Healthy Participants Research Articles

The effect of sprouted wheat wholemeal inclusion in bread recipes on postprandial blood glucose and satiety responses in healthy adults: a randomized trial

Sprouted wheat wholemeal was reported to enhance the nutritional and sensory properties of cereal products, but few human studies exist. The effect of blending 50 % sprouted wheat wholemeal in a bread recipe on the postprandial glycemic and satiety responses, and sensory-related sensations was investigated in this randomized crossover human study with 12 healthy participants. Capillary blood samples were collected and glycemic response was determined at 0, 15, 30, 45, 60, 90, 120 min. Satiety visual analogue scales were given every 30 min. While substituting bread wheat flour with sprouted wheat wholemeal significantly increased the α-amylase activity in the dough (p < 0.05), it did not alter in vitro digestibility or postprandial glycemic and satiety responses (p > 0.05). Likewise, participant overall acceptability was not adversely affected. Sprouted wheat wholemeal can be used as a functional ingredient in breadmaking, although it did not, in this study, significantly affect digestibility parameters.

Lifestyle deterioration linked to elevated inflammatory cytokines over a two-month follow-up

Healthy lifestyle reduces the risk of inflammation-related diseases. This study assessed how lifestyle changes affect inflammatory cytokines over 2 months. Involving 179 apparently healthy participants recruited from community, collecting data on lifestyles (smoking, alcohol, BMI, daily activity, sleep, diet) and measured inflammatory cytokines (TNF-α, IL-1β, IL-17A, CRP, IL-8, IL-18, IFN-γ) plus pepsinogens (PG I, PG II) at the baseline and 2-month follow-up. The combined adverse lifestyle score is the sum of scores across six lifestyles, with higher scores indicating more adverse lifestyle factors. Use multiple linear regression and mixed linear models to analyze the relationship between the changes in lifestyle and inflammatory cytokines (follow-up values minus baseline values). For every 1-point increase in combined adverse lifestyle score, IL-17A increased by 0.98 (95% CI 0.23, 1.73) pg/mL, IFN-γ increased by 1.79 (95% CI 0.39, 3.18) pg/mL. Decreased changes in daily activity were associated with higher IL-17A (β = 1.83, 95% CI 0.53, 3.13) and IFN-γ (β = 2.59, 95% CI 0.9, 4.98). Excluding daily activity, changes in combined adverse lifestyle scores were not associated with changes in inflammatory cytokines. Lifestyle improvements at 2-month intervals may reduce TNF-α, IL-17A and IFN-γ, with daily activity making the greatest contribution.

The role of variation in phonological and semantic working memory capacities in sentence comprehension: neural evidence from healthy and brain-damaged individuals.

Research on the role of working memory (WM) in language processing has typically focused on WM for phonological information. However, considerable behavioral evidence supports the existence of a separate semantic WM system that plays a greater role in language processing. We review the neural evidence that supports the distinction between phonological and semantic WM capacities and discuss how individual differences in these capacities relate to sentence processing. In terms of neural substrates, findings from multivariate functional MRI for healthy participants and voxel-based lesion-symptom mapping for brain-damaged participants imply that the left supramarginal gyrus supports phonological WM, whereas the left inferior frontal gyrus (LIFG) and angular gyrus support semantic WM. In sentence comprehension, individual variation in semantic but not phonological WM related to performance in resolving semantic information and the LIFG region implicated in semantic WM showed fMRI activation during the resolution of semantic interference. Moreover, variation for brain-damaged participants in the integrity of a fiber tract supporting semantic WM had a greater relation to the processing of complex sentences than did the integrity of fiber tracts supporting phonological WM. Overall, the neural findings provide converging evidence regarding the distinction of these two capacities and the greater contribution of individual differences in semantic than phonological WM capacity to sentence processing.

Co-administration of midazolam and psilocybin: differential effects on subjective quality versus memory of the psychedelic experience

Aspects of the acute experience induced by the serotonergic psychedelic psilocybin predict symptomatic relief in multiple psychiatric disorders and improved well-being in healthy participants, but whether these therapeutic effects are immediate or are based on memories of the experience is unclear. To examine this, we co-administered psilocybin (25 mg) with the amnestic benzodiazepine midazolam in 8 healthy participants and assayed the subjective quality of, and memory for, the dosing-day experience. We identified a midazolam dose that allowed a conscious psychedelic experience to occur while partially impairing memory for the experience. Furthermore, midazolam dose and memory impairment tended to associate inversely with salience, insight, and well-being induced by psilocybin. These data suggest a role for memory in therapeutically relevant behavioral effects occasioned by psilocybin. Because midazolam blocks memory by blocking cortical neural plasticity, it may also be useful for evaluating the contribution of the pro-neuroplastic properties of psychedelics to their therapeutic activity.

Effect of Food on the Pharmacokinetics, Safety, and Tolerability of Budesonide Oral Suspension in Healthy Adult Participants: A Randomized Phase 1 Study.

Budesonide oral suspension (BOS) is a swallowed corticosteroid indicated for 12-week therapy in eosinophilic esophagitis with minimal systemic exposure following administration. We aimed to assess the relative bioavailability of a single dose of BOS administered under fasting and fed (high-fat/high-calorie meal) conditions. Healthy adult volunteers (N = 20) were enrolled in an open-label, single-center, crossover study and were randomized (1:1) to receive a single oral dose of BOS 2.0 mg under fasting or fed conditions, with a 48-h washout period before crossover to the alternative conditions. Serial plasma samples were collected before and up to 24 h after dosing. Pharmacokinetic (PK) parameters were calculated from plasma budesonide concentration-time profiles by noncompartmental analysis. The mean peak budesonide concentration (Cmax) was ∼13% lower under fed than under fasting conditions (604.1 vs 692.9 pg/mL). Areas under the concentration-time curves from dosing to the last measurable budesonide concentration and from dosing to infinity were ∼26% higher and ∼27% higher under fed than fasting conditions (3529 vs 2811 pg h/mL and 3892 vs 3075 pg h/mL, respectively). The median time to peak plasma budesonide concentration was significantly longer (∼1 h) under fed than fasting conditions (2.516 vs 1.286 h, P <.001). Safety and tolerability were also assessed throughout the study; all adverse events were mild or moderate in severity. Despite slight differences in budesonide PK parameters between fed and fasting conditions, the effect of food on systemic exposure to budesonide (BOS formulation) is not expected to be clinically meaningful.

Spontaneous neural activity underlying neutral and happy speech recognition in noise and its association with psychiatric symptoms in patients with schizophrenia

BackgroundDeficits in speech and emotion perception are intertwined with psychiatric symptoms. How the happy prosody embedded in speech affects target speech-in-noise recognition (TSR) and relates to psychiatric symptoms in patients with schizophrenia (SCHs) remains unclear. This study examined spontaneous brain activity underlying happy TSR and its association with psychiatric symptom dimensions in SCHs. MethodsFifty-four SCHs and 59 healthy control participants (HCs) underwent the TSR task, Positive and Negative Syndrome Scale (PANSS) assessment, and magnetic resonance imaging scanning. Multivariate analyses of partial least squares (PLS) regression were used to explore the associations between whole-brain fractional amplitude of low-frequency fluctuations (fALFF), happy-neutral TSR (target pseudo-sentences were uttered in happy and neutral prosodies), and five PANSS factor scores (excitement/hostility, depression/anxiety, cognition, positive, and negative). ResultsThe happy prosody did not alter TSR or TSR changing rates in either SCHs or HCs. SCHs exhibited lower happy and neutral TSR than HCs. A fALFF PLS component (including precentral/postcentral gyrus, Subcallosal Cortex, several temporal regions, and cerebellum) was associated with happy and neutral TSR. SCHs demonstrated higher PLS fALFF scores and PLS TSR scores than HCs. In SCHs, PLS fALFF scores were correlated with the PANSS positive factor score, and PLS TSR scores were correlated with the PANSS cognition factor score. ConclusionsThe positive-psychiatric-symptoms-related spontaneous activity profile was associated with happy and neutral TSR, contributing to the cognition psychiatric symptoms dimension. The findings suggest the potential to improve positive and cognitive symptoms by enhancing happy and neutral TSR in schizophrenia based on neuroplasticity.

Is predictability of the conditioning stimulus (CS) a critical factor in conditioned pain modulation (CPM)?

Introduction Conditioned pain modulation (CPM) allows to investigate endogenous pain modulation and its clinical outcomes. Although co-activation of emotions has been shown to affect CPM, the impact of ‘threat,’ which may accompany CPM stimulation itself, has been mostly neglected. A critical factor for the threat level of the conditioning stimulus (CS) may be its predictability. Methods 38 healthy participants (18 female) took part in a CPM study with pressure stimulation on the leg (blood-pressure cuff) serving as CS and heat stimulation on the forearm (contact thermode; CHEPS) serving as test stimulus (TS). While CS varied in intensity and –as operationalisation of threat– in temporary predictability, TS was kept constant. CPM effects were studied by EEG parameters (N2P2) and pain ratings. Results We found a significant CPM effect when considering N2P2, with low CS predictability augmenting CPM inhibition; in contrast, a surprisingly facilitatory CPM effect occurred in pain ratings (in the high CS predictability condition). The threat manipulation was only partially successful because CS intensity increased the threat ratings but not -as intended- CS predictability. Correlations between subjective and psychophysiological CPM responses were low. Discussion The differing CPM effects in subjective and psychophysiological responses, with both inhibitory and facilitatory effects, is puzzling but has already been observed earlier. The consideration of the CPM stimulation as major threat that is emotionally active is theoretically clearly justifiable but the operationalisation by means of different levels of CS predictability as in the present study might not have been ideal. Thus, further attempts of experimental verification are warranted.

B - 6 The BRIEF-2A Pattern of Self and Informant Executive Functioning Difficulties in Adults with Epilepsy

Abstract Objective People with epilepsy (PWE) commonly have executive functioning (EF) difficulties on objective testing. However, less is known about subjective EF difficulties in everyday life. We examined self- and informant-rated EF in PWE using the Behavior Rating Inventory of Executive Function for Adults-2 (BRIEF-2A). We hypothesized that PWE and their informants would endorse greater EF difficulties relative to healthy participants. Method Participants included 43 PWE who completed comprehensive clinical neuropsychological evaluation at a large Northeastern academic medical center, which included BRIEF-2A Informant and Self Report Forms (Age M = 40.4 ± 17.2 years, 53% female, Education M = 13.0 ± 1.8 years). Twenty-four participants completed self-reports, while 19 had both self and informant reports. The comparison sample included 43 age- and gender-matched healthy controls (HC). We analyzed BRIEF-2A subscales using MANOVAs, where elevated T scores indicated worse EF. Repeated measures ANOVAs compared self and informant ratings. Multi-rater comparisons (90% CIs) and chi-squares analyzed patterns of discrepant ratings. Results Self-reported EF difficulties in PWE were elevated across all scales, compared to HC (p’s0.25), with greatest difference observed for working memory (PWE = 69.7 ± 12.7, HC = 44.5 ± 16.7, ηp2 = 0.61). Similar elevations across all scales were observed for PWE informant reports (p’s0.14). PWE rated greater self-monitoring (p = 0.03, ηp2 &amp;gt; 0.23) and emotional control (p = 0.08, ηp2 &amp;gt; 0.16) difficulties than informants. There was 42.1–68.4% concordance between self and informant reports for PWE, compared to 84–95% in HC. Patterns of self and informant ratings were similar between PWE and HC for initiation, planning/organization, and task-monitoring (p’s &amp;gt; 0.20). Conclusions PWE and their informants report high, yet relatively similar, levels of EF difficulties in daily life.

Drawing promotes memory retention in a patient with sleep-related anterograde amnesia.

Drawing is a powerful tool to enhance memory in healthy participants and patients with probable dementia. Here, we investigated whether the drawing effect could extend to patient CT, a young woman with severe anterograde amnesia. Following surgery for a midline tumor involving her septum pellucidium and extending down into her fornices bilaterally, CT experienced a severe case of sleep-related amnesia. She can remember information encountered throughout the day, but when waking up in the morning or following a nap she forgets information learned prior to sleep. Here, we tested CT and 21 age-matched controls in a 3-day within-subjects design, during which participants encoded words by either drawing or writing them down. Memory for encoded words was tested in two conditions that each followed a 12-h delay, once after a night of sleep, and once after 12 h of wake. Despite her severe memory impairment, CT showed a drawing effect that was comparable to controls in both sleep and wake conditions. Whereas CT's memory for written words was consistently impaired relative to controls, her memory for drawn words was at the lower control range following a waking delay and above chance following a sleep delay. We suggest that amnesic patients may benefit from the drawing effect due to the recruitment of brain regions outside of the hippocampal system for encoding and consolidation. Furthermore, in control participants, sleep benefited memory for written words, but not for drawn words, suggesting that sleep preferentially consolidates memories that are more dependent on the hippocampal system.

The cervico-ocular reflex changes following treatment in individuals with subclinical neck pain: a randomized control trial.

Individuals with subclinical neck pain (SCNP) exhibit altered cerebellar processing, likely due to disordered sensorimotor integration of inaccurate proprioceptive input. This association between proprioceptive feedback and SMI has been captured in cervico-ocular reflex (COR) differences where SCNP showed higher gain than healthy participants. Previous neurophysiological research demonstrated improved cerebellar processing in SCNP participants following a single treatment session, but it is unknown whether these neurophysiological changes transfer to cerebellar function. In a parallel group, randomized control trial conducted at Ontario Tech University, 27 right-hand dominant SCNP participants were allocated to the 8-week chiropractic care (n = 15; 7M & 8F) or 8-week control (n = 12; 6M & 6F) group. COR gain (ratio of eye movement to trunk movement) was assessed using an eye-tracking device at baseline and at post 8-weeks (treatment vs. no treatment). COR gain (10 trials): participants gazed at a circular target that disappeared after 3s, while a motorized chair rotated their trunk at a frequency of 0.04Hz, with an amplitude of 5º, for 2 minutes. A 2 × 2 repeated measures ANOVA was performed. COR gain was significantly reduced following 8-weeks of chiropractic care compared to the SCNP control (8-weeks of no treatment) group (p = 0.012, ηp2 = 0.237). The decrease in COR gain following treatment is likely due to normalized proprioceptive feedback from the neck, enabling improved processing and integration within the flocculonodular lobe of the cerebellum.

Does Periodontitis Increase the Risk for Future Cardiovascular Events? Long-Term Follow-Up of the PAROKRANK Study.

The study 'Periodontitis and Its Relation to Coronary Artery Disease' (PAROKRANK) reported an association between periodontitis (PD) and the first myocardial infarction (MI). This follow-up study aims to test the hypothesis that those with PD-compared to periodontally healthy individuals-are at increased risk for cardiovascular (CV) events and death. A total of 1587 participants (age <75 years; females 19%) had a dental examination including panoramic radiographs between 2010 and 2014. PD was categorized as healthy (≥80% alveolar bone height), mild/moderate (79%-66%) or severe (<66%). A composite CV event (first of all-cause death, non-fatal MI or stroke and hospitalization following to heart failure) was investigated during a mean follow-up period of 9.9 years (range 0.2-12.5 years). Participants were divided into two groups: those with and without PD. The primary event rate, stratified by periodontal status at baseline, was calculated using the Kaplan-Meier method and Cox regression. The number of events was 187 in the 985 periodontally healthy participants (19%) and 174 in the 602 participants with PD (29%; p < 0.0001). Those with PD had a higher likelihood for a future event (hazard ratio [HR] = 1.26; 95% CI: 1.01-1.57; p = 0.038), following adjustment for age, smoking and diabetes. The PAROKRANK follow-up revealed that CV events were more common among participants with PD, which supports the assumption that there might be a direct relation between PD and CV disease.

Relationship between dietary inflammatory index, plant-based dietary index, and bacterial vaginosis: A case-control study.

Bacterial vaginosis (BV) is a common inflammatory condition affecting the vaginal microbiome. In the present study we aimed to explore the relationship between dietary inflammatory index, plant-based dietary index, and BV. In this case-control study, 143 individuals with BV and 151 healthy participants aged 15-45 years were included. Bacterial vaginosis diagnosis was based on the Amsel criteria by a gynecologist. Participants' dietary intakes over the past year were assessed using a 168-item food frequency questionnaire. Logistic regression models were employed to analyze the association between dietary inflammatory index, plant-based dietary index, and BV odds. Our study revealed that elevated dietary inflammatory index scores were strongly associated with higher BV odds in the crude model (odds ratio [OR]: 2.88, 95% confidence interval [CI]: 1.57-5.30, P value <0.001), and even after accounting for potential confounding factors (adjusted OR: 3.52, 95% CI: 1.66-7.46, P value = 0.001). While no significant relationship was observed between total plant-based dietary index and healthy plant-based dietary index scores with BV odds, a clear positive association existed between unhealthy plant-based dietary index and the odds of BV (aOR: 2.13, 95% CI: 1.09-4.15, P value = 0.018). A positive correlation may exist between unhealthy plant-based dietary index and the likelihood of BV. Furthermore, the dietary inflammatory index may remain linked to increased BV odds.

Comparison of Isometric and Dynamic Bridging Exercises on Low Back Muscle Oxygenation.

Bridging exercises are commonly performed by people with low back pain (LBP). However, the effect of the contraction mode in a bridging exercise on the hemodynamics of the low back muscle has not been investigated in people with and without LBP. The objective of this study was to assess the effect of the mode of bridging exercise on oxygenation of the low back muscle. A near-infrared spectroscopy was used to measure hemodynamic responses of the erector spinae between isometric and dynamic bridging exercises in 16 healthy participants. The results demonstrated that during exercise, the isometric bridging exercise significantly decreased oxyhemoglobin and deoxy-hemoglobin compared to the dynamic bridging exercise (oxyhemoglobin, t=- 3.109, p=0.007, Cohen's d=0.68 and deoxy-hemoglobin, t=- 2.193, P=0.046, Cohen's d=0.60). The results also demonstrated that after exercise, the dynamic bridging exercise induced a significantly higher oxygenation response (oxygenation, t=- 2.178, P=0.048, Cohen's d=0.43). This study indicates that the dynamic bridging exercise is more effective in improving oxygenation of low back muscles.

Effects of auricular vagus nerve stimulation and electrical earlobe stimulation on motor-evoked potential changes induced by paired associative stimulation.

Paired associative stimulation (PAS) is a combination of transcranial magnetic stimulation (TMS) and peripheral nerve stimulation (PNS). PAS can induce long-term potentiation (LTP)-like plasticity in humans, manifested as motor-evoked potential (MEP) enhancement. We have developed a variant of PAS ("high-PAS"), which consists of high-frequency PNS and high-intensity TMS and targets spinal plasticity and promotes rehabilitation after spinal cord injury (SCI). Vagus nerve stimulation (VNS) promotes LTP-like plasticity and enhances recovery in SCI and stroke in humans and animals when combined with repetitive motor training. We combined high-PAS with simultaneous noninvasive transcutaneous auricular VNS (aVNS) to determine if aVNS enhances the extent of PAS-induced MEP amplitude increase. Sixteen healthy participants were stimulated for 20 min in four different sessions (PAS, PAS + aVNS, PAS + shamVNS, and aVNS) in a randomized single-blind setup. MEPs were measured before, immediately after, and at 30, 60, and 90 min post-stimulation. Stimulation protocols with PAS significantly potentiated MEPs (p= 0.005) when compared with aVNS (p= 0.642). Although not significant, MEP enhancement observed after PAS (43.5%) is further increased by aVNS (49.7%) and electrical earlobe stimulation (63.9%). Our aVNS setup failed to significantly enhance the effect of PAS, but sham VNS revealed a trend towards enhanced plasticity. Optimization of auricular VNS stimulation setup is required for possible tests of patients with SCI.

Association between resting-state neurovascular coupling and neural signals as revealed by a combined fMRI and magnetoencephalography (MEG) study in humans.

The Blood Oxygenation Level-Dependent (BOLD) activation reflects hemodynamic events mediated by neurovascular coupling. During task performance, the BOLD hemodynamic response in a relevant area is mainly driven by the high levels of synaptic activity (reflected in local field potentials, LFP) but, in contrast, during a task-free, resting state, the contribution to BOLD of such neural events is small, as expected by the comparatively (to the task state) low level of neural events. Concomitant recording of BOLD and LFP at rest in animal experiments has estimated the neural contribution to BOLD to ~10%. Such experiments have not been performed in humans. As an approximation, we recorded (in the same subject, N = 57 healthy participants) at a task-free, resting state the BOLD signal and, in a different session, the magnetoencephalographic (MEG) signal, which reflects purely neural (synaptic) events. We then calculated the turnover of these signals by computing the successive moment-to-moment difference in the BOLD and MEG time series and retaining the median of the absolute value of the differenced series (TBOLD and TMEG, respectively). A linear regression of normalized TBOLD vs. TMEG revealed that ~30% of TMEG contributes to TBOLD, accounting for 11.3% of the latter's variance. This percentage estimate is close to the ~10% estimate above obtained by direct recordings in animal experiments.

Psychometric validation of the Italian Self-Report Symptoms inventory (SRSI): Factor structure, construct validity, and diagnostic accuracy

The Self-Report Symptom Inventory (SRSI) is a novel tool designed to detect symptom overreporting and other forms of noncredible responding. Unlike existing scales, the SRSI includes genuine and pseudosymptoms scales covering cognitive, affective, motor, pain, and post-traumatic stress disorder domains. The present study aims to investigate the psychometric properties of the Italian Version of the SRSI (SRSI-It), in particular, its factor structure, reliability, convergent and discriminant validity, and diagnostic accuracy. Data from 1180 healthy participants showed a hierarchical structure with higher-order constructs for genuine symptoms and pseudosymptoms, each comprising five subscales. The SRSI-It showed a strong convergent validity with the Structured Inventory of Malingered Symptomatology and discriminant validity through low correlations with the Psychopathic Personality Inventory-Revised. Receiver operating characteristic analysis determined cut scores of 6 (95% specificity) and 9 (98% specificity) for pseudosymptoms, with a Ratio Index score of 0.289 (82% specificity). In summary, the SRSI-It appears to be a promising tool for identifying symptom exaggeration in clinical and forensic contexts, ultimately enhancing the quality and reliability of evaluations in these contexts.

The quantified method for blood clot detection in the extraction socket

Background Currently, there is no objective and quantified measurement for detecting blood clots during extraction socket hemostasis. It has relied solely on clinical observation, even when conducting clinical research by using extraction sockets as samples. This study aimed to assess the in vitro reliability and clinical-relevant validity of a new objective measurement providing quantified data called blood clot detection (BCD) using a standard capillary tube. Methods The in vitro part of the study was conducted using surplus blood samples from ten healthy participants. Two identical sets of blood samples in simulation reservoirs mimicking bleeding sockets were prepared for reliability tests. Then, the capillary tubes were concurrently placed in the reservoirs. The blood-filled distances were measured. The part of clinical-relevant validity study was conducted in sixteen extraction sockets from each healthy participant. Clinical observation and BCD measurement were evaluated by two calibrated assessors. The total duration of the assessment was a 30-minute. Results The distances of the blood-filled capillary tube were decreased by time. Test and retest reliability analysis of the BCD measurement showed an excellent intraclass correlation coefficient of 0.980 (0.968 to 0.988). The medians of blood-filled distance categorized by clinical observation into active bleeding, sluggish oozing, and clot formation were 13.0 mm (Q1 = 11.7, Q3 = 13.8), 5.6 mm (Q1 = 4.3, Q3 = 7.0), and 0.9 mm (Q1 = 0.5, Q3 = 1.3), respectively. The blood-filled distance of the clot formation group was significantly less than the active bleeding and sluggish oozing (p&lt;0.001). Therefore, the BCD measurement also significantly indicated the completion of extraction socket hemostasis Conclusions A distance of blood-filled in capillary tube of 0.9 mm from the BCD measurement significantly ensured complete clot formation. The BCD measurement proved to be a quantified tool for objectively measuring hemostasis of bleeding socket.

Zinc-alpha2-glycoprotein modulates blood pressure by regulating renal lipid metabolism reprogramming - mediated urinary Na+ excretion in hypertension.

Organs modulating blood pressure are associated with a common cytokine known as adipokines. We chose Zinc-alpha2-glycoprotein (ZAG) due to its prioritized transcriptional level in the database. Previous studies showed that ZAG is involved in metabolic disorders. The aim of this study was to investigate its role in hypertension. Serum ZAG levels were assessed in hypertensive and healthy participants. Blood pressure was monitored in Azgp1-/- mice and other animal models by 24-hour ambulatory implanted telemetric transmitters and tail-cuff method. Multi-omics analysis of proteomics and metabolomics were performed to explore possible mechanisms. Serum ZAG levels were significantly decreased and associated with morning urine Na+ excretion in hypertensive participants in a cross-sectional study. This study firstly reported that Azgp1-/- mice exhibited increased blood pressure and impaired urinary Na+ excretion, which were restored by AAV9-mediated renal tubule Azgp1 rescue. Azgp1 knockout caused the reprogramming of renal lipid metabolism, and increased Na+/H+-exchanger (NHE) activity in the renal cortex. Administration with a NHE inhibitor EIPA reversed the impaired urinary Na+ excretion in Azgp1-/- mice. Moreover, the activity of carnitine palmitoyltransferase 1 (CPT1), a key enzyme of fatty acid β-oxidation, was decreased, and the levels of malonyl-CoA, an inhibitor of CPT1, were increased in renal cortex of Azgp1-/- mice. Renal Cpt1 rescue improved urinary Na+ excretion and blood pressure in Azgp1-/- mice, accompanied by decreased renal fatty acid levels and NHE activity. Finally, administration of recombinant ZAG protein improved blood pressure and urinary Na+ excretion in SHRs. Deficiency of Azgp1 increased the malonyl CoA-mediated inhibition of CPT1 activity, leading to renal lipid metabolism reprogramming, resulting in accumulated fatty acids and increased NHE activity, subsequently decreasing urinary Na+ excretion and causing hypertension. These findings may provide a potential kidney-targeted therapy in the prevention and treatment of hypertension.

Composite activity type and stride-specific energy expenditure estimation model for thigh-worn accelerometry

BackgroundAccurately measuring energy expenditure during physical activity outside of the laboratory is challenging, especially on a large scale. Thigh-worn accelerometers have gained popularity due to the possibility to accurately detect physical activity types. The use of machine learning techniques for activity classification and energy expenditure prediction may improve accuracy over current methods. Here, we developed a novel composite energy expenditure estimation model by combining an activity classification model with a stride specific energy expenditure model for walking, running, and cycling.MethodsWe first trained a supervised deep learning activity classification model using pooled data from available adult accelerometer datasets. The composite energy expenditure model was then developed and validated using additional data based on a sample of 69 healthy adult participants (49% female; age = 25.2 ± 5.8 years) who completed a standardised activity protocol with indirect calorimetry as the reference measure.ResultsThe activity classification model showed an overall accuracy of 99.7% across all five activity types during validation. The composite model for estimating energy expenditure achieved a mean absolute percentage error of 10.9%. For running, walking, and cycling, the composite model achieved a mean absolute percentage error of 6.6%, 7.9% and 16.1%, respectively.ConclusionsThe integration of thigh-worn accelerometers with machine learning models provides a highly accurate method for classifying physical activity types and estimating energy expenditure. Our novel composite model approach improves the accuracy of energy expenditure measurements and supports better monitoring and assessment methods in non-laboratory settings.

Central and peripheral physiological responses to decision making in hoarding disorder

Individuals with hoarding disorder (HD) have difficulty parting with personal possessions, which leads to the accumulation of excessive clutter. According to a proposed biphasic neurobiological model, HD is characterized by blunted central and peripheral nervous system activity at rest and during neutral (non-discarding) decisions, and exaggerated activity during decision-making about discarding personal possessions. Here, we compared the error-related negativity (ERN) and psychophysiological responses (skin conductance, heart rate and heart rate variability, and end tidal CO2) during neutral and discarding-related decisions in 26 individuals with HD, 37 control participants with anxiety disorders, and 28 healthy control participants without psychiatric diagnoses. We also compared alpha asymmetry between the HD and control groups during a baseline resting phase. Participants completed a series of Go/No Go decision-making tasks, one involving choosing certain shapes (neutral task) and the other involving choosing images of newspapers to imaginally “discard” (discarding task). While all participants showed expected increased frontal negativity to commission of an error, contrary to hypotheses, there were no group differences in the ERN or any psychophysiological measures. Alpha asymmetry at rest also did not differ between groups. The findings suggest that the ERN and psychophysiological responses may not differ in individuals with HD during simulated discarding decisions relative to control participants, although the null results may be explained by methodological challenges in using Go/No Go tasks as discarding tasks. Future replication and extension of these results will be needed using ecologically valid discarding tasks.