Early evidence of efficacy for orally administered SPM-enriched marine lipid fraction on quality of life and pain in a sample of adults with chronic pain.

BACKGROUND: Marine lipids contain omega-3 fatty acids that can be metabolized into anti-inflammatory and pro-resolving mediators-namely 17-HDHA and 18-HEPE-which can serve as modulators of the pain experience. The purpose of this study was to determine the impact of 4 weeks of oral supplementation with a fractionated marine lipid concentration, standardized to 17-HDHA and 18-HEPE, on health-related quality of life and inflammation in adults with chronic pain. METHODS: This study was a prospective, non-randomized, open-label clinical trial. Forty-four adults with ≥ moderate pain intensity for at least 3 months were recruited. The primary outcome was change in health-related quality of life (QOL) using the Patient Reported Outcomes Measurement Information System-43 Profile (PROMIS-43) and the American Chronic Pain Association (ACPA) QOL scale. Exploratory outcomes assessed safety and tolerability, changes in anxiety and depression, levels of pain intensity and interference, patient satisfaction, and impression of change. Changes in blood biomarkers of inflammation (hs-CRP and ESR) were also explored. RESULTS: Outcome measures were collected at Baseline, Week 2, and Week 4 (primary endpoint). At Week 4, PROMIS-43 QOL subdomains changed with significance from baseline (p < 0.05), with borderline changes in the ACPA Quality of Life scale (p < 0.052). Exploratory analyses revealed significant changes (p < 0.05) in all measures of pain intensity, pain interference, depression, and anxiety. There were no statistically significant changes in either hs-CRP or ESR, which stayed within normal limits. CONCLUSION: We conclude that oral supplementation with a fractionated marine lipid concentration standardized to 17-HDHA and 18-HEPE may improve quality of life, reduce pain intensity and interference, and improve mood within 4 weeks in adults with chronic pain. The consistency and magnitude of these results support the need for placebo-controlled clinical trials of marine lipid concentrations standardized to 17-HDHA and 18-HEPE. Trial registration ClinicalTrials.gov: Influence of an Omega-3 SPM Supplement on Quality of Life, NCT02683850. Registered 17 February 2016-retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02683850 .

Effect of the Anti-Inflammatory Diet in People with Diabetes and Pre-Diabetes: A Randomized Controlled Feeding Study.

INTRODUCTION: Inflammation underlies a variety of chronic medical conditions, including diabetes. The anti-inflammatory diet, one that excludes foods that may stimulate inflammation and includes foods that reduce inflammation, may improve inflammatory biomarkers in people with diabetes and pre-diabetes. STUDY DESIGN: Thirty participants with diabetes or pre-diabetes were randomized (2:1) in a controlled feeding study that compared the anti-inflammatory diet (n=20) to a control diet (n=10) based on the American Diabetes Association recommendations. Diets were matched for protein, carbohydrate, fat, and fiber content as closely as possible. Participants were fed an isocaloric diet for 2 weeks, followed by continued ad libitum feeding in their dietary group assignment for an additional 4 weeks. All meals were prepared by the study team. OUTCOMES: Primary outcomes included inflammatory markers, including cytokines and hsCRP. Secondary outcomes included body weight and biomarkers for cardiovascular disease and diabetes. RESULTS: Both diets resulted in trends in reduced markers of inflammation, especially with weight loss. In addition, glucose, lipids, and triglycerides all trended downward, also non-significantly and equally in both groups. CONCLUSION: Dietary change can improve inflammation as well as other cardiometabolic risk factors. In this study, the anti-inflammatory diet did not affect markers of inflammation more than the control diet.

Design of a Multidisciplinary Training Program in Complementary and Integrative Health Clinical Research: Building Research Across Interdisciplinary Gaps.

Despite wide use by the public, limited evidence is available for many complementary and integrative health (CIH) practices. Thus, clinical researchers knowledgeable about CIH disciplines are necessary to study the efficacy and effectiveness of CIH practices to benefit the public health. To partially address the need for clinical researchers versed in CIH, the authors of this study report the design of an interprofessional clinical research training program focused on CIH, the Building Research across Interdisciplinary Gaps (BRIDG) program, supported by a 5-year T90/R90 grant from the National Center for Complementary and Integrative Health. The T90-supported arm of the program trains doctoral-level CIH providers in clinical research at the research-intensive University of Washington. The R90-supported arm of the program trains researchers with conventional backgrounds in the practices of CIH at the clinic-intensive National University of Natural Medicine. The "Translational Science Spectrum" provides a common conceptual framework for both programs. Specific program elements include: individualized didactic training in clinical research and CIH disciplines; placement with clinical research mentors; placement with clinical mentors in CIH disciplines; shared and independent research project development; and interdisciplinary experiences through seminars and retreats. Program evaluation includes annual completion of the Clinical Research Appraisal Inventory (CRAI), which queries confidence in research skills and methods and periodic evaluation of training elements using the Supplemental Kellogg Logic-World Health Organization model, which emphasizes relevance, adequacy, efficiency, effectiveness, process, impact, equity, and sustainability. The BRIDG program exemplifies a new standard in interprofessional clinical research training, made possible through strong collaboration between disparate research- and clinically intensive institutions.

Effects of a topical botanically-enriched salve on cutaneous oxygenation.

OBJECTIVE: There is a medical need to evaluate new treatments that may improve wound healing. This study aimed to determine if Original Healing Salve (OHS, Puremedy, Inc.) a topical, botanically-enriched salve (BES), changes distal leg tissue oxygenation in people with type 2 diabetes. METHOD: A randomised, controlled, crossover, double-blinded clinical trial comparing changes in cutaneous oxygen delivery (mean TcPO2) on multiple sites of the lower extremity following application of a botanically-enriched topical salve, as compared with application of the salve's base in patients with type 2 diabetes. Subjects were recruited from the general population as a convenience sample. RESULTS: A total of 16 participants were recruited. Analysis of the primary outcome demonstrated no statistically significant difference in TcPO2 at 30 minutes postapplication when comparing the BES to the base salve (BS) on the leg (-0.39±8.54mmHg; p=0.86). Analyses of secondary outcomes at 30 minutes postapplication indicated that mean TcPO2 was significantly higher than preapplication levels among subjects receiving both the BES (3.70±6.62mmHg; p=0.04) and BS on the leg (4.08±5.21mmHg; p=0.007). On the foot, mean TcPO2 at 30 minutes postapplication was higher in the BES compared with the BS, this difference was not significant (0.98±8.59mmHg; p=0.66). Mean TcPO2 was higher than preapplication levels among subjects receiving both the BES (1.21±7.70mmHg; p=0.54) and BS on the foot (2.19±7.27mmHg; p=0.25). These differences were non-significant. CONCLUSION: These findings support consideration of topical treatments containing botanical ingredients to increase cutaneous oxygen delivery in the lower extremity in patients with type 2 diabetes.

Direct moxibustion to treat spleen qi and yang deficiency fatigue: a pilot study.

Limited research suggests that indirect moxibustion may be beneficial for treating fatigue, but no studies to evaluate direct moxibustion have been conducted in the United States. Thus, we explored the usefulness of four outcome measures for evaluating the effectiveness of direct moxibustion for patients with spleen qi and yang deficiency fatigue (SQYDF). Eleven female volunteers, ages 25-60 years, were enrolled. Three to five rice grains in thread-sized moxa cones were burned on 11 acupuncture points once per week for 8 weeks. Eight participants completed the study. The most common adverse events (AEs) were temporary worsening of fatigue, lightheadedness, and headache. Symptomatic improvement was seen on the SF-36 energy/fatigue scale (p=0.003), SF-36 social function scale (p=0.008) and Flinders fatigue scale (p=0.014). The skin conductance at acupoints showed no consistent diagnostic baseline meridian patterns. Heart rate variability data showed an improved low frequency/high frequency (LF/HF) ratio in three of four participants. Direct moxibustion is safe in patients with SQYDF. The Flinders Fatigue Scale (FFS) and the SF-36 are useful outcome measures for evaluating the effects of direct moxibustion, and the heart rate variability (HRV) may be, but the skin conductance did not correlate with SQYDF diagnosis or with symptomatic improvement.

Relation of frontal eye field activity to saccade initiation during a countermanding task.

The countermanding (or stop signal) task probes the control of the initiation of a movement by measuring subjects' ability to withhold a movement in various degrees of preparation in response to an infrequent stop signal. Previous research found that saccades are initiated when the activity of movement-related neurons reaches a threshold, and saccades are withheld if the growth of activity is interrupted. To extend and evaluate this relationship of frontal eye field (FEF) activity to saccade initiation, two new analyses were performed. First, we fit a neurometric function that describes the proportion of trials with a stop signal in which neural activity exceeded a criterion discharge rate as a function of stop signal delay, to the inhibition function that describes the probability of producing a saccade as a function of stop signal delay. The activity of movement-related but not visual neurons provided the best correspondence between neurometric and inhibition functions. Second, we determined the criterion discharge rate that optimally discriminated between the distributions of discharge rates measured on trials when saccades were produced or withheld. Differential activity of movement-related but not visual neurons could distinguish whether a saccade occurred. The threshold discharge rates determined for individual neurons through these two methods agreed. To investigate how reliably movement-related activity predicted movement initiation; the analyses were carried out with samples of activity from increasing numbers of trials from the same or from different neurons. The reliability of both measures of initiation threshold improved with number of trials and neurons to an asymptote of between 10 and 20 movement-related neurons. Combining the activity of visual neurons did not improve the reliability of predicting saccade initiation. These results demonstrate how the activity of a population of movement-related but not visual neurons in the FEF contributes to the control of saccade initiation. The results also validate these analytical procedures for identifying signals that control saccade initiation in other brain structures.

Influence of history on saccade countermanding performance in humans and macaque monkeys.

The stop-signal or countermanding task probes the ability to control action by requiring subjects to withhold a planned movement in response to an infrequent stop signal which they do with variable success depending on the delay of the stop signal. We investigated whether performance of humans and macaque monkeys in a saccade countermanding task was influenced by stimulus and performance history. In spite of idiosyncrasies across subjects several trends were evident in both humans and monkeys. Response time decreased after successive trials with no stop signal. Response time increased after successive trials with a stop signal. However, post-error slowing was not observed. Increased response time was observed mainly or only after cancelled (signal inhibit) trials and not after noncancelled (signal respond) trials. These global trends were based on rapid adjustments of response time in response to momentary fluctuations in the fraction of stop signal trials. The effects of trial sequence on the probability of responding were weaker and more idiosyncratic across subjects when stop signal fraction was fixed. However, both response time and probability of responding were influenced strongly by variations in the fraction of stop signal trials. These results indicate that the race model of countermanding performance requires extension to account for these sequential dependencies and provide a basis for physiological studies of executive control of countermanding saccade performance.

Recovery of saccadic dysmetria following localized lesions in monkey superior colliculus.

Damage to the monkey superior colliculus (SC) produces deficits in the generation of saccadic eye movements. Recovery of the accuracy of saccades is rapid, but saccadic latency and peak velocity recover slowly or not at all. In the present experiments we revisited the issue of recovery of function following localized lesions of the SC using three methodological advances: implantation of wire recording electrodes into the SC for the duration of the experiment to ensure that we were recording from the same site on the SC map on successive days; quantification of changes in saccadic accuracy, latency, and velocity using a standard grid of target points in the visual field contralateral to the SC lesion; measurement of movement field size to quantitatively determine any changes following the lesion. We confirmed a decrease in saccadic accuracy following electrolytic lesions of the SC, and we found that this dysmetria recovered within about 4 days. Saccadic latency increased for saccades to the lesion area and this deficit persisted. Peak saccadic velocity decreased immediately after the lesion and decreased further during the 10 days to 2 weeks of the experiment. We found no indication of an expansion of the movement fields of neurons adjacent to the lesion area. This lack of reorganization suggests that movement field changes within the SC cannot mediate the recovery in accuracy of the saccade. The persistence of the latency and velocity deficits despite the recovery of amplitude deficits indicates that saccadic latency and peak velocity are dependent upon the SC whereas saccadic amplitude is not.

Controlled movement processing: superior colliculus activity associated with countermanded saccades.

We investigated whether the monkey superior colliculus (SC), an important midbrain structure for the regulation of saccadic eye movements, contains neurons with activity patterns sufficient to control both the cancellation and the production of saccades. We used a countermanding task to manipulate the probability that, after the presentation of a stop signal, the monkeys canceled a saccade that was planned in response to an eccentric visual stimulus. By modeling each animal's behavioral responses, with a race between GO and STOP processes leading up to either saccade initiation or cancellation, we estimated that saccade cancellation took on average 110 msec. Neurons recorded in the superior colliculus intermediate layers during this task exhibited the discharge properties expected from neurons closely involved in behavioral control. Both saccade- and fixation-related discharged differently when saccades were counter-manded instead of executed, and the time at which they changed their activity preceded the behavioral estimate of saccade cancellation obtained from the same trials by 10 and 13 msec, respectively. Furthermore, these intervals exceed the minimal amount of time needed for SC activity to influence eye movements. The additional observation that saccade-related neurons discharged significantly less when saccades were countermanded instead of executed suggests that saccades are triggered when these neurons reach a critical activation level. Altogether, these findings provide solid evidence that the superior colliculus contains the necessary neural signals to be directly involved in the decision process that regulates whether a saccade is to be produced.