Healthy Participants Research Articles

Electrophysiological signature of interoceptive attention: a spectral and source localization analysis.

The ability to attend to and consciously process interoceptive signals is deemed critical for the development of minimal self, adaptive self-regulation and affective experience, and optimal expression of both instrumental and executive cognitive functions. Yet, notwithstanding the richness of theoretical proposals concerning inferential accounts of interoception, empirical evidence is still scarce. Building on such premises, this study was designed to investigate the electrophysiological signature of cognitive processes leading to aware coding of interoceptive signals via EEG source localization. Thirty-six healthy participants completed an interoceptive accuracy task, i.e., the Heartbeat Counting Task (HCT), while we collected task-related and resting state electrophysiological activity. eLORETA modelling and statistical nonparametric mapping were used to estimate intracortical current density and link such estimates to participants' performance at the task. Source analysis highlighted higher current density estimates for alpha frequencies during HCT with respect to rest, with the primary cortical generator in the right parahippocampal gyrus. Also, a set of medial cortical structures-primarily represented by the cingulate gyrus-showed significant relation between task-related changes in current density estimates for beta oscillations and HCT scores. Findings suggest the informativity of EEG task-related measures of neural activation when used to assess interoceptive skills, as well as of the potential of metrics and analysis based on source localization in the quest to improve our understanding of interoceptive accuracy and neurofunctional correlates of related active inferences.

Changes in the reactive hyperemia index after continuous and interval exercise.

High-intensity interval exercise (HIIE) is more effective than moderate-intensity interval exercise (MICE) for improving macrovascular function (e.g., flow-mediated dilation), but less is known regarding the effect of HIIE on microvascular function. We used peripheral artery tonometry to measure the reactive hyperemia index (RHI) and examine the acute effects of HIIE and MICE on microvascular function. Ten healthy participants (50% men, age: 26 ± 5 years, mass: 75.6 ± 15.1 kg, height: 170 ± 10 cm, body mass index: 26.0 ± 3.1 kg∙m-2) performed single bouts of HIIE and MICE cycling on separate occasions. The MICE protocol was 20 min at 60% of maximum power output. The HIIE protocol was a 12-min warm up at 50% of maximum power output immediately followed by an 8-min Tabata protocol where participants alternated between cycling at ⩾ 100% max power (20 sec) and rest (10 sec). The RHI was measured before, immediately after, and 1 h after exercise and compared by two-way repeated measures analysis of variance (condition [MICE, HIIE] and time [pre-, post-, and 1-h postexercise]). Compared to baseline, RHI increased 1 h after MICE only (p = 0.02). Heart rate was higher during MICE at 5 and 10 min (p = 0.02) and higher during HIIE at min 20 (p < 0.01). Within a sample of healthy adults, the RHI was improved 1 h after a single session of MICE but not HIIE. Future research is needed to determine the significance of the differential effects of exercise regimens on the macro- and microvasculature.

Comparing cadence-based energy expenditure and oxygen cost indices in able-bodied male people.

Walking is a fundamental aspect of daily life and exercise, with clinical benefits for cardiovascular health and muscle strength. However, accurately measuring energy efficiency during walking poses challenges due to equipment and spatial constraints. In this study, we proposed the cadence-based energy expenditure index (cEEI) and analyzed its correlation with the previously proposed index for measuring energy expenditure under various gait conditions. We enrolled 15 healthy participants and conducted an experimental protocol on a treadmill to measure the following energy expenditure-related indices: oxygen cost index (OCI), energy expenditure index (EEI), and cEEI. The participants underwent stages of walking at different speeds and inclinations that comply with the modified Bruce protocol while their heart rate, oxygen uptake, and cadence were recorded. Participants showed significant increases in heart rate, oxygen uptake, and cadence with higher walking speeds and inclinations. Correlation analysis revealed strong associations between cEEI and OCI, especially during walking conditions. Bland-Altman plots and interclass correlation coefficient analysis demonstrated a favorable agreement between cEEI and OCI, outperforming EEI. In conclusion, this study proposes cEEI as a reliable metric for estimating energy expenditure during walking by proving a strong correlation and agreement with OCI across various gait conditions. This suggests the potential for cEEI to provide real-time, individualized feedback on energy expenditure during walking, facilitating more personalized exercise prescriptions.

The Impact of Makgeolli Consumption on Gut Microbiota: An Enterotype-Based Preliminary Study.

Makgeolli, a traditional Korean liquor, contains components such as lactic acid bacteria and dietary fiber, which can induce changes in the gut microbiome. Since variations in microbiome responses may exist between enterotypes-classifications based on the dominant bacterial populations in the gut-we hypothesized that the consumption of makgeolli leads to enterotype-dependent differences in gut microbial structures among healthy participants. This study aimed to determine the effect of makgeolli consumption on gut microbial structures by stratifying all participants into two enterotype groups: Bacteroides-dominant type (B-type, n = 7) and Prevotella-dominant type (P-type, n = 4). The B-type showed an increase in alpha diversity, while no significant difference was observed in the P-type following makgeolli consumption. The composition of gut microbiota significantly changed in the B-type, whereas no noticeable alteration was observed in the P-type after makgeolli consumption. Notably, Prevotella exhibited the most significant changes only in the P-type. In line with the increased abundance of Prevotella, the genes associated with carbohydrate metabolism, including pentose/glucuronate interconversions, fructose/mannose metabolism, starch/sucrose metabolism and amino sugar/nucleotide sugar metabolism were significantly enriched following makgeolli consumption in the P-type. These findings suggest that makgeolli consumption induces enterotype-dependent alterations in gut microbial composition and metabolic pathways, highlighting the potential for personalized dietary interventions.

Metabolic obesity phenotypes and the risk of cancer: a prospective study of the Kailuan cohort.

Obesity is as an important risk factor for chronic diseases. Metabolically healthy obesity (MHO) is considered a benign state. The association between metabolic health and obesity categories and cancer risk remains unclear. This study aimed to investigate the relationship between metabolic health status combined with obesity phenotypes and the risk of cancer. Data from 91,834 participants in the Kailuan cohort were analyzed, excluding individuals with a body mass index (BMI) < 18.5 kg/m² and those with a history of cancer. Obesity phenotypes were classified based on BMI and waist circumference (WC) combined with metabolic health status, resulting in six phenotypes. Cox proportional hazard regression models were used to assess the association between metabolic health and obesity phenotypes with cancer risk and all-cause mortality. The prevalence of metabolically healthy obesity and metabolically unhealthy obesity defined by BMI was 6.86% and 12.18%, while that defined by WC was 20.79% and 25.76%, respectively. Compared to metabolically healthy participants, individuals with an unhealthy metabolic status had a significantly higher risk of cancer (HR, 1.09; 95% CI, 1.03-1.15; p=0.004). The hazard ratios for cancer were 1.19, 1.23, 1.20, and 1.55 for individuals with one, two, three, and four metabolic disorders, respectively. Among those classified as metabolically unhealthy, both overweight and obesity were associated with a protective effect on cancer risk (HR, 0.88; 95% CI, 0.80-0.96; p=0.006 for overweight; HR, 0.87; 95% CI, 0.78-0.97; p=0.010 for obesity). However, abdominal obesity significantly increased cancer risk in both metabolically healthy and unhealthy participants. In subgroup analysis, simple obesity showed a protective trend against cancer in those with respiratory cancers, while abdominal obesity consistently posed a risk for various cancer types. Metabolically unhealthy status and abdominal obesity are risk factors for cancer and all-cause mortality, whereas simple obesity offers protective effects against cancer and all-cause mortality in metabolically unhealthy individuals. These findings suggest that maintaining metabolic health and reducing the metabolic risks associated with abdominal obesity should be key targets for cancer prevention.

Oral microbiocenosis state under different approaches of replacing dental crown defects

Dental caries is one of the most common health problems. The aim of the research was to study the spectrum of microbiota, which is part of the dental biofilm, and its biological properties. The study involved 90 participants of the study group and 20 of the control group. Dental plaque and saliva were used as principal clinical specimens. The main research method was bacteriological. All samples from study participants were positive for microbiota. At the initial collection of material, 395 unique isolates were obtained: 338 from patients with caries and 57 from healthy volunteers. The microbiocenosis of the oral cavity associated with the development of caries contained such eudodominants as Streptococcus mutans, Peptostreptococcus spp., Fusobacterium spp., Prevotella spp. and dominants Streptococcus pyogenes, Enterobacterales, Prevotella spp. and Candida albicans. In contrast the eudominants of the healthy oral cavity were microorganisms with known commensal properties, in particular Streptococcus salivarius, Aerococcus viridans, Veillonella spp. After the dental treatment, significant shifts in the taxonomic composition of the dental biofilm were observed. Therefore, the composition of the oral cavity microbiocenosis in participants who underwent restoration of the dental crown defects with zirconium inserts approached patients to the healthy cohort participants. The eudodominants of the oral microbiocenosis of the participants who underwent direct restoration were S. mitis, Peptostreptococcus spp. and Veillonella spp. In zirconium restoration, the commensals S. salivarius and A. viridans were eudodominants. The obtained isolates of opportunists possessed high virulence properties. Streptococcus spp. cultures were sensitive to norfloxacin screening in only 28.6% of cases. Among cultures of the genus Staphylococcus, 23.8% were methicillin resistant. Representatives of Enterobacterales had chemotherapeutic sensitivity that varied significantly depending on the group of antimicrobial agents. Using disks with phenylboronic acid, ethylenediaminetetraacetic acid and cloxacillin, it was established that Klebsiella spp. were producers of class A carbapenemases (n=3) and contained AmpC (n=3). Carbapenemases were also produced by at least 65.2% of the studied cultures of non-fermenting gram-negative microorganisms. In our study, all obtained isolates were also endowed with the ability to form a biofilm. Therefore, microbiological research in dentistry should be considered as one of the objective methods for assessment of health of the oral cavity and will also have advantages in choosing a method of correcting defects of dental crown parts and in some cases, making an informed decision about the prescription of antimicrobial treatment.

Nomogram for predicting asymptomatic intracranial atherosclerotic stenosis in a neurologically healthy population

Asymptomatic intracranial atherosclerotic stenosis (aICAS) is a major risk factor for cerebrovascular events. The study aims to construct and validate a nomogram for predicting the risk of aICAS. Participants who underwent health examinations at our center from September 2019 to August 2023 were retrospectively enrolled. The participants were randomly divided into a training set and a testing set in a 7:3 ratio. Firstly, in the training set, least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were performed to select variables that were used to establish a nomogram. Then, the receiver operating curves (ROC) and calibration curves were plotted to assess the model’s discriminative ability and performance. A total of 2563 neurologically healthy participants were enrolled. According to LASSO-Logistic regression analysis, age, fasting blood glucose (FBG), systolic blood pressure (SBP), hypertension, and carotid atherosclerosis (CAS) were significantly associated with aICAS in the multivariable model (adjusted P < 0.005). The area under the ROC of the training and testing sets was, respectively, 0.78 (95% CI: 0.73–0.82) and 0.65 (95% CI: 0.56–0.73). The calibration curves showed good homogeneity between the predicted and actual values. The nomogram, consisting of age, FBG, SBP, hypertension, and CAS, can accurately predict aICAS risk in a neurologically healthy population.

A chronometric relationship between circuits underlying learning and error monitoring in the basal ganglia and salience network

Abstract Healthy individuals readily adjust their behaviour in response to errors using learning mechanisms. This raises the question of how error-related neural mechanisms underlie the learning process and its progress. In this study, 21 healthy participants performed a challenging functional magnetic resonance imaging (fMRI) task to answer this question. We assessed the evolution of error-related neural response as a function of learning progress. We tested the hypothesis that the dorsal anterior cingulate cortex (dACC) and anterior insula, key regions of the error monitoring neural circuitry, reflect both the performance of an action and its improvement. Given the nature of trial-and-error learning, we also expected an involvement of the striatum, particularly the putamen. We found that error-related neural activity (in the dACC and anterior insula) was similar following correct responses and errors in an initial learning period. However, as learning progressed, the activity continuously decreased in response to correct events and increased after errors. In opposition, during the initial learning phase, the putamen activity was modulated by errors, but, as it progressed, this region became unaffected by response outcomes. In sum, our study provides neural evidence for an interaction between the mechanisms underlying error monitoring and learning, contributing to clarifying how error-related neural responses evolve with learning.

Deciphering the neural responses to a naturalistic persuasive message

Effective health promotion may benefit from understanding how persuasion emerges. While earlier research has identified brain regions implicated in persuasion, these studies often relied on event-related analyses and frequently simplified persuasive communications. The present study investigates the neural basis of valuation change induced by a persuasive healthy eating call, employing naturalistic stimuli. Fifty healthy participants performed two blocks of a bidding task, in which they had to bid on sugar-containing, sugar-free, and nonedible products during functional MRI. In between the two blocks, they listened to a persuasive healthy eating call that influenced their bidding behavior. Intriguingly, participants who resisted persuasion exhibited increased synchronization of brain activity during listening in several regions, including default mode network structures. Additionally, intersubject functional connectivity among these brain regions was found to be weaker in persuaded individuals. These results emphasize the individualized nature of processing persuasive messages, challenging conventional interpretations of synchronized neural activity. Our findings support the emerging practice of tailoring persuasive messages in health promotion campaigns.

Alpha transcranial alternating current stimulation modulates pain anticipation and perception in a context-dependent manner.

Pain perception is closely tied to the brain's anticipatory processes, particularly involving the suppression of sensorimotor α-oscillations, which reflect the system's readiness for incoming pain. Higher sensorimotor α-oscillation levels are correlated with lower pain sensitivity. Alpha transcranial alternating current stimulation (α-tACS) can enhance these oscillations, potentially reducing pain perception, with effects that may be sustained and influenced by the certainty of pain expectations. Hence, this study investigated the immediate and sustained effects of α-tACS on pain anticipation and perception, focusing on how these effects are shaped by the certainty of expectations. In a double-blind, sham-controlled design, 80 healthy participants underwent a 20-minute session of real or sham α-tACS over the right sensorimotor region. Behavioral and neural responses related to pain anticipation and perception were recorded before, immediately after, and 30 minutes poststimulation under both certain and uncertain conditions. Compared with sham stimulation, real α-tACS disrupted the habituation of laser-evoked potentials (N2-P2 complex), particularly under certain expectations, with effects persisting 30 minutes poststimulation. In anticipatory brain oscillations, real α-tACS enhanced somatosensory α1-oscillations and increased midfrontal θ-oscillations in conditions of certainty, with θ-oscillation modulation showing sustained effects. Mediation analysis revealed that α-tACS reduced pain reactivity by enhancing somatosensory α1-oscillations but increased pain reactivity through the enhancement of midfrontal θ-oscillations, with the latter effect being more pronounced. These findings suggest that while α-tACS may provide pain relief through somatosensory α-oscillation augmentation, its stronger and longer-lasting impact on midfrontal θ-oscillations could lead to hyperalgesia, particularly in the context of certain pain expectations.

Regional variations in cingulate cortex glutamate levels: A magnetic resonance spectroscopy study at 3T.

Regional variations in glutamate levels across the cingulate cortex, decreasing rostral-to-caudal, have been observed previously in healthy volunteers using proton magnetic resonance spectroscopy (1H-MRS) at 7T. This study sought to explore cingulate cortex glutamate trends further by investigating whether a similar gradient could be detected at 3T, the effect of sex, as well as whether individual variations gave rise to more than one regional glutamate pattern. 1H-MRS at 3T (Phillips Elition, semi-Localization by Adiabatic Selective Refocusing, TE/TR = 32/5000) was acquired in four cingulate regions: the anterior, mid-anterior, mid-posterior, and posterior cortices, in 50 healthy participants (26F) scanned at a fixed time of day and with controlled food intake. K-means clustering was used to characterize the presence of distinct regional patterns, which were then compared between sex and clusters. In addition, cortical thickness was compared between clusters, and in relation to glutamate. Aligned with 7T findings, we demonstrated that average glutamate levels decreased rostral-to-caudal in the healthy cingulate cortex. No effect of sex was found, suggesting similar resting glutamate levels in both sexes. Interestingly, the majority of participants were characterized by glutamate levels that did not significantly change across the cingulate (65%). Different regional patterns in cortical thickness between clusters offer further evidence into these distinct glutamate variations and suggest both a neuroanatomical and functional role may lead to these findings. This study provides a much needed foundation for further research to determine the implications of neurotransmission patterns in health and disease.

Characterization of patients with major psychiatric disorders with AMPA receptor positron emission tomography.

Synaptic phenotypes in living patients with psychiatric disorders are poorly characterized. Excitatory glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) is a fundamental component for neurotransmission. We recently developed a positron emission tomography (PET) tracer for AMPAR, [11C]K-2, the first technology to visualize and quantify AMPARs density in living human brain. In this study, we characterized patients with major psychiatric disorders with [11C]K-2. One hundred forty-nine patients with psychiatric disorders (schizophrenia, n = 42; bipolar disorder, n = 37; depression, n = 35; and autism spectrum disorder, n = 35) and 70 healthy participants underwent a PET scan with [11C]K-2 for measurement of AMPAR density. We detected brain regions that showed correlation between AMPAR density and symptomatology scores in each of four disorders. We also found brain areas with significant differences in AMPAR density between patients with each psychiatric disorder and healthy participants. Some of these areas were observed across diseases, indicating that these are commonly affected areas throughout psychiatric disorders. Schizophrenia, bipolar disorder, depression, and autism spectrum disorder are uniquely characterized by AMPAR distribution patterns. Our approach to psychiatric disorders using [11C]K-2 can elucidate the biological mechanisms across diseases and pave the way to develop novel diagnostics and therapeutics based on the synapse physiology.

Evaluating Models of the Ageing BOLD Response.

Neural activity cannot be directly observed using fMRI; rather it must be inferred from the hemodynamic responses that neural activity causes. Solving this inverse problem is made possible through the use of forward models, which generate predicted hemodynamic responses given hypothesised underlying neural activity. Commonly-used hemodynamic models were developed to explain data from healthy young participants; however, studies of ageing and dementia are increasingly shifting the focus toward elderly populations. We evaluated the validity of a range of hemodynamic models across the healthy adult lifespan: from basis sets for the linear convolution models commonly used to analyse fMRI studies, to more advanced models including nonlinear fitting of a parameterised hemodynamic response function (HRF) and nonlinear fitting of a biophysical generative model (hemodynamic modelling, HDM). Using an exceptionally large sample of participants, and a sensorimotor task optimized for detecting the shape of the BOLD response to brief stimulation, we first characterised the effects of age on descriptive features of the response (e.g., peak amplitude and latency). We then compared these to features from more complex nonlinear models, fit to four regions of interest engaged by the task, namely left auditory cortex, bilateral visual cortex, left (contralateral) motor cortex and right (ipsilateral) motor cortex. Finally, we validated the extent to which parameter estimates from these models have predictive validity, in terms of how well they predict age in cross-validated multiple regression. We conclude that age-related differences in the BOLD response can be captured effectively by models with three free parameters. Furthermore, we show that biophysical models like the HDM have predictive validity comparable to more common models, while additionally providing insights into underlying mechanisms, which go beyond descriptive features like peak amplitude or latency, and include estimation of nonlinear effects. Here, the HDM revealed that most of the effects of age on the BOLD response could be explained by an increased rate of vasoactive signal decay and decreased transit rate of blood, rather than changes in neural activity per se. However, in the absence of other types of neural/hemodynamic data, unique interpretation of HDM parameters is difficult from fMRI data alone, and some brain regions in some tasks (e.g., ipsilateral motor cortex) can show responses that are more difficult to capture using current models.

Effect of weekly practice of Laghu Shankhaprakshalana Kriya (yogic bowel cleansing) on appetite in healthy adults: An exploratory study

ABSTRACT Introduction: Shankhaprakshalana (SP) kriya is one of the shatkarma (hatha yogic cleansing practices) used to cleanse the entire gastrointestinal tract with water. This technique involves the consumption of lukewarm saline water in conjunction with dynamic yoga asanas followed by a phase of deep relaxation. Past studies have reported the benefits of SP in managing digestive issues such as constipation, migraine-associated abdominal discomfort, and irritable bowel syndrome. However, there is a notable lack of literature investigating the impact of yoga-based cleansing practices on appetite status. Objective: This study aimed to investigate the effect of Laghu Shankhaprakshalana (LSP) kriya on the appetite status of healthy individuals. Materials and Methods: Sixty-five healthy male participants naïve to yoga with a mean age of 26.92 ± 5.35 years were recruited and randomly divided into an LSP group (n = 32) and a control group (n = 33). The LSP group engaged in LSP practice once a week for 8 weeks, while the control group received no intervention. Appetite status was assessed using the Council of Nutrition Appetite Questionnaire before and after completing eight sessions of LSP. The data were analyzed using the mixed model analysis of variance followed by post hoc Bonferroni correction for a total of 60 participants (five participants withdrew from the study). Results: Following eight sessions of LSP practice, a significant increase in appetite levels was observed (p &lt; 0.001). No significant change was found in the control group. Conclusion: This study provides preliminary evidence suggesting that LSP practice tends to enhance appetite levels in apparently healthy individuals. Further research is needed with a larger sample and physiological assessment of appetite.

Characterization of the Biological Variability of the Angiome Biomarkers over Time in Healthy Subjects.

Biomarker analyses are an integral part of cancer research. Despite the intense efforts to identify and characterize biomarkers in cancer patients, little is known regarding the natural variation of biomarkers in healthy populations. Here we conducted a clinical study to evaluate the natural variability of biomarkers over time in healthy participants. The angiome multiplex array, a panel of 25 circulating protein biomarkers, was assessed in 28 healthy participants across 8 timepoints over the span of 60 days. We utilized the intraclass correlation coefficient (ICC) to quantify the reliability of the biomarkers. Adjusted ICC values were calculated under the framework of a linear mixed-effects model, taking into consideration age, sex, body mass index (BMI), fasting status, and sampling factors. ICC was calculated to determine the reliability of each biomarker. HGF was the most stable marker (ICC=0.973), while PDGF-BB was the most variable marker (ICC=0.167). In total, ICC analyses revealed that 22 out of 25 measured biomarkers display good (≥0.4) to excellent (>0.75) ICC values. Three markers (PDGF-BB, TGF-1, PDGF-AA) had ICC values <0.4. Greater age was associated with higher IL-6 (p=0.0114). Higher BMI was associated with higher levels of IL-6 (p=0.0003) and VEGF-R3 (p=0.0045). Of the 25 protein biomarkers measured over this short time period, 22 markers were found to have good or excellent ICC values, providing additional validation for this biomarker assay. This data further supports the validation of the angiome biomarker assay and its application as an integrated biomarker in clinical trial testing.

Validation of On-Head OPM MEG for Language Laterality Assessment.

Pre-surgical localization of language function in the brain is critical for patients with medically intractable epilepsy. MEG has emerged as a valuable clinical tool for localizing language areas in clinical populations, however, it is limited for widespread application due to the low availability of the system. Recent advances in optically pumped magnetometer (OPM) systems account for some of the limitations of traditional MEG and have been shown to have a similar signal-to-noise ratio. However, the novelty of these systems means that they have only been tested for limited sensory and motor applications. In this work, we aim to validate a novel on-head OPM MEG procedure for lateralizing language processes. OPM recordings, using a soft cap with flexible sensor placement, were collected from 19 healthy, right-handed controls during an auditory word recognition task. The resulting evoked fields were assessed for hemispheric laterality of the response. Principal component analysis (PCA) of the grand average language response indicated that the first two principal components were lateralized to the left hemisphere. The PCA also revealed that all participants had evoked topographies that closely resembled the average left-lateralized response. Left-lateralized responses were consistent with what is expected for a group of healthy right-handed individuals. These findings demonstrate that language-related evoked fields can be elucidated from on-head OPM MEG recordings in a group of healthy adult participants. In the future, on-head OPM MEG and the associated lateralization methods should be validated in patient populations as they may have utility in the pre-surgical mapping of language functions in patients with epilepsy.

Pharmacokinetic interaction between single and multiple doses of darunavir, in combination with cobicistat or ritonavir, and single-dose dabigatran etexilate in healthy adults

ObjectiveDarunavir (DRV) is a P-glycoprotein (P-gp) inhibitor. Dabigatran etexilate, prodrug of the anticoagulant dabigatran, is a P-gp probe substrate. This study evaluated the effect of single and multiple doses of DRV, coadministered with cobicistat (COBI) or ritonavir (rtv), on the pharmacokinetics (PK) of single-dose dabigatran etexilate.MethodsThis was an open-label, fixed-sequence, single-center, 2-panel, phase 1 study in which healthy adult participants were equally divided over 2 panels. In panel 1, participants received single and multiple doses of DRV/COBI 800/150 mg coadministered with single-dose dabigatran etexilate 150 mg. In panel 2, participants received single and multiple doses of DRV 800 mg + rtv 100 mg coadministered with single-dose dabigatran etexilate 150 mg. Key PK parameters evaluated were maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero to infinity (AUCinf) for free and total dabigatran.ResultsOverall, 28 participants were enrolled and treated (n = 14 per panel). Dabigatran Cmax and AUCinf increased 2.64-fold after a single dose of DRV/COBI and 1.99- and 1.88-fold, respectively, after multiple doses of DRV/COBI. Dabigatran Cmax and AUCinf increased 1.64- and 1.72-fold, respectively, after a single dose of DRV + rtv and 1.22- and 1.18-fold, respectively, after multiple doses of DRV + rtv. In both panels, the most commonly reported adverse events were diarrhea and headache.ConclusionFindings of increased dabigatran exposure with DRV/COBI or DRV + rtv coadministration indicate an inhibitory effect of single-dose boosted DRV on P-gp, and a mixed inhibitory/inductive effect of multiple doses of boosted DRV on P-gp.Trial registrationClinicalTrials.gov, NCT04208061. Registered December 19, 2019

Comparing the Psychophysical Capabilities on Fingertip and Wrist using Method of Adjustment

Haptic technology, which refers to creating the sense of touch artificially, offers a crucial source of communication between humans and computers or machines. While conventional haptic devices are designed to render vibrotactile information on the fingertip, recent trends in the field expand the tactile communication to other body locations, like the wrist. Even though the literature has many successful applications showing the validity of such haptic applications, there is no study comparing the user perception for meaningful virtual or teleoperated task scenarios due to the lack of calibration methods between alternative body locations. In this paper, we attempt to compare the perceived intensities at the fingertip and the wrist through psychophysical experiments and to answer: (i) Is there a perpetual difference between the haptic stimuli on the wrist compared to the fingertip? (ii) Is possible to form a reasonable, linear relationship (or a pattern) between the stimuli rendered at the fingertip and the wrist? (iii) If so, do different users require different relationships that would need to be obtained through calibration? We designed a user study with 13 healthy participants, receiving three levels of haptic stimuli at their fingertips while adjusting the intensities of the stimuli rendered at their wrist using the method of adjustments. Our results indicate that there is a linear pattern between the vibrotactile stimuli rendered at the fingertip and the wrist, and each participant exhibits a different pattern. Our results can be used to equalize the perceived intensities of different forms of tactile stimuli for future research investigating the perceived performance under different haptic scenarios.

Vestibular Dysfunction in Euthyroid Children with Hashimoto's Thyroiditis.

A relationship exists between autoimmune thyroid disorders and vestibular dysfunction. This study aimed to analyze cervicalevoked myogenic potentials (cVEMP) and video head impulse test (vHIT) results between children with Hashimoto thyroiditis (HT) and healthy controls to determine vestibular end-organ problems. Thirty-six children with HT and 30 healthy subjects were recruited. The main inclusion criteria for the healthy group were the presence of normal thyroid function and no clinical history of vestibular problems. Each participant (both HT and healthy groups) was assessed using audiovestibular tests, cVEMP, and vHIT. There was no significant difference between the groups in terms of cVEMP (p1 and n1) latencies for both ears. There was no significant difference in cVEMP amplitudes (p1-n1 peak-to-peak) between the groups. There were statistically significant differences in the VOR gain of the right and left ears between the groups (P < .001, P < .001). When we considered lower cutoff value as 0.80 for VOR gain, 29 of 36 patients with HT (80.6%) had lower VOR gain scores. Only 1 of 30 healthy participants (3.3%) had a lower VOR gain score. This difference was statistically significant (P < .001). Subclinical vestibulopathy may occur in children with HT. The vHIT seems to be a valuable tool for identifying and screening preclinical vestibular pathologies in this patient group.

Using Network Analysis to Examine the Brain Regions Connectivity of Functional Neurological Disorder Patient and Healthy Participant

Introduction: Functional neurological disorder (FND) is one of the most common causes of neuropathy, However, its cause continues to be mysterious. Understanding the underlying mechanisms of that is crucial for treatment strategies. The study was conducted on brain images resting state fMRI taken from two volunteers (functional neurological disorder patient and healthy subject)who had the same characteristics. Methods: We fitted Gaussian Graphical Models to a single subject data using a network approach. Results: Based on the results of the networks, the number of significant edges was more in the left hemisphere in the patient, but in the healthy person, the number of these non-zero edges was more in the right hemisphere. Both the networks related to the healthy person and the patient had high density. Therefore, it indicated that the regions considered by these 2 people were strongly related to each other. The results showed the existence of more links and positive relationships between the regions, most of which showed a strong relationship. Among these connections, there were also negative connections. The networks of the healthy participant with almost symmetrical structures and the patient with Functional neurological disorder showed different characteristics, including asymmetry between the hemispheres. Conclusion: this study is the first to demonstrate that the brain regions of both functional neurological disorder patient and healthy participant can be conceptualized as networks. The findings of this study add to a growing body of literature that functional neurological disorder patient brain regions can be analyzed using network approaches.