Search

Abstract Background and aims Pain is common in older individuals. In order to understand and treat pain in this group, reliable and valid measures are needed. This study aimed to evaluate: (1) the validity, utility, incorrect response rates and preference rates of 5 pain rating scales in older individuals; and (2) the associations between age, education level, and cognitive function and both (a) incorrect response and (b) preference rates. Methods Two hundred and one orthopedic clinic outpatients ≥ 65 years old were asked to rate their current pain, and least, average, and worst pain intensity in the past week using 5 scales: Verbal Numerical Rating Scale (VNRS), Faces Pain Scale - Revised (FPS-R), Verbal Rating Scale (VRS), Numerical Rating Scale (NRS), and Visual Analogue Scale (VAS). Participants were also asked to indicate scale preference. We computed the associations between each measure and a factor score representing the shared variance among the scales, the incorrect response and scale preference rates, and the associations between incorrect response and preference rates and age, education level, and cognitive function. The incorrect responses included being unable to respond, providing more than one response, responses outside a range, providing range answers rather than fixed answers, and responses indicating ‘least > average,’ ‘least > worst,’ and ‘average > worst’. Results The findings support validity of all 5 scales in older individuals who are able to use all measures. The VNRS had the lowest (2%) and the VAS had the highest (6%) incorrect response rates. The NRS was the most (35%) and the VAS was the least (5%) preferred. Age was associated with the incorrect response rates of the VRS and VAS, such that older individuals were less likely to use these scales correctly. Education level was associated with the incorrect response rates of the FPS-R, NRS and VAS, such that those with less education were less likely to use these measures correctly. Cognitive function was not significantly associated with incorrect response rates. Age, education level and cognitive function were not significantly associated with scale preference. Conclusions Although all five scales are valid, the VNRS evidences the best overall utility in this sample of older individuals with pain. The NRS or FPS-R would be fine alternatives if it is not practical or feasible to use the VNRS.

Abstract. Systematic reviews suggest that stand-alone hypnotic suggestions may improve pain outcomes compared with no treatment, waitlist, or usual care. However, in clinical practice, hypnosis is often provided adjunctively with other interventions, which might have different effects than those reported in previous reviews. This systematic review aimed to summarize the analgesic effects of adjunctive hypnosis in adults with clinical pain. Seven databases (MEDLINE, Embase, PsycINFO, Emcare, SCOPUS, CENTRAL, Cochrane) were searched up to January 2024. Randomised controlled trials comparing the analgesic effects of adjunctive hypnosis (hypnosis + primary intervention) with those of the primary intervention alone were included. Meta-analyses (random-effects model) calculated mean differences (MD, [95% confidence intervals]) for pain intensity (0–100). Seventy studies were pooled in meta-analyses (n = 6078). Hypnosis adjunctive to usual care had a small additional analgesic effect (chronic pain: −8.2 [−11.8, −1.9]; medical procedures/surgical pain: −6.9 [−10.4, −3.3]; burn wound care: −8.8 [−13.8, −3.9]). Hypnosis adjunctive to education had a medium additional analgesic effect for chronic pain (−11.5 [−19.7, 3.3]) but not postsurgery pain (−2.0 [−7.8, 3.7]). When paired with psychological interventions, hypnosis slightly increased analgesia in chronic pain only at the three-month follow-up (−2 [−3.7, −0.3]). Hypnosis adjunctive to medicines had a medium additional analgesic effect for chronic pain (−13.2, [−22.5, −3.8]). The overall evidence certainty is very low; therefore, there is still uncertainty about the analgesic effects of adjunctive hypnosis. However, hypnosis adjunct to education may reduce pain intensity for chronic pain. Clarification of proposed therapeutic targets of adjunctive hypnosis to evaluate underlying mechanisms is warranted.

Abstract 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.

Abstract Background The study aimed to cross-culturally adapt the Patient-Reported Outcomes Measurement Information System Short Form v1.0 - Depression 8a (PROMIS SF v1.0 - Depression 8a) into Thai and evaluate its psychometric properties in individuals with chronic low back pain (CLBP). Methods The PROMIS SF v1.0– Depression 8a was translated and cross-culturally adapted into Thai using the Functional Assessment of Chronic Illness Therapy translation methodology. Two hundred and sixty-nine individuals with CLBP completed the Thai version of PROMIS SF v1.0– Depression 8a (T-PROMIS-D-8a) scale and a set of measures assessing validity criterion domains. Structural validity, internal consistency, and test-retest reliability at a 7-day interval of the T-PROMIS-D-8a scale were computed and its construct validity was evaluated by computing correlations with the Thai version of Patient Health Questionnaire-9 (T-PHQ-9), Numeric Rating Scale of pain intensity (T-NRS), and Fear Avoidance Beliefs Questionnaire (T-FABQ). Results Data from 269 participants were analyzed. Most participants were women (70%), and the sample had a mean age of 42.5 (SD 16.6) years. The findings supported the unidimensionality, internal consistency (Cronbach’s alpha = 0.94), and test-retest reliability (ICC [2,1] = 0.86) of the T-PROMIS-D-8a. A floor effect was observed for 16% of the sample. Associations with the T-PHQ-9, T-NRS, and T-FABQ supported the construct validity of the T-PROMIS-D-8a. Conclusions The T-PROMIS-D-8a was successfully translated and culturally adapted. The findings indicated that the scale is reliable and valid for assessing depression in Thai individuals with CLBP.

Abstract. Introduction:. Depression and anxiety are the most commonly reported mental health conditions. The Patient-Reported Outcomes Measurement Information System Short Form v1.0—Depression 8a (PROMIS-D-8a), Anxiety 8a (PROMIS-Anx8a), and Pain Anxiety Symptoms Scale-20 (PASS-20) measures were designed to assess depression, general anxiety, and pain-related anxiety, respectively. Objectives:. To examine the responsiveness and estimate the clinically important differences (CIDs) of the Thai version of these measures in individuals with chronic low back pain (CLBP). Methods:. The study sample comprised 144 participants with CLBP. Responsiveness was evaluated by calculating the change scores, effect sizes (ESs), standardized response means (SRMs), area under the curve (AUC), and correlations between the change scores and associated Global Perceived Effect (GPE). We also estimated CIDs by the difference in mean change score between improved and unchanged groups and standard error of measurement (SEM) for each measure. Results:. Statistically significant differences in the mean change scores, ESs, and SRMs supported the responsiveness of all measures. The AUCs achieved acceptable discriminatory ability (0.71–0.72) for moderate improvement but not for any improvement (0.65–0.68). The correlations between GPE and change scores on all measures were low (r ranging 0.28–0.33). The estimated CIDs for the PROMIS-D-8a, PROMIS-Anx8a, and PASS-20 were 3.64, 4.20, and 8.80, respectively. Conclusion:. The PROMIS-D-8a, PROMIS-Anx8a, and PASS-20 measures were sensitive for detecting clinical changes over time in individuals with CLBP. The CID values can be used as reference points for assessing meaningful improvements in the domains assessed by these scales in clinical and research practice.

Objective: To translate and cross-culturally adapt the Patient-Reported Outcomes Measurement Information System Short Form v1.0–Anxiety 8a and the Pain Anxiety Symptoms Scale-20 into Thai versions (T-PROMIS-Anx8a and T-PASS-20, respectively) and evaluate their psychometric properties in individuals with chronic low back pain (CLBP). Material and Methods: The translations and cultural adaptations were performed using the Functional Assessment of Chronic Illness Therapy (FACIT) guidelines. Thai individuals with CLBP completed the T-PROMIS-Anx8a and T-PASS-20. Psychometric evaluation including: internal consistency, test-retest reliability, and dimensionality. Construct validity was evaluated by computing correlations among the scores on the T-PROMIS-Anx8a, T-PASS-20, Thai version of the Hospital Anxiety and Depression Scale–Anxiety (T-HADS-A), and Thai version of the Fear Avoidance Beliefs Questionnaire (T-FABQ). Results: A total of 269 individuals with CLBP were included in the analyses. The T-PROMIS-Anx8a showed unidimensionality and the T-PASS-20 evidenced a 4-factor structure. Both measures demonstrated good to excellent internal consistency (Cronbach’s alphas ranged from 0.85 to 0.95), good test-retest reliability (ICC(2,1) ranged from 0.79 to 0.88), and neither ceiling nor floor effects were observed for any of the scales. Both measures evidenced acceptable convergent and discriminant validity, based on their associations with the T-HADS-A and T-FABQ. Conclusion: The T-PROMIS-Anx8a and T-PASS-20 were culturally adapted and evidenced acceptable psychometric properties for assessing anxiety in Thai individuals with CLBP.

Abstract We aimed to evaluate the potential anxiolytic effects of premedication with pregabalin, compared with diazepam and placebo. We conducted this non-inferiority, double-blind, randomized controlled trial in ASA classification I-II patients aged 18–70 years, scheduled for elective surgery under general anesthesia. They were allocated to receive pregabalin (75 mg the night before surgery and 150 mg 2 h before surgery), diazepam (5 and 10 mg in the same manner) or placebo. Preoperative anxiety was evaluated using verbal numerical rating scale (VNRS) and Amsterdam Preoperative Anxiety and Information Scale (APAIS) before and after premedication. Sleep quality, sedation level, and adverse effects were assessed as secondary outcomes. A total of 231 patients were screened and 224 completed the trial. The mean change (95%CI) in anxiety scores from before to after medication in pregabalin, diazepam, and placebo groups for VNRS were − 0.87 (− 1.43, − 0.30), − 1.17 (− 1.74, − 0.60), and − 0.99 (− 1.56, − 0.41), and for APAIS were − 0.38 (− 1.04, 0.28), − 0.83 (− 1.49, − 0.16), and − 0.27 (− 0.95, 0.40). The difference in change for pregabalin versus diazepam was 0.30 (− 0.50, 1.11) for VNRS and 0.45 (− 0.49, 1.38) for APAIS, exceeding the limit of inferiority for APAIS of 1.3. Sleep quality was statistically different between pregabalin and placebo groups (p = 0.048). Sedation in pregabalin and diazepam groups were significantly higher than placebo group (p = 0.008). No significant differences of other side effects, except dry mouth was higher in placebo group compared with diazepam (p = 0.006). The study filed to provide evidence at non-inferiority of pregabalin compared to diazepam. Furthermore, premedication with either pregabalin or diazepam did not significantly reduce the preoperative anxiety in comparison to placebo, despite the fact that both resulted in higher levels of sedation. Clinicians should weigh the benefits and risks of premedication with these 2 drugs. Thai Clinical Trials Registry: TCTR20190424001 (24/04/2019) Registry URL: https://www.thaiclinicaltrials.org/ .

Research supports the efficacy of therapeutic hypnosis for reducing acute and chronic pain. However, little is known about the mechanisms underlying these effects. This paper provides a review of the evidence regarding the role that electroencephalogram-assessed bandwidth power has in identifying who might benefit the most from hypnotic analgesia and how these effects occur. Findings are discussed in terms of the slow wave hypothesis, which posits that brain activity in slower bandwidths (e.g., theta and alpha) can facilitate hypnosis responsivity. Although the extant research is limited by small sample sizes, the findings from this research are generally consistent with the slow wave hypothesis. More research, including and especially studies with larger sample sizes, is needed to confirm these preliminary positive findings.

ObjectiveElectronic devices have become an indispensable part of our daily lives. The frequency and duration of device use in children and adolescents have increased drastically over the years and the study of its negative musculoskeletal, visual and psychosocial health impacts is necessary.Materials and methodsThis cross-sectional study aimed to evaluate the associations between electronic device use and the prevalence and severity of musculoskeletal symptoms, visual symptoms, psychosocial health, and quality of life in children and adolescents studying at primary and secondary schools. Data were collected through confidential online and paper-and-pencil questionnaires. Primary 4–5 and Secondary 1–4 students were recruited from 3 schools in Hong Kong. Demographics, frequency and duration of electronic device use, frequencies of musculoskeletal symptoms, visual symptoms, psychosocial health, and quality of life outcomes were measured.Results1,058 children and adolescents aged 9–17 years participated. Sixty-one percent and 78% of all students spent more than 2 h per day using electronic devices during school days and weekend/holidays, respectively. Extended electronic device use was associated with increased prevalence and severity of musculoskeletal symptoms (ρ’s = 0.28–0.33, P’s

Abstract Background Although it is generally accepted that physical activity and flares of low back pain (LBP) are related, evidence for the directionality of this association is mixed. The Flares of Low back pain with Activity Research Study (FLAReS) takes a novel approach to distinguish the short-term effects of specific physical activities on LBP flares from the cumulative effects of such activities, by conducting a longitudinal case-crossover study nested within a cohort study. The first aim is to estimate the short-term effects (≤ 24 h) of specific physical activities on LBP flares among Veterans in primary care in the Veterans Affairs healthcare system. The second aim is to estimate the cumulative effects of specific activities on LBP-related functional limitations at 1-year follow-up. Methods Up to 550 adults of working age (18—65 years) seen for LBP in primary care complete up to 36 “Scheduled” surveys over 1-year follow-up, and also complete unscheduled “Flare Window” surveys after the onset of new flares. Each survey asks about current flares and other factors associated with LBP. Surveys also inquire about activity exposures over the 24 h, and 2 h, prior to the time of survey completion (during non-flare periods) or prior to the time of flare onset (during flares). Other questions evaluate the number, intensity, duration, and/or other characteristics of activity exposures. Other exposures include factors related to mood, lifestyle, exercise, concurrent treatments, and injuries. Some participants wear actigraphy devices for weeks 1–4 of the study. The first aim will examine associations between 10 specific activity categories and participant-reported flares over 1-year follow-up. The second aim will examine associations between the frequency of exposure to 10 activity categories over weeks 1–4 of follow-up and long-term functional limitations at 12 months. All analyses will use a biopsychosocial framework accounting for potential confounders and effect modifiers. Discussion FLAReS will provide empirically derived estimates of both the short-term and cumulative effects of specific physical activities for Veterans with LBP, helping to better understand the role of physical activities in those with LBP. Trial Registration ClinicalTrials.gov NCT04828330 , registered April 2, 2021.

Abstract Background English versions of the University of Washington Caregiver Stress (UW-CSS) and Benefit (UW-CBS) Scales were developed in the United States (US) to measure impact on caregivers of caring for a child/children. Caregiving stress and benefit are important constructs to study worldwide. The purpose of this study was to translate and validate the UW-CSS and UW-CBS into French, German, Italian, and Spanish languages. Method UW-CSS and UW-CBS were translated using forward and backward translation with reconciliation. Cognitive interviews (CIs) were completed with caregivers of children

Abstract. Introduction:. Neck and low back pain are significant health problem in sedentary office workers. Active break and postural shift interventions has been proved to reduce the incidence of new onset of both neck and low back pain. Objectives:. To identify variables that moderate the effects of active breaks and postural shift interventions on the development of neck and low back pain in office workers. Methods:. Using data from a 3-arm (active break, postural shift, and control group) cluster randomized controlled trial (N = 193), we evaluated the moderating effects of age, job position, education level, sex, perceived psychological work demands, number of working hours, and using a chair with lumbar support on the benefits of 2 interventions designed to prevent the development of neck and low back pain in office workers. Moderation analyses were conducted using the Hayes PROCESS macro, with post hoc Johnson–Neyman techniques and logistic regressions. Results:. Significant interactions between intervention groups and 3 moderators assessed at baseline emerged. For the prevention of neck pain, the effect of the active break intervention was moderated by the number of working hours and the effect of the postural shift intervention was moderated by the level of perceived psychological work demands and the number of working hours. For the prevention of low back pain, the effect of postural shift intervention was moderated by having or not having a chair with lumbar support. Conclusions:. The study findings can be used to help determine who might benefit the most from 2 treatments that can reduce the risk of developing neck and low back pain in sedentary workers and may also help us to understand the mechanisms underlying the benefits of these interventions.

Abstract Background Chronic pain is one of the most prevalent and disabling symptoms associated with multiple sclerosis (MS). Individuals with MS are interested in nonpharmacologic pain management approaches. Cognitive-behavioral therapy (CBT) is efficacious in improving MS-related pain outcomes. Mindfulness-based cognitive therapy (MBCT) is a promising, alternative approach. Little is known about moderators of these treatments’ outcomes, however. This article describes the study protocol for the first randomized controlled trial comparing MBCT, CBT, and usual care and examining treatment effect moderators in individuals with chronic pain and MS. Methods We will conduct a single-center, randomized, single blind, parallel-group trial comparing MBCT, CBT, and usual care in adults with MS and chronic pain. Both interventions will be delivered via eight group sessions using videoconferencing technology. Primary (average pain intensity) and secondary outcomes (including pain interference, depressive symptoms, fatigue, and sleep) will be assessed pre-treatment, mid-treatment, post-treatment, and at 6-month follow up. Potential treatment moderators will be assessed pre-treatment. We hypothesize that participants randomly assigned to MBCT or CBT will report significantly greater reductions in average pain intensity than participants assigned to usual care at post-treatment (primary study endpoint) and 6-month follow up. We also hypothesize that mindfulness, pain catastrophizing, and behavioral activation pre-treatment will moderate response to both active treatments, but not response to usual care. Discussion Findings will provide important new information about the efficacy and moderators of two nonpharmacologic pain management approaches delivered using technology to overcome common barriers to treatment access. The knowledge gained may lead to better patient-treatment matching and, ultimately, better pain treatment outcomes in MS. Trial registration ClinicalTrials.gov, NCT03782246. Registered on 20 December 2018.

Abstract Background Migraine ranks as the third most prevalent disease and the seventh most common cause of disability worldwide. To better understand the impact of migraine on the quality of life of individuals with this diagnosis, and how these might differ from one country or culture to another, reliable and valid measures of quality of life that are available in different languages are needed. To address this need, here we (1) translated the Migraine-Specific Quality of Life Questionnaire into Chinese (MSQv2.1-C), and (2) examined the psychometric properties of the measure. Methods Forward and backward translation was conducted using four bilingual experts. One native speaker finalized the translation. Cognitive testing was performed by interviewing 11 monolingual migraineurs, and modifications were made to the MSQv2.1-C, as appropriate. Next, 174 individuals with a history of migraine completed the MSQv2.1-C, along with the SF-12, Migraine Disability Assessment Scale, and numerical rating scale s assessing pain intensity. We then evaluated the reliability and validity of the MSQv2.1-C by performing analyses to evaluate its internal consistency, test-retest reliability, convergent validity, criterion validity, and construct validity. Results The MSQv2.1-C scales demonstrated (1) good internal consistency (Cronbach’s alpha s ≥ 0.81); (2) good 1-week test-retest reliability (intra-class coefficients ≥0.69 and Spearman’s rho correlation coefficients ≥0.74); (3) convergent validity (positive correlations with the MSQ and SF-12 scales [rho range = 0.27 to 0.37, ps 0.5]). Conclusions The MSQv2.1-C exhibited satisfactory reliability and validity in a sample of individuals with migraine who speak Chinese. The availability of this measure will facilitate research, including cross-cultural research, on the quality of life of individuals with migraine.

Background There has been an increasing interest in studying the potential benefits of so-called complementary and alternative approaches for pain management, such as hypnosis and mindfulness-based interventions. More recently, researchers have been interested in studying the effects of spiritual practices on pain experience as well. These practices may increase pain tolerance, result in a positive re-appraisal of pain and influence other psychological variables that are known to be associated with pain experience. The purpose of this study is to evaluate and compare the immediate effects of self-hypnosis, mindfulness meditation, and a spiritual intervention relative to a control condition for increasing pain tolerance and reducing pain intensity and pain-related stress, in response to experimental painful stimulation.Methods and analysis Recruitment is anticipated to start in November 2020. This is a randomised quantitative experimental mixed-design repeated-measures study with three assessment points: baseline (T0), pre-test (T1) and post-test (T2). Eligible healthy adults will be randomised to one of the four study conditions. Interventions will be a 20-minute audio-guided practice of either self-hypnosis, mindfulness meditation, or Christian prayer. Participants in the control group will not be instructed to use any specific strategy during the painful stimulation. Participants will be submitted to a first cycle of Cold Pressor Arm Wrap. They will then listen to a 20-minute audio recording inducing one of the three interventions, or, in the case of the control group, to a 20-minute audio recording of text from a natural history textbook. Primary outcomes are pain intensity and pain tolerance. Pain-related stress as measured by salivary cortisol level and heart rate variability are secondary outcomes.Ethics and dissemination This study was approved by ISPA—University Institute’s internal Ethics Committee for Research on 3rd December 2018 (reference I/010/12/2018). Findings will be published in peer-reviewed indexed journals and presented at conferences.Trial registration number ClinicalTrials.gov registry (NCT04491630). Stage: pre-results.

Abstract. Clinical outcome assessments (COAs) measure outcomes that are meaningful to patients in clinical trials and are critical for determining whether a treatment is effective. The objectives of this study are to (1) describe the different types of COAs and provide an overview of key considerations for evaluating COAs, (2) review COAs and other outcome measures for chronic pain treatments that are recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) or other expert groups, and (3) review advances in understanding pain-related COAs that are relevant to clinical trials. The authors reviewed relevant articles, chapters, and guidance documents from the European Medicines Agency and U.S. Food and Drug Administration. Since the original core set of outcome measures were recommended by IMMPACT 14 years ago, several new advancements and publications relevant to the measurement or interpretation of COAs for chronic pain trials have emerged, presenting new research opportunities. Despite progress in the quality of measurement of several outcome domains for clinical trials of chronic pain, there remain some measurement challenges that require further methodological investigation.

Background: Chronic pain is a significant global health issue. For most individuals with chronic pain, biomedical treatments do not provide adequate relief. Given the evidence that neurophysiological abnormalities are associated with pain, it is reasonable to consider treatments that target these factors, such as neurofeedback (NF). The primary objectives of this review were to summarize the current state of knowledge regarding: (1) the different types of NF and NF protocols that have been evaluated for pain management; (2) the evidence supporting each NF type and protocol; (3) if targeted brain activity changes occur with NF training; and (4) if such brain activity change is associated with improvements on treatment outcomes.Methods: Inclusion criteria were intentionally broad to encompass every empirical study using NF in relation to pain. We considered all kinds of NF, including both electroencephalogram- (EEG-) and functional magnetic resonance imagining- (fMRI-) based. We searched the following databases from inception through September 2019: Pubmed, Ovid, Embase, Web of Science, PsycINFO. The search strategy consisted of a combination of key terms referring to all NF types and pain conditions (e.g., neurofeedback, rt-fMRI-NF, BOLD, pain, migraine).Results: A total of 6,552 citations were retrieved; 24 of these that were included in the review. Most of the studies were of moderate quality, included a control condition and but did not include a follow-up. They focused on studying pain intensity (83%), pain frequency, and other variables (fatigue, sleep, depression) in samples of adults (n = 7–71) with headaches, fibromyalgia and other pain conditions. Most studies (79%) used EEG-based NF. A wide variety of NF types and protocols have been used for pain management aiming to either increase, decrease or regulate brain activity in certain areas theoretically associated with pain.Conclusions: Given the generally positive results in the studies reviewed, the findings indicate that NF procedures have the potential for reducing pain and improving other related outcomes in individuals with chronic pain. However, the current evidence does not provide definitive conclusions or allow for reliable recommendations on which protocols or methods of administration may be the most effective. These findings support the need for continued – but higher quality – research in this area.

Abstract. Before determining the pain research priorities for a country, a comprehensive literature review of existing research is warranted. We aimed to (1) identify and describe the extent and nature of pain research performed in Nepal, (2) identify existing knowledge and significant knowledge gaps, and (3) provide recommendations for future studies. We conducted a systematic scoping review of the literature, in accordance with recommended guidelines. We searched local and international databases to identify research conducted in Nepal on individuals with a diagnosis of clinical pain conditions. A pair of independent reviewers screened the studies for inclusion. We identified 1396 records and included 116 studies. Most studies were published in Nepalese journals (75%) and were conducted in clinical settings (73%). Postsurgical pain was the most commonly studied pain condition (33%), followed by musculoskeletal pain (16%), headache (14%), and low back pain (13%). The most common research topics, in order of frequency, were (1) medical management (40%), (2) pain prevalence/incidence (21%), (3) diagnostic procedures (15%), (4) surgical management (8%), and (5) patient-reported outcome measurement (8%). Research gaps and potential areas of research waste were identified. Although a large number of research articles about pain in Nepal have been published, the majority of these have focused on the biomedical diagnosis and management of pain. Other topic areas (eg, psychological and social aspects of pain) are under-represented. The findings may inform future research directions for maximizing the knowledge that could be gained.

Abstract. Introduction:. One psychosocial factor in the biopsychosocial model is pain-related self-efficacy, which has been shown to be a strong predictor of response to pain treatment. Objectives:. To cross-culturally adapt the University of Washington Pain-Related Self-Efficacy Scale (UW-PRSE6) into Thai and evaluate its psychometric properties. Methods:. The study was approved by the Chulalongkorn University Human Ethics Committee (COA No. 156/2018). The original UW-PRSE6 was cross-culturally adapted using the Functional Assessment of Chronic Illness Therapy translation methodology. Two hundred forty-one individuals with chronic low back pain completed the Thai version of UW-PRSE6 (T-UW-PRSE6), Thai Fear Avoidance Beliefs Questionnaire (T-FABQ), and Thai Medical Outcome Study Short-Form 36 (T-SF-36). A subset of 152 participants completed the T-UW-PRSE6 again after a 7-day interval. Cronbach's alpha and intraclass correlation coefficients were calculated to estimate internal consistency and test–retest reliability, respectively. The construct validity of the T-UW-PRSE6 was evaluated by computing Spearman correlation coefficients between the T-UW-PRSE6 score and the measures of the validity criterion variables. Results:. The T-UW-PRSE6 had good internal consistency (Cronbach's alpha = 0.85) and moderate test–retest reliability (intraclass correlation coefficient [2,1] = 0.72). The T-UW-PRSE6 was negatively correlated with the T-FABQ Work and Physical Activity subscales (rs = −0.34 and −0.34, respectively) and positively correlated with the General Health, Physical Functioning, Role Physical, Role Emotional, Social Functioning, Bodily Pain, Vitality, and Mental Health scales of the T-SF-36 (rs = 0.38, 0.42, 0.54, 0.51, 0.47, 0.54, 0.41, and 0.40, respectively). Conclusion:. The T-UW-PRSE6 demonstrated acceptable psychometric properties for assessing pain-related self-efficacy in individuals with chronic low back pain, making available a measure for facilitating future cross-cultural research on pain self-efficacy.

Abstract Background Resilience is an individual’s ability to recover or “bounce back” from stressful events. It is commonly identified as a protective factor against psychological dysfunctions in wide range of clinical conditions including chronic pain. Resilience is commonly assessed using the Connor Davidson Resilience Scale (CD-RISC). Translation and cross-cultural adaptation of the CD-RISC into Nepali will allow for a deeper understanding of resilience as an important domain in health in Nepal, and will allow for cross-cultural comparison with other cultures. Therefore, the aims of the study were to translate and culturally adapt 10- and 2-item versions of the CD-RISC into Nepali and evaluate their psychometric properties. Methods After translating the measures, we performed exploratory and confirmatory factor analyses of the 10-item version in two independent samples (ns = 131 and 134) of individuals with chronic pain. We then evaluated the internal consistency, test-retest stability, and construct validity of the 10- and 2-item measures in these samples. We also evaluated the internal consistency, and the construct and concurrent validity of the 2-item version in an additional sample of 140 individuals. Results The results supported a single factor model for the 10-item measure; this measure also evidenced good to excellent internal consistency and excellent test-retest stability. Construct validity was supported via moderate associations with pain catastrophizing. The internal consistency of 2-item version was marginal, although construct validity was supported via weak to moderate associations with measures of pain catastrophizing, depression and anxiety, and concurrent validity was supported by strong association with the 10-item CD-RISC scale. Conclusion The findings support the reliability and validity of the 10-item Nepali version of the CD-RISC, and use of the 2-item version in survey studies in individuals with chronic pain. The availability of these translated measures will allow for cross-cultural comparisons of resilience in samples of individuals with chronic pain.

Successful school re-entry is important for children following cancer treatment. However, this process is a challenge for teachers. Objectives: To identify (1) the difficulties and needs that teachers have in helping youth cancer survivors be successful in school, (2) the most effective resources that teachers are currently using for helping them, and (3) the ideal contents for a program that could help teachers in this area. Methods: Twenty-eight teachers participated in a Delphi study. Results: A lack of knowledge regarding how to best help and having to deal with the student’s problems were identified as difficulties. Specific training, psychological support, and advice from health professionals were the most commonly reported needs. Maintaining contact with the family and the students and providing personalized attention were viewed as the most useful resources. Finally, knowledge about the disease itself and how to facilitate successful school re-entry were identified as important program components. Conclusion: The findings provide important new information regarding the lack of both resources and support for teachers who seek to help youth cancer survivors. The findings can be used to inform the development of an intervention to help teachers become more successful in facilitating successful school re-entry.

The objective of this cross-sectional study was to evaluate the extent to which non-pain intensity factors influence the ratings of pain intensity on two commonly used measures: the Wong-Baker Faces pain rating scale (FACES) and the Verbal Rating Scale (VRS) in a sample of youths with physical disabilities and bothersome pain. Study participants came from a convenience sample of 115 youths (age: X¯ = 14.4 years; SD = 3.3), who participated in a survey on the impact of pain in young people with a physical disability. They were administered measures of pain intensity, pain catastrophizing, depressive symptoms, pain interference, and pain control beliefs. Zero-order correlation analyses were used to examine the associations among the pain intensity scores, while regression analyses were used to test the influence of the non-pain intensity factors on the pain intensity scores. Although pain intensity scores from all scales were significantly associated with one another, the correlations were moderate. Regression analyses showed that the FACES and VRS also reflect pain interference, in addition to pain intensity. The fact that the FACES and VRS ratings reflect more than pain intensity should be considered when selecting a pain measure. The results of this study also provide information to help interpret results after treatment.

Abstract. Introduction:. Randomized clinical trials (RCTs) are considered the gold standard when assessing the efficacy of interventions because randomization of treatment assignment minimizes bias in treatment effect estimates. However, if RCTs are not performed with methodological rigor, many opportunities for bias in treatment effect estimates remain. Clear and transparent reporting of RCTs is essential to allow the reader to consider the opportunities for bias when critically evaluating the results. To promote such transparent reporting, the Consolidated Standards of Reporting Trials (CONSORT) group has published a series of recommendations starting in 1996. However, a decade after the publication of the first CONSORT guidelines, systematic reviews of clinical trials in the pain field identified a number of common deficiencies in reporting (eg, failure to identify primary outcome measures and analyses, indicate clearly the numbers of participants who completed the trial and were included in the analyses, or report harms adequately). Objectives:. To provide a reporting checklist specific to pain clinical trials that can be used in conjunction with the CONSORT guidelines to optimize RCT reporting. Methods:. Qualitative review of a diverse set of published recommendations and systematic reviews that addressed the reporting of clinical trials, including those related to all therapeutic indications (eg, CONSORT) and those specific to pain clinical trials. Results:. A checklist designed to supplement the content covered in the CONSORT checklist with added details relating to challenges specific to pain trials or found to be poorly reported in recent pain trials was developed. Conclusion:. Authors and reviewers of analgesic RCTs should consult the CONSORT guidelines and this checklist to ensure that the issues most pertinent to pain RCTs are reported with transparency.

There is growing interest in interventions that enhance placebo responses in clinical practice, given the possibility that this would lead to better patient health and more effective therapy outcomes. Previous studies suggest that placebo effects can be maximized by optimizing patients’ outcome expectations. However, expectancy interventions are difficult to validate because of methodological challenges, such as reliable blinding of the clinician providing the intervention. Here we propose a novel approach using mobile apps that can provide highly standardized expectancy interventions in a blinded manner, while at the same time assessing data in everyday life using experience sampling methodology (e.g., symptom severity, expectations) and data from smartphone sensors. Methodological advantages include: 1) full standardization; 2) reliable blinding and randomization; 3) disentangling expectation effects from other factors associated with face-to-face interventions; 4) assessing short-term (days), long-term (months), and cumulative effects of expectancy interventions; and 5) investigating possible mechanisms of change. Randomization and expectancy interventions can be realized by the app (e.g., after the clinic/lab visit). As a result, studies can be blinded without the possibility for the clinician to influence study outcomes. Possible app-based expectancy interventions include, for example, verbal suggestions and imagery exercises, although a large number of possible interventions (e.g., hypnosis) could be evaluated using this innovative approach.

Abstract. Introduction:. Although evidence supports efficacy of treatments that enhance self-management of chronic pain, the efficacy of these treatments has been hypothesized to be influenced by patient readiness for self-management. The Pain Stage of Change Questionnaire (PSOCQ) is a reliable and valid measure of patient readiness to self-manage pain. However, there is not yet a Japanese version of the PSOCQ (PSOCQ-J), which limits our ability to evaluate the role of readiness for pain self-management in function and treatment response in Japanese patients with chronic pain. Objective:. Here, we sought to develop the PSOCQ-J and evaluate its psychometric properties. Methods:. We recruited 201 patients with chronic pain. The study participants were asked to complete the PSOCQ-J and other measures assessing pain severity, pain interference, catastrophizing, self-efficacy, and pain coping strategies. Results:. The results supported a 4-factor structure of the PSOCQ-J. We also found good to excellent internal consistencies and good test–retest reliabilities for the 4 scales. The Precontemplation scale had weak to moderate positive correlations with measures of pain-related dysfunction and maladaptive coping. The Action and Maintenance scales had weak to moderate positive correlations with measures of self-efficacy and adaptive coping. The Contemplation scale had weak positive correlations with measures of pain interference and both adaptive and maladaptive coping. Conclusions:. The PSOCQ-J demonstrated adequate psychometric properties in a sample of Japanese patients with chronic pain. This measure can be used to evaluate the role that readiness to self-manage pain may play in adjustment to chronic pain in Japanese pain populations.

Abstract. Introduction:. Pain intensity is the domain most often assessed in pain research. Although the Numerical Rating Scale is recommended for use in western countries, the utility and validity of this scale, relative to others, has not been established in non–western developing countries, such as Nepal. Objectives:. Here, we sought to (1) identify which of 4 commonly used pain scales is most preferred by Nepalese, (2) compare error rates, (3) determine whether preference and error rates are influenced by age or education level, and (4) evaluate construct validity of each scale using factor analysis. Methods:. Two hundred two adults with musculoskeletal pain from Nepal rated their worst and average pain intensity using all 4 scales and selected their most preferred scale. Results:. The results indicate that the Faces Pain Scale-Revised is the most preferred scale, followed by a Verbal Rating Scale. The Numerical Rating Scale and Visual Analogue Scale were both least preferred and had higher rates of incorrect responses, especially among the older participants. However, all the scales demonstrated adequate construct validity as measures of pain intensity among those participants who could accurately use all 4 scales. Conclusion:. The findings indicate that the Faces Pain Scale-Revised should be the first choice for assessing pain intensity in Nepalese adults. Research is needed to determine whether these findings replicate in other non–western and developing countries, to identify the pain intensity measure that would be the best choice for use in cross-cultural pain research.

Gray's Reinforcement Sensitivity Theory postulates two distinct neurophysiological systems that underlie thoughts, emotions, and behavior: the Behavioral Inhibition System (BIS) and the Behavioral Approach System (BAS). Preliminary research suggests that both systems may play relevant roles in the adjustment of individuals with chronic pain. However, there is a lack of research on the extent to which emotional regulation (i.e., cognitive reappraisal and expressive suppression) mediates the associations between BIS and BAS activation and emotional responses in individuals with chronic pain. The aim of this study was to test a model of the associations between the BIS and BAS, cognitive reappraisal and expressive suppression, and positive and negative affect in individuals with chronic musculoskeletal pain. In total, 516 participants were interviewed. Structural Equation Modeling was used to estimate the associations between variables. The empirical model showed a good fit to the data (χ2/df = 1.95; RMSEA = 0.04; GFI = 0.99; AGFI = 0.98; CFI = 0.99). The hypothesized model received partial support. The BIS was associated with cognitive reappraisal and expressive suppression; cognitive reappraisal was associated with negative and positive affect; expressive suppression was positively associated with affect; and the BAS was not associated with the emotional regulation strategies assessed. However, the BIS and BAS were both directly associated with negative and positive affect. The results suggest that individuals with chronic pain with higher BIS activation appear to use greater expressive suppression. Cognitive reappraisal strongly mediated the BIS-negative affect association. The results also suggest that BAS activation may have a weak or inconsistent association with emotional regulation approaches in individuals with chronic pain. These data provide new and relevant information on the potential role of the BIS and BAS as predictors of psychological functioning in individuals with chronic pain. They suggest that the BIS-BAS model of chronic pain may need to be modified to take into account the potential negative effects of BAS activation. The findings suggest that treatments for emotional regulation could potentially reduce the negative impact of chronic pain via BIS.

El dolor crónico es un importante problema de salud que afecta al funcionamiento diario de la persona con dolor, a su bienestar psicológico y a la calidad de vida. Con el fin de prestar cuidados sanitarios adecuados, a monitorear los cambios en el dolor y en el funcionamiento y en vista a la investigación transcultural, se necessitan instrumentos válidos y fiables de evaluación de la interferencia del dolor. El objetivo de este estudio es evaluar la fiabilidad y validez de la versión portuguesa de la Escala de Interferencia de lo Brief Pain Inventory (P-BPI). Doscientos catorze participantes con dolor crónico músculoesquelético respondieron al P-BPI, al 0-10 NRS, al Short Form-12 Health Status Questionnaire (SF-12) y al Hospital Anxiety and Depression Scale (HADS). El P-BPI mostró una excelente consistencia interna (alfa de Cronbach = 0.91) y correlaciones moderadas con las medidas de critério (rs ¿ 0.30). El análisis factorial confirmatorio apoyó la solución de un factor. Los resultados apoyan la fiabilidad y validez de construto de la Escala de Interferencia del P-BPI. Es necesario que futuras investigaciónes evaluen la responsividad de la escala a los cambios en la interferencia del dolor a lo largo del tiempo.

Abnormal synaptic maturation and connectivity are possible etiologies of autism. Previous studies showed significantly less alpha activity in autism than normal children. Therefore, we studied the effects of anodal tDCS on peak alpha frequency (PAF) related to autism treatment evaluation checklist (ATEC). Twenty male children with autism were randomly assigned in a crossover design to receive a single session of both active and sham tDCS stimulation (11 mA) over F3 (left dorsolateral prefrontal cortex). Pre- to postsession changes in a measure of cortical activity impacted by tDCS (PAF) and ATEC were compared between groups. We also examined the associations between pre- and postsession changes in the PAF and ATEC. The results show significant pre- to postsession improvements in two domains of ATEC (social and health/behavior domains) following active tDCS, relative to sham treatment. PAF also significantly increased at the stimulation site, and an increase in PAF was significantly associated with improvements in the two domains of ATEC impacted by tDCS. The findings suggest that a single session of anodal tDCS over the F3 may have clinical benefits in children with autism and that those benefits may be related to an increase in PAF.

The treatment of young people with chronic pain is a complex endeavor. Many of these youth do not obtain adequate relief from available interventions. Psychological neuromodulatory treatments have been shown to have potential benefit for adults with chronic pain. Here, we review and summarize the available information about the efficacy of three promising psychological neuromodulatory treatments—neurofeedback, meditation and hypnosis—when provided to young people with chronic pain. A total of 16 articles were identified and reviewed. The findings from these studies show that hypnotic treatments are effective in reducing pain intensity for a variety of pediatric chronic pain problems, although research suggests variability in outcomes as a function of the specific pain problem treated. There are too few studies evaluating the efficacy of neurofeedback or meditation training in young people with chronic pain to draw firm conclusions regarding their efficacy. However, preliminary data indicate that these treatments could potentially have positive effects on a variety of outcomes (e.g., pain intensity, frequency of pain episodes, physical and psychological function), at least in the short term. Clinical trials are needed to evaluate the effects of neurofeedback and meditation training, and research is needed to identify the moderators of treatment benefits as well as better understand the mechanisms underlying the efficacy of all three of these treatments. The findings from such research could enhance overall treatment efficacy by: (1) providing an empirical basis for better patient-treatment matching; and (2) identifying specific mechanisms that could be targeted with treatment.

Autoimmune diseases vary in the magnitude and diversity of autoantibody profiles, and these differences may be a consequence of different types of breaks in tolerance. Here, we compared the disparate autoimmune diseases autoimmune polyendocrinopathy–candidiasis–ecto-dermal dystrophy (APECED), systemic lupus erythematosus (SLE), and Sjogren’s syndrome (SjS) to gain insight into the etiology of breaks in tolerance triggering autoimmunity. APECED was chosen as a prototypical monogenic disease with organ-specific pathology while SjS and SLE represent polygenic autoimmunity with focal or systemic disease. Using protein microarrays for autoantibody profiling, we found that APECED patients develop a focused but highly reactive set of shared mostly anti-cytokine antibodies, while SLE patients develop broad and less expanded autoantibody repertoires against mostly intracellular autoantigens. SjS patients had few autoantibody specificities with the highest shared reactivities observed against Ro-52 and La. RNA-seq B-cell receptor analysis revealed that APECED samples have fewer, but highly expanded, clonotypes compared with SLE samples containing a diverse, but less clonally expanded, B-cell receptor repertoire. Based on these data, we propose a model whereby the presence of autoreactive T-cells in APECED allows T-dependent B-cell responses against autoantigens, while SLE is driven by breaks in peripheral B-cell tolerance and extrafollicular B-cell activation. These results highlight differences in the autoimmunity observed in several monogenic and polygenic disorders and may be generalizable to other autoimmune diseases.

Effective masking policies to prevent the spread of airborne infections depend on public access to masks with high filtration efficacy. However, poor face-fit is almost universally present in pleated multilayer disposable face masks, severely limiting both individual and community respiratory protection. We developed a set of simple mask modifications to mass-manufactured disposable masks, the most common type of mask used by the public, that dramatically improves both their personalized fit and performance in a low-cost and scalable manner. These modifications comprise a user-moldable full mask periphery wire, integrated earloop tension adjusters, and an inner flange to trap respiratory droplets. We demonstrate that these simple design changes improve quantitative fit factor by 320%, triples the level of protection against aerosolized droplets, and approaches the model efficacy of N95 respirators in preventing the community spread of COVID-19, for an estimated additional cost of less than 5 cents per mask with automated production.

Effective masking policies to prevent the spread of airborne infections depend on public access to masks with high filtration efficacy. However, poor face-fit is almost universally present in pleated multilayer disposable face masks, severely limiting both individual and community respiratory protection. We developed a set of simple mask modifications to mass-manufactured disposable masks, the most common type of mask used by the public, that dramatically improves both their personalized fit and performance in a low-cost and scalable manner. These modifications comprise a user-moldable full mask periphery wire, integrated earloop tension adjusters, and an inner flange to trap respiratory droplets. We demonstrate that these simple design changes improve quantitative fit factor by 320%, triples the level of protection against aerosolized droplets, and approaches the model efficacy of N95 respirators in preventing the community spread of COVID-19, for an estimated additional cost of less than 5 cents per mask with automated production.

Abstract Background We performed expression quantitative trait locus (eQTL) analysis in single classical (CL) and non-classical (NCL) monocytes from patients with systemic lupus erythematosus (SLE) to quantify the impact of well-established genetic risk alleles on transcription at single-cell resolution. Methods Single-cell gene expression was quantified using qPCR in purified monocyte subpopulations (CD14++CD16− CL and CD14dimCD16+ NCL) from SLE patients. Novel analysis methods were used to control for the within-person correlations observed, and eQTLs were compared between cell types and risk alleles. Results The SLE-risk alleles demonstrated significantly more eQTLs in NCLs as compared to CLs (p = 0.0004). There were 18 eQTLs exclusive to NCL cells, 5 eQTLs exclusive to CL cells, and only one shared eQTL, supporting large differences in the impact of the risk alleles between these monocyte subsets. The SPP1 and TNFAIP3 loci were associated with the greatest number of transcripts. Patterns of shared influence in which different SNPs impacted the same transcript also differed between monocyte subsets, with greater evidence for synergy in NCL cells. IRF1 expression demonstrated an on/off pattern, in which expression was zero in all of the monocytes studied from some individuals, and this pattern was associated with a number of SLE risk alleles. We observed corroborating evidence of this IRF1 expression pattern in public data sets. Conclusions We document multiple SLE-risk allele eQTLs in single monocytes which differ greatly between CL and NCL subsets. These data support the importance of the SPP1 and TNFAIP3 risk variants and the IRF1 transcript in SLE patient monocyte function.

To study the shape of objects using geometric morphometrics, landmarks are oftentimes collected digitally from a 3D scanned model. The expert may annotate landmarks using software that visualizes the 3D model on a flat screen, and interaction is achieved with a mouse and a keyboard. However, landmark annotation of a 3D model on a 2D display is a tedious process and potentially introduces error due to the perception and interaction limitations of the flat interface. In addition, digital landmark placement can be more time-consuming than direct annotation on the physical object using a tactile digitizer arm. Since virtual reality (VR) is designed to more closely resemble the real world, we present a VR prototype for annotating landmarks on 3D models. We study the impact of VR on annotation performance by comparing our VR prototype to Stratovan Checkpoint, a commonly used commercial desktop software. We use an experimental setup, where four operators placed six landmarks on six grey seal (Halichoerus grypus) skulls in six trials for both systems. This enables us to investigate multiple sources of measurement error. We analyse both for the configuration and for single landmarks. Our analysis shows that annotation in VR is a promising alternative to desktop annotation. We find that annotation precision is comparable between the two systems, with VR being significantly more precise for one of the landmarks. We do not find evidence that annotation in VR is faster than on the desktop, but it is accurate.

Background Pain is a universal experience and the most common reason for seeking healthcare. Inadequate pain management negatively impacts numerous aspects of patient health. Multidisciplinary treatment programmes, including psychosocial interventions, are more useful for pain management than purely biomedical treatment alone. Recently, researchers showed increasing interest in understanding the role of spirituality/religiosity and spiritual/religious practices on pain experience, with engagement in religious practices, such as prayer, showing to positively impact pain experience in religious individuals. This systematic review will seek to summarise and integrate the existing findings from randomised controlled trials assessing the effects of prayer and prayer-based interventions on pain experience.Methods The systematic review procedures and its report will follow the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. Electronic searches in nine databases (Web of Science Core Collection, MEDLINE, SCIELO Citation Index, PubMed, Cochrane Central Register of Controlled Clinical Trial, PsycINFO, Scopus, LILACS and Open-SIGLE) will be performed to identify randomised controlled trials of prayer-based interventions. Two independent researchers will assess studies for inclusion and extract data from each paper. Risk of bias assessment will be assessed independently by two reviewers based on the Consolidated Standards of Reporting Trials statement. Qualitative synthesis of the body of research will be conducted using a narrative summary synthesis method. Meta-analysis will be limited to studies reporting on the same primary outcome. Formal searches are planned to start in June 2021. The final report is anticipated to be completed by September 2021.Discussion Findings will be useful to (1) understand the condition of our knowledge in this field and (2) provide evidence for prayer effectiveness in reducing pain intensity and pain-related stress and increasing pain tolerance in adults experiencing acute or chronic pain.PROSPERO registration number CRD42020221733.

Objective Type I interferon (IFN) is important to systemic lupus erythematosus (SLE) pathogenesis, but it is not clear how chronic elevations in IFN alter immune function. We compared cytokine responses after whole blood stimulation with Toll‐like receptor (TLR) agonists in high‐ and low‐IFN SLE patient subgroups. Methods SLE patients and nonautoimmune controls were recruited, and SLE patients were categorized as either high or low IFN. Whole blood was dispensed into tubes coated with lipopolysaccharide (LPS), oligonucleotides with cytosine‐guanine repeats, Resiquimod, IFN‐α, and IFN‐α + LPS. Cytokine production in patient sera and after whole blood TLR stimulation was measured by multiplex assay, and type I IFN was assessed using a functional assay. Results Circulating plasmacytoid dendritic cell numbers were specifically reduced in high‐IFN SLE patients and not in low‐IFN SLE patients. In serum, we observed that the correlations between cytokines in serum differed to a much greater degree between the high‐ and low‐IFN groups (P < 0.0001) than the absolute cytokine levels differed between these same groups. In stimulated conditions, the high‐IFN patients had less cytokine production in response to TLR ligation than the low‐IFN SLE patients. LPS produced the most diverse response, and a number of interactions between type I IFN and LPS were observed. Conclusion We find striking differences in resting and stimulated cytokine patterns in high‐ vs. low‐IFN SLE patients, which supports the biological importance of these patient subsets. These data could inform personalized treatment approaches and the pathogenesis of SLE flare following infection.

Previously, we demonstrated in test and validation cohorts that type I IFN (T1IFN) activity can predict non-response to tumor necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA). In this study, we examine the biology of non-classical and classical monocytes from RA patients defined by their pre-biologic treatment T1IFN activity. We compared single cell gene expression in purified classical (CL, n = 342) and non-classical (NC, n = 359) monocytes. In our previous work, RA patients who had either high IFNβ/α activity (>1.3) or undetectable T1IFN were likely to have EULAR non-response to TNFi. In this study comparisons were made among patients grouped according to their pre-biologic treatment T1IFN activity as clinically relevant: “T1IFN undetectable (T1IFN ND) or IFNβ/α >1.3” (n = 9) and “T1IFN detectable but IFNβ/α ≤ 1.3” (n = 6). In addition, comparisons were made among patients grouped according to their T1IFN activity itself: “T1IFN ND,” “T1IFN detected and IFNβ/α ≤ 1.3,” and “IFNβ/α >1.3.” Major differences in gene expression were apparent in principal component and unsupervised cluster analyses. CL monocytes from the T1IFN ND or IFNβ/α >1.3 group were unlikely to express JAK1 and IFI27 (p < 0.0001 and p 0.0005, respectively). In NC monocytes from the same group, expression of IFNAR1, IRF1, TNFA, TLR4 (p ≤ 0.0001 for each) and others was enriched. Interestingly, JAK1 expression was absent in CL and NC monocytes from nine patients. This pattern most strongly associated with the IFNβ/α>1.3 group. Differences in gene expression in monocytes among the groups suggest differential IFN pathway activation in RA patients who are either likely to respond or to have no response to TNFi. Additional transcripts enriched in NC cells of those in the T1IFN ND and IFNβ/α >1.3 groups included MYD88, CD86, IRF1, and IL8. This work could suggest key pathways active in biologically defined groups of patients, and potential therapeutic strategies for those patients unlikely to respond to TNFi.

Semisynthetic glycosaminoglycan ethers (SAGEs) are short, sulfated hyaluronans which combine the natural properties of hyaluronan with chemical sulfation. In a murine model, SAGEs provide protection against radiation induced proctitis (RIP), a side effect of lower abdominal radiotherapy for cancer. The anti-inflammatory effects of SAGE have been studied in inflammatory diseases at mucosal barrier sites; however, few mechanisms have been uncovered necessitating high throughput methods. SAGEs were combined with silk-elastinlike polymers (SELPs) to enhance rectal accumulation in mice. After high radiation exposure to the lower abdominal area, mice were followed for 3 days or until they met humane endpoints, before evaluation of behavioral pain responses and histological assessment of rectal inflammation. RNA sequencing was conducted on tissues from the 3-day cohort to determine molecular mechanisms of SAGE–SELP. After 3 days, mice receiving the SAGE–SELP combination yielded significantly lowered pain responses and amelioration of radiation-induced rectal inflammation. Mice receiving the drug–polymer combination survived 60% longer than other irradiated mice, with a fraction exhibiting long term survival. Sequencing reveals varied regulation of toll like receptors, antioxidant activities, T-cell signaling, and pathways associated with pain. This investigation elucidates several molecular mechanisms of SAGEs and exhibits promising measures for prevention of RIP.

Geoscientific investigations for a proposed deep geologic repository at the Bruce Site, located on the eastern flank of the Michigan Basin, have identified unique and significant underpressured conditions. Along with the measurement of environmental tracer profiles (e.g., helium), this study aims to explore, through a series of numerical simulations, the nature of long-term phenomena responsible for the generation and preservation of formation underpressures. Three families of inverse numerical experiments for underpressure formation were examined by means of one-dimensional hydromechanically coupled models through the vertical hydrostratigraphic column: (i) uncertainty in glaciation scenarios; (ii) uncertainty in initial heads prior to glaciation; and (iii) uncertainty in the degree of hydraulic connectivity between the more permeable Guelph Formation at the Bruce Site and the applied glacial loading, for a total of 20 scenarios, assuming fully saturated conditions. Underpressured initial heads for the paleohydrogeologic simulations lead to lower calibrated vertical hydraulic conductivities. The robustness and resilience of the groundwater system to external perturbations are greater for the state where underpressured conditions predate the onset of glaciation and are better able to preserve the present day helium tracer profile in 260 Ma exhumation analyses.

We characterized the variation in the reconstructed ancestor of 118 HIV-1 envelope gene sequences arising from the methods used for (a) estimating and (b) rooting the phylogenetic tree, and (c) reconstructing the ancestor on that tree, from (d) the sequence format, and from (e) the number of input sequences. The method of rooting the tree was responsible for most of the sequence variation both among the reconstructed ancestral sequences and between the ancestral and observed sequences. Variation in predicted 3-D structural properties of the ancestors mirrored their sequence variation. The observed sequence consensus and ancestral sequences from center-rooted trees were most similar in all predicted attributes. Only for the predicted number of N-glycosylation sites was there a difference between MP and ML methods of reconstruction. Taxon sampling effects were observed only for outgrouprooted trees, not center-rooted, reflecting the occurrence of several divergent basal sequences. Thus, for sequences exhibiting a radial phylogenetic tree, as does HIV-1, most of the variation in the estimated ancestor arises from the method of rooting the phylogenetic tree. Those investigating the ancestors of genes exhibiting such a radial tree should pay particular attention to alternate rooting methods in order to obtain a representative sample of ancestors.

INTRODUCTION: Chronic pain is a significant health problem worldwide, with a prevalence in the general population of approximately 40%. Alexithymia -- the personality trait of having difficulties with emotional awareness and self-regulation -- has been reported to contribute to an increased risk of several chronic diseases and health conditions, and limited research indicates a potential role for alexithymia in the development and maintenance of chronic pain. However, no study has yet examined the associations between alexithymia and chronic pain in the general population. METHODS: We administered measures assessing alexithymia, pain, disability, anxiety, depression, and life satisfaction to 927 adults in Hisayama, Japan. We classified the participants into four groups (low-normal alexithymia, middle-normal alexithymia, high-normal alexithymia, and alexithymic) based on their responses to the alexithymia measure. We calculated the risk estimates for the criterion measures by a logistic regression analysis. RESULTS: Controlling for demographic variables, the odds ratio (OR) for having chronic pain was significantly higher in the high-normal (OR: 1.49, 95% CI: 1.07-2.09) and alexithymic groups (OR: 2.56, 95% CI: 1.47-4.45) compared to the low-normal group. Approximately 40% of the participants belonged to these two high-risk groups. In the subanalyses of the 439 participants with chronic pain, the levels of pain intensity, disability, depression, and anxiety were significantly increased and the degree of life satisfaction was decreased with elevating alexithymia categories. CONCLUSIONS: The findings demonstrate that, in the general population, higher levels of alexithymia are associated with a higher risk of having chronic pain. The early identification and treatment of alexithymia and negative affect may be beneficial in preventing chronic pain and reducing the clinical and economic burdens of chronic pain. Further research is needed to determine if this association is due to a causal effect of alexithymia on the prevalence and severity of chronic pain.

Comparative sequence analyses, including such fundamental bioinformatics techniques as similarity searching, sequence alignment and phylogenetic inference, have become a mainstay for researchers studying type 1 Human Immunodeficiency Virus (HIV-1) genome structure and evolution. Implicit in comparative analyses is an underlying model of evolution, and the chosen model can significantly affect the results. In general, evolutionary models describe the probabilities of replacing one amino acid character with another over a period of time. Most widely used evolutionary models for protein sequences have been derived from curated alignments of hundreds of proteins, usually based on mammalian genomes. It is unclear to what extent these empirical models are generalizable to a very different organism, such as HIV-1-the most extensively sequenced organism in existence. We developed a maximum likelihood model fitting procedure to a collection of HIV-1 alignments sampled from different viral genes, and inferred two empirical substitution models, suitable for describing between-and within-host evolution. Our procedure pools the information from multiple sequence alignments, and provided software implementation can be run efficiently in parallel on a computer cluster. We describe how the inferred substitution models can be used to generate scoring matrices suitable for alignment and similarity searches. Our models had a consistently superior fit relative to the best existing models and to parameter-rich data-driven models when benchmarked on independent HIV-1 alignments, demonstrating evolutionary biases in amino-acid substitution that are unique to HIV, and that are not captured by the existing models. The scoring matrices derived from the models showed a marked difference from common amino-acid scoring matrices. The use of an appropriate evolutionary model recovered a known viral transmission history, whereas a poorly chosen model introduced phylogenetic error. We argue that our model derivation procedure is immediately applicable to other organisms with extensive sequence data available, such as Hepatitis C and Influenza A viruses.

The ability of human immunodeficiency virus type 1 (HIV-1) to develop high levels of genetic diversity, and thereby acquire mutations to escape immune pressures, contributes to the difficulties in producing a vaccine. Possibly no single HIV-1 sequence can induce sufficiently broad immunity to protect against a wide variety of infectious strains, or block mutational escape pathways available to the virus after infection. The authors describe the generation of HIV-1 immunogens that minimizes the phylogenetic distance of viral strains throughout the known viral population (the center of tree [COT]) and then extend the COT immunogen by addition of a composite sequence that includes high-frequency variable sites preserved in their native contexts. The resulting COT(+) antigens compress the variation found in many independent HIV-1 isolates into lengths suitable for vaccine immunogens. It is possible to capture 62% of the variation found in the Nef protein and 82% of the variation in the Gag protein into immunogens of three gene lengths. The authors put forward immunogen designs that maximize representation of the diverse antigenic features present in a spectrum of HIV-1 strains. These immunogens should elicit immune responses against high-frequency viral strains as well as against most mutant forms of the virus.

We characterized the variation in the reconstructed ancestor of 118 HIV-1 envelope gene sequences arising from the methods used for (a) estimating and (b) rooting the phylogenetic tree, and (c) reconstructing the ancestor on that tree, from (d) the sequence format, and from (e) the number of input sequences. The method of rooting the tree was responsible for most of the sequence variation both among the reconstructed ancestral sequences and between the ancestral and observed sequences. Variation in predicted 3-D structural properties of the ancestors mirrored their sequence variation. The observed sequence consensus and ancestral sequences from center-rooted trees were most similar in all predicted attributes. Only for the predicted number of N-glycosylation sites was there a difference between MP and ML methods of reconstruction. Taxon sampling effects were observed only for outgroup-rooted trees, not center-rooted, reflecting the occurrence of several divergent basal sequences. Thus, for sequences exhibiting a radial phylogenetic tree, as does HIV-1, most of the variation in the estimated ancestor arises from the method of rooting the phylogenetic tree. Those investigating the ancestors of genes exhibiting such a radial tree should pay particular attention to alternate rooting methods in order to obtain a representative sample of ancestors.