Bidirectional Associations Between Pain and Perceived Stress Among Veterans: Depressive Disorder as a Predisposing Factor.

OBJECTIVE: Military veterans who were injured in combat very often report pain along with co-occurring perceived stress and preexisting depressive disorder. The systems model of pain is a theoretical model suggesting that pain and perceived stress are bidirectionally associated at the within-person level, and associations are heightened among those with depressive disorder. However, the systems model of pain has not been adequately tested. Testing the systems model of pain could illuminate salient treatment targets for combat-injured veterans with pain and co-occurring psychological problems. METHODS: The present study empirically tests the systems model of pain among a sample of combat-injured veterans ( N = 902) surveyed five times during an 18-month period. We used a multigroup, autoregressive latent trajectory with structured residual statistical model to test the within-person associations between pain and perceived stress and determine whether associations differ between veterans with and without a positive screen for depressive disorder. RESULTS: In line with the systems model of pain, pain and perceived stress were bidirectionally associated only among combat-injured veterans with depressive disorder. Among such veterans, perceived stress was positively associated with subsequent pain ( b = 0.12; 95% confidence interval = 0.06-0.17), and pain was positively associated with subsequent perceived stress ( b = 0.44; 95% CI = 0.11-0.77). CONCLUSIONS: Our work highlights the interplay between pain and its psychological correlates among a particularly at-risk population. Clinicians addressing pain and perceived stress among combat-injured veterans should be prepared to identify and address depressive disorder.

Alcohol use disorder, cannabis use disorder, and eating disorder symptoms among male and female college students.

BACKGROUND AND OBJECTIVES: Eating disorders (EDs) and substance use disorders are prevalent among college students in the United States, with underlying common mechanisms suggesting co-occurrence of these in the student population. As treatment prognosis of EDs improves when they are identified and treated with early intervention, it is essential to understand which substance use behaviors associate with EDs in students. METHODS: Using a sample of 471 college students recruited for a study on high risk drinking (i.e., students needed to pregame regularly to be included), we explored the associations between ED symptomatology and two common substances used in this population: alcohol and cannabis. As most research on EDs focuses on female students only or does not separate out males and females, we examined whether sex assigned at birth moderated the association between ED symptomatology and substance use outcomes. RESULTS: About one-third (32.4%) of the sample screened positive for an ED, with females significantly more likely to screen positive. Males were significantly more likely to screen positive for an alcohol or cannabis use disorder. Screening positive for an ED associated with cannabis use frequency and cannabis use disorder symptoms, but not with alcohol outcomes. Sex moderated the association between ED and cannabis use disorder symptoms, with positive ED screen male students experiencing the highest cannabis use disorder symptoms. DISCUSSION AND CONCLUSIONS: It is necessary to further assess how sex differences in substance use and ED symptomatology inform each other. SCIENTIFIC SIGNIFICANCE: Findings underscore the need to assess and screen for cannabis use disorder among students who screen positive for an ED, and, more specifically, with focused attention on male students with ED symptoms.

A Deeper Dive into Young Adults' Experiences with E-Cigarettes, E-Cigarette Cessation, and Transitioning to Cigarette Smoking.

Introduction: E-cigarette use among young adults is prevalent, with some voicing their desire to quit using e-cigarettes but needing support to do so. Young adults who use e-cigarettes are at risk for progressing to smoking combustible cigarettes, placing them at risk for severe health consequences. Limited research exists describing young adults' lived experiences with using e-cigarettes, e-cigarette cessation, and progression to combustible cigarettes. Methods: Between July and August 2022, nine focus groups were conducted with 33 young adults who either (1) currently used e-cigarettes, (2) formerly used e-cigarettes, or (3) transitioned to cigarettes. Transcripts were coded and themes were identified independently by two research team members while a third researcher reviewed the coding and themes. Results: Participants described social influences, stress, and curiosity as primary reasons why they initiated e-cigarette use. The most reported negative experiences or consequences associated with e-cigarettes include the health effects, addiction, and financial costs. Participants who transitioned to cigarettes reported social influences, a desire to reduce or quit using e-cigarettes by replacing them with cigarettes, curiosity, and stress as the primary reasons for this progression to combustible cigarettes. Participants described barriers to quitting e-cigarettes, including social influences, withdrawal, and easy access to e-cigarettes, as well as facilitators of quitting, such as social support, change in environment, and finding healthier ways to manage stress. Conclusions: This qualitative work provides an in-depth look into factors that may be helpful in the development of prevention and intervention programs for both e-cigarette and combustible cigarette use in young individuals.

An Examination of Pregaming Behavior and Motives among Sexual and Gender Minority College Students.

Introduction: Pregaming is a popular but high-risk drinking behavior common among college students. Although sexual and gender minority (SGM) college students are a vulnerable population with regards to hazardous alcohol use and alcohol consequences, there is currently limited research investigating the pregaming behavior of this group. The present study aimed to (1) examine mean level differences in pregaming behaviors and motives between SGM and non-SGM college students and (2) explore how SGM status was associated with pregaming behaviors and if SGM status moderated the association between motives and pregaming behaviors. Methods: The sample consisted of 485 college student drinkers in the US, with 19% (n = 93) identifying as SGM. All participants completed measures of past 30-day pregaming frequency and quantity (yielding a total pregaming drinks outcome) and drinking consequences experienced on pregaming days. Results: SGM participants consumed significantly fewer pregaming drinks than non-SGM participants, but did not significantly differ on alcohol-related consequences or drinking motives. The pregaming motive of intimate pursuit moderated the association between SGM status and total pregaming drinks, such that non-SGM participants with high intimate pursuit motives drank the heaviest. Conclusions: Our findings suggest that SGM students consume significantly fewer pregaming drinks than their non-SGM counterparts. However, they may be at a similar risk of experiencing pregaming consequences as non-SGM students. SGM students were less susceptible to the effect of intimate pursuit motives on pregaming drink consumption. This study offers support for past research regarding the effects of certain pregaming motives on pregaming drink consumption and consequences.

Insight into the molecular basis of substrate recognition by the wall teichoic acid glycosyltransferase TagA.

Wall teichoic acid (WTA) polymers are covalently affixed to the Gram-positive bacterial cell wall and have important functions in cell elongation, cell morphology, biofilm formation, and ß-lactam antibiotic resistance. The first committed step in WTA biosynthesis is catalyzed by the TagA glycosyltransferase (also called TarA), a peripheral membrane protein that produces the conserved linkage unit, which joins WTA to the cell wall peptidoglycan. TagA contains a conserved GT26 core domain followed by a C-terminal polypeptide tail that is important for catalysis and membrane binding. Here, we report the crystal structure of the Thermoanaerobacter italicus TagA enzyme bound to UDP-N-acetyl-d-mannosamine, revealing the molecular basis of substrate binding. Native MS experiments support the model that only monomeric TagA is enzymatically active and that it is stabilized by membrane binding. Molecular dynamics simulations and enzyme activity measurements indicate that the C-terminal polypeptide tail facilitates catalysis by encapsulating the UDP-N-acetyl-d-mannosamine substrate, presenting three highly conserved arginine residues to the active site that are important for catalysis (R214, R221, and R224). From these data, we present a mechanistic model of catalysis that ascribes functions for these residues. This work could facilitate the development of new antimicrobial compounds that disrupt WTA biosynthesis in pathogenic bacteria.

Childhood adversity, combat experiences, and military sexual trauma: a test and extension of the stress sensitization hypothesis.

BACKGROUND: U.S. veterans report high rates of traumatic experiences and mental health symptomology [e.g. posttraumatic stress disorder (PTSD)]. The stress sensitization hypothesis posits experiences of adversity sensitize individuals to stress reactions which can lead to greater psychiatric problems. We extend this hypothesis by exploring how multiple adversities such as early childhood adversity, combat-related trauma, and military sexual trauma related to heterogeneity in stress over time and, subsequently, greater risk for PTSD. METHODS: 1230 veterans were recruited for an observational, longitudinal study. Veterans responded to questionnaires on PTSD, stress, and traumatic experiences five times over an 18-month study period. We used latent transition analysis to understand how heterogeneity in adverse experiences is related to transition into stress trajectory classes. We also explored how transition patterns related to PTSD symptomology. RESULTS: Across all models, we found support for stress sensitization. In general, combat trauma in combinations with other types of adverse experiences, namely early childhood adversity and military sexual trauma, imposed a greater probability of transitioning into higher risk stress profiles. We also showed differential effects of early childhood and military-specific adversity on PTSD symptomology. CONCLUSION: The present study rigorously integrates both military-specific and early life adversity into analysis on stress sensitivity, and is the first to examine how sensitivity might affect trajectories of stress over time. Our study provides a nuanced, and specific, look at who is risk for sensitization to stress based on previous traumatic experiences as well as what transition patterns are associated with greater PTSD symptomology.

Cigarette Smoking and Depression Among U.S. Veterans: Longitudinal Associations With Posttraumatic Stress Disorder.

INTRODUCTION: Cigarette smoking and depression are associated with morbidity and mortality. Among veterans, approximately 22% are current smokers and 11%-15% have been diagnosed with depression. Although prior research suggests a strong association between smoking and depression among veterans, little research has examined trajectories of smoking and depressive symptoms and their correlates over time in this population. AIMS AND METHODS: Using parallel process growth curve modeling, we examined the longitudinal relationship between smoking and depression and tested whether posttraumatic stress disorder (PTSD) symptoms predict smoking and depression trajectories over 18 months (February 2020-August 2021). Veterans were recruited for an online, longitudinal study and responded to surveys across five-time points (baseline N = 1230; retention = 79.3%-83.3% across waves). RESULTS: Associations indicated that more frequent smoking at baseline was associated with steeper increases in depression symptom severity, and greater depression severity at baseline was associated with a less steep decrease in smoking frequency over time. PTSD was associated with less smoking at time 1 but more frequent smoking at times 3-5 as well as greater depression across all time points. CONCLUSIONS: Findings provide support that the growth trajectories of smoking and depression are linked, and PTSD symptoms are associated with these trajectories among veterans. Addressing these factors simultaneously in veteran treatment centers or through tobacco cessation efforts may be beneficial. IMPLICATIONS: This study offers strong evidence that the growth trajectories of smoking and depression are linked, and PTSD symptoms affect these trajectories among veterans, who represent a largely understudied population despite high rates of substance use and mental health problems. Results of this study strengthen the case for a more integrated treatment approach in which both smoking and mental health concerns are simultaneously addressed, which may yield more beneficial physical health and clinical outcomes for post-9/11 veterans.

Associations between depression, stress, and e-cigarette use among OEF/OIF veterans.

The COVID-19 pandemic has had profound mental and behavioral health implications for the general U.S. population. However, little is known regarding outcomes for U.S. veterans, who represent a population with high rates of depression, stress, and e-cigarette use. One month prior to the pandemic-related closures (February 2020), 1230 OEF/OIF veterans (ages 18-40) completed an online baseline survey. Six months later, participants completed a follow-up survey (83% retention rate). Hierarchical negative binomial regressions were used to examine the relationship between baseline depression and past 30-day e-cigarette use at follow-up and whether baseline stress moderated this relationship. Veterans who screened positive for depression or who endorsed higher stress levels reported greater e-cigarette use at follow-up. Stress also moderated the relationship between depression and e-cigarette use, such that regardless of stress levels, a positive depression screen was associated with greater rates of later e-cigarette use. However, for those with a negative depression screen, higher stress levels were associated with greater e-cigarette use relative to lower stress levels. Veterans with pre-pandemic depression and stress may be at highest risk for e-cigarette use. Ongoing assessment and treatment for depression and promoting stress management skills for veterans in e-cigarette use prevention and intervention programs may be valuable.

Disposable E-Cigarette Use Prevalence, Correlates, and Associations With Previous Tobacco Product Use in Young Adults.

INTRODUCTION: Novel, inexpensive disposable e-cigarettes widely sold in attractive flavors might be exempt from US federal regulations. To inform regulatory and public health priorities, this study examined young adult disposable e-cigarette use uptake among existing tobacco users versus non-users and possible use correlates that could be potential regulatory targets. AIMS AND METHODS: Prospective cohort data were analyzed in 2021. Among baseline (2018-2019) never disposable e-cigarette users (n = 1903; mean [SD]: 19.3 [0.8] years-old), we tested prospective associations of baseline tobacco product use with follow-up (2020) disposable e-cigarette use initiation, followed by stratified analyses distinguishing baseline exclusive and dual e-cigarette/combustible tobacco use. Exploratory cross-sectional associations of tobacco-related correlate with vaping frequency among current disposable users (n = 266) were tested. RESULTS: Follow-up ever disposable e-cigarette use initiation was higher among baseline former (22.1%) and current (50.2%) versus never (6.3%) rechargeable (non-disposable) e-cigarette users. In stratified analyses, follow-up disposable e-cigarette use initiation was 0% in baseline never-vaping exclusive current smokers, higher in baseline never-vaping former smokers versus never users of any tobacco product (18.2% vs. 5.7%; adjusted odds ratio [95% CI] = 3.9 [2.1-7.5]), and higher among baseline current dual users versus never-smoking exclusive current vapers (61.3% vs. 42.2%; adjusted odds ratio [95% CI] = 3.0 [1.5-6.0]). Among follow-up current disposable e-cigarette users (overall prevalence = 10.9%), using ice-flavored (vs. fruit/sweet-flavored) e-cigarettes (adjusted rate ratio [95% CI] = 1.5 [1.0-2.1]) and vaping dependence symptoms (adjusted rate ratio [95% CI] = 2.2 [1.5-3.2]) were cross-sectionally associated with more past-month disposable e-cigarette use days. CONCLUSIONS: Young adult disposable e-cigarette use was of appreciable prevalence, including among tobacco product never users and former smokers. Regulation of disposable e-cigarettes, including ice-flavored products, might benefit young adult health. IMPLICATIONS: Sales of disposable e-cigarette products increased significantly in the United States from 2019 to 2020. These products contain high nicotine concentrations and various flavors that may appeal to young people. This study provides the first evidence that disposable e-cigarette use may be common among young adults, including among tobacco product never users and former smokers. Frequency of disposable e-cigarette use was positively associated with using ice-flavored e-cigarettes and vaping dependence. Regulatory policies and enforcement strategies addressing disposable e-cigarettes merit consideration in young adult health policy and prevention priorities.

Trajectories and biopsychosocial predictors of daily acute pain in adolescents receiving treatment for pain: a daily diary study.

Research regarding daily acute pain and its correlates has primarily been conducted with adolescents who have had major surgery or musculoskeletal pain, restraining efforts towards adapting interventions for adolescents with other sources of acute pain. We explored the trajectories and correlates of pain intensity. Adolescents with an opioid prescription to treat acute pain (N = 157) completed demographic questions, and the PROMIS pediatric depression and anxiety subscales. A 10-day daily diary assessed pain intensity, pain interference, sleep quality, and opioid use. Three trajectories of pain intensity emerged: (1) slow decreases in pain, (2) rapid decreases in pain, and (3) stable or slight increases in pain. Teens with stable pain demonstrated the greatest anxiety levels. Higher sleep quality predicted lower next day pain intensity and pain interference, when controlling for opioid use. Future research should employ intensive longitudinal methodology to further guide intervention development and prevent the transition to chronic pain.

Reassembling protein complexes after controlled disassembly by top-down mass spectrometry in native mode.

The combined use of electrospray ionization run in so-called "native mode" with top-down mass spectrometry (nTDMS) is enhancing both structural biology and discovery proteomics by providing three levels of information in a single experiment: the intact mass of a protein or complex, the masses of its subunits and non-covalent cofactors, and fragment ion masses from direct dissociation of subunits that capture the primary sequence and combinations of diverse post-translational modifications (PTMs). While intact mass data are readily deconvoluted using well-known software options, the analysis of fragmentation data that result from a tandem MS experiment - essential for proteoform characterization - is not yet standardized. In this tutorial, we offer a decision-tree for the analysis of nTDMS experiments on protein complexes and diverse bioassemblies. We include an overview of strategies to navigate this type of analysis, provide example data sets, and highlight software for the hypothesis-driven interrogation of fragment ions for localization of PTMs, metals, and cofactors on native proteoforms. Throughout we have emphasized the key features (deconvolution, search mode, validation, other) that the reader can consider when deciding upon their specific experimental and data processing design using both open-access and commercial software.

Biomimetic synthetic studies on meroterpenoids from the marine sponge Aka coralliphaga: Divergent total syntheses of siphonodictyal B, liphagal and corallidictyals A-D.

The marine sponge Aka coralliphaga is a rich source of biologically active and structurally interesting meroterpenoids. Inspired by these natural products, we have used biosynthetic speculation to devise biomimetic syntheses of siphonodictyal B, liphagal and corallidictyals A-D from sclareolide. This work resulted in the development of new cascade reactions in the synthesis of liphagal, the reassignment of the structure of siphonodictyal B, and the realisation that corallidictyals A and B are possibly isolation artefacts.

Predictors of Housing Trajectories Among Young Adults Experiencing Homelessness in Los Angeles.

Experiencing homelessness during young adulthood is associated with negative health outcomes and understanding housing trajectories of young adults experiencing homelessness may aid in the development of evidence-based public health programs designed to serve this at-risk age group. In the present study, the authors examined baseline predictors of 24-month trajectories of housing stability and unsheltered housing among a sample of 271 young adults aged 18 to 25 recruited from drop-in centers in Los Angeles. In multivariate models, the authors found that identifying as multi-racial/other and better friendship quality at baseline were associated with less steep increases in the likelihood of stable housing over time. Being employed at baseline was associated with a less steep decrease in the probability of being unsheltered over time, while illicit drug use days associated with a steeper decrease in the probability of being unsheltered over time. Continued research is needed to establish important factors determining young adults' long-term housing trajectories in the effort to promote greater access and engagement with housing services.

Barriers and Facilitators to Behavioral Healthcare for Women Veterans: a Mixed-Methods Analysis of the Current Landscape.

Women veterans have historically faced barriers to behavioral health treatment, particularly through the VA. In conjunction, there have been changes in behavioral healthcare delivery resulting from efforts to improve care for women veterans and the COVID-19 pandemic (e.g., widespread telehealth implementation). The current study draws on a quantitative and qualitative study centering current perspectives of women veterans in their choices to seek or not seek behavioral healthcare in VA and non-VA settings through interviewing 18 women recruited from a larger survey study on veteran behavioral health (n = 83 women, n = 882 men) on their experiences with behavioral health care access and satisfaction, including barriers and facilitators to seeking care. Quantitative findings are descriptively reported from the larger study, which outlined screening for behavioral health problems, behavioral health utilization, treatment modality preferences, and barriers/facilitators to care. While women in the survey sample screened for various behavioral health disorders, rates of treatment seeking remained relatively low. Women reported positive and negative experiences with telehealth and endorsed many barriers to treatment seeking in interviews not captured by survey findings, including lack of women-specific care (e.g., care for military sexual trauma, women-only groups), reports of stranger harassment at the VA, and lack of female providers. Women veterans continue to face barriers to behavioral healthcare; however, ongoing efforts to improve care access and quality, including the implementation of telehealth, show promise in reducing these obstacles. Continued efforts are needed to ensure diverse treatment modalities continue to reach women veterans as this population grows.

Order of Cannabis and Alcohol Use on Pregaming and Non-Pregaming Days Among College Students.

OBJECTIVE: Pregaming is common among college students and is associated with heavy drinking and negative alcohol-related consequences. The use of cannabis on pregaming days may exacerbate negative alcohol-related consequences, and the ordering of when cannabis is used on these days may buffer against or intensify these consequences. Considering the growing rates of simultaneous use of cannabis and alcohol among college students, it is necessary to examine the role of pregaming behaviors in the context of cannabis use and its effects on alcohol-related consequences. METHOD: In the present study, college students (N = 485) completed a baseline survey and 14 days of daily surveys, reporting on daily alcohol and cannabis use and alcohol-related negative consequences. Multilevel structural equation models were fit to evaluate cannabis outcomes on pregaming versus non-pregaming drinking days and ordering effects on alcohol-related consequences, controlling for number of drinks, age, and sex. RESULTS: Across all drinking days, pregaming on that day as well as cannabis use during drinking on that day were associated with a greater risk for alcohol-related consequences. On days that did not involve pregaming, the use of cannabis before drinking was associated with a greater risk for negative alcohol-related consequences, whereas cannabis use after drinking was associated with less risk for consequences. These effects were observed on non-pregaming days only and not on days with pregaming. CONCLUSIONS: Findings have implications for brief interventions with students, as analyses suggested that both cannabis use and pregaming--independent of number of drinks consumed--are risky behaviors associated with alcohol-related consequences.

A latent profile analysis of social anxiety, depression, and pregaming motives among heavy-drinking college students.

BACKGROUND: Pregaming is a high-risk drinking behavior that is associated with heavy drinking and negative alcohol-related consequences. College students may engage in pregaming for several reasons, including to enhance social experiences or cope with negative affect. Research shows that associations between drinking, social anxiety, and depression are multifaceted. However, our understanding of the complex associations of mental health symptoms with pregaming motives and behaviors remains limited. METHODS: This study examined heterogeneity in how pregaming motives, social anxiety, and depression associate with past 30-day pregaming variables (quantity, frequency, and negative consequences). We used latent profile analysis (LPA) in a sample of heavy-drinking university students (N = 479). RESULTS: LPA results indicated four profiles: mild/moderate social anxiety and depression symptoms, moderate motives (n = 285), minimal social anxiety and depression symptoms, low motives (n = 61), subclinical/elevated social anxiety and depression symptoms, high motives (n = 75), and clinically elevated social anxiety and depression symptoms, moderate motives (n = 58). The subclinical/elevated symptoms, high motives profile reported the highest pregaming frequency and consequences, including blackouts. Individuals in the clinically elevated symptoms, moderate motives profile reported more consequences than those in the minimal symptoms, low motives and mild/moderate symptoms, moderate motives profiles. Individuals in the minimal symptoms, low motives profile reported the fewest consequences. CONCLUSIONS: Among these students, social anxiety and pregaming motives were associated with more frequent pregaming and social anxiety and depression were associated with greater negative consequences. Interventions that target pregaming-specific motives among students with mental health symptoms may be warranted to reduce this risky behavior and associated drinking-related harm.

Reducing Alcohol Misuse and Promoting Treatment Initiation Among Veterans Through a Brief Internet-Based Intervention: Protocol for a Randomized Controlled Trial.

BACKGROUND: Young adult veterans who served after the September 11 attacks on the United States in 2001 (ie, post-9/11) are at heightened risk for experiencing behavioral health distress and disorders including hazardous drinking, posttraumatic stress disorder, and depression. These veterans often face significant barriers to behavioral health treatment, and reaching them through brief mobile phone-based interventions may help reduce drinking and promote treatment engagement. OBJECTIVE: Following a successful pilot study, this randomized controlled trial (RCT) aims to further test the efficacy of a brief (ie, single session) mobile phone-delivered personalized normative feedback intervention enhanced with content to promote treatment engagement. METHODS: We will conduct an RCT with 800 post-9/11 young adult veterans (aged 18 to 40 years) with potentially hazardous drinking and who have not recently received treatment for any behavioral health problems. Participants will be randomly assigned to the personalized intervention or a control condition with resources for seeking care. The personalized normative feedback module in the intervention focuses on the correction of misperceived norms of peer alcohol use and uses empirically informed approaches to increase motivation to address alcohol use and co-occurring behavioral health problems. Past 30-day drinking, alcohol-related consequences, and treatment-seeking behaviors will be assessed at baseline and 3, 6, 9, and 12 months post intervention. Sex, barriers to care, posttraumatic stress disorder, depression, and severity of alcohol use disorder symptoms will be explored as potential moderators of outcomes. RESULTS: We expect recruitment to be completed within 6 months, with data collection taking 12 months for each enrolled participant. Analyses will begin within 3 months of the final data collection point (ie, 12 months follow-up). CONCLUSIONS: This RCT will evaluate the efficacy of a novel intervention for non-treatment-seeking veterans who struggle with hazardous drinking and possible co-occurring behavioral health problems. This intervention has the potential to improve veteran health outcomes and overcome significant barriers to treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT04244461; https://clinicaltrials.gov/study/NCT04244461. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/59993.

Integrating Phenotypic and Chemoproteomic Approaches to Identify Covalent Targets of Dietary Electrophiles in Platelets.

A large variety of dietary phytochemicals has been shown to improve thrombosis and stroke outcomes in preclinical studies. Many of these compounds feature electrophilic functionalities that potentially undergo covalent addition to the sulfhydryl side chain of cysteine residues within proteins. However, the impact of such covalent modifications on the platelet activity and function remains unclear. This study explores the irreversible engagement of 23 electrophilic phytochemicals with platelets, unveiling the unique antiplatelet selectivity of sulforaphane (SFN). SFN impairs platelet responses to adenosine diphosphate (ADP) and a thromboxane A2 receptor agonist while not affecting thrombin and collagen-related peptide activation. It also substantially reduces platelet thrombus formation under arterial flow conditions. Using an alkyne-integrated probe, protein disulfide isomerase A6 (PDIA6) was identified as a rapid kinetic responder to SFN. Mechanistic profiling studies revealed SFN's nuanced modulation of PDIA6 activity and substrate specificity. In an electrolytic injury model of thrombosis, SFN enhanced the thrombolytic activity of recombinant tissue plasminogen activator (rtPA) without increasing blood loss. Our results serve as a catalyst for further investigations into the preventive and therapeutic mechanisms of dietary antiplatelets, aiming to enhance the clot-busting power of rtPA, currently the only approved therapeutic for stroke recanalization that has significant limitations.

E-Cigarette Use: The Effects of Psychological Vulnerabilities, Perceptions, and Intentions to Use E-Cigarettes.

Little research has examined the effects that psychological vulnerabilities (i.e., difficulty with emotion regulation, depressed mood, distress tolerance) have on the perceptions of e-cigarettes, intent to use e-cigarettes, and actual e-cigarette use. Data were collected via an online survey from 837 adults (55.6% male, Mage = 29.2, 71.7% Caucasian). The two path analytic models predicting lifetime and current use fit the data well. Difficulty with emotion regulation was positively associated with depressed mood and negatively associated with distress tolerance, while distress tolerance was negatively associated with depressed mood. Depressed mood was positively associated with perceived benefits of e-cigarette use, and perceived benefits was positively associated with intent to use. Perceived benefits and intent to use were significantly associated with both lifetime and current use. Findings enhance our understanding of the effects that mood and emotion-related factors have on perceptions of, intent to use, and actual use of e-cigarettes, which may have important implications for prevention and cessation.

Mapping Molecular Interaction Interface Between Diaphanous Formin-2 and Neuron-Specific Drebrin A.

Actin cytoskeleton is critical for neuronal shape and function. Drebrin and formins are key regulators of neuronal actin networks. Neuron-specific drebrin A is highly enriched in dendritic spines (postsynaptic terminals) of mature excitatory neurons. Decreased levels of drebrin in dendritic spines is a hallmark of Alzheimer's disease, epilepsy, and other complex disorders, which calls for better understanding of its regulatory functions. Drebrin A was previously shown to inhibit actin nucleation and bundling by the diaphanous formin-2 (mDia2) - an actin nucleator that is involved in the initiation of dendritic spines. Characterization of the molecular binding interface between mDia2 and drebrin is necessary to better understand the functional consequences of this interaction and its biological relevance. Prior work suggested a multi-pronged interface between mDia2 and drebrin, which involves both N-terminal and C-terminal regions of the drebrin molecule. Here we used mass spectrometry analysis, deletion mutagenesis, and an array of synthetic peptides of neuronal drebrin A to map its formin-binding interface. The mDia2-interacting interface on drebrin was narrowed down to three highly conserved 9-16 residue sequences that were used to identify some of the key residues involved in this interaction. Deletion of the C-terminal region of drebrin greatly reduces its binding to mDia2 and the extent of its inhibition of formin-driven actin assembly. Moreover, our experiments with formins from different subfamilies showed that drebrin is a specific rather than general inhibitor of these proteins. This work contributes to a molecular level understanding of the formin-drebrin interaction and will help to unravel its biological significance.