Transcutaneous electrical nerve stimulation for the treatment of acute postoperative pain following spine surgery: a scoping review.

OBJECTIVE: Given the ubiquity and severity of postoperative pain following spine surgery, developing adequate pain management modalities is critical. Transcutaneous electrical nerve stimulation (TENS) is a promising noninvasive modality that is well studied for managing postoperative pain following a variety of surgeries, but data on using TENS for pain management in the acute postoperative period of spine surgery are limited. Therefore, this review aimed to recapitulate the existing evidence for the use of TENS in postoperative pain management for spine surgery and explore the potential of this modality moving forward. METHODS: A scoping review was conducted according to 2020 PRISMA guidelines. Two independently operating reviewers then conducted a systematic search of PubMed, Embase, and Scopus databases to identify studies that reported the use of TENS for the treatment of acute postoperative pain following spine surgery. The following data were abstracted from included studies: study type, sample size, demographics, surgery details, comparison group, assessment parameters, timing of postoperative assessment, TENS technical characteristics, relevant findings, length of hospital stay, complications with TENS, and notable limitations. RESULTS: Nine hundred thirty-two publications were screened, resulting in 6 studies included in this review, all of which were prospective clinical trials. The publication dates ranged from 1980 to 2011. Spine surgery types varied; the most common was posterior lumbar interbody fusion. No studies evaluated pain control in cervical- or thoracic-only surgeries. All 6 studies evaluated the level of postoperative pain directly. Five of the 6 studies that directly examined postoperative pain reported lower levels of pharmacological analgesia usage in the TENS groups compared with controls, with 4 of these studies reporting this difference as statistically significant. Length of hospital stay was evaluated in 2 studies, both of which reported decreases in mean length of stay, but these differences were not significant. Notably, every study reported distinct TENS administration parameters while also reporting similar results. CONCLUSIONS: This review concludes that TENS is effective at reducing postoperative pain in spine surgery. Further investigation is needed regarding the optimal settings for TENS administration, as well as efficacy in the thoracic and cervical spine.

Erratum: Mechanical Frustration of Phase Separation in the Cell Nucleus by Chromatin [Phys. Rev. Lett. 126, 258102 (2021)].

This corrects the article DOI: 10.1103/PhysRevLett.126.258102.

Condensate interfaces can accelerate protein aggregation.

Protein aggregates, formed from the assembly of aberrant, misfolded proteins, are a hallmark of neurodegenerative diseases. Disease-associated aggregates such as mutant Huntingtin polyQ inclusions, are typically enriched in p62/SQSTM1, an oligomeric protein that binds to and sequesters aberrant proteins. p62 has been suggested to sequester proteins through formation of liquid-like biomolecular condensates, but the physical mechanisms by which p62 condensates may regulate pathological protein aggregation remain unclear. Here, we use a light-inducible biomimetic condensate system to show that p62 condensates enhance coarsening of mutant polyQ aggregates through interface-mediated sequestration, which accelerates polyQ accumulation into larger aggregates. However, the resulting large aggregates accumulate polyubiquitinated proteins, which depletes free p62, ultimately suppressing further p62 condensation. This dynamic interplay between interface-mediated coarsening of solid aggregates and downstream consequences on the phase behavior of associated regulatory proteins could contribute to the onset and progression of protein aggregation diseases.

Viscoelasticity and advective flow of RNA underlies nucleolar form and function.

The nucleolus is the largest biomolecular condensate and facilitates transcription, processing, and assembly of ribosomal RNA (rRNA). Although nucleolar function is thought to require multiphase liquid-like properties, nucleolar fluidity and its connection to the highly coordinated transport and biogenesis of ribosomal subunits are poorly understood. Here, we use quantitative imaging, mathematical modeling, and pulse-chase nucleotide labeling to examine nucleolar material properties and rRNA dynamics. The mobility of rRNA is several orders of magnitude slower than that of nucleolar proteins, with rRNA steadily moving away from the transcriptional sites in a slow (∼1 Å/s), radially directed fashion. This constrained but directional mobility, together with polymer physics-based calculations, suggests that nascent rRNA forms an entangled gel, whose constant production drives outward flow. We propose a model in which progressive maturation of nascent rRNA reduces its initial entanglement, fluidizing the nucleolar periphery to facilitate the release of assembled pre-ribosomal particles.

Engineered molecular sensors for quantifying cell surface crowding.

Cells mediate interactions with the extracellular environment through a crowded assembly of transmembrane proteins, glycoproteins and glycolipids on their plasma membrane. The extent to which surface crowding modulates the biophysical interactions of ligands, receptors, and other macromolecules is poorly understood due to the lack of methods to quantify surface crowding on native cell membranes. In this work, we demonstrate that physical crowding on reconstituted membranes and live cell surfaces attenuates the effective binding affinity of macromolecules such as IgG antibodies in a surface crowding-dependent manner. We combine experiment and simulation to design a crowding sensor based on this principle that provides a quantitative readout of cell surface crowding. Our measurements reveal that surface crowding decreases IgG antibody binding by 2 to 20 fold in live cells compared to a bare membrane surface. Our sensors show that sialic acid, a negatively charged monosaccharide, contributes disproportionately to red blood cell surface crowding via electrostatic repulsion, despite occupying only ~1% of the total cell membrane by mass. We also observe significant differences in surface crowding for different cell types and find that expression of single oncogenes can both increase and decrease crowding, suggesting that surface crowding may be an indicator of both cell type and state. Our high-throughput, single-cell measurement of cell surface crowding may be combined with functional assays to enable further biophysical dissection of the cell surfaceome.

Size distributions of intracellular condensates reflect competition between coalescence and nucleation.

Phase separation of biomolecules into condensates has emerged as a mechanism for intracellular organization and affects many intracellular processes, including reaction pathways through the clustering of enzymes and pathway intermediates. Precise and rapid spatiotemporal control of reactions by condensates requires tuning of their sizes. However, the physical processes that govern the distribution of condensate sizes remain unclear. Here we show that both native and synthetic condensates display an exponential size distribution, which is captured by Monte Carlo simulations of fast nucleation followed by coalescence. In contrast, pathological aggregates exhibit a power-law size distribution. These distinct behaviours reflect the relative importance of nucleation and coalescence kinetics. We demonstrate this by utilizing a combination of synthetic and native condensates to probe the underlying physical mechanisms determining condensate size. The appearance of exponential distributions for abrupt nucleation versus power-law distributions under continuous nucleation may reflect a general principle that determines condensate size distributions.

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.

High Spirits? Exploring "Halloweekend" Alcohol and Cannabis Use Among Heavy-Drinking College Students.

OBJECTIVE: Specific events are associated with heavier and riskier substance use behaviors among college students, including holidays like Halloween, which may include several days of themed parties/events ("Halloweekend"). The current study compared drinking, pregaming (i.e., fast-paced drinking before going out for the night), cannabis use, same-day alcohol and cannabis co-use, and negative alcohol-related consequences over Halloweekend compared with two adjacent non-Halloween weekends among a sample of heavy-drinking university students. METHOD: Participants (N = 228; 65% female) provided 28 days of daily diary data. We used a three-level generalized linear mixed model (GLMM) approach estimating zero-inflated Conway-Maxwell Poisson regressions to assess the effect of weekend and specific weekend day on number of overall drinks, number of pregaming drinks, and negative alcohol-related consequences. Proportions tests assessed for differences in any cannabis use and daily co-use between Halloweekend and non-Halloween weekends. RESULTS: Zero-inflated portions of the GLMMs indicated that general drinking, pregaming, and negative consequences were most prevalent on Halloweekend and Fridays and Saturdays. Count portions of the models indicated that general drinking quantity was highest during these periods, and participants experienced a greater number of negative consequences on Halloweekend compared with the weekend before; no differences were observed in the quantity of pregaming drinks consumed across weekends or days. No significant differences in cannabis use or co-use were observed between weekends. CONCLUSIONS: Given risk associated with Halloweekend compared with weekends immediately before and after, interventions targeting alcohol use and pregaming on Halloweekend may be beneficial to reduce related harm for heavy-drinking students.

American Veterans in the Era of COVID-19: Reactions to the Pandemic, Posttraumatic Stress Disorder, and Substance Use Behaviors.

The COVID-19 pandemic may have a compounding effect on the substance use of American veterans with posttraumatic stress disorder (PTSD). This study investigated the relationship between PTSD and current reactions to COVID-19 on alcohol and cannabis use among veterans who completed a survey 1 month prior to the pandemic in the USA and a 6-month follow-up survey. We hypothesized that veterans with PTSD would experience more negative reactions to COVID-19 and increased alcohol and cannabis use behaviors over those without PTSD. Veterans with PTSD prior to the pandemic, relative to those without, endorsed poorer reactions, greater frequency of alcohol use, and greater cannabis initiation and use during the pandemic. Veterans with PTSD may use substances to manage COVID-related stress. Clinicians may see an increase in substance use among this group during and after the pandemic and may need to implement specific behavioral interventions to mitigate the negative effects of COVID-19.

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.

Maternal and adolescent depressive symptoms and family conflict: An autoregressive cross-lagged examination of competing models in multi-stressed mothers and adolescents.

Maternal and adolescent depression are challenges that often co-occur. Many studies have drawn bivariate associations between maternal depressive symptoms, adolescent depressive symptoms, and family conflict, but few have examined reciprocal effects. Even among extant studies, there is a lack of clarity related to directionality of influence. Three competing theoretical models may explain the relationship between maternal depressive symptoms, adolescent depressive symptoms, and family conflict, and these processes may differ by adolescents' sex. Using three time points of data from 187 diverse mother-adolescent dyads, we fit a taxonomy of autoregressive cross-lagged structural equation models to simultaneously evaluate the competing theoretical models and also examine differences by sex using multiple-group analyses. Results indicate a symptom-driven model whereby adolescent depressive symptoms predicted increases in family conflict. Sex differences were also found. For males, but not females, greater adolescent depressive symptoms predicted subsequent increases in maternal depressive symptoms, which then predicted lower family conflict-possibly indicating maternal disengagement/withdrawal. Our findings suggest addressing adolescent depressive symptoms in order to prevent family conflict and that distinctive targets for the prevention/intervention of family conflict should account for differences by adolescents' sex.

Influences of poly-victimization on adolescents' pre-treatment cognitive motivations and post-treatment outcomes.

INTRODUCTION: Substance use treatment outcomes are challenging to predict: myriad potentially relevant factors influence outcomes, including age, sex, motivations, and history of victimization. METHODS: The current study seeks to assess these factors in adolescents through an evaluation of the relationship between distinct victimization profiles, sex, and cognitive factors related to substance use treatment outcomes-specifically motivation, self-efficacy, and reasons for quitting-and the relationship between these factors and posttreatment outcomes. We report sex differences in the prevalence of specific types of victimization; females are more likely than males to report poly-victimization alongside higher levels of traumagenic characteristics such as fearing for your life, chronic abuse, abuse by a trusted individual, or negative reactions to disclosure. RESULTS: Adolescents who endorsed high levels of poly-victimization and high traumagenic characteristics reported a) higher motivation for treatment, b) more reasons for quitting substance use, c) lower self-efficacy, and d) fewer adjusted days abstinent posttreatment relative to their peers. We report several sex differences: emergent poly-victimization profiles are different for males and females, class membership has a differential proportion, and, last, associations between class membership and pre-treatment cognitive motivations and posttreatment outcomes vary by sex. CONCLUSION: Clinicians working with adolescents who report poly-victimization should aim to leverage their motivation and reasons for quitting, as these factors are traditionally associated with positive outcomes. Last, interventions aimed at fostering self-efficacy may also be particularly important to improve long-term outcomes, specifically among adolescents with a history of poly-victimization.

Moral injury events and behavioral health outcomes among American veterans.

Among American veterans, the behavioral health impact of potentially morally injurious experiences (PMIEs) has recently garnered attention. There is heterogeneity in the types of experiences that are classified as PMIEs, and different PMIEs may be differentially associated with various outcomes. We aimed to explore heterogeneity in PMIEs among veterans, and whether PMIE classes are differentially associated with several behavioral health outcomes (i.e., symptoms of posttraumatic stress disorder, depression, anxiety, and anger). Data were from a survey study of veteran health attitudes and behavior (N=1004). We employed a Latent Class Analysis approach to identify sub-groups of participants with similar PMIE response patterns on the Moral Injury Events Scale and to determine the relationship between class membership and behavioral health outcomes. A 4-class solution best fit our data, with classes including (1) high all, (2) witnessed transgressions, (3) troubled by failure to act, and (4) moderate all. There was a link between class membership and behavioral health, with the high all class and moderate all classes consistently reporting especially poor outcomes. Our results are in line with cumulative stress models suggesting exposure to multiple forms of adversity may place individuals at particular risk of poor health and functioning. Clinicians working with veterans should screen for exposure to the full range of PMIE types and be prepared to address the multitude of behavioral health impacts.

What's sleep got to do with it? Longitudinal associations between insomnia, PTSD, and alcohol use among U.S. Veterans.

U.S. veterans are at risk for insomnia, which often co-occurs with symptoms of posttraumatic stress disorder (PTSD) and alcohol use. Much of the research on veterans and these three constructs is cross-sectional and focused on unidirectional pathways. Recent theoretical and empirical evidence suggests a dynamic interplay between insomnia, PTSD, and alcohol use, yet few longitudinal studies exist. A clearer understanding of these pathways is needed to help inform integrated treatments. Using a sample of 1,230 post-9/11 veterans assessed over four time points across 12 months, we used a latent difference score modeling approach to examine proportional and dynamic change between insomnia, PTSD, and alcohol. Results revealed a complex interplay between all three constructs. Higher prior levels of both PTSD and alcohol use were associated with greater subsequent changes in insomnia symptoms (i.e., worse sleep). Moreover, although veterans drank less frequently as their insomnia symptoms worsened over time, greater changes in insomnia symptoms (i.e., worse symptoms) was a mechanism linking PTSD and more frequent drinking. As the research on interventions addressing insomnia, PTSD, and alcohol is limited, there are opportunities for researchers and clinicians to develop programs that effectively target all three in integrated treatments.

The mechanobiology of nuclear phase separation.

The cell nucleus can be thought of as a complex, dynamic, living material, which functions to organize and protect the genome and coordinate gene expression. These functions are achieved via intricate mechanical and biochemical interactions among its myriad components, including the nuclear lamina, nuclear bodies, and the chromatin itself. While the biophysical organization of the nuclear lamina and chromatin have been thoroughly studied, the concept that liquid-liquid phase separation and related phase transitions play a role in establishing nuclear structure has emerged only recently. Phase transitions are likely to be intimately coupled to the mechanobiology of structural elements in the nucleus, but their interplay with one another is still not understood. Here, we review recent developments on the role of phase separation and mechanics in nuclear organization and discuss the functional implications in cell physiology and disease states.

Changes in perceived stress during the COVID-19 pandemic among American veterans.

American veterans are a population that suffer from both context specific stressors as well as many population-specific major-life events. The present exploratory study utilises a longitudinal cohort of 1230 U.S. veterans surveyed from February 2020 through February 2021. We sought to understand heterogeneity in perceived stress, using growth mixture modelling, over this time period, how COVID-specific factors such as negative reactions to the pandemic, loneliness, and employment disruptions influence perceived stress trajectories, and how veterans vary across distal outcomes including posttraumatic stress disorder (PTSD), pain, depression, sleep problems, physical health, and alcohol use disorder. Results revealed a 4-class solution: Stable High, Stable Low, Steady Increasing, and Steady Decreasing classes. In terms of COVID specific factors, negative reactions to COVID were consistently associated with perceived stress for those in the Stable High and Steady Increasing classes whereas loneliness was associated with stress trajectories for all emergent classes. Finally, in terms of our distal outcomes, results showed a relatively robust pattern with veterans in the Stable High or Steady Increasing classes reporting worse scores across all outcomes including PTSD, pain, sleep problems, physical health, depression, and alcohol use disorder. Understanding the interplay between existing vulnerabilities, ongoing stressors, and behavioural health outcomes among veterans is crucial for prevention and intervention efforts.

Expanding adverse child experiences to inequality and racial discrimination.

There is a well-established correlation between health and adverse childhood experiences (ACEs). Arguments have been made to expand ACE scales to include indicators of racism and structural inequalities. In this paper, we use nationally representative data to examine the relationships between latent groups of an expanded adversity scale and a broad range of child health outcomes. Data were obtained from a merger of the 2017 and 2018 National Survey of Children's Health (NSCH) and analyzed in 2021 (n = 52,129). Adversities were defined as violent victimization, violence exposure, a range of parental problems, racial discrimination, food insecurity, and unkempt housing. Latent class analysis (LCA) was used to uncover emergent groups of adversities, and logistic regression was used to assess group relationship to global and diagnosed measures of health. Four groups emerged: high all (3.6%), material and food hardship (11.9%), parental problems (10.3%), and low all (74.2%). Results showed the high all groups at greater odds of almost all outcomes. Compared to low all group, high all had particularly higher odds of any special (OR = 2.29) or complex (OR = 2.53) healthcare need, frequent severe headaches (OR = 2.07), and depression (OR = 3.4) or anxiety (OR = 2.11). Our analysis noted separation of experiences based on additional items related to structural inequalities: food insecurity, poverty, and unkempt housing. However, augmenting existing ACE scales with these indicators may be unnecessary as children most at-risk for poor health were a very small group (1 in 28) that experienced multiple forms of violence and parental problems.

Compartmentalization of telomeres through DNA-scaffolded phase separation.

Telomeres form unique nuclear compartments that prevent degradation and fusion of chromosome ends by recruiting shelterin proteins and regulating access of DNA damage repair factors. To understand how these dynamic components protect chromosome ends, we combine in vivo biophysical interrogation and in vitro reconstitution of human shelterin. We show that shelterin components form multicomponent liquid condensates with selective biomolecular partitioning on telomeric DNA. Tethering and anomalous diffusion prevent multiple telomeres from coalescing into a single condensate in mammalian cells. However, telomeres coalesce when brought into contact via an optogenetic approach. TRF1 and TRF2 subunits of shelterin drive phase separation, and their N-terminal domains specify interactions with telomeric DNA in vitro. Telomeric condensates selectively recruit telomere-associated factors and regulate access of DNA damage repair factors. We propose that shelterin mediates phase separation of telomeric chromatin, which underlies the dynamic yet persistent nature of the end-protection mechanism.

Cumulative Violence Exposure and Alcohol Use Among College Students: Adverse Childhood Experiences and Dating Violence.

Multiple types of childhood adversities are risk factors for dating violence among college-age youth and in turn, dating violence is associated with alcohol use. This work quantitatively examines associations of childhood adversity and dating violence with alcohol use among college students using a cumulative stress approach. Multi-campus surveys were collected from March to December 2016 in four universities across the United States and Canada (n = 3,710). Latent class analysis identified patterns of childhood adversity and dating violence. Regression analyses investigated the associations of latent class patterns with past year number of drinks, alcohol use frequency, and problematic drinking. Latent class analysis produced seven classes: "low violence exposure" (18.5%), "predominantly peer violence" (28.9%), "peer violence and psychological child abuse" (10.8%), "peer and parental domestic violence" (9.9%), "peer and psychological dating violence" (17%), "peer and dating violence" (6.6%), and "childhood adversity and psychological dating violence" (8.3%). Compared to the "low violence exposure" group, "peer and psychological dating violence" (B = .114, p < .05), "peer and dating violence" (B = .143, p < .05), and "childhood adversity and psychological dating violence" (B = .183, p < .001) groups were significantly associated with problematic drinking. Results highlight how childhood adversity and dating violence contribute to problematic alcohol use, suggesting interventions that address both childhood adversity and dating violence may be most effective at reducing alcohol misuse among college students.

Applying polyvictimization theory to veterans: Associations with substance use and mental health.

OBJECTIVE: Prior work has linked exposure to multiple types of trauma (i.e., polyictimization) to increased risk of negative behavioral health outcomes compared with exposure to any single event. However, few studies have attempted to understand how polyvictimization theory relates specifically to veterans' experiences and behavioral health outcomes. The present study assessed heterogeneity in reports of childhood trauma, combat trauma, and military sexual trauma. METHOD: We recruited 1,230 veterans outside of traditional Veterans Health Administration settings to participate in a study assessing behavioral health. On average, participants were 34.5 years old with the majority identifying as White (79.3%) and male (88.7%). We used latent class analysis to extract classes of traumatic experience exposure including childhood trauma, combat trauma, and military sexual trauma. RESULTS: Five classes emerged: (a) high all; (b) moderate combat trauma, high military sexual trauma; (c) high combat trauma, moderate military sexual harassment; (d) moderate childhood trauma and combat trauma; and (e) combat trauma only. Overall, veterans in profiles that endorsed multiple trauma types (i.e., polyvictimization) evidenced greater symptoms of depression, posttraumatic stress disorder, and hazardous alcohol or cannabis use. Further, women were overly represented in profiles that included multiple victimization typologies, especially when profiles included elevated endorsement of military sexual trauma. CONCLUSION: A polyvictimization framework was partially supported, with differential effects on behavioral health outcomes noted across trauma experiences. (PsycInfo Database Record (c) 2022 APA, all rights reserved).