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BackgroundFailure of Alzheimer's disease and related diseases (ADRD) research studies to include and engage Black participants is a major issue, which limits the impact and generalizability of research findings. Little is known about participation of Black adults in online ADRD-related research registries.ObjectivesAs part of the Community Engaged Digital Alzheimer's Research (CEDAR) Study, this study aims to increase our understanding of facilitators and barriers of Black adults to participating in ADRD-related online registries, as well as to understand their preferences for communication channels.Design, setting, participants, measurementsWe invited all Black participants enrolled in the Brain Health Registry (BHR) to complete a cross-sectional online survey. The survey consisted of rating scales and open-text questions asking about their attitudes towards brain health research, reasons for joining and continuing to participate in BHR, difficulties with participating, and preferences for modes of contact and website usage.ResultsOf all invited Black BHR participants (N=3,636), 198 (5.5%) completed the survey. The mean age was 58.4 (SD=11.3), mean years of education were 16.3 (SD=2.4), and 85.5% identified as female. Reported facilitators for joining and continuing to participate in BHR were personal interest (e.g., learning more about own brain health) and altruism (e.g., helping research). Among additional registry features which could encourage return, receiving feedback or scores about BHR tasks was rated the highest. Of those who found BHR participation difficult (21%), the most frequent reason was time burden. The most preferred way of receiving study information was via email. Participants reported that the websites that they used the most were YouTube and Facebook.DiscussionThe results of our study can inform the development of culturally-responsive registry features and engagement efforts to improve inclusion and participation of Black adults in online ADRD research. Providing participants with feedback about their registry performance and reducing the number of registry tasks are among the recommended strategies.

Context: Surgical site infection (SSI) is responsible for significant morbidity, prolonged hospital stays, and increased costs. Infectious endocarditis (IE) is a rare but serious complication of bacteremia, particularly that resulting from Staphylococcus aureus SSI. The VIRSTA score predicts the risk of IE and determines the priority of transthoracic echocardiography (TTE) in patients with S. aureus bacteremia. The aim of the study was to (1) assess the performance of the VIRSTA score and (2) determine the usefulness of TTE in S. aureus bacteremia related to spinal SSI. Materials and Methods: We carried out a retrospective study of consecutive patients with spinal SSI and S. aureus bacteremia at two university hospitals in France (Bordeaux and Tours) from January 2009 to January 2023. We collected the patients' clinical and surgical characteristics at baseline, VIRSTA score items, TTE results, and medicosurgical management. The associations of these parameters with IE were assessed using the chi-square test and logistic regression models. Results: Of 82 patients with spinal SSI and S. aureus bacteremia, only 1 (1.21%) developed IE. Thirteen patients did not benefit from TTE during hospitalization and were considered free of IE after clinical follow-up. Diabetes mellitus (p < 0.04) and the presence of severe sepsis or septic shock (p < 0.03) were significantly associated with the presence of IE in this population. Conclusions: Incidence of IE in patients with spinal SSI and S. aureus bacteremia is low. The VIRSTA score has high sensitivity but is not accurate for identifying patients at high risk for IE and systematic performance of TTE is complex and not useful in this setting. Level of Evidence: IV.

Oxidative stress plays a critical role in numerous pathological processes. Under these stress conditions, the free radical-catalyzed lipid peroxidation generates in vivo a large number of key products that are involved in many physiological and pathophysiological processes. Among these products are neuroprostanes, which arise from the peroxidation of docosahexaenoic acid (DHA), and isoprostanes, resulting from arachidonic acid (AA) and eicosapentaenoic acid (EPA) through the same peroxidation process. These non-enzymatic oxygenated metabolites newly appointed NEO-PUFAs have gained recognition as reliable markers of oxidative stress in neurogenerative and cardiovascular diseases. Moreover, some of them display a wide range of biological activities. The ability to detect and measure these metabolites offers precious insights into the mechanisms of oxidative damage and holds potential therapeutic implications for various health conditions, including neurodegenerative diseases. This review focuses on the role of neuroprostanes as biomarkers for oxidative stress and related diseases, highlighting their potential applications in medical research and treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Considering that diagnostic decisions about mTBI are often predicated on clinical symptom criteria, it is imperative to determine which initial presentation features of mTBI have prognostic significance for identifying those at high risk for long-term functional impairment., Setting: Zoom interview Participants: Male, former NCAA Division I, and professional-level National Football League (NFL) athletes ( n  = 177) between the ages of 27 and 85 ( M  = 54.1, SD = 14.7)., Design: Cross-sectional case-control. Main Measures: History of mild TBI, history of loss of consciousness (LOC), depression symptoms, insomnia, neurobehavioral symptoms., Results: Number of mTBI exposures did not predict neurobehavioral symptoms (B = 0.21, SE = 0.18, p  = 0.23), but number of mTBI + LOC events did (B = 2.27, SE = 0.64, p  = <.001). Further analysis revealed that the number of mTBI + LOC events predicted neurobehavioral symptoms indirectly through both depression (B = 0.85, 95% CI = [0.27, 1.52) and insomnia (B = 0.81, 95% CI = [0.3, 1.4]). Further, the direct effect of mTBI + LOC events on neurobehavioral symptoms became non-significant when depression and insomnia were added to the model (B = 0.78, SE = 0.45, p  = 0.08)., Conclusions: Findings support LOC at time of injury as an important predictor of long-term outcomes. Additionally, results suggest depression and insomnia as potential mediators in the association between mTBI + LOC and neurobehavioral symptoms. These findings provide justification for early depression and insomnia symptom monitoring following mTBI + LOC.

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).)

Oxylipins, small polar molecules derived from the peroxidation of polyunsaturated fatty acids (PUFAs), serve as biomarkers for many diseases and play crucial roles in human physiology and inflammation. Despite their significance, many non-enzymatic oxygenated metabolites of PUFAs (NEO-PUFAs) remain poorly reported, resulting in a lack of public datasets of experimental data and limiting their dereplication in further studies. To overcome this limitation, we constructed a high-resolution tandem mass spectrometry (MS/MS) dataset comprising pure NEO-PUFAs (both commercial and self-synthesized) and in vitro free radical-induced oxidation of diverse PUFAs. By employing molecular networking techniques with this dataset and the existent ones in public repositories, we successfully mapped a wide range of NEO-PUFAs, expanding the strategies for annotating oxylipins, and NEO-PUFAs and offering a novel workflow for profiling these molecules in biological samples., (© 2024. The Author(s).)

Background: In Alzheimer's disease (AD) research, subjective reports of cognitive and functional decline from participant-study partner dyads is an efficient method of assessing cognitive impairment and clinical progression., Methods: Demographics and subjective cognitive/functional decline (Everyday Cognition Scale [ECog]) scores from dyads enrolled in the Brain Health Registry (BHR) Study Partner Portal were analyzed. Associations between dyad characteristics and both ECog scores and study engagement were investigated., Results: A total of 10,494 BHR participants (mean age = 66.9 ± 12.16 standard deviations, 67.4% female) have enrolled study partners (mean age = 64.3 ± 14.3 standard deviations, 49.3% female), including 8987 dyads with a participant 55 years of age or older. Older and more educated study partners were more likely to complete tasks and return for follow-up. Twenty-five percent to 27% of older adult participants had self and study partner-report ECog scores indicating a possible cognitive impairment., Discussion: The BHR Study Partner Portal is a unique digital tool for capturing dyadic data, with high impact applications in the clinical neuroscience and AD fields. Highlights The Brain Health Registry (BHR) Study Partner Portal is a novel, digital platform of >10,000 dyads. Collection of dyadic online subjective cognitive and functional data is feasible. The portal has good usability as evidenced by positive study partner feedback. The portal is a potential scalable strategy for cognitive impairment screening in older adults., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

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.)

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disorder characterized by progressive muscle weakness. Adenine nucleotide translocator 1 (ANT1), the only 4q35 gene involved in mitochondrial function, is strongly expressed in FSHD skeletal muscle biopsies. However, its role in FSHD is unclear. In this study, we evaluated ANT1 overexpression effects in primary myoblasts from healthy controls and during Xenopus laevis organogenesis. We also compared ANT1 overexpression effects with the phenotype of FSHD muscle cells and biopsies. Here, we report that the ANT1 overexpression-induced phenotype presents some similarities with FSHD muscle cells and biopsies. ANT1-overexpressing muscle cells showed disorganized morphology, altered cytoskeletal arrangement, enhanced mitochondrial respiration/glycolysis, ROS production, oxidative stress, mitochondrial fragmentation and ultrastructure alteration, as observed in FSHD muscle cells. ANT1 overexpression in Xenopus laevis embryos affected skeletal muscle development, impaired skeletal muscle, altered mitochondrial ultrastructure and led to oxidative stress as observed in FSHD muscle biopsies. Moreover, ANT1 overexpression in X. laevis embryos affected heart structure and mitochondrial ultrastructure leading to cardiac arrhythmia, as described in some patients with FSHD. Overall our data suggest that ANT1 could contribute to mitochondria dysfunction and oxidative stress in FSHD muscle cells by modifying their bioenergetic profile associated with ROS production. Such interplay between energy metabolism and ROS production in FSHD will be of significant interest for future prospects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

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.