Effects of Savoring Meditation on Positive Emotions and Pain-Related Brain Function: A Mechanistic Randomized Controlled Trial in People With Rheumatoid Arthritis.

Positive emotions are a promising target for intervention in chronic pain, but mixed findings across trials to date suggest that existing interventions may not be optimized to efficiently engage the target. The aim of the current pilot mechanistic randomized controlled trial was to test the effects of a positive emotion-enhancing intervention called Savoring Meditation on pain-related neural and behavioral targets in patients with rheumatoid arthritis. Participants included 44 patients with a physician-confirmed diagnosis of rheumatoid arthritis (n = 29 included in functional magnetic resonance imaging (fMRI) analyses), who were randomized to either Savoring Meditation or a Slow Breathing control. Both meditation interventions were brief (four 20-minute sessions). Self-report measures were collected pre-and post-intervention. An fMRI task was conducted at post-intervention, during which participants practiced the meditation technique on which they had been trained while exposed to non-painful and painful thermal stimuli. Savoring significantly reduced experimental pain intensity ratings relative to rest (P < .001). Savoring also increased cerebral blood flow in the ventromedial prefrontal cortex and increased connectivity between the ventromedial prefrontal cortex and caudate during noxious thermal stimulation relative to Slow Breathing (z = 2.3 voxelwise, false discovery rate cluster corrected P = .05). Participants in the Savoring condition also reported significantly increased positive emotions (ps < .05) and reduced anhedonic symptoms (P < .01) from pre- to post-intervention. These findings suggest that Savoring recruits reward-enhancing corticostriatal circuits in the face of pain, and future work should extend these findings to evaluate if these mechanisms of Savoring are associated with improved clinical pain outcomes in diverse patient populations. PERSPECTIVE: Savoring Meditation is a novel positive emotion-enhancing intervention designed for patients with chronic pain. The present findings provide preliminary evidence that Savoring Meditation is acutely analgesic, and engages neural and subjective emotional targets that are relevant to pain self-management. Future work should evaluate the clinical translation of these findings.

Effects of Savoring Meditation on Positive Emotions and Pain-Related Brain Function: A Mechanistic Randomized Controlled Trial in People With Rheumatoid Arthritis.

Positive emotions are a promising target for intervention in chronic pain, but mixed findings across trials to date suggest that existing interventions may not be optimized to efficiently engage the target. The aim of the current mechanistic randomized controlled trial was to test the effects of a single skill positive emotion-enhancing intervention called Savoring Meditation on pain-related neural and behavioral targets in patients with rheumatoid arthritis (RA). Participants included 44 patients with a physician-confirmed diagnosis of RA (n=29 included in fMRI analyses), who were randomized to either Savoring Meditation or a Slow Breathing control. Both meditation interventions were brief (four 20-minute sessions). Self-report measures were collected pre- and post-intervention. An fMRI task was conducted at post-intervention, during which participants practiced the meditation technique on which they had been trained while exposed to non-painful and painful thermal stimuli. Relative to Slow Breathing, Savoring significantly reduced experimental pain intensity ratings relative to rest (p<.001), increased cerebral blood flow in the ventromedial prefrontal cortex (vmPFC) and increased connectivity between the vmPFC and caudate during noxious thermal stimulation (z=2.3 voxelwise, FDR cluster corrected p=0.05). Participants in the Savoring condition also reported significantly increased positive emotions (ps<.05) and reduced anhedonic symptoms (p<.01) from pre- to post-intervention. These findings suggest that that Savoring recruits reward-enhancing corticostriatal circuits in the face of pain, and future work should extend these findings to evaluate if these mechanisms of Savoring are associated with improved clinical pain outcomes in diverse patient populations.

Randomized Controlled Trial of Omega-3 and -6 Fatty Acid Supplementation to Reduce Inflammatory Markers in Children with Autism Spectrum Disorder.

This double-blind, randomized controlled trial, tested fatty acid (FA) supplementation in children (ages 2- < 6 years) recently diagnosed with Autism Spectrum Disorder (ASD). Participants received daily oral FA supplement containing omega-3 and omega-6 FA, or a placebo for 90 days based on participant weight. Erythrocyte FAs and the cytokines, IL-1ß, IL-2, IFNγ, were measured in plasma obtained from serial blood collections. Treatment increased omega-3 and omega-6 FA levels (1.40 mol% for EPA and 1.62 mol% for DHA) and reduced IL-2 levels compared to placebo (- 0.17 pg/mL, 95% CI - 0.31, - 0.02, d = - 0.62). Omega 3-6 treatment was tolerable and adherence was greater than 70%. Future research will assess the effects of Omega 3-6 treatment on ASD symptoms. Registered on 06/08/2018 with ClinicalTrials.gov: NCT03550209.

Evaluation of the Efficacy of a Smoking Cessation Intervention for Cervical Cancer Survivors and Women With High-Grade Cervical Dysplasia: Protocol for a Randomized Controlled Trial.

BACKGROUND: The prevalence of smoking among cervical cancer survivors is strikingly high, yet no smoking cessation interventions to date have specifically targeted this population. This paper describes the study design, methods, and data analysis plans for a randomized clinical trial designed to evaluate the efficacy of a theoretically and empirically based Motivation And Problem Solving (MAPS) approach for promoting and facilitating smoking cessation among cervical cancer survivors. MAPS is a comprehensive, dynamic, and holistic intervention that incorporates empirically supported cognitive behavioral and social cognitive theory-based treatment strategies within an overarching motivational framework. MAPS is designed to be appropriate for all smokers regardless of their motivation to change and views motivation as dynamically fluctuating from moment to moment throughout the behavior change process. OBJECTIVE: This 2-group randomized controlled trial compares the efficacy of standard treatment to MAPS in facilitating smoking cessation among women with a history of high-grade cervical dysplasia or cervical cancer. METHODS: Participants (N=202) are current smokers with a history of high-grade cervical dysplasia or cervical cancer recruited nationally and randomly assigned to one of two treatment conditions: (1) standard treatment (ST) or (2) MAPS. ST consists of repeated letters referring participants to their state's tobacco cessation quitline, standard self-help materials, and free nicotine replacement therapy when ready to quit. MAPS has all ST components along with 6 proactive telephone counseling sessions delivered over 12 months. The primary outcome is abstinence from tobacco at 18 months. Secondary outcomes include abstinence over time across all assessment points, abstinence at other individual assessment time points, quit attempts, cigarettes per day, and use of state quitlines. Hypothesized treatment mechanisms and cost-effectiveness will also be evaluated. RESULTS: This study was approved by the institutional review boards at the University of Texas MD Anderson Cancer Center, the University of Oklahoma Health Sciences Center, and Moffitt Cancer Center. Participant enrollment concluded at Moffitt Cancer Center in January 2020, and follow-up data collection was completed in July 2021. Data analysis is ongoing. CONCLUSIONS: This study will yield crucial information regarding the efficacy and cost-effectiveness of a MAPS approach for smoking cessation tailored to the specific needs of women with a history of high-grade cervical dysplasia or cervical cancer. Findings indicating that MAPS has substantially greater efficacy than existing evidence-based tobacco cessation treatments would have tremendous public health significance. TRIAL REGISTRATION: ClinicalTrials.gov NCT02157610; https://clinicaltrials.gov/ct2/show/NCT02157610. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/34502.

Time restricted eating as a weight loss intervention in adults with obesity.

OBJECTIVES: Time-restricted eating (TRE) is a weight management approach in which food is consumed only within a specific period each day. The simplicity of this approach is appealing, but its efficacy is not known. The aim of this pilot cohort study was to assess adherence to TRE and its effects on weight and lipid profile. METHODS: Fifty participants with obesity attempted to follow TRE for 12 weeks. Surveys were conducted weekly over the phone to assess treatment adherence and ratings; and at 6 and 12 weeks, participants attended the clinic to be weighed, have their blood pressure taken and provide a blood sample for lipid profile. Treatment results were compared with data from previous comparable cohorts using other weight management methods. RESULTS: Mean age of the participants was 50 (SD = 12.0), mean weight 97kg (SD = 17.1), mean BMI = 35 (SD = 4.0) and most were female (74%). At weeks 6 and 12, 64% and 58% of participants continued to practice TRE on at least five days/week. Using the 'last observation carried forward' imputation, mean (SD) weight loss was 2.0 (1.7) kg and 2.6 (2.6) kg at 6 and 12 weeks. Among participants who provided follow-up data, those who adhered to the intervention for at least five days/week recorded greater weight loss than those with lower adherence (week 6: 2.5 (1.7) vs 1.0 (1.3), p = 0.003; week 12: 3.5 (2.7) vs 1.3 (2.0), p = 0.001). A total of 26% of the sample lost at least 5% of their body weight at 12 weeks. The intervention had no effect on blood pressure or lipid profile. CONCLUSIONS: TRE results were modest, but at least on par with those achieved with more complex interventions, and weight loss did not decline at 12 weeks. A formal trial of the intervention is warranted.

Creating Virtual Integration and Improved Oncology Care Quality Through a Co-Management Services Agreement.

PURPOSE: Implementation of a co-management services agreement (Co-MSA) creates agreed-upon cancer care delivery quality metrics, a forum for discussion of service line oversight, and virtually integrated care without institutional employment of oncologists. The goal of this project was to demonstrate that a Co-MSA improved predefined quality metrics and provided enhanced communications between a health system's oncology service line and a group of independent oncologists. METHODS: Iterative planning discussions were scheduled biweekly over an 18-month period. Contractual, quality, and clinical data with benchmarking were considered in the creation of the Co-MSA. Review of the first year's implementation occurred through examination of the metric achievements and qualitative themes that arose through committee meetings, clinical implementation processes, and cross-organizational discussions. RESULTS: Metrics designed for the Co-MSA included improved adherence to the breast cancer, colon cancer, and non-small-cell lung cancer level I pathways; improvement of the medical oncology physician communication component of the hospital system's Hospital Consumer Assessment of Healthcare Providers and Systems survey scores; and increased delivery of survivorship care plans to appropriate patients. Nonquantifiable themes from the first year of implementation included the need for technology to collect data, both organizations needing a wider understanding of quality improvement techniques, and a need for greater executive leadership involvement. CONCLUSION: In its first year, the Co-MSA resulted in improvement of the delivery of survivorship care plans and adherence to value pathways powered by the National Comprehensive Cancer Network. Improvement of Hospital Consumer Assessment of Healthcare Providers and Systems scores did not occur.

Reducing Current Spread by Use of a Novel Pulse Shape for Electrical Stimulation of the Auditory Nerve.

Improving the electrode-neuron interface to reduce current spread between individual electrodes has been identified as one of the main objectives in the search for future improvements in cochlear-implant performance. Here, we address this problem by presenting a novel stimulation strategy that takes account of the biophysical properties of the auditory neurons (spiral ganglion neurons, SGNs) stimulated in electrical hearing. This new strategy employs a ramped pulse shape, where the maximum amplitude is achieved through a linear slope in the injected current. We present the theoretical framework that supports this new strategy and that suggests it will improve the modulation of SGNs' activity by exploiting their sensitivity to the rising slope of current pulses. The theoretical consequence of this sensitivity to the slope is a reduction in the spread of excitation within the cochlea and, consequently, an increase in the neural dynamic range. To explore the impact of the novel stimulation method on neural activity, we performed in vitro recordings of SGNs in culture. We show that the stimulus efficacy required to evoke action potentials in SGNs falls as the stimulus slope decreases. This work lays the foundation for a novel, and more biomimetic, stimulation strategy with considerable potential for implementation in cochlear-implant technology.

Discovery of bile salt hydrolase inhibitors using an efficient high-throughput screening system.

The global trend of restricting the use of antibiotic growth promoters (AGP) in animal production necessitates the need to develop valid alternatives to maintain productivity and sustainability of food animals. Previous studies suggest inhibition of bile salt hydrolase (BSH), an intestinal bacteria-produced enzyme that exerts negative impact on host fat digestion and utilization, is a promising approach to promote animal growth performance. To achieve the long term goal of developing novel alternatives to AGPs, in this study, a rapid and convenient high-throughput screening (HTS) system was developed and successfully used for identification of BSH inhibitors. With the aid of a high-purity BSH from a chicken Lactobacillus salivarius strain, we optimized various screening conditions (e.g. BSH concentration, reaction buffer pH, incubation temperature and length, substrate type and concentration) and establish a precipitation-based screening approach to identify BSH inhibitors using 96-well or 384-well microplates. A pilot HTS was performed using a small compound library comprised of 2,240 biologically active and structurally diverse compounds. Among the 107 hits, several promising and potent BSH inhibitors (e.g. riboflavin and phenethyl caffeate) were selected and validated by standard BSH activity assay. Interestingly, the HTS also identified a panel of antibiotics as BSH inhibitor; in particular, various tetracycline antibiotics and roxarsone, the widely used AGP, have been demonstrated to display potent inhibitory effect on BSH. Together, this study developed an efficient HTS system and identified several BSH inhibitors with potential as alternatives to AGP. In addition, the findings from this study also suggest a new mode of action of AGP for promoting animal growth.