The increasing prevalence of functional and motility gastrointestinal (GI) disorders is at odds with bottlenecks in their diagnosis, treatment, and follow-up. Lack of noninvasive approaches means that only specialized centers can perform objective assessment procedures. Abnormal GI muscular activity, which is coordinated by electrical slow-waves, may play a key role in symptoms. As such, the electrogastrogram (EGG), a noninvasive means to continuously monitor gastric electrical activity, can be used to inform diagnoses over broader populations. However, it is seldom used due to technical issues: inconsistent results from single-channel measurements and signal artifacts that make interpretation difficult and limit prolonged monitoring. Here, we overcome these limitations with a wearable multi-channel system and artifact removal signal processing methods. Our approach yields an increase of 0.56 in the mean correlation coefficient between EGG and the clinical “gold standard”, gastric manometry, across 11 subjects (p < 0.001). We also demonstrate this system’s usage for ambulatory monitoring, which reveals myoelectric dynamics in response to meals akin to gastric emptying patterns and circadian-related oscillations. Our approach is noninvasive, easy to administer, and has promise to widen the scope of populations with GI disorders for which clinicians can screen patients, diagnose disorders, and refine treatments objectively.
Objective: Although the importance of sleep is increasingly recognized, the lack of robust and efficient algorithms hinders scalable sleep assessment in healthy persons and those with sleep disorders. Polysomnography (PSG) and visual/manual scoring remain the gold standard in sleep evaluation, but more efficient/automated systems are needed. Most previous works have demonstrated algorithms in high agreement with the gold standard in healthy/normal (HN) individuals-not those with sleep disorders. Methods: This paper presents a statistical framework that automatically estimates whole-night sleep architecture in patients with obstructive sleep apnea (OSA)-the most common sleep disorder. Single-channel frontal electroencephalography was extracted from 65 HN/OSA sleep studies, and decomposed into 11 spectral features in 60 903 30 s sleep epochs. The algorithm leveraged kernel density estimation to generate stage-specific likelihoods, and a 5-state hidden Markov model to estimate per-night sleep architecture. Results: Comparisons to full PSG expert scoring revealed the algorithm was in fair agreement with the gold standard (median Cohen's kappa = 0.53). Further, analysis revealed modest decreases in median scoring agreement as OSA severity increased from HN (kappa = 0.63) to severe (kappa = 0.47). A separate implementation on HN data from the Physionet Sleep-EDF Database resulted in a median kappa = 0.65, further indicating the algorithm's broad applicability. Conclusion: Results of this work indicate the proposed single-channel framework can emulate expert-level scoring of sleep architecture in OSA. Significance: Algorithms constructed to more accurately model physiological variability during sleep may help advance automated sleep assessment, for practical and general use in sleep medicine.
New classes of ultrathin flexible and stretchable devices have changed the way modern electronics are designed to interact with their target systems. Though more and more novel technologies surface and steer the way we think about future electronics, there exists an unmet need in regards to optimizing the fabrication procedures for these devices so that large-scale industrial translation is realistic. This article presents an unconventional approach for facile microfabrication and processing of adhesive-peeled (AP) flexible sensors. By assembling AP sensors on a weakly-adhering substrate in an inverted fashion, we demonstrate a procedure with 50% reduced end-to-end processing time that achieves greater levels of fabrication yield. The methodology is used to demonstrate the fabrication of electrical and mechanical flexible and stretchable AP sensors that are peeled-off their carrier substrates by consumer adhesives. In using this approach, we outline the manner by which adhesion is maintained and buckling is reduced for gold film processing on polydimethylsiloxane substrates. In addition, we demonstrate the compatibility of our methodology with large-scale post-processing using a roll-to-roll approach.
Transplanting metabolic reactions from one species into another has many uses as a research tool with applications ranging from optogenetics to crop production. Ferredoxin (Fd), the enzyme that most often supplies electrons to these reactions, is often overlooked when transplanting enzymes from one species to another because most cells already contain endogenous Fd. However, we have shown that the production of chromophores used in Phytochrome B (PhyB) optogenetics, is greatly enhanced in mammalian cells by expressing bacterial and plant Fds with ferredoxin-NADP+ reductases (FNR). We delineated the rate limiting factors and found that the main metabolic precursor, heme, was not the primary limiting factor for producing either the cyanobacterial or plant chromophores, phycocyanobilin or phytochromobilin, respectively. In fact, Fd is limiting, followed by Fd+FNR and finally heme. Using these findings, we optimized the PCB production system and for the first time, combined it with a tissue penetrating red/far-red sensing PhyB optogenetic gene switch in animal cells. We further characterized this system in several mammalian cell lines using red and far-red light. Importantly, we found that the light-switchable gene system remains active for several hours upon illumination, even with a short light pulse and requires very small amounts of light for maximal activation. Boosting chromophore production by matching metabolic pathways with specific ferredoxin systems will enable the unparalleled use of the many PhyB optogenetic tools and has broader implications for optimizing synthetic metabolic pathways.
Recent studies, using high resolution magnetoencephalography (MEG) and electrogastrography (EGG), have shown that during resting state, rhythmic gastric physiological signals are linked with cortical brain oscillations. Yet, gut-brain coupling has not been investigated with electroencephalography (EEG) during cognitive brain engagement or during hunger-related gut engagement. In this study in 14 young adults (7 females, mean ± SD age 25.71 ± 8.32 years), we study gut-brain coupling using simultaneous EEG and EGG during hunger and satiety states measured in separate visits, and compare responses both while resting as well as during a cognitively demanding working memory task. We find that EGG-EEG phase-amplitude coupling (PAC) differs based on both satiety state and cognitive effort, with greater PAC modulation observed in the resting state relative to working memory. We find a significant interaction between gut satiation levels and cognitive states in the left fronto-central brain region, with larger cognitive demand based differences in the hunger state. Furthermore, strength of PAC correlated with behavioral performance during the working memory task. Altogether, these results highlight the role of gut-brain interactions in cognition and demonstrate the feasibility of these recordings using scalable sensors.