morphological Data Using Convolutional Neural Networks.

Integrative taxonomy is central to modern taxonomy and systematic biology, including behavior, niche preference, distribution, morphological analysis, and DNA barcoding. However, decades of use demonstrate that these methods can face challenges when used in isolation, for instance, potential misidentifications due to phenotypic plasticity for morphological methods, and incorrect identifications because of introgression, incomplete lineage sorting, and horizontal gene transfer for DNA barcoding. Although researchers have advocated the use of integrative taxonomy, few detailed algorithms have been proposed. Here, we develop a convolutional neural network method (morphology-molecule network [MMNet]) that integrates morphological and molecular data for species identification. The newly proposed method (MMNet) worked better than four currently available alternative methods when tested with 10 independent data sets representing varying genetic diversity from different taxa. High accuracies were achieved for all groups, including beetles (98.1% of 123 species), butterflies (98.8% of 24 species), fishes (96.3% of 214 species), and moths (96.4% of 150 total species). Further, MMNet demonstrated a high degree of accuracy ($>$98%) in four data sets including closely related species from the same genus. The average accuracy of two modest subgenomic (single nucleotide polymorphism) data sets, comprising eight putative subspecies respectively, is 90%. Additional tests show that the success rate of species identification under this method most strongly depends on the amount of training data, and is robust to sequence length and image size. Analyses on the contribution of different data types (image vs. gene) indicate that both morphological and genetic data are important to the model, and that genetic data contribute slightly more. The approaches developed here serve as a foundation for the future integration of multimodal information for integrative taxonomy, such as image, audio, video, 3D scanning, and biosensor data, to characterize organisms more comprehensively as a basis for improved investigation, monitoring, and conservation of biodiversity. [Convolutional neural network; deep learning; integrative taxonomy; single nucleotide polymorphism; species identification.].

The impact of heavy metal pollution on wild bee communities in smallholder farmlands.

Wild bees provide important pollination services, but they face numerous stressors that threaten them and their ecosystem services. Wild bees can be exposed to heavy metal pollution through the consumption of nectar, pollen, and water, which might cause bee decline. While some studies have measured heavy metal concentrations in honeybees, few studies have monitored heavy metal concentrations in wild bees or explored their potential effects on wild bee communities. To investigate the impact of heavy metal pollution on wild bee communities, heavy metal concentrations, including vanadium (V), chromium (Cr), nickel (Ni), cadmium (Cd), Zinc (Zn) and lead (Pb) in multiple wild bee species were measured. Multiple wild bee species, including: Xylocopa tranquabaroroum, Eucera floralia, Apis cerana, and small bee mixtures (representing multiple small wild bee species) were sampled from 18 sites in Quzhou, Zhejiang Province, China. The findings demonstrated that there were significant differences in heavy metal concentrations among different bee species. The concentrations of V, Zn, Cd, and Pb in X. tranquabaroroum, the largest bee species in this study, were lower than that in the other three sample groups. Furthermore, there were significant negative correlations between heavy metal pollution and wild bee diversity and species richness, but not with abundance. Particularly, there was no significant relationship between heavy metal pollution and the abundance of small bees. Given these worrying findings, monitoring multiple heavy metals in wild bees should be conducted for protecting wild bee diversity and securing their pollination services.

Renin-Angiotensin System Modulation With Synthetic Angiotensin (1-7) and Angiotensin II Type 1 Receptor-Biased Ligand in Adults With COVID-19: Two Randomized Clinical Trials.

Importance: Preclinical models suggest dysregulation of the renin-angiotensin system (RAS) caused by SARS-CoV-2 infection may increase the relative activity of angiotensin II compared with angiotensin (1-7) and may be an important contributor to COVID-19 pathophysiology. Objective: To evaluate the efficacy and safety of RAS modulation using 2 investigational RAS agents, TXA-127 (synthetic angiotensin [1-7]) and TRV-027 (an angiotensin II type 1 receptor-biased ligand), that are hypothesized to potentiate the action of angiotensin (1-7) and mitigate the action of the angiotensin II. Design, Setting, and Participants: Two randomized clinical trials including adults hospitalized with acute COVID-19 and new-onset hypoxemia were conducted at 35 sites in the US between July 22, 2021, and April 20, 2022; last follow-up visit: July 26, 2022. Interventions: A 0.5-mg/kg intravenous infusion of TXA-127 once daily for 5 days or placebo. A 12-mg/h continuous intravenous infusion of TRV-027 for 5 days or placebo. Main Outcomes and Measures: The primary outcome was oxygen-free days, an ordinal outcome that classifies a patient's status at day 28 based on mortality and duration of supplemental oxygen use; an adjusted odds ratio (OR) greater than 1.0 indicated superiority of the RAS agent vs placebo. A key secondary outcome was 28-day all-cause mortality. Safety outcomes included allergic reaction, new kidney replacement therapy, and hypotension. Results: Both trials met prespecified early stopping criteria for a low probability of efficacy. Of 343 patients in the TXA-127 trial (226 [65.9%] aged 31-64 years, 200 [58.3%] men, 225 [65.6%] White, and 274 [79.9%] not Hispanic), 170 received TXA-127 and 173 received placebo. Of 290 patients in the TRV-027 trial (199 [68.6%] aged 31-64 years, 168 [57.9%] men, 195 [67.2%] White, and 225 [77.6%] not Hispanic), 145 received TRV-027 and 145 received placebo. Compared with placebo, both TXA-127 (unadjusted mean difference, -2.3 [95% CrI, -4.8 to 0.2]; adjusted OR, 0.88 [95% CrI, 0.59 to 1.30]) and TRV-027 (unadjusted mean difference, -2.4 [95% CrI, -5.1 to 0.3]; adjusted OR, 0.74 [95% CrI, 0.48 to 1.13]) resulted in no difference in oxygen-free days. In the TXA-127 trial, 28-day all-cause mortality occurred in 22 of 163 patients (13.5%) in the TXA-127 group vs 22 of 166 patients (13.3%) in the placebo group (adjusted OR, 0.83 [95% CrI, 0.41 to 1.66]). In the TRV-027 trial, 28-day all-cause mortality occurred in 29 of 141 patients (20.6%) in the TRV-027 group vs 18 of 140 patients (12.9%) in the placebo group (adjusted OR, 1.52 [95% CrI, 0.75 to 3.08]). The frequency of the safety outcomes was similar with either TXA-127 or TRV-027 vs placebo. Conclusions and Relevance: In adults with severe COVID-19, RAS modulation (TXA-127 or TRV-027) did not improve oxygen-free days vs placebo. These results do not support the hypotheses that pharmacological interventions that selectively block the angiotensin II type 1 receptor or increase angiotensin (1-7) improve outcomes for patients with severe COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04924660.

Anxiety, depression, and opioid misuse among adults with chronic pain: the role of emotion dysregulation.

The opioid epidemic is a significant public health concern in the United States, particularly among adults with chronic pain. Considerable research suggests that people with mental health problems, including anxiety and depression, may experience more opioid-related problems in the context of chronic pain. Yet, little work has examined potential mechanisms underyling these relations. Emotion dysregulation is one mechanistic factor that may link anxiety and depression and opioid-related problems among persons with chronic pain. Therefore, the current study examined the explanatory role of emotion dysregulation in the cross-sectional relationship between anxiety and depression problems and current opioid misuse and severity of opioid dependence among 431 adults with chronic pain who reported currently using opioid medications (74% female, Mage=38.32 years, SD = 11.11). Results indicated that emotion dysregulation explained, in part, the relationship between anxiety and depression symptoms and opioid-related problems. These findings highlight the need to further consider the role of emotion dysregulation among adults with chronic pain who use prescription opioids and experience symptoms of anxiety or depression. Future prospective research will be needed to further establish emotion dysregulation as a mechanism in anxiety/depression-opioid misuse/dependence processes.

Comparison of two criteria on the essential number calculation of Andrena camellia.

Andrena camellia Wu is one of the primary pollinators of Camellia oleifera A. in China. In this paper, the essential number of individuals for efficient pollination by this species was calculated via two criteria, based on various indicators including counts of pollen grains in provisions, from single visits, and from single foraging trips overall; single flower visit duration; single flight period duration; number of eggs laid by a single female over their lifetime; and the average number of flowers per plant. Based on the number of pollen grains collected per flower visit, the essential number of females necessary is 2107 in a 1-ha Camellia oleifera garden with 1800 plants, while only 1998 female individuals are essentially needed when estimated based on the mean number of pollen grains collected in a single flight period. We argue that the essential number estimated by the former method is more reasonable and accurate for practical applications.

Environmental Cadmium Enhances Lung Injury by Respiratory Syncytial Virus Infection.

Cadmium (Cd) is a naturally occurring environmental toxicant that disrupts mitochondrial function at occupational exposure levels. The impacts of Cd exposure at low levels through dietary intake remain largely uncharacterized. Human respiratory syncytial virus (RSV) causes severe morbidity, which can require hospitalization and result in death in young children and elderly populations. The impacts of environmental Cd exposure on the severity of RSV disease are unknown. Herein, we used a mouse model to examine whether Cd pre-exposure at a level of dietary intake potentiates pulmonary inflammation on subsequent infection with RSV. Mice were given Cd or saline in drinking water for 28 days. Subsets of these mice were infected with RSV at 5 days before the end of the study. Cd pre-exposure caused relatively subtle changes in lung; however, it elevated the IL-4 level and altered metabolites associated with fatty acid metabolism. After RSV infection, mice pre-exposed to Cd had elevated lung RSV titer and increased inflammation, as measured by histopathology, immune cell infiltration, cytokines, and chemokines. RSV infection after Cd pre-exposure also caused widespread perturbation in metabolism of glycerophospholipids and amino acids (Trp, Met, and Cys, branched-chain amino acids), as well as carnitine shuttle associated with mitochondrial energy metabolism. The results show that Cd burden by dietary intake potentiates RSV infection and severe disease with associated mitochondrial metabolic disruption.

Health Literacy, Opioid Misuse, and Pain Experience Among Adults with Chronic Pain.

BACKGROUND: Chronic pain is a significant public health problem that is associated with several negative health outcomes, including increased health care cost, decreased productivity, and prescription opioid misuse. Although efforts have been made to curb the growing opioid epidemic in the United States, further research is needed to better understand individual difference factors that may be associated with greater pain and opioid misuse. Lower levels of health literacy, defined as the ability to obtain, understand, and use health information to make important decisions regarding health and medical care, has been associated with several chronic illnesses. Yet little work has examined the relationship between health literacy, pain, and opioid misuse among individuals with chronic pain. METHODS: The current study examined health literacy in relation to current opioid misuse, severity of opioid dependence, pain severity, and pain disability among 445 adults with chronic pain (74.6% female, Mage [SD] = 38.45 [11.06] years). RESULTS: Results indicated that health literacy was significantly negatively associated with each of the criterion variables. CONCLUSIONS: These results suggest that health literacy may contribute to opioid misuse and pain experience among individuals with chronic pain. Interventions targeting health literacy among individuals with chronic illness may help to address the opioid public health crisis.

Is there a relationship between cannabis use problems, emotion dysregulation, and mental health problems among adults with chronic pain?

Cannabis is often used to manage pain among persons who suffer from chronic pain. Yet, despite much literature suggesting cannabis use problems are associated with mental health problems, little work has examined mechanisms of this relationship among a chronic pain population. Chronic pain is also associated with emotion dysregulation. Individuals with chronic pain who experience cannabis use problems may have less capacity to regulate negative emotions, which could relate to greater anxiety, depression, and suicidal ideation. Thus, the current study explored whether emotion dysregulation explained, in part, the relation between cannabis use problems and anxiety, depression, and suicidal ideation among adults with chronic pain. Participants were 431 opioid-using adults with current moderate to severe chronic pain, 176 were current cannabis users, of which 30.20% reported cannabis use problems. Results indicated a significant indirect relationship between cannabis use problems and anxiety [95% CI (.03, .05)], depression [95% CI (.03, .06)], and suicidal ideation [95% CI (.01, .01)] via emotion dysregulation. Tests of specificity suggested potential for a bi-directional effect for suicidal ideation (p < .001). Initial findings suggest that emotion dysregulation may be an important mechanism in the relationship between cannabis use problems and mental health among adults with chronic pain.

Comparison of large-scale citizen science data and long-term study data for phenology modeling.

Large-scale observational data from citizen science efforts are becoming increasingly common in ecology, and researchers often choose between these and data from intensive local-scale studies for their analyses. This choice has potential trade-offs related to spatial scale, observer variance, and interannual variability. Here we explored this issue with phenology by comparing models built using data from the large-scale, citizen science USA National Phenology Network (USA-NPN) effort with models built using data from more intensive studies at Long Term Ecological Research (LTER) sites. We built statistical and process based phenology models for species common to each data set. From these models, we compared parameter estimates, estimates of phenological events, and out-of-sample errors between models derived from both USA-NPN and LTER data. We found that model parameter estimates for the same species were most similar between the two data sets when using simple models, but parameter estimates varied widely as model complexity increased. Despite this, estimates for the date of phenological events and out-of-sample errors were similar, regardless of the model chosen. Predictions for USA-NPN data had the lowest error when using models built from the USA-NPN data, while LTER predictions were best made using LTER-derived models, confirming that models perform best when applied at the same scale they were built. This difference in the cross-scale model comparison is likely due to variation in phenological requirements within species. Models using the USA-NPN data set can integrate parameters over a large spatial scale while those using an LTER data set can only estimate parameters for a single location. Accordingly, the choice of data set depends on the research question. Inferences about species-specific phenological requirements are best made with LTER data, and if USA-NPN or similar data are all that is available, then analyses should be limited to simple models. Large-scale predictive modeling is best done with the larger-scale USA-NPN data, which has high spatial representation and a large regional species pool. LTER data sets, on the other hand, have high site fidelity and thus characterize inter-annual variability extremely well. Future research aimed at forecasting phenology events for particular species over larger scales should develop models that integrate the strengths of both data sets.

Current pain severity and electronic cigarettes: an initial empirical investigation.

The present study examined past-month pain severity in relation to e-cigarette dependence, perceived barriers for quitting e-cigarettes, and beliefs about risks associated with using e-cigarettes. Participants were 322 e-cigarette users from the United States (60.2% female, Mage= 36.78 years, SD = 10.62). Results indicated that pain severity was significantly and positively related to e-cigarette dependence, perceived risks of e-cigarette use, and perceived barriers to quitting e-cigarettes. The observed effects were evident above and beyond the variance accounted for by sex, age, education, income, dual cigarette use, frequency of e-cigarette use, and perceived health status. The present study provides novel empirical evidence that pain experience is related to a moderate, yet clinically-meaningful, proportion of the variance in e-cigarette dependence, perceived barriers for quitting e-cigarettes, and beliefs about e-cigarette risks. These findings suggest there is merit to exploring the role of pan experience in the onset and maintenance of e-cigarette use.

The Interaction of Alcohol Use and Cannabis Use Problems in Relation to Opioid Misuse Among Adults with Chronic Pain.

BACKGROUND: The opioid epidemic is a significant public health crisis and prescription opioids are often used to manage chronic pain, despite questionable long-term efficacy. Furthermore, co-substance (mis)use is also common among individuals with chronic pain who use opioids. Alcohol has been consistently used to manage chronic pain, partly due to its acute analgesic properties. Cannabis has also recently garnered attention in the context of pain management, though research examining its efficacy for pain has produced mixed results. Nevertheless, there is accumulating evidence that concurrent substance co-use is positively associated with use and misuse of additional substances, particularly among individuals with chronic pain. Thus, the goal of this study was to examine the main and interactive effects of alcohol use problems and cannabis use problems in relation to opioid misuse among adults with chronic pain who use opioids. METHODS: The current sample was comprised of 440 adults with chronic pain using prescription opioids. Substance use problems were assessed using the ASSIST, Current Opioid Misuse Measure, and the Severity of Dependence Scale. Moderated regressions using the PROCESS macro were utilized. RESULTS: Results indicated that alcohol use problems and cannabis use problems each uniquely related to opioid dependence severity and opioid misuse. The interaction of alcohol and cannabis use problems was uniquely related to only opioid misuse, whereby alcohol use was most strongly associated to opioid misuse among those with higher levels of cannabis use problems. CONCLUSIONS: Collectively, these findings suggest there may be utility in assessing and treating alcohol and cannabis use problems among persons with chronic pain who are using opioids for pain management.

Selenium Supplementation Alters Hepatic Energy and Fatty Acid Metabolism in Mice.

Background: Human and animal studies have raised concerns that supplemental selenium can increase the risk of metabolic disorders, but underlying mechanisms are unclear. Objective: We used an integrated transcriptome and metabolome analysis of liver to test for functional pathway and network responses to supplemental selenium in mice. Methods: Male mice (8-wk-old, C57BL/6J) fed a standard diet (0.41 ppm Se) were given selenium (Na2SeO4, 20 µmol/L) or vehicle (drinking water) for 16 wk. Livers were analyzed for selenium concentration, activity of selenoproteins, reduced glutathione (GSH) redox state, gene expression, and high-resolution metabolomics. Transcriptomic and nontargeted metabolomic data were analyzed with biostatistics, bioinformatics, pathway enrichment analysis, and combined transcriptome-metabolome-wide association study (TMWAS). Results: Mice supplemented with selenium had greater body mass gain from baseline to 16 wk (55% ± 5%) compared with controls (40% ± 3%) (P < 0.05); however, no difference was observed in liver selenium content, selenoenzyme transcripts, or enzyme activity. Selenium was higher in the heart, kidney, and urine of mice supplemented with selenium. Gene enrichment analysis showed that supplemental selenium altered pathways of lipid and energy metabolism. Integrated transcriptome and metabolome network analysis showed 2 major gene-metabolite clusters, 1 centered on the transcript for the bidirectional glucose transporter 2 (Glut2) and the other centered on the transcripts for carnitine-palmitoyl transferase 2 (Cpt2) and acetyl-CoA acyltransferase (Acaa1). Pathway analysis showed that highly associated metabolites (P < 0.05) were enriched in fatty acid metabolism and bile acid biosynthesis, including acylcarnitines, triglycerides and glycerophospholipids, long-chain acyl-coenzyme As, phosphatidylcholines, and sterols. TMWAS of body weight gain confirmed changes in the same pathways. Conclusions: Supplemental selenium in mice alters hepatic fatty acid and energy metabolism and causes increases in body mass. A lack of effect on hepatic selenium content suggests that signaling involves an extrahepatic mechanism.

Decreases in smoking during treatment for methamphetamine-use disorders: preliminary evidence.

Despite high rates of smoking (70-90%) and the severely negative impact of smoking on physical and mental health, only 12% of individuals receiving stimulant-use disorder treatment also receive smoking-cessation treatment. The aim of this investigation was to examine the effect of a contingency management (CM) intervention targeting methamphetamine (MA) use on cigarette smoking. Sixty-one adults with MA-use disorders who were smokers were assigned to CM or standard psychosocial treatment. Rates of smoking-negative breath samples (carbon monoxide <3 ppm) were compared between the two groups while controlling for baseline carbon monoxide level, marijuana use, MA use, and time. This subgroup of mostly male (59%) participants included 44 participants in the CM group and 17 participants in the standard psychosocial treatment. Tobacco smoking participants who received CM targeting MA use were 140% (odds ratio: 2.395; 95% confidence interval: 1.073-5.346) more likely to submit a smoking-negative breath sample relative to standard psychosocial treatment during the treatment period, holding constant several other prespecified covariates. This study provides evidence that a behavioral treatment for MA use results in reductions in cigarette smoking in adults with MA-use disorder.

Pilot investigation: randomized-controlled analog trial for alcohol and tobacco smoking co-addiction using contingency management.

Contingency management (CM) is associated with decreases in off-target drug and alcohol use during primary target treatment. The primary hypothesis for this trial was that targeting alcohol use or tobacco smoking would yield increased abstinence in the opposite, nontargeted drug. We used a 2 [CM vs. noncontingent control (NC) for alcohol]×2 (CM vs. NC for smoking tobacco) factorial design, with alcohol intake (through urinary ethyl glucuronide) and tobacco smoking (through urinary cotinine) as the primary outcomes. Thirty-four heavy-drinking smokers were randomized into one of four groups, wherein they received CM, or equivalent NC reinforcement, for alcohol abstinence, smoking abstinence, both drugs, or neither drug. The CM for alcohol and tobacco group had only two participants and therefore was not included in analysis. Compared with the NC for alcohol and tobacco smoking group, both the CM for the tobacco smoking group [odds ratio (OR)=12.03; 95% confidence interval (CI): 1.50-96.31] and the CM for the alcohol group (OR=37.55; 95% CI: 4.86-290.17) submitted significantly more tobacco-abstinent urinalyses. Similarly, compared with the NC for the alcohol and tobacco group, both the CM for smoking (OR=2.57; 95% CI: 1.00-6.60) and the CM for alcohol groups (OR=3.96; 95% CI: 1.47-10.62) submitted significantly more alcohol-abstinent urinalyses. These data indicate cross-over effects of CM on indirect treatment targets. Although this is a pilot investigation, it could help to inform the design of novel treatments for alcohol and tobacco co-addiction.

Contingency management intervention targeting co-addiction of alcohol and drugs among American Indian adults: Design, methodology, and baseline data.

BACKGROUND/AIMS: American Indian adults have some of the highest alcohol abstinence rates compared to the overall US population. Despite this, many American Indian people are more likely to concurrently use alcohol and illicit drugs and are less likely to participate and remain in outpatient treatment for alcohol and other drug use compared to the general US population. There is limited knowledge about effective interventions targeting alcohol and drug co-addiction among American Indian adults. Contingency management is a behavioral intervention designed to increase drug abstinence by offering monetary incentives in exchange for drug and alcohol negative urine samples. We aim to evaluate and describe a culturally tailored contingency management intervention to increase alcohol and other drug abstinence among American Indian adults residing in a Northern Plains reservation. METHODS: This 2 × 2 factorial, randomized controlled trial currently includes 114 American Indian adults with alcohol and/or drug dependence who are seeking treatment. Participants were randomized into one of four groups that received (1) contingency management for alcohol, (2) contingency management for other drug, (3) contingency management for both substances, or (4) no contingency management for either substance. We present descriptive, baseline data to characterize the sample and describe the modified contingency management approach that is specific to the community wherein this trial was being conducted. RESULTS: The sample is 49.1% male, with an average age of 35.8 years (standard deviation = 10.4 years). At baseline, 43.0% of the sample tested positive for ethyl glucuronide, 50.9% of participants self-reported methamphetamine as their most used drug, 36.8% self-reported cannabis, and 12.3% self-reported prescription opiates as their most used drug. Among randomized participants, 47.4% tested positive for cannabis, 28.1% tested positive for methamphetamine, 16.7% tested positive for amphetamines, and 2.1% tested positive for opiates. CONCLUSION: This is the first study to examine a culturally tailored contingency management intervention targeting co-addiction of two substances among American Indian adults. By establishing a tribal-university partnership to adapt, implement, and evaluate contingency management, we will increase the literature on evidence-based addiction treatments and research, while improving trust for addiction interventions among American Indian communities through ongoing collaboration. Moreover, results have implications for the use of contingency management as an intervention for co-addiction in any population.