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 to 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 (N = 9; 77.8% female, Mage = 33.86, SD = 8.75) participants to refine intervention content and evaluate treatment acceptability and feasibility. For phase 1B, individuals (N=118; 57.3% male, Mage = 35.24, SD = 11.90) participated in a pilot randomized clinical trial for our novel PFI compared to 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 provided support for the feasibility of using a PFI to target pain-related anxiety, and 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.

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.

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.

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).

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.

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.

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.

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).

Opioid coping motives and pain intensity among adults with chronic low back pain: associations with mood, pain reactivity, and opioid misuse.

Chronic low back pain (CLBP) is a significant public health problem that is associated with opioid misuse and use disorder. Despite limited evidence for the efficacy of opioids in the management of chronic pain, they continue to be prescribed and people with CLBP are at increased risk for misuse. Identifying individual difference factors involved in opioid misuse, such as pain intensity as well as reasons for using opioids (also known as motives), may provide pertinent clinical information to reduce opioid misuse among this vulnerable population. Therefore, the aims of the current study were to examine the relationships between opioid motives-to cope with pain-related distress and pain intensity, in terms of anxiety, depression, pain catastrophizing, pain-related anxiety, and opioid misuse among 300 (Mage= 45.69, SD = 11.17, 69% female) adults with CLBP currently using opioids. Results from the current study suggest that both pain intensity and motives to cope with pain-related distress with opioids were associated with all criterion variables, but the magnitude of variance explained by coping motives was larger than pain intensity in terms of opioid misuse. The present findings provide initial empirical evidence for the importance of motives to cope with pain-related distress with opioids and pain intensity in efforts to better understand opioid misuse and related clinical correlates among adults with CLBP.

The Rvv two-component regulatory system regulates biofilm formation and colonization in Vibrio cholerae.

The facultative human pathogen, Vibrio cholerae, employs two-component signal transduction systems (TCS) to sense and respond to environmental signals encountered during its infection cycle. TCSs consist of a sensor histidine kinase (HK) and a response regulator (RR); the V. cholerae genome encodes 43 HKs and 49 RRs, of which 25 are predicted to be cognate pairs. Using deletion mutants of each HK gene, we analyzed the transcription of vpsL, a biofilm gene required for Vibrio polysaccharide and biofilm formation. We found that a V. cholerae TCS that had not been studied before, now termed Rvv, controls biofilm gene transcription. The Rvv TCS is part of a three-gene operon that is present in 30% of Vibrionales species. The rvv operon encodes RvvA, the HK; RvvB, the cognate RR; and RvvC, a protein of unknown function. Deletion of rvvA increased transcription of biofilm genes and altered biofilm formation, while deletion of rvvB or rvvC lead to no changes in biofilm gene transcription. The phenotypes observed in ΔrvvA depend on RvvB. Mutating RvvB to mimic constitutively active and inactive versions of the RR only impacted phenotypes in the ΔrvvA genetic background. Mutating the conserved residue required for kinase activity in RvvA did not affect phenotypes, whereas mutation of the conserved residue required for phosphatase activity mimicked the phenotype of the rvvA mutant. Furthermore, ΔrvvA displayed a significant colonization defect which was dependent on RvvB and RvvB phosphorylation state, but not on VPS production. We found that RvvA's phosphatase activity regulates biofilm gene transcription, biofilm formation, and colonization phenotypes. This is the first systematic analysis of the role of V. cholerae HKs in biofilm gene transcription and resulted in the identification of a new regulator of biofilm formation and virulence, advancing our understanding of the role TCSs play in regulating these critical cellular processes in V. cholerae.

Opioid and cannabis co-use: The role of opioid use to cope with negative affect.

INTRODUCTION: The opioid epidemic is a significant public health concern, particularly among adults with chronic pain. There are high rates of cannabis co-use among these individuals and co-use is related to worse opioid-related outcomes. Yet, little work has examined mechanisms underlying this relationship. In line with affective processing models of substance use, it is possible that those who use multiple substances do so in a maladaptive attempt to cope with psychological distress. METHOD: We tested whether, among adults with chronic lower back pain (CLBP), the relation between co-use and more severe opioid-related problems would occur via the serial effects of negative affect (anxiety, depression) and more coping motivated opioid use. RESULTS: After controlling for pain severity and relevant demographics, co-use remained related to more anxiety, depression, and opioid-related problems (but not more opioid use). Further, co-use was indirectly related to more opioid-related problems via the serial effect of negative affect (anxiety, depression) and coping motives. Alternative model testing found co-use was not indirectly related to anxiety or depression via serial effects of opioid problems and coping. CONCLUSIONS: Results highlight the important role negative affect may play in opioid problems among individuals with CLBP who co-use opioid and cannabis.

Intraindividual change in pain tolerance and negative affect over 20 years: findings from the MIDUS study.

Pain tolerance, defined as the ability to withstand physical pain states, is a clinically important psychobiological process associated with several deleterious outcomes, including increased pain experience, mental health problems, physical health problems, and substance use. A significant body of experimental work indicates that negative affect is associated with pain tolerance, such that increased negative affect is associated with decreased pain tolerance. Although research has documented the associations between pain tolerance and negative affect, little work has examined these associations over time, and how change in pain tolerance is related to changes in negative affect. Therefore, the current study examined the relationship between intraindividual change in self-reported pain tolerance and intraindividual change in negative affect over 20 years in a large, longitudinal, observation-based national sample of adults (n = 4,665, Mage = 46.78, SD =12.50, 53.8% female). Results from parallel process latent growth curve models indicated that slope of pain tolerance and negative affect were associated with each other over time (r = .272, 95% CI [.08, .46] p = .006). Cohen's d effect size estimates provide initial, correlational evidence that changes in pain tolerance may precede changes in negative affect. Given the relevance of pain tolerance to deleterious health outcomes, better understanding how individual difference factors, including negative affect, influence pain tolerance over time, are clinically important to reduce disease-related burden.

Posttraumatic stress and pain-related anxiety among trauma-exposed adults with chronic pain in terms of opioid misuse and dependence.

Trauma-exposure and posttraumatic stress symptoms increase risk for opioid-related problems in the context of chronic pain. Yet, there has been little exploration of moderators of the posttraumatic stress-opioid misuse association. Pain-related anxiety, defined as worry about pain and the negative consequences of pain, has shown relations to both posttraumatic stress symptoms and opioid misuse, and it may moderate the association between posttraumatic stress symptoms and opioid misuse, as well as dependence. The current study examined the moderating role of pain-related anxiety on the relationship between posttraumatic stress symptoms and opioid misuse and dependence among 292 (71.6 % female, Mage = 38.03 years, SD = 10.93) trauma exposed adults with chronic pain. Results indicated that pain-related anxiety significantly moderated the observed relations, such that compared to those with low pain-related anxiety, the relationship between posttraumatic stress symptoms and opioid misuse and dependence was stronger for those with elevated pain-related anxiety. These results highlight the importance of assessing and targeting pain-related anxiety among this trauma-exposed segment of the chronic pain population with elevated posttraumatic stress symptoms.