Transcutaneous auricular Vagus Nerve Stimulation and Median Nerve Stimulation reduce acute stress in young healthy adults: a single-blind sham-controlled crossover study.

Stress is a major determinant of health and wellbeing. Conventional stress management approaches do not account for the daily-living acute changes in stress that affect quality of life. The combination of physiological monitoring and non-invasive Peripheral Nerve Stimulation (PNS) represents a promising technological approach to quantify stress-induced physiological manifestations and reduce stress during everyday life. This study aimed to evaluate the effectiveness of three well-established transcutaneous PNS modalities in reducing physiological manifestations of stress compared to a sham: auricular and cervical Vagus Nerve Stimulation (taVNS and tcVNS), and Median Nerve Stimulation (tMNS). Using a single-blind sham-controlled crossover study with four visits, we compared the stress mitigation effectiveness of taVNS, tcVNS, and tMNS, quantified through physiological markers derived from five physiological signals peripherally measured on 19 young healthy volunteers. Participants underwent three acute mental and physiological stressors while receiving stimulation. Blinding effectiveness was assessed via subjective survey. taVNS and tMNS relative to sham resulted in significant changes that suggest a reduction in sympathetic outflow following the acute stressors: Left Ventricular Ejection Time Index (LVETI) shortening (tMNS: p = 0.007, taVNS: p = 0.015) and Pre-Ejection Period (PEP)-to-LVET ratio (PEP/LVET) increase (tMNS: p = 0.044, taVNS: p = 0.029). tMNS relative to sham also reduced Pulse Pressure (PP; p = 0.032) and tonic EDA activity (tonicMean; p = 0.025). The nonsignificant blinding survey results suggest these effects were not influenced by placebo. taVNS and tMNS effectively reduced stress-induced sympathetic arousal in wearable-compatible physiological signals, motivating their future use in novel personalized stress therapies to improve quality of life.

Validating Adhesive-Free Bioimpedance of the Leg in Mid-Activity and Uncontrolled Settings.

OBJECTIVE: Musculoskeletal health monitoring is limited in everyday settings where patient symptoms can substantially change - delaying treatment and worsening patient outcomes. Wearable technologies aim to quantify musculoskeletal health outside clinical settings but sensor constraints limit usability. Wearable localized multi-frequency bioimpedance assessment (MFBIA) shows promise for tracking musculoskeletal health but relies on gel electrodes, hindering extended at-home use. Here, we address this need for usable technologies for at-home musculoskeletal health assessment by designing a wearable adhesive-free MFBIA system using textile electrodes in extended uncontrolled mid-activity settings. METHODS: An adhesive-free multimodal wearable leg MFBIA system was developed in-lab under realistic conditions (5 participants, 45 measurements). Mid-activity textile and gel electrode MFBIA was compared across multiple compound movements (10 participants). Accuracy in tracking long-term changes in leg MFBIA was assessed by correlating gel and textile MFBIA simultaneously recorded in uncontrolled settings (10 participants, 80+ measurement hours). RESULTS: Mid-activity MFBIA measurements with textile electrodes agreed highly with (ground truth) gel electrode measurements (average [Formula: see text], featuring <1-Ohm differences (0.618 ± 0.340 Ω) across all movements. Longitudinal MFBIA changes were successfully measured in extended at-home settings (repeated measures r = 0.84). Participant responses found the system to be comfortable and intuitive (8.3/10), and all participants were able to don and operate the system independently. CONCLUSION: This work demonstrates wearable textile electrodes can be a viable substitute for gel electrodes when monitoring leg MFBIA in dynamic, uncontrolled settings. SIGNIFICANCE: Adhesive-free MFBIA can improve healthcare by enabling robust wearable musculoskeletal health monitoring in at-home and everyday settings.

Wearable Seismocardiography-Based Assessment of Stroke Volume in Congenital Heart Disease.

Background Patients with congenital heart disease (CHD) are at risk for the development of low cardiac output and other physiologic derangements, which could be detected early through continuous stroke volume (SV) measurement. Unfortunately, existing SV measurement methods are limited in the clinic because of their invasiveness (eg, thermodilution), location (eg, cardiac magnetic resonance imaging), or unreliability (eg, bioimpedance). Multimodal wearable sensing, leveraging the seismocardiogram, a sternal vibration signal associated with cardiomechanical activity, offers a means to monitoring SV conveniently, affordably, and continuously. However, it has not been evaluated in a population with significant anatomical and physiological differences (ie, children with CHD) or compared against a true gold standard (ie, cardiac magnetic resonance). Here, we present the feasibility of wearable estimation of SV in a diverse CHD population (N=45 patients). Methods and Results We used our chest-worn wearable biosensor to measure baseline ECG and seismocardiogram signals from patients with CHD before and after their routine cardiovascular magnetic resonance imaging, and derived features from the measured signals, predominantly systolic time intervals, to estimate SV using ridge regression. Wearable signal features achieved acceptable SV estimation (28% error with respect to cardiovascular magnetic resonance imaging) in a held-out test set, per cardiac output measurement guidelines, with a root-mean-square error of 11.48 mL and R2 of 0.76. Additionally, we observed that using a combination of electrical and cardiomechanical features surpassed the performance of either modality alone. Conclusions A convenient wearable biosensor that estimates SV enables remote monitoring of cardiac function and may potentially help identify decompensation in patients with CHD.

A Wearable Multimodal Sensing System for Tracking Changes in Pulmonary Fluid Status, Lung Sounds, and Respiratory Markers.

Heart failure (HF) exacerbations, characterized by pulmonary congestion and breathlessness, require frequent hospitalizations, often resulting in poor outcomes. Current methods for tracking lung fluid and respiratory distress are unable to produce continuous, holistic measures of cardiopulmonary health. We present a multimodal sensing system that captures bioimpedance spectroscopy (BIS), multi-channel lung sounds from four contact microphones, multi-frequency impedance pneumography (IP), temperature, and kinematics to track changes in cardiopulmonary status. We first validated the system on healthy subjects (n = 10) and then conducted a feasibility study on patients (n = 14) with HF in clinical settings. Three measurements were taken throughout the course of hospitalization, and parameters relevant to lung fluid status-the ratio of the resistances at 5 kHz to those at 150 kHz (K)-and respiratory timings (e.g., respiratory rate) were extracted. We found a statistically significant increase in K (p < 0.05) from admission to discharge and observed respiratory timings in physiologically plausible ranges. The IP-derived respiratory signals and lung sounds were sensitive enough to detect abnormal respiratory patterns (Cheyne-Stokes) and inspiratory crackles from patient recordings, respectively. We demonstrated that the proposed system is suitable for detecting changes in pulmonary fluid status and capturing high-quality respiratory signals and lung sounds in a clinical setting.

An Integrated Multimodal Knee Brace Enabling Mid-Activity Tracking for Joint Health Assessment.

Developments in wearable technologies created opportunities for non-invasive joint health assessment while subjects perform daily activities during rehabilitation and recovery. However, existing state-of-art solutions still require a health professional or a researcher to set up the device, and most of them are not convenient for at-home use. In this paper, we demonstrate the latest version of the multimodal knee brace that our lab previously developed. This knee brace utilizes four sensing modalities: joint acoustic emissions (JAEs), electrical bioimpedance (EBI), activity and temperature. We designed custom printed-circuit boards and developed firmware to acquire high quality data. For the brace material, we used a commercial knee brace and modified it for the comfort of patients as well as to secure all electrical connections. We updated the electronics to enable rapid EBI measurements for mid-activity tracking. The performance of the multimodal knee brace was evaluated through a proof-of-concept human subjects study (n=9) with 2 days of measurement and 3 sessions per day. We obtained consistent EBI data with less than 1 Ω variance in measured impedance within six full frequency sweeps (each sweep is from 5 kHz to 100 kHz with 256 frequency steps) from each subject. Then, we asked subjects to perform 10 unloaded knee flexion/extensions, while we measured continuous 5 kHz and 100 kHz EBI at every 100 ms. The ratio of the range of reactance (ΔX5kHz/ΔX100kHz) was found to be less than 1 for all subjects for all cycles, which indicates lack of swelling and thereby a healthy joint. We also conducted intra and inter session reliability analysis for JAE recordings through intraclass correlation analysis (ICC), and obtained excellent ICC values (>0.75), suggesting reliable performance on JAE measurements. The presented knee brace could readily be used at home in future work for knee health monitoring of patients undergoing rehabilitation or recovery.

Lithium choreography: intramolecular arylations of carbamate-stabilised carbanions and their mechanisms probed by in situ IR spectroscopy and DFT calculations.

Deprotonation of O-allyl, O-propargyl or O-benzyl carbamates in the presence of a lithium counterion leads to carbamate-stabilised organolithium compounds that may be quenched with electrophiles. We now report that when the allylic, propargylic or benzylic carbamate bears an N-aryl substituent, an aryl migration takes place, leading to stereochemical inversion and C-arylation of the carbamate α to oxygen. The aryl migration is an intramolecular S(N) Ar reaction, despite the lack of anion-stabilising aryl substituents. Our in situ IR studies reveal a number of intermediates along the rearrangement pathway, including a "pre-lithiation complex," the deprotonated carbamate, the rearranged anion, and the final arylated carbamate. No evidence was obtained for a dearomatised intermediate during the aryl migration. DFT calculations predict that during the reaction the solvated Li cation moves from the carbanion centre, thus freeing its lone pair for nucleophilic attack on the remote phenyl ring. This charge separation leads to several alternative conformations. The one having Li(+) bound to the carbamate oxygen gives rise to the lowest-energy transition structure, and also leads to inversion of the configuration. In agreement with the IR studies, the DFT calculations fail to locate a dearomatised intermediate.

The synthesis of bioactive indolocarbazoles related to K-252a.

A range of functionalised indolocarbazoles, related to the natural product K-252a, have been prepared, starting from a readily available bridged cyclopentene. Sequences of transformations, involving initial hydroboration-oxidation to give a ketone, or by dihydroxylation and cyclic sulfate formation, enable the preparation of diverse indolocarbazole products. Issues of imide nitrogen protection for the indolocarbazole, and opportunities for asymmetric desymmetrisation of key intermediates were also explored. A novel chiral lithium amide base mediated transformation of a cyclic sulfate intermediate gave the anticipated ketone product in up to 87% ee. A number of compounds, in the form of unprotected imide substituted indolocarbazoles, were screened for biological activity and were found to be potent inhibitors of a number of kinase enzymes.

Hsp70 dynamics in vivo: effect of heat shock and protein aggregation.

The molecular chaperone Hsp70 interacts with misfolded proteins and also accumulates in the nucleus during heat shock. Using GFP-Hsp70 and fluorescence recovery after photobleaching, we show that Hsp70 accumulates in the nucleus during heat shock not only because its inflow rate increases but also because of a marked decrease in its outflow rate. Dynamic imaging also shows that GFP-Hsp70 has greatly reduced mobility when it interacts with organelles such as nucleoli in heat-shocked cells or the large inclusions formed from fragments of mutant huntingtin protein. In heat-shocked cells, nucleoplasmic Hsp70 has reduced mobility relative to the cytoplasm, whereas the ATPase-deficient mutant of Hsp70, Hsp70(K71E), is almost completely immobilized both in the nucleoplasm and the cytoplasm. Moreover, the Hsp70 mutant shows reduced mobility in the presence of diffusive huntingtin fragments with expanded polyglutamine repeats. This provides strong evidence that Hsp70 interacts not only with organelles but also with diffusive proteins in the nucleoplasm and cytoplasm during heat shock as well as with diffusive huntingtin fragments.