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TREK-1 is a mechanosensitive channel activated by polyunsaturated fatty acids (PUFAs). Its activation is supposed to be linked to changes in membrane tension following PUFAs insertion. Here, we compared the effect of 11 fatty acids and ML402 on TREK-1 channel activation using the whole cell and the inside-out configurations of the patch-clamp technique. Firstly, TREK-1 activation by PUFAs is variable and related to the variable constitutive activity of TREK-1. We observed no correlation between TREK-1 activation and acyl chain length or number of double bonds suggesting that the bilayer-couple hypothesis cannot explain by itself the activation of TREK-1 by PUFAs. The membrane fluidity measurement is not modified by PUFAs at 10 µM. The spectral shift analysis in TREK-1-enriched microsomes indicates a K D,TREK1 at 44 µM of C22:6 n-3. PUFAs display the same activation and reversible kinetics than the direct activator ML402 and activate TREK-1 in both whole-cell and inside-out configurations of patch-clamp suggesting that the binding site of PUFAs is accessible from both sides of the membrane, as for ML402. Finally, we proposed a two steps mechanism: first, insertion into the membrane, with no fluidity or curvature modifications at 10 µM, and then interaction with TREK-1 channel to open it., (© 2024. The Author(s).)

The TREK-1 channel belongs to the TREK subfamily of two-pore domains channels that are activated by stretch and polyunsaturated fatty acids and inactivated by Protein Kinase A phosphorylation. The activation of this potassium channel must induce a hyperpolarization of the resting membrane potential and a shortening of the action potential duration in neurons and cardiac cells, two phenomena being beneficial for these tissues in pathological situations like ischemia-reperfusion. Surprisingly, the physiological role of TREK-1 in cardiac function has never been thoroughly investigated, very likely because of the lack of a specific inhibitor. However, possible roles have been unraveled in pathological situations such as atrial fibrillation worsened by heart failure, right ventricular outflow tract tachycardia or pulmonary arterial hypertension. The inhomogeneous distribution of TREK-1 channel within the heart reinforces the idea that this stretch-activated potassium channel might play a role in cardiac areas where the mechanical constraints are important and need a particular protection afforded by TREK-1. Consequently, the main purpose of this mini review is to discuss the possible role played by TREK -1 in physiological and pathophysiological conditions and its potential role in mechano-electrical feedback. Improved understanding of the role of TREK-1 in the heart may help the development of promising treatments for challenging cardiac diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bechard, Bride, Le Guennec, Brette and Demion.)

The use of zebrafish to explore cardiac physiology has been widely adopted within the scientific community. Whether this animal model can be used to determine drug cardiac toxicity via electrocardiogram (ECG) analysis is still an ongoing question. Several reports indicate that the recording configuration severely affects the ECG waveforms and its derived-parameters, emphasizing the need for improved characterization. To address this problem, we recorded ECGs from adult zebrafish hearts in three different configurations (unexposed heart, exposed heart, and extracted heart) to identify the most reliable method to explore ECG recordings at baseline and in response to commonly used clinical therapies. We found that the exposed heart configuration provided the most reliable and reproducible ECG recordings of waveforms and intervals. We were unable to determine T wave morphology in unexposed hearts. In extracted hearts, ECG intervals were lengthened and P waves were unstable. However, in the exposed heart configuration, we were able to reliably record ECGs and subsequently establish the QT-RR relationship (Holzgrefe correction) in response to changes in heart rate.

Background: Excess gestational weight gain (EGWG) is associated with multiple pregnancy complications and health risks for birthing people and their infants. Likewise, postpartum weight retention (PPWR), or not losing all pregnancy weight, has long-term health consequences. EGWG among people who enter pregnancy with overweight or obesity have worse obstetric outcomes and increased PPWR compared to women who gain within Institute of Medicine guidelines., Methods: This study protocol describes the details of a blinded, randomized clinical trial of GROWell: Goals for Reaching Optimal Wellness, a mHealth tool designed to improve diet quality among people who enter pregnancy with overweight or obese BMIs to help them achieve appropriate GWG and safe postpartum pregnancy weight loss. Individuals with overweight and obesity will be randomly assigned to an attention control or intervention arm. The intervention group will receive personalized, goal-oriented text messages regarding dietary choices, while the attention control group will receive text messages about healthy pregnancy, labor, delivery, and early infancy. Both groups will complete online surveys at baseline, follow up, 3 and 6 months postpartum., Results and Discussion: Currently, 162 subjects have been enrolled. Outcomes associated with GWG and pregnancy are expected in late 2023, while outcomes on postpartum weight retention GROWell adherence are expected in late 2024. The results of this trial will support the use of an evidence-based mHealth tool to be integrated into clinical practice to reduce EGWG and PPWR among pregnant people with overweight and obese BMIs, a resource that is currently lacking., Trial Registration: ClinicalTrials.gov identifier: NCT04449432. Registered on June 26, 2020., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Exercise is a foundational treatment for nonalcoholic fatty liver disease (NAFLD); however, the majority of patients are unable to initiate and maintain effective exercise habits and remain at increased risk for progressive liver disease. Barriers and limitations to exercise in patients with NAFLD have not been fully identified. We performed a single survey of 94 patients with biopsy-proven NAFLD to understand baseline physical activity and sedentary behavior, self-perceived fitness, limitations to exercise, potential solutions to increase physical activity behavior, and perception of exercise as a foundational treatment for NAFLD. For exploratory analyses, we evaluated differences in responses to the survey by grouping severity of hepatic fibrosis as follows: nonalcoholic fatty liver (NAFL); early stage (nonalcoholic steatohepatitis [NASH] F0, NASH F1, NASH F2); and late stage (NASH F3, NASH F4). Zero weekly total physical activity was reported by 29% of patients with NAFLD. Late-stage NASH had significantly lower vigorous (P = 0.024), walking (P = 0.029), total weekly activity (P = 0.043), and current fitness level (P = 0.022) compared to early stage NASH. Overall, 72% of patients with NAFLD reported limitations to exercise, with the greatest proportion citing lack of energy (62%), fatigue (61%), prior/current Injury (50%), and shortness of breath (49%). A preference for personal training to increase their physical activity was indicated by 66% of patients with NAFLD, and 63% preferred exercise over medication to treat NAFLD. Conclusion: The majority of patients with NAFLD have limitations to exercise but prefer exercise as a treatment option for NAFLD in the form of personal training. Patients with NAFLD may have unique physiologic limitations to exercise that worsen with fibrosis severity. Exercise interventions or services that are personalized and scalable may improve sustainability of exercise habits in the long term., (© 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Background & Purpose: The COVID-19 pandemic has negatively impacted mental health in the general population. In this trial, our objective was to assess whether a 6-week expressive writing intervention improves resilience in a sample from the general population in the midst of the COVID-19 pandemic., Materials & Methods: This 6-week trial was conducted online. Eligible participants (n=63) were a sample of adults who self-identified as having been significantly affected by the COVID-19 pandemic., Primary Outcome: Connor-Davidson Resilience Scale (CD-RISC)., Secondary Outcomes: Perceived Stress Scale - 10-Item (PSS-10); Center for Epidemiologic Studies Depression Scale - Revised (CESD-R); Post-Traumatic Growth Inventory (PTGI)., Results: Resilience measures (CD-RISC) increased from baseline (66.6 ± 14.9) to immediately post-intervention (73.0 ± 12.4; p=0.014; Cohen's d =0.31), and at a 1- month follow-up (72.9 ± 13.6; p=0.024; Cohen's d =0.28). Across the same timepoints, perceived stress scores (PSS-10) decreased from baseline (21.8 ± 6.6) to immediately post-intervention (18.3 ± 7.0; p=0.008; Cohen's d =0.41), and at the 1- month follow-up to (16.8 ± 6.7; p=0.0002; Cohen's d =0.56). Depression symptoms (CESD-R) decreased from baseline (23.3 ± 15.3) at 6 weeks (17.8 ± 15.4; p=0.058; Cohen's d =0.22), and 10 weeks (15.5 ± 12.7; p=0.004; Cohen's d =0.38). Posttraumatic growth (PTGI) increased from baseline (41.7 ± 23.4) at 6 weeks (55.8 ± 26.4; p=0.004; Cohen's d =0.44), and at the 1-month follow-up (55.9 ± 29.3; p=0.008; Cohen's d =0.49)., Conclusion: An online expressive writing intervention was effective at improving resilience in the midst of the COVID-19 pandemic. NCT#: NCT04589104., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Current treatment options for knee osteoarthritis have limited effectiveness and potentially adverse side effects. Massage may offer a safe and effective complement to the management of knee osteoarthritis., Objective: Examine effects of whole-body massage on knee osteoarthritis, compared to active control (light-touch) and usual care., Design: Multisite RCT assessing the efficacy of massage compared to light-touch and usual care in adults with knee osteoarthritis, with assessments at baseline and weeks 8, 16, 24, 36, and 52. Subjects in massage or light-touch groups received eight weekly treatments, then were randomized to biweekly intervention or usual care to week 52. The original usual care group continued to week 24. Analysis was performed on an intention-to-treat basis., Participants: Five hundred fifty-one screened for eligibility, 222 adults with knee osteoarthritis enrolled, 200 completed 8-week assessments, and 175 completed 52-week assessments., Intervention: Sixty minutes of protocolized full-body massage or light-touch., Main Measures: Primary: Western Ontario and McMaster Universities Arthritis Index. Secondary: visual analog pain scale, PROMIS Pain Interference, knee range of motion, and timed 50-ft walk., Key Results: At 8 weeks, massage significantly improved WOMAC Global scores compared to light-touch (- 8.16, 95% CI = - 13.50 to - 2.81) and usual care (- 9.55, 95% CI = - 14.66 to - 4.45). Additionally, massage improved pain, stiffness, and physical function WOMAC subscale scores compared to light-touch (p < 0.001; p = 0.04; p = 0.02, respectively) and usual care (p < 0.001; p = 0.002; p = 0.002; respectively). At 52 weeks, the omnibus test of any group difference in the change in WOMAC Global from baseline to 52 weeks was not significant (p = 0.707, df = 3), indicating no significant difference in change across groups. Adverse events were minimal., Conclusions: Efficacy of symptom relief and safety of weekly massage make it an attractive short-term treatment option for knee osteoarthritis. Longer-term biweekly dose maintained improvement, but did not provide additional benefit beyond usual care post 8-week treatment., Trial Registration: clinicaltrials.gov NCT01537484.

Background and Purpose: Trauma is highly prevalent, with estimates that up to 90% of the U.S. population have been exposed to a traumatic event. The adverse health consequences of trauma exposure are diverse and often long-lasting. While expressive writing has been shown to improve emotional and physical health in numerous populations, the feasibility and potential effectiveness of a novel expressive writing program provided in a clinical setting to improve resilience is unknown. Our objective was to determine the feasibility and potential effectiveness of a 6-week expressive writing course provided in a clinical setting to improve resilience in individuals with a history of trauma., Materials and Methods: This prospective, observational trial of a 6-week expressive writing intervention (Transform Your Life: Write to Heal) was conducted in an academic outpatient integrative clinic. Eligible participants were a self-referred sample of 39 English-speaking adults who identified as having had a trauma, or significant emotional/physical upheaval, within the past year. Main outcome measures included: Feasibility: Enrollment, Retention in Program and Trial, Adherence. Acceptability: Adverse Events; Participant Ratings. Primary Psychological Outcome: Connor-Davidson Resilience Scale (CD-RISC). Secondary Psychological Outcomes: Perceived Stress Scale - 10 item (PSS-10); Center for Epidemiologic Studies Depression Scale (CES-D); Rumination Response Scale (RRS)., Results: All measures of feasibility including those related to enrollment, retention, and adherence support feasibility. All measures of acceptability including adverse events and participant ratings support the intervention as being safe, well-received and personally valuable. Resilience scores increased from baseline (64.3 ± 14.40) to post-intervention (74.2 ± 13.15), t(37) = 4.61, p < 0.0005; Cohen's d = 0.75. In addition, across the same period, Perceived Stress scores decreased close to a standard deviation (20.5 ± 7.43 to 14.3 ± 6.64), t(37) = -4.71, p < 0.0005, Cohen's d = 0.76; depression symptoms decreased (from 19.0 ± 13.48 to 12.7 ± 11.68), t(37) = -3.21, p = 0.003, Cohen's d = 0.52; and rumination scores decreased from 48.5 ± 12.56 to 39.8 ± 10.07), t(37) = -5.03, p < 0.0005, Cohen's d = 0.82. Effect sizes ranged from medium to large., Conclusion: The Transform Your Life: Write to Heal program is feasible to offer in a clinical setting, was well-received by participants, and demonstrated preliminary findings of effectiveness. Our study suggests that this novel 6-week writing intervention including expressive, transactional, poetic, affirmative, legacy, and mindful writing prompts increases resilience, and decreases depressive symptoms, perceived stress, and rumination in an outpatient sample of those reporting trauma in the past year. The program appears suitable to be evaluated in a larger randomized controlled trial., (Copyright © 2018. Published by Elsevier Ltd.)