Adolescent predictors of substance use in young adulthood among individuals with childhood-onset chronic pain: A follow-up study.

BACKGROUND: Adolescent chronic pain is a substantial public health problem, and pain symptoms often persist into adulthood. Young adults with chronic pain are at elevated risk for more frequent tobacco, alcohol and cannabis use, and cross-sectional research highlights the importance of psychosocial vulnerability factors. Limited research has examined how adolescent predictors, including mental health symptoms, pain, sleep and family functioning, impact later, young adult substance use. METHODS: A prospective cohort of 229 young adults (77.3% female; Mage = 21.0, SD = 1.6) with childhood-onset chronic pain completed measurements in adolescence and a follow-up assessment in young adulthood of past 3-month substance use frequency. RESULTS: Adolescent sleep quality and male sex were associated with more frequent tobacco use; adolescent depression was associated with more frequent alcohol use, and adolescent pain severity was associated with less frequent, and male sex was associated with more frequent cannabis use. CONCLUSIONS: Adolescent predictors of young adult substance use among youth with childhood-onset chronic pain represent important factors that may inform assessment, prevention and treatment of substance use in this population. Identifying and testing psychological interventions that target these vulnerability factors may reduce overall substance use risk in young adulthood. SIGNIFICANCE: This prospective observational study of young adults with childhood-onset chronic pain identified adolescent depression and sleep quality as vulnerability factors associated with substance use. Given the increasing risk for substance use during adolescence and young adulthood, these findings highlight the potential importance of early intervention to reduce substance use among young adults with childhood-onset chronic pain.

Salmonella re-engineers the intestinal environment to break colonization resistance in the presence of a compositionally intact microbiota.

The gut microbiota prevents harmful microbes from entering the body, a function known as colonization resistance. The enteric pathogen Salmonella enterica serovar (S.) Typhimurium uses its virulence factors to break colonization resistance through unknown mechanisms. Using metabolite profiling and genetic analysis, we show that the initial rise in luminal pathogen abundance was powered by a combination of aerobic respiration and mixed acid fermentation of simple sugars, such as glucose, which resulted in their depletion from the metabolome. The initial rise in the abundance of the pathogen in the feces coincided with a reduction in the cecal concentrations of acetate and butyrate and an increase in epithelial oxygenation. Notably, these changes in the host environment preceded changes in the microbiota composition. We conclude that changes in the host environment can weaken colonization resistance even in the absence of overt compositional changes in the gut microbiota.

Ecological momentary assessment of sleep, pain, and opioid use among adolescents following surgery.

Background: Opioids are effective for acute pain management following surgery among adolescents, yet are associated with significant negative consequences, including respiratory depression and opioid misuse. Sleep deficiency is common following surgery and extant research indicates strong cross-sectional associations between sleep deficiency and increased problematic opioid use. Objective: This study examined longitudinal associations between postsurgical sleep deficiency and opioid use among adolescents undergoing outpatient surgery. We also examined daily pain and mood as mechanisms linking previous night's sleep deficiency and next day prescription opioid use. Methods: This prospective, observational study enrolled 106 adolescents (11-19 years) who underwent orthopedic outpatient surgery and collected pre-surgery and longitudinal measurements. Participants were 52% female, African-American (7%), American Indian/Alaska Native (7%), Hispanic (9%), Native Hawaiian or Other Pacific Islander (4%), or white, non-Hispanic (66%). Using ecological momentary assessment methods, participants reported sleep, pain, and mood in real time over the first 14 days following surgery. Postsurgical opioid use was measured using an electronic medication cap monitoring device, eCAPTM. Associations between variables were measured using multilevel structural equation modeling. Results: Using multi-level mediation models, pain, but not mood-mediated associations between postsurgical sleep deficiency (sleep quality, total sleep time, sleep onset latency, and wake after sleep onset) and opioid use, at both the within-person and between-person levels. Results highlight that greater previous night's sleep deficiency (both generally and greater than a person's mean level) was associated with higher next day pain (both generally and greater than a person's mean level), which, in turn, was associated with higher opioid use. Furthermore, between-person total effect models provide support for sleep deficiency predicting higher opioid use. Conclusions: Our findings should be considered preliminary yet underscore the need for a comprehensive and personalized approach to postsurgical pain management and opioid use, potentially implementing interventions targeting sleep quality and quantity to reduce pain and opioid use.

Posttraumatic Stress and Opioid Use and Pain among Individuals with Probable Posttraumatic Stress Disorder and Self-Reported Chronic Pain: The Role of Health Literacy.

BACKGROUND: Chronic pain and opioid misuse are a prevalent comorbidity with deleterious health outcomes. Growing work indicates that posttraumatic stress disorder (PTSD) can increase the risk for chronic pain and opioid misuse and dependence. However, there is little understanding of social determinants of health (SDoH) that may account for interrelations of PTSD with chronic pain and opioid misuse and dependence. Health literacy is one relevant SDoH construct, reflecting the ability to gather, process, and comprehend health-related information required to engage in a healthcare setting. OBJECTIVE: The purpose of the present cross-sectional study was to examine the indirect effect of health literacy in the association between PTSD and opioid misuse, opioid dependence, pain intensity, and pain disability. METHOD: The sample included 142 adults (Mage = 35.2, SD = 9.9; 67.4% female; 70.1% White/Caucasian) with self-reported chronic pain and probable PTSD who were using opioid medication. RESULTS: Results demonstrated that PTSD symptom severity had a small indirect effect on opioid misuse and opioid dependence via health literacy; no indirect effects were evident for pain intensity and disability. CONCLUSION: The present investigation provides evidence that health literacy may serve as an important explanatory factor in associations between PTSD symptom severity and opioid misuse and dependence among adults with co-occurring probable PTSD and chronic pain.

Development of a Personalized Feedback Intervention Targeting Pain-Related Anxiety for Adults Reporting Hazardous Drinking and Chronic Pain: A Randomized Controlled Trial.

OBJECTIVE: Among individuals with chronic pain, the rate of hazardous alcohol use is elevated compared with the general population. Yet, hazardous drinkers with chronic pain remain an underserved group. There is a need to develop and test alternative and complementary interventions to reduce hazardous alcohol use among this high-risk segment of the general population. Targeting pain-related anxiety, a candidate mechanism, is one theoretically informed route. METHOD: Our approach followed a staged model (1A/1B) to develop and test a novel personalized feedback intervention (PFI). Phase 1A collected qualitative feedback from participants (N = 9; 77.8% female, mean age = 33.86 years, SD = 8.75) to refine intervention content and evaluate treatment acceptability and feasibility. For Phase 1B, individuals (N = 118; 57.3% male, mean age = 35.24 years, SD = 11.90) participated in a pilot randomized clinical trial for our novel PFI compared with a health information control condition on alcohol use, intention/motivation to reduce drinking, pain-related anxiety, and expectancies for alcohol analgesia/pain coping for hazardous drinkers with chronic pain. RESULTS: Phase 1A results supported the feasibility of using a PFI to target pain-related anxiety. Results from Phase 1B indicated that participants reduced drinking and primary outcomes changed in the expected directions, but there were no differential effects of the intervention. CONCLUSIONS: The current data provide preliminary evidence for the utility of computer-based brief interventions to encourage behavior change. However, further refinement of the intervention to target pain-related anxiety is warranted.

Ciliopathy patient variants reveal organelle-specific functions for TUBB4B in axonemal microtubules.

Tubulin, one of the most abundant cytoskeletal building blocks, has numerous isotypes in metazoans encoded by different conserved genes. Whether these distinct isotypes form cell type- and context-specific microtubule structures is poorly understood. Based on a cohort of 12 patients with primary ciliary dyskinesia as well as mouse mutants, we identified and characterized variants in the TUBB4B isotype that specifically perturbed centriole and cilium biogenesis. Distinct TUBB4B variants differentially affected microtubule dynamics and cilia formation in a dominant-negative manner. Structure-function studies revealed that different TUBB4B variants disrupted distinct tubulin interfaces, thereby enabling stratification of patients into three classes of ciliopathic diseases. These findings show that specific tubulin isotypes have distinct and nonredundant subcellular functions and establish a link between tubulinopathies and ciliopathies.

High fat intake sustains sorbitol intolerance after antibiotic-mediated Clostridia depletion from the gut microbiota.

Carbohydrate intolerance, commonly linked to the consumption of lactose, fructose, or sorbitol, affects up to 30% of the population in high-income countries. Although sorbitol intolerance is attributed to malabsorption, the underlying mechanism remains unresolved. Here, we show that a history of antibiotic exposure combined with high fat intake triggered long-lasting sorbitol intolerance in mice by reducing Clostridia abundance, which impaired microbial sorbitol catabolism. The restoration of sorbitol catabolism by inoculation with probiotic Escherichia coli protected mice against sorbitol intolerance but did not restore Clostridia abundance. Inoculation with the butyrate producer Anaerostipes caccae restored a normal Clostridia abundance, which protected mice against sorbitol-induced diarrhea even when the probiotic was cleared. Butyrate restored Clostridia abundance by stimulating epithelial peroxisome proliferator-activated receptor-gamma (PPAR-γ) signaling to restore epithelial hypoxia in the colon. Collectively, these mechanistic insights identify microbial sorbitol catabolism as a potential target for approaches for the diagnosis, treatment, and prevention of sorbitol intolerance.

Indirect effects of emotion regulation in the relationship between pain and cannabis use in adults 18-64 years.

INTRODUCTION: Individuals with chronic pain often receive prescription opioid medication, and they may use cannabis to treat pain as well, although the risks of cannabis-opioid co-use are significant. This study aimed to investigate whether two transdiagnostic factors, emotion regulation and distress tolerance, had significant indirect effects in the relationship between pain and cannabis use in adults with chronic pain and an opioid prescription. METHODS: Participants (n = 450; mean age = 38.6 ± 11.09) were recruited using Qualtrics panel service and were 75 % female and 79 % White, non-Hispanic. Participants completed a 30-minute self-report survey capturing three-month cannabis use, the Difficulties in Emotional Regulation Scale (DERS), and the Distress Tolerance Scale (DTS). The Graded Pain Scale (GCPS) assessed pain severity/intensity and disability. Analyses used the SPSS PROCESS macro, with both single (i.e., one transdiagnostic factor) and parallel indirect effects (i.e., both the DERS and DTS) examined. RESULTS: There were statistically significant indirect effects for both the DERS and DTS in the relationship between pain intensity or disability and three-month cannabis use in single factor models. In the parallel indirect effect model, only the DERS was statistically significant (intensity indirect effect coefficient = 0.0195 % confidence interval [95 %CI] = 0.0065, 0.390; disability indirect effect coefficient = 0.0147, 95 %CI = 0.0055, 0.0274). CONCLUSIONS: When examining parallel indirect effects, only emotional regulation and not distress tolerance mediated the relationship between chronic pain and cannabis use among those with an opioid prescription. Clinically, interventions aimed at improving emotional regulation in individuals with chronic pain can help limit cannabis and opioid co-use.

Momentary Emotion Regulation Strategies and Pain Experience Among Adults With Chronic Pain: An Ecological Momentary Assessment Study.

OBJECTIVES: The intention of this study was to characterize the real-time momentary relationship between emotion regulation strategies and the pain experience (ie intensity, interference, and negative affect) among adults with chronic pain. Chronic pain is a significant public health concern. Psychological treatments are effective for treating chronic pain, but long-term follow-up studies are limited, and treatment effect sizes are small. Identifying modifiable treatment targets, such as emotion regulation (ER), is critical to improve interventions. ER (ie, cognitive and attentional strategies to modulate or maintain emotional experience) has been linked to psychopathology and pain experience in adults. Yet, the existing work is limited and has largely focused on the relationship between emotional experience, not ER, and pain. MATERIALS AND METHODS: The current study utilized ecological momentary assessment 53 adults with chronic pain. Participants completed ecological momentary assessments of pain experience and ER strategies 5 times a day for 7 days. Associations by specific strategy type were also examined, highlighting the importance of worry, experiential avoidance, rumination, and expressive suppression in pain experience. RESULTS: Results of the current study provide evidence for the association between within-person maladaptive ER strategies and pain intensity ( b = 2.11, SE = 0.37, P < 0.001), pain interference ( b = 1.25, SE = 0.40, P = 0.002), and pain-related negative affect ( b = 2.20, SE = 0.41, P < 0.001). (77.4% females; M age = 27.10 y, SD = 5.16 y). DISCUSSION: Given that ER is readily targeted in psychological treatments for chronic pain, the results from the current study provide initial evidence to target these ER strategies in treatment.

Characterizing the Impact of Disorders of the Gut-Brain Interaction on Mental and Physical Health Functioning Among Spanish-Speaking Latino Adults Living in the United States.

INTRODUCTION: Latino individuals are underrepresented in the disorders of the gut-brain interaction (DGBI) literature, and no work has explored how disorders of the gut-brain interaction affect health and well-being in this group. METHODS: This study sought to explore how disorders of the gut-brain interaction affect health factors in a sample of Latino individuals (N = 292; 80.80% female; M age = 37.65 years, SD = 11.98) with (n = 60) and without (n = 232) a disorder of the gut-brain interaction based on current Rome Foundation diagnostic criteria (Rome IV). RESULTS: DGBI was associated with increased pain intensity, pain disability, cardiovascular risk, depressive symptoms, and anxiety/panic symptoms and lower physical health-related quality of life and mental health-related quality of life controlling for age, sex, and nativity. DISCUSSION: Better understanding mental health and treatment-seeking behaviors among Latino individuals may help clinical gastroenterologists engage their Latino patients to a greater extent and thus provide higher quality of care.

A 3D In Vitro Cortical Tissue Model Based on Dense Collagen to Study the Effects of Gamma Radiation on Neuronal Function.

Studies on gamma radiation-induced injury have long been focused on hematopoietic, gastrointestinal, and cardiovascular systems, yet little is known about the effects of gamma radiation on the function of human cortical tissue. The challenge in studying radiation-induced cortical injury is, in part, due to a lack of human tissue models and physiologically relevant readouts. Here, a physiologically relevant 3D collagen-based cortical tissue model (CTM) is developed for studying the functional response of human iPSC-derived neurons and astrocytes to a sub-lethal radiation exposure (5 Gy). Cytotoxicity, DNA damage, morphology, and extracellular electrophysiology are quantified. It is reported that 5 Gy exposure significantly increases cytotoxicity, DNA damage, and astrocyte reactivity while significantly decreasing neurite length and neuronal network activity. Additionally, it is found that clinically deployed radioprotectant amifostine ameliorates the DNA damage, cytotoxicity, and astrocyte reactivity. The CTM provides a critical experimental platform to understand cell-level mechanisms by which gamma radiation (GR) affects human cortical tissue and to screen prospective radioprotectant compounds.

External Validation of a Tool to Identify Low-Risk Patients With Isolated Subdural Hematoma and Preserved Consciousness.

STUDY OBJECTIVE: The SafeSDH Tool was derived to identify patients with isolated (no other type of intracranial hemorrhage) subdural hematoma who are at very low risk of neurologic deterioration, neurosurgical intervention, or death. Patients are low risk by the tool if they have none of the following: use of anticoagulant or nonaspirin antiplatelet agent, Glasgow Coma Score (GCS) <14, more than 1 discrete hematoma, hematoma thickness >5 mm, or midline shift. We attempted to externally validate the SafeSDH Tool. METHODS: We performed a retrospective chart review of patients aged ≥16 with a GCS ≥13 and isolated subdural hematoma who presented to 1 of 6 academic and community hospitals from 2005 to 2018. The primary outcome, a composite of neurologic deterioration (seizure, altered mental status, or symptoms requiring repeat imaging), neurosurgical intervention, discharge on hospice, and death, was abstracted from discharge summaries. Hematoma thickness, number of hematomas, and midline shift were abstracted from head imaging reports. Anticoagulant use, antiplatelet use, and GCS were gathered from the admission record. RESULTS: The validation data set included 753 patients with isolated subdural hematoma. Mortality during the index admission was 2.1%; 26% of patients underwent neurosurgical intervention. For the composite outcome, sensitivity was 99% (95% confidence interval [CI] 97 to 100), and specificity was 31% (95% CI 27 to 35). The tool identified 162 (21.5%) patients as low risk. Negative likelihood ratio was 0.03 (95% CI 0.01 to 0.11). CONCLUSION: The SafeSDH Tool identified patients with isolated subdural hematoma who are at low risk for poor outcomes with high sensitivity. With prospective validation, these low-risk patients could be safe for management in less intensive settings.

Pain interference among adult dual combustible and electronic tobacco users in terms of perceived barriers for quitting.

Electronic cigarette (e-cigarette) use has become increasingly common among combustible cigarette users, and dual use may represent a more severe type of nicotine addiction. Experiencing pain is one prevalent domain that may be important to understand quit processes and behavior among dual users. Although most past research on pain and nicotine/tobacco has focused on combustible cigarette use, initial work on e-cigarette users has found that greater pain severity is associated with higher levels of dependence and negative thinking patterns about e-cigarette use. Yet, there has been no effort to explore the experience of pain among dual users in terms of perceived barriers for quitting combustibles or e-cigarettes. The present study sought to examine pain interference among dual combustible and e-cigarette users in terms of perceived barriers for quitting among 138 (45.9% female; Mage = 35.96 years, SD = 7.16) adult dual users (i.e., users of both combustible cigarette and e-cigarettes). Hierarchical linear regression models indicated that pain interference was significantly associated with both perceived barriers for cessation of combustible cigarettes and perceived barriers for cessation of e-cigarettes. Overall, the present investigation served as an initial evaluation of the role of pain interference in terms of perceived barriers for quitting combustible and e-cigarettes among adult daily dual users. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Anxiety sensitivity in terms of mental health among a racially and ethnically diverse sample of sexual minority college students.

Objective: Limited work has focused on understanding the function of individual difference factors in terms of mental health among sexual minority college students. Anxiety sensitivity is one individual difference factor which has received substantial empirical attention, but its role is presently understudied among racially/ethnically diverse sexual minority college students.Participants: Participants included a racially and ethnically diverse sample of sexual minority college students (N = 217; Mage = 20.82 years; SD = 3.06).Methods: The present investigation evaluated the role of anxiety sensitivity in relation to anxious arousal, social anxiety, depression, and suicidality.Results: Results indicated that anxiety sensitivity was significantly related to increased anxious arousal, social anxiety, depression, and suicidality after adjusting for age, sex, relationship status, subjective social status, and neuroticism.Conclusions: This investigation provides the first empirical evidence that anxiety sensitivity is related to poorer mental health outcomes for racially/ethnically diverse sexual minority college students.

Alien vs. Predator: Impacts of Invasive Species and Native Predators on Urban Nest Box Use by Native Birds.

Many bird species in Australia require tree hollows for breeding. However, assessing the benefits of urban nest boxes to native birds requires frequent monitoring that allows to assess nesting success. To better understand the benefits of nest boxes for native birds, we examined the impact of local habitat characteristics, invasive species (common myna, Acridotheres tristis), and native mammalian predators on urban nest box use and nesting success of native birds. We installed 216 nest boxes across nine locations in southeastern Australia (S.E. Queensland and northern New South Wales) in both long-invaded sites (invaded before 1970) and more recently invaded sites (after 1990). We monitored all boxes weekly over two breeding seasons. We recorded seven bird species and three mammal species using the nest boxes. Weekly box occupancy by all species averaged 8% of all boxes, with the species most frequently recorded in the nest boxes being the common brushtail possum (Trichosurus vulpecula), a native cavity user and nest predator. We recorded 137 nesting attempts in the boxes across all bird species. The most frequent nesting species were the invasive alien common mynas (72 nesting attempts). We recorded an average nesting failure rate of 53.3% for all bird species. We did not record any common mynas evicting other nesting birds, and found that several native species used the same box after the common myna completed its nesting. We recorded native possums in 92% of the boxes, and possum occupancy of boxes per site was negatively correlated with bird nesting success (p = 0.021). These results suggest that when boxes are accessible to invasive species and native predators, they are unlikely to significantly improve nesting opportunities for native birds. To ensure efficient use of limited conservation resources, nest boxes should be designed to target species of high conservation importance and limit other species of both predators and competitors.

Mechanical loading due to muscle movement regulates establishment of the collagen network in the developing murine skeleton.

Mechanical loading is critical for collagen network maintenance and remodelling in adult skeletal tissues, but the role of loading in collagen network formation during development is poorly understood. We test the hypothesis that mechanical loading is necessary for the onset and maturation of spatial localization and structure of collagens in prenatal cartilage and bone, using in vivo and in vitro mouse models of altered loading. The majority of collagens studied was aberrant in structure or localization, or both, when skeletal muscle was absent in vivo. Using in vitro bioreactor culture system, we demonstrate that mechanical loading directly modulates the spatial localization and structure of collagens II and X. Furthermore, we show that mechanical loading in vitro rescues aspects of the development of collagens II and X from the effects of fetal immobility. In conclusion, our findings show that mechanical loading is a critical determinant of collagen network establishment during prenatal skeletal development.

Mass Cytometry as a Tool for Investigating Senescence in Multiple Model Systems.

Cellular senescence is a durable cell cycle arrest as a result of the finite proliferative capacity of cells. Senescence responds to both intrinsic and extrinsic cellular stresses, such as aging, mitochondrial dysfunction, irradiation, and chemotherapy. Here, we report on the use of mass cytometry (MC) to analyze multiple model systems and demonstrate MC as a platform for senescence analysis at the single-cell level. We demonstrate changes to p16 expression, cell cycling fraction, and histone tail modifications in several established senescent model systems and using isolated human T cells. In bone marrow mesenchymal stromal cells (BMSCs), we show increased p16 expression with subsequent passage as well as a reduction in cycling cells and open chromatin marks. In WI-38 cells, we demonstrate increased p16 expression with both culture-induced senescence and oxidative stress-induced senescence (OSIS). We also use Wanderlust, a trajectory analysis tool, to demonstrate how p16 expression changes with histone tail modifications and cell cycle proteins. Finally, we demonstrate that repetitive stimulation of human T cells with CD3/CD28 beads induces an exhausted phenotype with increased p16 expression. This p16-expressing population exhibited higher expression of exhaustion markers such as EOMES and TOX. This work demonstrates that MC is a useful platform for studying senescence at a single-cell protein level, and is capable of measuring multiple markers of senescence at once with high confidence, thereby improving our understanding of senescent pathways.

Posttraumatic stress and distress tolerance in relation to opioid misuse and dependence among trauma-exposed adults with chronic pain.

Posttraumatic stress symptoms have been associated with opioid misuse and dependence among adults with chronic pain. Lower levels of perceived distress tolerance (i.e., perceived ability to withstand negative emotional states) have been independently associated with posttraumatic stress symptoms and opioid-related problems among nonchronic pain samples. However, there has not been a test of whether distress tolerance interacts with posttraumatic stress in terms of opioid misuse among trauma-exposed persons with chronic pain. Therefore, the present study examined the interaction between distress tolerance and posttraumatic stress symptoms in relation to opioid misuse and dependence among trauma-exposed adults with chronic pain who were using opioids (N = 289; 70.9% female, Mage = 37.75, SD = 10.83). Results indicated a significant negative interaction of distress tolerance with posttraumatic stress in terms of opioid misuse and dependence, as the relationship between posttraumatic stress symptoms and opioid misuse and dependence was diminished at higher levels of distress tolerance. The current findings help refine our understanding of the subgroups of persons with chronic pain distinguished by low distress tolerance and at the greatest risk for misusing opioids. Furthermore, current models of chronic pain and opioid misuse could be refined by integrating distress tolerance. These findings may help inform interventions for trauma-exposed persons with chronic pain who use opioids. (PsycInfo Database Record (c) 2023 APA, all rights reserved).