The effects of telehealth-delivered mindfulness meditation, cognitive therapy, and behavioral activation for chronic low back pain: a randomized clinical trial.

BACKGROUND: Chronic low back pain (CLBP) is a significant problem affecting millions of people worldwide. Three widely implemented psychological techniques used for CLBP management are cognitive therapy (CT), mindfulness meditation (MM), and behavioral activation (BA). This study aimed to evaluate the relative immediate (pre- to post-treatment) and longer term (pre-treatment to 3- and 6-month follow-ups) effects of group, videoconference-delivered CT, BA, and MM for CLBP. METHODS: This is a secondary analysis of a three-arm, randomized clinical trial comparing the effects of three active treatments-CT, BA, and MM-with no inert control condition. Participants were N = 302 adults with CLBP, who were randomized to condition. The primary outcome was pain interference, and other secondary outcomes were also examined. The primary study end-point was post-treatment. Intent-to-treat analyses were undertaken for each time point, with the means of the changes in outcomes compared among the three groups using an analysis of variance (ANOVA). Effect sizes and confidence intervals are also reported. RESULTS: Medium-to-large effect size reductions in pain interference were found within BA, CT, and MM (ds from - .71 to - 1.00), with gains maintained at both follow-up time points. Effect sizes were generally small to medium for secondary outcomes for all three conditions (ds from - .20 to - .71). No significant between-group differences in means or changes in outcomes were found at any time point, except for change in sleep disturbance from pre- to post-treatment, improving more in BA than MM (d = - .49). CONCLUSIONS: The findings from this trial, one of the largest telehealth trials of psychological treatments to date, critically determined that group, videoconference-delivered CT, BA, and MM are effective for CLBP and can be implemented in clinical practice to improve treatment access. The pattern of results demonstrated similar improvements across treatments and outcome domains, with effect sizes consistent with those observed in prior research testing in-person delivered and multi-modal psychological pain treatments. Thus, internet treatment delivery represents a tool to scale up access to evidence-based chronic pain treatments and to overcome widespread disparities in healthcare. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03687762.

The Moderating Effects of Cognitive Processes on Pain-related Outcomes.

Although evidence supports the importance of pain-related thoughts (ie, cognitive content, or what people think) as predictors of pain and pain-related function, evidence regarding the role of cognitive processes (ie, how people think about pain, eg, by accepting pain, not making judgments about pain, or being absorbed by the pain experience) in adjustment to chronic pain is in its early stages. Using baseline data from a clinical trial of individuals with chronic low back pain (N = 327), the study aimed to increase knowledge regarding the associations between cognitive processes, pain intensity, pain interference, and depression. The results indicate that a number of cognitive processes are significantly related to pain intensity when controlling for catastrophizing, although the pattern of associations found was opposite to those anticipated. One cognitive process (pain absorption) was found to be significantly associated with pain interference, and 9 of 10 cognitive processes were significantly associated with depression when controlling for catastrophizing. In each case, the processes thought to be adaptive were negatively associated with pain interference and depression, and processes thought to be maladaptive evidenced the opposite pattern. The findings are consistent with-but do not prove, given the cross-sectional nature of the data-the possibility that cognitive processes play an important role in adjustment to chronic pain. The potential role these variables play in depression was particularly noteworthy. Longitudinal and experimental studies to evaluate the causal nature of the associations identified are warranted. PERSPECTIVE: The study findings highlight the potential importance of cognitive process variables (ie, how people think) in adjustment to chronic pain. Research to evaluate cognitive processes as potential mechanism variables in pain treatment is warranted.

Examining the learning effects of concrete and abstract materials among university students using a two-dimensional approach.

BACKGROUND: The debate on using concrete versus abstract materials in learning mathematics has been longstanding. For decades, research has focused on the physical characteristics of materials when defining them as concrete or abstract. AIMS: This study extends the field by proposing a two-dimensional classification, which defines materials as concrete or abstract based on the two dimensions of representation, namely object (i.e., appearance) and language (i.e., label). SAMPLE: A total of 120 university students participated in the study. METHODS: Participants were randomly assigned to learn the concept of modular arithmetic with one of four types of learning materials: concrete object labelled with concrete language, concrete object labelled with abstract language, abstract object labelled with concrete language and abstract object labelled with abstract language. They were also divided into high and low maths anxiety groups. RESULTS: Results showed that the students who learnt with abstract objects, regardless of the level of maths anxiety, outperformed their peers who learnt with concrete objects. However, for students with low maths anxiety only, those who learnt with materials labelled with abstract language showed better far-transfer performance compared with those who learnt with materials labelled with concrete language. CONCLUSIONS: The findings offer a new direction in the conceptualization of concrete and abstract learning materials by specifying the dimensions of representation.

Pain-Related Beliefs, Coping, and Function: An Observational Study on the Moderating Influence of Country of Origin.

Chronic pain is a multidimensional experience and pain treatments targeting psychosocial factors reduce pain and improve function. These treatments often overlook the sociocultural factors that influence pain and the psychological factors associated with function in people with chronic pain. Although preliminary findings suggest that cultural background may influence pain and function via their effects on beliefs and coping, no previous study has directly tested if the country of origin moderates the associations between these psychological factors and pain and function. This study sought to address this knowledge gap. Five hundred sixty-one adults with chronic pain, born and living in the USA (n = 273) or Portugal (n = 288), completed measures of pain, function, pain-related beliefs, and coping. Between-country similarities were found in the endorsement of beliefs related to disability, pain control, and emotion, and in asking for assistance, task persistence, and coping self-statement responses. Portuguese participants reported greater endorsement of harm, medication, solicitude, and medical cure beliefs, more frequent use of relaxation and support seeking, and less frequent use of guarding, resting, and exercising/stretching. In both countries, disability and harm beliefs and guarding responses were associated with worse outcomes; pain control and task persistence were associated with better outcomes. Six country-related small effect-size moderation effects emerged, such that task persistence and guarding are stronger predictors of pain and function in adults from the USA, but pain control, disability, emotion, and medication beliefs are more important in adults from Portugal. Some modifications may be needed when adapting multidisciplinary treatments from one country to another. PERSPECTIVE: This article examines the similarities and differences in beliefs and coping endorsed by adults with chronic pain from 2 countries, and the potential moderation effects of country on the associations between these variables and pain and function. The findings suggest that some modifications may be needed when culturally customizing psychological pain treatments.

Facial diplegia with paresthesia associated with anti-GD1a antibodies.

A 26-year-old previously healthy man presented with progressive facial diplegia and sensory deficits to pinprick in a stocking-glove distribution. Lumbar puncture revealed cytoalbuminologic dissociation, and a nerve conduction study of the right facial nerve demonstrated a proximal demyelinating process. He was started on intravenous immunoglobulin given concern for a Guillain-Barré syndrome variant, and his symptoms improved over several days. This case illustrates the clinical features of facial diplegia with paresthesias, a rare variant of Guillain-Barré syndrome. Unlike most reported cases of facial diplegia with paresthesias that have demonstrated positive anti-ganglioside M2 antibodies, this case is unique given the positivity of anti-ganglioside D1a IgG/IgM antibodies.

Effects of hypnosis, cognitive therapy, hypnotic cognitive therapy, and pain education in adults with chronic pain: a randomized clinical trial.

Chronic pain is a significant health problem worldwide with limited pharmacological treatment options. This study evaluated the relative efficacy of 4 treatment sessions each of 4 nonpharmacological treatments: (1) hypnotic cognitive therapy (using hypnosis to alter the meaning of pain); (2) standard cognitive therapy; (3) hypnosis focused on pain reduction, and (4) pain education. One hundred seventy-three individuals with chronic pain were randomly assigned to receive 4 sessions of 1 of the 4 treatments. Primary (pain intensity) and secondary outcome measures were administered by assessors unaware of treatment allocation at pretreatment, posttreatment, and 3-, 6-, and 12-month follow-up. Treatment effects were evaluated using analysis of variance, a generalized estimating equation approach, or a Fisher exact test, depending on the outcome domain examined. All 4 treatments were associated with medium to large effect size improvements in pain intensity that maintained up to 12 months posttreatment. Pretreatment to posttreatment improvements were observed across the 4 treatment conditions on the secondary outcomes of pain interference and depressive symptoms, with some return towards pretreatment levels at 12-month follow-up. No significant between-group differences emerged in omnibus analyses, and few statistically significant between-group differences emerged in the planned pairwise analyses, although the 2 significant effects that did emerge favored hypnotic cognitive therapy. Future research is needed to determine whether the significant differences that emerged are reliable.

Case Study: Cognitive Restructuring Hypnosis for Chronic Pain in a Quadriplegic Patient.

This case study reports on a 28-year-old male with spinal cord injury (SCI), quadriplegia, and chronic pain with neuropathic characteristics. The treatment had to be adapted to address the patient's needs, as he was on a respirator and paralyzed from the chin down. The intervention consisted of eight 90-minute sessions. The first four sessions were based on a standardized hypnotic cognitive therapy protocol developed for a randomized controlled trial (RCT). The sessions included training in cognitive restructuring skills and a hypnosis session with suggestions that was audiorecorded. Instructions to practice at home, both with the recording and by using self-hypnosis, were provided as well. Most of the outcome domains assessed (i.e., pain intensity, pain interference, sleep quality) showed clinically meaningful improvements that were maintained (or increased) at one-year follow-up. The patient reported that he was still using self-hypnosis at one-year follow-up. His subjective impression of change was positive and he did not report any negative side effects. Results show that the hypnotic cognitive therapy protocol used is a promising intervention that can benefit individuals with SCI presenting with complex symptomatology. Such therapy helps patients by teaching them effective coping strategies that they can use on their own to manage pain and its effects. In addition, it is important to note that this therapy provided benefits to someone who had not experienced any benefits from numerous medications he had tried before treatment. Therefore, the findings support continued efforts to make this treatment more accessible to patients who could benefit from this approach.

USE OF NEUROFEEDBACK AND MINDFULNESS TO ENHANCE RESPONSE TO HYPNOSIS TREATMENT IN INDIVIDUALS WITH MULTIPLE SCLEROSIS: Results From a Pilot Randomized Clinical Trial.

This pilot study evaluated the possibility that 2 interventions hypothesized to increase slower brain oscillations (e.g., theta) may enhance the efficacy of hypnosis treatment, given evidence that hypnotic responding is associated with slower brain oscillations. Thirty-two individuals with multiple sclerosis and chronic pain, fatigue, or both, were randomly assigned to 1 of 2 interventions thought to increase slow wave activity (mindfulness meditation or neurofeedback training) or no enhancing intervention, and then given 5 sessions of self-hypnosis training targeting their presenting symptoms. The findings supported the potential for both neurofeedback and mindfulness to enhance response to hypnosis treatment. Research using larger sample sizes to determine the generalizability of these findings is warranted.

Thy-1 dependent uptake of mesenchymal stem cell-derived extracellular vesicles blocks myofibroblastic differentiation.

Bone marrow-derived mesenchymal stem cells (MSC) have been promoted for multiple therapeutic applications. Many beneficial effects of MSCs are paracrine, dependent on extracellular vesicles (EVs). Although MSC-derived EVs (mEVs) are beneficial for acute lung injury and pulmonary fibrosis, mechanisms of mEV uptake by lung fibroblasts and their effects on myofibroblastic differentiation have not been established. We demonstrate that mEVs, but not fibroblast EVs (fEVs), suppress TGFß1-induced myofibroblastic differentiation of normal and idiopathic pulmonary fibrosis (IPF) lung fibroblasts. MEVs display increased time- and dose-dependent cellular uptake compared to fEVs. Removal or blocking of Thy-1, or blocking Thy-1-beta integrin interactions, decreased mEV uptake and prevented suppression of myofibroblastic differentiation. MicroRNAs (miRs) 199a/b-3p, 21-5p, 630, 22-3p, 196a-5p, 199b-5p, 34a-5p and 148a-3p are selectively packaged in mEVs. In silico analyses indicated that IPF lung fibroblasts have increased expression of genes that are targets of mEV-enriched miRs. MiR-630 mimics blocked TGFß1 induction of CDH2 in normal and IPF fibroblasts, and antagomiR-630 abrogated the effect of mEV on CDH2 expression. These data suggest that the interaction of Thy-1 with beta integrins mediates mEV uptake by lung fibroblasts, which blocks myofibroblastic differentiation, and that mEVs are enriched for miRs that target profibrotic genes up-regulated in IPF fibroblasts.

Relationship Between HIV Infection, Antiretroviral Therapy, Inflammatory Markers, and Cerebrovascular Endothelial Function Among Adults in Urban China.

BACKGROUND: Cerebrovascular risk is increased in people living with HIV infection compared with age-matched uninfected individuals. Cerebrovascular endothelial dysfunction related to antiretroviral therapy (ART) and inflammation may contribute to higher stroke risk in HIV infection. METHODS: We compared cerebral vasoreactivity-a measure of cerebrovascular endothelial function assessed by the breath-holding index (BHI) using transcranial Doppler ultrasound-between virologically suppressed Chinese HIV-infected individuals followed in an HIV clinic in Beijing, China, and uninfected controls. We constructed mixed-effects models to evaluate the association of HIV, ART, and inflammatory markers with cerebral vasoreactivity. RESULTS: In an unadjusted model, HIV infection was associated with a trend toward lower cerebral vasoreactivity (BHI 1.08 versus 1.26, P = 0.079). In multivariable analyses, cholesterol modified the association between HIV infection and cerebral vasoreactivity (P = 0.015 for interaction). At a lower total cholesterol of 4.15 mmol/L, HIV was associated with lower cerebral vasoreactivity (BHI -0.28, P = 0.019), whereas at a cholesterol of 5.15 mmol/L, the reduction in cerebral vasoreactivity associated with HIV was no longer statistically significant (BHI -0.05, P = 0.64). Among HIV-infected individuals, use of lopinavir/ritonavir compared with efavirenz was associated with lower cerebral vasoreactivity (BHI -0.24, P = 0.040). We did not find a significant association between inflammatory markers and cerebral vasoreactivity. CONCLUSIONS: Cerebrovascular endothelial dysfunction associated with HIV infection may be most relevant for individuals with less traditional vascular risk, such as those with lower cholesterol. Further study of the impact of ART on cerebrovascular endothelial function is warranted to aid with ART selection in individuals at high cerebrovascular risk.

The Looi suture technique for anchoring the lateral tarsal strip to the lateral orbital wall.

INTRODUCTION: The lateral tarsal strip procedure (LTS) was first reported by Anderson and Gordy in 1979 for the management of paralytic or senile eyelid laxity. Since its description, the LTS procedure has been subject to several modifications by various authors. In this study, we described the Looi suture technique, a small modification in the technique of suturing the LTS to the lateral orbital wall periosteum. Using this technique, the surgeon achieves a larger area of contact between the anterior surface of the tarsal strip and the lateral orbital wall periosteum, promoting a stronger adhesion. With a double-armed suture, the technique also allows for adjustment of the lower lid tension to avoid over- or under-correction of horizontal lid laxity. This study aimed to evaluate the technique. MATERIALS AND METHODS: This was a retrospective non-comparative case series of 39 eyelids of 31 patients who underwent LTS with Looi suturing technique for the correction of involutional lower lid laxity which had resulted in either entropion or ectropion. In this procedure, a novel technique utilising a double armed 5/0 Ethibond suture is used to secure the LTS to the lateral orbital rim, with the aim of increasing appositional contact between the LTS and periosteum. RESULTS: In 36 eyelids with entropion, the procedure was combined with lower lid retractor repair, and in 3 eyelids with ectropion, with medial tarsoconjunctivoplasty. Surgery was successful in 37 of 39 eyelids (94.87%) after one procedure. The remaining 2 eyelids required repeat procedures to achieve anatomical success. Both cases had been performed by trainee surgeons under supervision. Postoperative follow-up period ranged from 1 day (in a visiting overseas patient) to 2 years. CONCLUSION: This study described the Looi suturing technique in performing the LTS procedure and we found it a simple and effective modification when dealing with lower lid laxity.

Effect of the GPI anchor of human Thy-1 on antibody recognition and function.

Thymocyte differentiation antigen-1 (Thy-1) is a glycosylphosphatidylinositol (GPI)-linked cell surface glycoprotein expressed on numerous cell types, which regulates signals affecting cell adhesion, migration, differentiation, and survival. In addition, Thy-1 has been detected in the serum, cerebral spinal fluid, wound fluid from venous ulcers, synovial fluid from joints in rheumatoid arthritis, and, more recently, urine. We previously detected Thy-1 in the conditioned media of cytokine-stimulated lung fibroblasts, suggesting that Thy-1 shedding may be a response to cellular stress. Soluble and membrane-bound forms of Thy-1 from in vivo sources have been shown to be identical in size when deglycosylated, suggesting that soluble Thy-1 is separated from the diacyl glycerol portion of its GPI anchor by hydrolysis within the GPI moiety. For Thy-1- and other GPI-anchored proteins, delipidation induces a stable change in conformation that manifests itself in a change in antibody affinity for soluble forms. Using epitope-tagged recombinant soluble Thy-1, we report that widely available monoclonal antibodies to human Thy-1 are unable to detect soluble Thy-1 by immunoblotting. We re-evaluated the Thy-1 that we previously reported in the conditioned media of normal human lung fibroblasts and found it to be entirely insoluble. These findings suggest that most Thy-1 reported in body fluids retains its GPI anchor and may be associated with membrane fragments or vesicles. This phenomenon should be considered in the generation of antibodies and controls for Thy-1 bioassays. Furthermore, the changes in Thy-1 conformation with delipidation, beyond affecting antibody affinity, likely affect the ligand affinity and biological function of soluble vs released membrane-associated forms.

Racial stereotypes and interracial attraction: phenotypic prototypicality and perceived attractiveness of Asians.

What does it take to find a member of a different race attractive? In this research, we suggest that for Whites, attraction to Asians may be based, in part, on stereotypes and variations in Asians' racial appearance. Study 1 reveals that Asians are stereotyped as being more feminine and less masculine than other racial groups-characteristics considered appealing for women but not for men to possess. Study 2 examines how variation in racial appearance, phenotypic prototypicality (PP), shapes the degree to which Asians are gender stereotyped and how PP relates to perceptions of attractiveness. Higher PP Asian men are perceived as being less masculine and less physically attractive than lower PP Asian men. These findings inform theory on how within-group variation in racial appearance affects stereotyping and other social outcomes.

Reproducibility of cornea measurements in anterior segment OCT images of normal eyes and eyes with bullous keratopathy analyzed with the Zhongshan Assessment Program.

PURPOSE: To determine the interobserver and intraobserver measurement reproducibility of cornea parameters of both normal eyes and eyes with bullous keratopathy (BK) obtained with the Zhongshan Assessment Program (ZAP) on anterior segment optical coherence tomography (AS-OCT) images. METHODS: A comparative study was carried out on 24 healthy volunteers and 25 subjects with BK. AS-OCT images were independently analyzed by two examiners. Parameters examined: anterior chamber depth (ACD), central corneal thickness (CCT), posterior corneal curvature (PCC), and posterior corneal arc length (PCAL). Interobserver and intraobserver reproducibility of these parameters was calculated in terms of limits of agreement (mean of differences ± 1.96SD of differences). RESULTS: In the normal group, both horizontal and vertical ACD were successfully measured in 23 of 24 (96%) images. The mean bias for two measurements by two different observers ranged from 0.003 to 0.117 mm for ACD, PCC, and PCAL measurements and from 0.013 to 2.25 µm for CCT measurements, and there were no differences between the two observers (P > 0.05). Mean bias for two measurements by the same grader ranged from 0.005 to 0.327 mm for ACD, PCC, and PCAL measurements and 1.46 to 2.53 µm for CCT measurements. There was no difference between the two observations (P > 0.05). Similar results were found in the BK group. CONCLUSIONS: There was high inter- and intraobserver reproducibility for normal and pathologic corneas using the ZAP software. The ZAP software may serve as a new investigatory tool for accurately evaluating the anterior segment and corneal parameters for corneal procedures.

The first and third intracellular loops together with the carboxy terminal tail of the delta-opioid receptor contribute toward functional interaction with Galpha16.

Opioid peptides exert their regulatory effects on both central and peripheral nervous systems via multiple opioid receptors that are linked to seemingly identical sets of guanine nucleotide-binding regulatory proteins (G proteins). In contrast to the mu-opioid receptor, the delta-opioid receptor can efficiently stimulate phospholipase C via G16. We used a series of mu/delta-opioid receptor chimeras to examine the involvement of intracellular receptor domains in the recognition of G16. After ascertaining that the chimeras can bind opioid ligands with high affinity and elicit inhibition of adenylyl cyclase, COS-7 cells were cotransfected with cDNAs encoding Galpha16 and a mu/delta-opioid receptor chimera and assayed for [D-Ala2,D-Leu5]enkephalin-induced stimulation of phospholipase C. Our results indicate that (i) the carboxy terminal tail of the delta-opioid receptor is necessary but insufficient for conferring coupling to Galpha16, (ii) the third inner loop together with the carboxy terminal tail of the delta-opioid receptor can provide sufficient contact domains for Galpha16, and (iii) the first inner loop of the delta-opioid receptor, in particular Leu80, as well as the fifth transmembrane domain and/or the third extracellular loop may also contribute in defining the fidelity of interaction between the delta-opioid receptor and Galpha16. These results indicate that efficient coupling of the delta-opioid receptor to Galpha16 requires the participation of most of the intracellular regions, including the first intracellular loop.