A comparative evaluation of bioequivalence of Gan & Lee glargine U300 and Toujeo® in Chinese healthy male participants.

Background: To assess the bioequivalence between Gan & Lee (GL) glargine U300 and Toujeo® regarding pharmacokinetics (PK), pharmacodynamics (PD), and safety in Chinese healthy male participants. Methods: A single-center, randomized, double-blind, single-dose, two-preparation, two-sequence, four-cycle repeated crossover design study was performed to compare GL glargine U300 and Toujeo® in 40 healthy participants. The primary PK endpoints were the area under the curve of glargine metabolites, M1 concentration from 0 to 24 hours (AUC0-24h), and the maximum glargine concentration within 24 hours post-dose (Cmax). The primary PD endpoints were the area under the glucose infusion rate (GIR) curve from 0 to 24 hours (AUCGIR.0-24h) and the maximum GIR within 24 hours post-dose (GIRmax). Results: GL Glargine U300 demonstrated comparable PK parameters (AUC0-24h, Cmax, AUC0-12h, and AUC12-24h of M1) and PD responses [AUCGIR.0-24h, GIRmax, AUCGIR.0-12h, and AUCGIR.12-24h] to those of Toujeo®, as indicated by 90% confidence intervals ranging from 80% to 125%. No significant disparities in safety profiles were observed between the two treatment groups, and there were no reported instances of serious adverse events. Conclusion: The PK, PD, and safety of GL glargine U300 were bioequivalent to that of Toujeo®. Clinical trial registration: https://www.chinadrugtrials.org.cn/, identifier CTR20212419.

First-in-human study evaluating safety, pharmacokinetics, and pharmacodynamics of lorundrostat, a novel and highly selective aldosterone synthase inhibitor.

Dysregulation of the mineralocorticoid hormone aldosterone is an increasingly prevalent cause of hypertension. Aldosterone synthase (CYP11B2) shares 93% homology to 11ß-hydroxylase (CYP11B1), which produces cortisol. Lorundrostat, a highly selective inhibitor of CYP11B2, is a potential safe and effective treatment for aldosterone-dependent, uncontrolled hypertension, including treatment-resistant hypertension. Lorundrostat showed highly selective inhibition of CYP11B2 in vitro, with 374-fold selectivity for CYP11B2 vs. CYP11B1. A first-in-human study of single ascending doses ranging from 5 to 800 mg and multiple ascending doses ranging from 40 to 360 mg once daily was conducted in healthy participants. After single- and multiple-dose administration, lorundrostat plasma levels peaked 1-3 h after administration with a t1/2 of 10-12 h. Plasma aldosterone decreased up to 40% with single 100-mg to 200-mg doses and up to 70% with single 400 to 800-mg doses. Plasma aldosterone returned to baseline within 16 h after single 100-mg doses and multiple once-daily 120-mg doses. Lorundrostat demonstrated a favorable safety profile in healthy participants. Dose- and exposure-dependent inhibition of renal tubular sodium reabsorption was observed across a clinically relevant dose range with no suppression of basal or cosyntropin-stimulated cortisol production and only a modest increase in mean serum potassium.

Novel cathepsin C inhibitor, BI 1291583, intended for treatment of bronchiectasis: Phase I characterization in healthy volunteers.

Novel treatments are needed to reduce inflammation, improve symptoms, address exacerbations, and slow disease progression in bronchiectasis. Cathepsin C (CatC) inhibition promises to achieve this through reduction of neutrophil-derived serine protease (including neutrophil elastase [NE] and proteinase 3 [PR3]) activation. Here, we present the phase I characterization of the novel CatC inhibitor, BI 1291583. Five phase I trials of BI 1291583 in healthy subjects are presented: a single-rising-dose study (NCT03414008) and two multiple-rising-dose studies (NCT03868540 and NCT04866160) assessing the safety, tolerability, pharmacodynamics, and pharmacokinetics of BI 1291583; a food effect study (NCT03837964); and a drug-drug interaction study (NCT03890887) of BI 1291583 and itraconazole. BI 1291583 was safe and well tolerated across the doses tested in these trials. Most adverse events (AEs) were mild or moderate in intensity, with no serious AEs, AEs of special interest or deaths reported in any trial. Drug-related skin exfoliation was not reported more frequently in subjects treated with BI 1291583 compared with placebo. BI 1291583 was readily absorbed, and pharmacokinetics were supra-proportional over the dose ranges assessed. Additionally, BI 1291583 inhibited CatC in a dose-dependent manner, inhibited downstream NE activity, and decreased PR3 levels. No food effect was observed. Co-administration of multiple doses of itraconazole increased BI 1291583 exposure approximately twofold. Due to these promising phase I results, a multinational phase II program of BI 1291583 in adults with bronchiectasis is ongoing (Airleaf™ [NCT05238675], Clairafly™ [NCT05865886], and Clairleaf™ [NCT05846230]).

Motion reconstruction and finite element analysis of the temporomandibular joint during swallowing in healthy adults.

There is a close physiological connection between swallowing and the temporomandibular joint (TMJ). However, a shortage of quantitative research on the biomechanical behavior of the TMJ during swallowing exists. The purpose of this study was to reconstruct the movement of the temporomandibular joint (TMJ) based on in vivo experiment and analyze the biomechanical responses during swallowing in healthy adults to investigate the role of the TMJ in swallowing. Motion capture of swallowing, computed tomography (CT), and magnet resonance images (MRI) were performed on six healthy subjects. The movements of the TMJ during swallowing were reconstructed from the motion capture data. The three-dimensional finite element model was constructed. The dynamic finite element analysis of the swallowing process was performed based on the motion data. The range of condylar displacement was within 1 mm in all subjects. The left and right condyle movements were asymmetrical in two-thirds of the subjects. The peak stresses of the discs were relatively low, with a maximum of 0.11 MPa. During swallowing, the condylar displacement showed two trends: slow retraction and slow extension. The tendency to extend could lead to a gradual increase in stress on the disc.

Wireless high-resolution surface facial electromyography mask for discrimination of standardized facial expressions in healthy adults.

Wired high resolution surface electromyography (sEMG) using gelled electrodes is a standard method for psycho-physiological, neurological and medical research. Despite its widespread use electrode placement is elaborative, time-consuming, and the overall experimental setting is prone to mechanical artifacts and thus offers little flexibility. Wireless and easy-to-apply technologies would facilitate more accessible examination in a realistic setting. To address this, a novel smart skin technology consisting of wireless dry 16-electrodes was tested. The soft electrode arrays were attached to the right hemiface of 37 healthy adult participants (60% female; 20 to 57 years). The participants performed three runs of a standard set of different facial expression exercises. Linear mixed-effects models utilizing the sEMG amplitudes as outcome measure were used to evaluate differences between the facial movement tasks and runs (separately for every task). The smart electrodes showed specific activation patterns for each of the exercises. 82% of the exercises could be differentiated from each other with very high precision when using the average muscle action of all electrodes. The effects were consistent during the 3 runs. Thus, it appears that wireless high-resolution sEMG analysis with smart skin technology successfully discriminates standard facial expressions in research and clinical settings.

Assessing Consciousness in Patients With Disorders of Consciousness Using a Musical Stimulation Paradigm and Verifiable Criteria.

Numerous studies have shown that musical stimulation can activate corresponding functional brain areas. Electroencephalogram (EEG) activity during musical stimulation can be used to assess the consciousness states of patients with disorders of consciousness (DOC). In this study, a musical stimulation paradigm and verifiable criteria were used for consciousness assessment. Twenty-nine participants (13 healthy subjects, 6 patients in a minimally conscious state (MCS) and 10 patients in a vegetative state (VS)) were recruited, and EEG signals were collected while participants listened to preferred and relaxing music. Fusion features based on differential entropy (DE), common spatial pattern (CSP), and EEG-based network pattern (ENP) features were extracted from EEG signals, and a convolutional neural network-long short-term memory (CNN-LSTM) model was employed to classify preferred and relaxing music.The results showed that the average classification accuracy for healthy subjects reached 85.58%. For two of the patients in the MCS group, the classification accuracies reached 78.18% and 66.14%, and they were diagnosed with emergence from MCS (EMCS) two months later. The accuracies of three patients in the VS group were 58.18%, 64.32% and 62.05%, with two patients showing slight increases in scale scores. Our study suggests that musical stimulation could be an effective method for consciousness detection, with significant diagnostic implications for patients with DOC.

Acoustically evoked K-complexes together with sleep spindles boost verbal declarative memory consolidation in healthy adults.

Over the past decade, phase-targeted auditory stimulation (PTAS), a neuromodulation approach which presents auditory stimuli locked to the ongoing phase of slow waves during sleep, has shown potential to enhance specific aspects of sleep functions. However, the complexity of PTAS responses complicates the establishment of causality between specific electroencephalographic events and observed benefits. Here, we used down-PTAS during sleep to specifically evoke the early, K-complex (KC)-like response following PTAS without leading to a sustained increase in slow-wave activity throughout the stimulation window. Over the course of two nights, one with down-PTAS, the other without, high-density electroencephalography (hd-EEG) was recorded from 14 young healthy adults. The early response exhibited striking similarities to evoked KCs and was associated with improved verbal memory consolidation via stimulus-evoked spindle events nested into the up-phase of ongoing 1 Hz waves in a central region. These findings suggest that the early, KC-like response is sufficient to boost memory, potentially by orchestrating aspects of the hippocampal-neocortical dialogue.

In vivo optimization of the experimental conditions for the non-invasive optical assessment of breast density.

In this study, time domain diffuse optical spectroscopy is performed in the range 600-1100 nm on 11 healthy volunteers with a portable system for the quantitative characterization of breast tissue in terms of optical properties and optically-derived blood parameters, tissue constituent concentrations, and scattering parameters. A measurement protocol involving different geometries (reflectance and transmittance), subject's positions (sitting and lying down), probing locations (outer, lower, and inner breast quadrants), and source-detector distances (2 and 3 cm) allowed us to investigate the effect of tissue heterogeneity and different measurement configurations on the results with the aim of identifying the best experimental conditions for the estimate of breast density (i.e., amount of fibro-glandular tissue in the breast) as a strong independent risk factor for breast cancer. Transmittance results, that in previous studies correlated strongly with mammographic density, are used as a reference for the initial test of the simpler and more comfortable reflectance measurement configuration. The higher source-detector distance, which probes deeper tissue, retrieves optical outcomes in agreement with higher average density tissue. Similarly, results on the outer quadrants indicate higher density than internal quadrants. These findings are coherent with breast anatomy since the concentration of dense fibro-glandular stroma is higher in deep tissue and towards the external portion of the breast, where the mammary gland is located. The dataset generated with this laboratory campaign is used to device an optimal measurement protocol for a future clinical trial, where optical results will be correlated with conventional mammographic density, allowing us to identify a subset of wavelengths and measurement configurations for an effective estimate of breast density. The final objective is the design of a simplified, compact and cost-effective optical device for a non-invasive, routine assessment of density-associated breast cancer risk.

Urinary excretion of gluten immunoreactive peptides as an indicator of gastrointestinal function after fasting and dietary provocation in healthy volunteers.

Introduction: Understanding intestinal permeability is paramount for elucidating gastrointestinal health and pathology. The size and nature of the molecule traversing the intestinal barrier offer crucial insights into various acute and chronic diseases, as well as the evolution of some conditions. This study aims to assess the urinary excretion kinetics of gluten immunogenic peptides (u-GIP), a unique class of dietary peptides detectable in urine, in volunteers under controlled dietary conditions. This evaluation should be compared to established probes like lactulose, a non-digestible disaccharide indicative of paracellular permeability, and mannitol, reflecting transcellular permeability. Methods: Fifteen participants underwent simultaneous ingestion of standardized doses of gluten (10 g), lactulose (10 g), and mannitol (1 g) under fasting conditions for at least 8 hours pre-ingestion and during 6 hours post-ingestion period. Urine samples were collected over specified time intervals. Excretion patterns were analyzed, and correlations between the lactulose-to-mannitol ratio (LMR) and u-GIP parameters were assessed. Results: The majority of u-GIP were detected within the first 12 hours post-ingestion. Analysis of the variability in cumulative excretion across two sample collection ranges demonstrated that lactulose and u-GIP exhibited similar onset and excretion dynamics, although GIP reached its maximum peak earlier than either lactulose or mannitol. Additionally, a moderate correlation was observed between the LMR and u-GIP parameters within the longest urine collection interval, indicating potential shared characteristics among permeability pathways. These findings suggest that extending urine collection beyond 6 hours may enhance data reliability. Discussion: This study sheds light on the temporal dynamics of u-GIP in comparison to lactulose and mannitol, established probes for assessing intestinal permeability. The resemblance between u-GIP and lactulose excretion patterns aligns with the anticipated paracellular permeability pathway. The capacity to detect antigenic food protein fragments in urine opens novel avenues for studying protein metabolism and monitoring pathologies related to the digestive and intestinal systems.

Visual Feedback Gain Modulates the Activation of Task-Related Networks and the Suppression of Non-Task Networks During Precise Grasping.

Visual feedback gain is a crucial factor influencing the performance of precision grasping tasks, involving multiple brain regions of the visual motor system during task execution. However, the dynamic changes in brain network during this process remain unclear. The aim of this study is to investigate the impact of changes in visual feedback gain during precision grasping on brain network dynamics. Sixteen participants performed precision grip tasks at 15% of MVC under low (0.1°), medium (1°), and high (3°) visual feedback gain conditions, with simultaneous recording of EEG and right-hand precision grip data during the tasks. Utilizing electroencephalogram (EEG) microstate analysis, multiple parameters (Duration, Occurrence, Coverage, Transition probability(TP)) were extracted to assess changes in brain network dynamics. Precision grip accuracy and stability were evaluated using root mean square error(RMSE) and coefficient of variation(CV) of grip force. Compared to low visual feedback gain, under medium/high gain, the Duration, Occurrence, and Coverage of microstates B and D increase, while those of microstates A and C decrease. The Transition probability from microstates A, C, and D to B all increase. Additionally, RMSE and CV of grip force decrease. Occurrence and Coverage of microstates B and C are negatively correlated with RMSE and CV. These findings suggest that visual feedback gain affects the brain network dynamics during precision grasping; moderate increase in visual feedback gain can enhance the accuracy and stability of grip force, whereby the increased Occurrence and Coverage of microstates B and C contribute to improved performance in precision grasping. Our results play a crucial role in better understanding the impact of visual feedback gain on the motor control of precision grasping.

Designing and Analyzing In-Place Motor Tasks in Virtual Reality With Goal Functions.

Goal functions make virtual goal-oriented motor tasks easier to analyze and manipulate by explicitly linking movement to outcome. However, they have only been used to study constrained (e.g., planar) upper limb movements. We present a design framework for integrating goal functions with unconstrained postural and upper limb movements in a virtual reality (VR) device. VR tasks designed with the framework can mimic unconstrained natural motions and thus train a range of functional movements yet remain analytically tractable. We created three in-place VR motor tasks: a bow-and-arrow, a reach-and-strike, and a punching bag task. Each task was adjusted to subject-specific workspace limits and anthropometrics. We studied the effects of 3 days of practice and 3 reach/lean distances on task performance in 12 healthy adults. Subjects performed all tasks on day 1 with moderate proficiency and improved with practice at all reach/lean distances. Task-specific results showed that performance decreased and movement variability increased near the edge of the reaching workspace; viewing angles and the imperfect depth cues in VR likely led to biases in performance and practice could attenuate the former effect; in reach-and-strike, subjects learned movement patterns similar to those seen in a real-world striking sport. These results show that our framework can deliver tasks useful for analyzing and training motor performance and can guide future in-place motor training. Post-hoc, we demonstrated the feasibility of generalizable methods that adjust required movement speeds and task difficulty for impaired populations.

Effects of unstable load and unstable surface ontrunk muscles activation and postural control in healthy subjects.

Exercise with an unstable load is considered a new training method to activate the core muscles. Research has shown consistency regarding an unstable surface but has not provided comprehensive findings about the effect of an unstable load. The study aimed to examine the impact of an unstable load and unstable surfaces on core muscle activation and postural control during lifting. Thirty-eight participants lifted a load equivalent to 10 % of their body weight under three conditions: a stable load on an unstable surface, a stable load on a stable surface, and an unstable load on a stable surface. The center of pressure (COP) displacement and electromyography activity of abdominal and back extensor muscles were measured during lifting. The results indicated that lifting on an unstable surface activated the lumbar erector spinae and multifidus muscles more than in a stable condition (P<0.05). However, there was no significant difference in the level of thoracic erector spinae muscle activity between the unstable load and unstable surface conditions. The stable condition increased activity in the internal oblique muscle (1.37 times) compared to the unstable conditions. The analysis of postural control revealed that lifting the load on an unstable surface significantly decreased COP displacement in the anteroposterior direction (P<0.05), while holding the load on the unstable surface significantly increased COP displacement in the anteroposterior direction compared to the other conditions. These findings could be valuable for future rehabilitation research, learning appropriate lifting techniques, and setting specific training goals in sports.

Reliability of Continuous Noninvasive Hemoglobin Monitoring in Healthy Participants During En Route Care Training.

INTRODUCTION: Current standards for hemoglobin monitoring during air transports of U.S. combat wounded are invasive and intermittent. Fielded pulse co-oximeters can noninvasively measure total hemoglobin, but this parameter is not currently utilized. The primary objective of this study was to assess the percentage of vital sign measurements with successful capture of total noninvasive hemoglobin measurement using spectrophotometry-based technology for Hb (SpHb) measurements in healthy participants during training flights. Secondary objectives were to assess the feasibility of a novel electronic data capture mechanism from usual patient movement items and perform a pilot analysis of SpHb changes in healthy participants during transitions from ground to air transport. METHODS: We conducted a feasibility study enrolling healthy participants who had hemodynamic monitoring during usual U.S. Air Force Critical Care Air Transport (CCAT) flight training exercises from 2022 to 2023. Usual CCAT monitoring equipment and currently used Masimo Rainbow® pulse co-oximeters had the capability to measure SpHb. After each training exercise, the study team wirelessly downloaded case files from patient monitors utilizing the Battlefield Assisted Trauma Distributed Observation Kit (BATDOKTM) Case Downloader application. We then calculated point and precision estimates for the percentage of time for successful SpHb capture during the exercise and compared this to pulse oximetry (SpO2) capture. An a priori precision analysis for percentage of flight-time with successful SpHb data capture and descriptive statistics were performed. This study received Exempt Determination by the 59th Medical Wing IRB. RESULTS: We analyzed 26 records with mean monitoring durations of 94.5 [59.3-119.9] minutes during ground phases and 78.0 [59.9-106.5] minutes during flight phases. SpHb measures were successfully captured for 97.7% (n = 4,620) of possible ground measurements and 97.2% (n = 3,973) of possible in-flight measurements compared to 99.5% ground and 98.2% in-flight capture for SpO2. Mean intervals of missing SpHb data were 2 ± 5 minutes on the ground and 4 ± 6 minutes in-flight. Mean SpHb increased by 0.93 ± 0.96 g/dL during the ground phase, but had minimal changes during ascent, cruising altitude or descent. The BATDOKTM Case downloader completed transfer for all files. CONCLUSION: Masimo Rainbow® SpHb pulse co-oximeters reliably captured continuous, noninvasive hemoglobin measurements using usual CCAT patient movement items in healthy participants during both ground and flight training. The BATDOKTM Case Downloader successfully imported case files from CCAT patient monitors. Mean SpHb measures had a small increase during the ground phase of monitoring followed by minimal changes when transitioning to flight altitude.

Monitoring Respiratory Rate Continuously Without Attaching a Sensor During a Challenging Ramped Protocol.

INTRODUCTION: Respiratory rate (RR) is a crucial vital sign in patient monitoring and is often the best marker of the deterioration of a sick patient. It can be used to help diagnose numerous medical conditions and has been demonstrated to be an independent predictor of patient outcomes in various critical care settings and is incorporated in many clinical early warning scores. Here, we report on the performance of depth-camera-based system for the noncontact monitoring of RR during a ramped RR protocol. The ramped breathing protocol was developed specifically to test the relatively rapid changes in rates, which include clinically important low and high ranges of RRs. MATERIALS AND METHODS: We performed a series of experimental runs with healthy volunteers who were instructed to breathe over a wide range of RRs, where the rates were ramped up from 4 breaths/min to 50 breaths/min then back down to 4 breaths/min in a series of ramped steps. Depth information was acquired from the scene and used to determine a respiratory rate (RRdepth), and this was compared to capnograph or spirometer respiratory rate reference (RRref). A total of 9,482 contemporaneous data pairs (RRdepth, RRref) were collected during the study for comparison. RESULTS: A Pearson correlation coefficient of 0.995 was achieved and a line of best fit given by RRdepth = 0.99 × RRref + 0.36 breaths/min. The overall root mean squared difference (RMSD) across the runs was 1.29 breaths/min with a corresponding bias of 0.16 breaths/min, respectively. The associated Bland-Altman analysis found limits of agreement of -2.45 and 2.75 breaths/min. When the data were subdivided according to low, medium, and high RRs, corresponding to ≤10, >10 to 20, and >20 breaths/min, the RMSD accuracies were found to be 0.94, 1.34, and 1.55 breaths/min, respectively. CONCLUSIONS: The technology performed well, exhibiting an RMSD accuracy well within our target of 3 breaths/min, both across the whole range and across each individual subrange. In summary, our results indicate the potential viability of continuous noncontact monitoring for the determination of RR over a clinically relevant range.

An integrated and flexible ultrasonic device for continuous bladder volume monitoring.

Bladder volume measurement is critical for early detection and management of lower urinary tract dysfunctions. Current gold standard is invasive, and alternative technologies either require trained personnel or do not offer medical grade information. Here, we report an integrated wearable ultrasonic bladder volume monitoring device for accurate and autonomous continuous monitoring of the bladder volume. The device incorporates flexible and air-backed ultrasonic transducers and miniaturized control electronics with wireless data transmission capability. We demonstrate the real-life application of the device on healthy volunteers with various bladder shapes and sizes with high accuracy. Apart from the lower urinary tract dysfunctions, the proposed technology could also be adapted for various wearable ultrasonic applications.

Ingestion of the Non-Nutritive Sweetener Erythritol, but Not Glucose, Enhances Platelet Reactivity and Thrombosis Potential in Healthy Volunteers-Brief Report.

BACKGROUND: Although artificial and non-nutritive sweeteners are widely used and generally recognized as safe by the US and European Union regulatory agencies, there have been no clinical trials to assess either long-term cardiovascular disease risks or short-term cardiovascular disease-relevant phenotypes. Recent studies report that fasting plasma levels of erythritol, a commonly used sweetener, are clinically associated with heightened incident cardiovascular disease risks and enhance thrombosis potential in vitro and in animal models. Effects of dietary erythritol on thrombosis phenotypes in humans have not been examined. METHODS: Using a prospective interventional study design, we tested the impact of erythritol or glucose consumption on multiple indices of stimulus-dependent platelet responsiveness in healthy volunteers (n=10 per group). Erythritol plasma levels were quantified with liquid chromatography tandem mass spectrometry. Platelet function at baseline and following erythritol or glucose ingestion was assessed via both aggregometry and analysis of granule markers released. RESULTS: Dietary erythritol (30 g), but not glucose (30 g), lead to a >1000-fold increase in erythritol plasma concentration (6480 [5930-7300] versus 3.75 [3.35-3.87] µmol/L; P<0.0001) and exhibited acute enhancement of stimulus-dependent aggregation responses in all subjects, agonists, and doses examined. Erythritol ingestion also enhanced stimulus-dependent release of the platelet dense granule marker serotonin (P<0.0001 for TRAP6 [thrombin activator peptide 6] and P=0.004 for ADP) and the platelet α-granule marker CXCL4 (C-X-C motif ligand-4; P<0.0001 for TRAP6 and P=0.06 for ADP). In contrast, glucose ingestion triggered no significant increases in stimulus-dependent release of either serotonin or CXCL4. CONCLUSIONS: Ingestion of a typical quantity of the non-nutritive sweetener erythritol, but not glucose, enhances platelet reactivity in healthy volunteers, raising concerns that erythritol consumption may enhance thrombosis potential. Combined with recent large-scale clinical observational studies and mechanistic cell-based and animal model studies, the present findings suggest that discussion of whether erythritol should be reevaluated as a food additive with the Generally Recognized as Safe designation is warranted. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04731363.

Correlations between Skin Condition Parameters and Ceramide Profiles in the Stratum Corneum of Healthy Individuals.

Ceramides are essential lipids for skin barrier function, and various classes and species exist in the human stratum corneum (SC). To date, the relationship between skin conditions and ceramide composition in healthy individuals has remained largely unclear. In the present study, we measured six skin condition parameters (capacitance, transepidermal water loss, scaliness, roughness, multilayer exfoliation, and corneocyte cell size) for the SC of the cheeks and upper arms of 26 healthy individuals and performed correlation analyses with their SC ceramide profiles, which we measured via liquid chromatography-tandem mass spectrometry. In the cheeks, high levels and/or ratios of two free ceramide classes containing an extra hydroxyl group in the long-chain moiety and a protein-bound ceramide class containing 6-hydroxysphingosine correlated with healthy skin conditions. In contrast, the ratios of two other free ceramide classes, both containing sphingosine, and a protein-bound ceramide class containing 4,14-sphingadiene correlated with unhealthy skin conditions, as did shortening of the carbon chain of the fatty acid portion of two ceramide classes containing non-hydroxy fatty acids. Thus, our findings help to elucidate the relationship between skin conditions and ceramide composition.

Detection of autoantibodies to heat shock protein 70 in the saliva and urine of normal individuals.

Cells exposed to stressors of various origin activate protective mechanisms that include the expression of heat shock proteins (Hsps)/molecular chaperones belonging to several families. Well-characterized inducible Hsp70 is present in all human cell-types and biological fluids, including blood, urine, and saliva. The presence of anti-Hsp70 autoantibodies in the serum of healthy individuals has already been confirmed, and their elevated titers positively correlated with the severity of several pathological conditions, including coeliac disease and dermatitis herpetiformis - a cutaneous manifestation of coeliac disease. Here, using an indirect enzyme-linked immunosorbent assay, we demonstrate, for the first time, that anti-Hsp70 autoantibodies are present in the saliva and urine of healthy individuals. Although the occurrence of anti-Hsp70 autoantibodies in the biological fluids of healthy individuals is intriguing, their physiological role is currently unknown. It is believed that antibodies reacting with self-molecules present in the serum of healthy individuals are part of natural autoantibody pool with multiple regulatory functions. On the other hand, some autoantibodies (e.g., typical of autoimmune bullous skin diseases or systemic lupus erythematosus) may be present before the onset of the disease and serve as specific predictive biomarkers. Therefore, we would like to initiate a discussion or future research direction on the use of anti-Hsp70 autoantibodies as a potential "biomarker" in the diagnosis or prediction of autoimmune diseases. Our findings can be considered in biomedical research to develop noninvasive, inexpensive and easy-to-use tests. Nevertheless, large-scale comparative studies should be initiated, involving the collection and analysis of biological samples such as saliva or urine from patients suffering from autoimmune diseases or other inflammatory or neoplastic diseases, to determine whether the levels of anti-Hsp70 autoantibodies are indeed elevated and whether they correlate with the clinical picture of any disease or established biomarkers.

Effects of a range of 6 prefabricated orthotic insole designs on plantar pressure in a healthy population: A randomized, open-label crossover investigation.

BACKGROUND: Prefabricated orthotic insoles are widely commercially available for self-selection to treat foot and lower-body musculoskeletal pain, without requiring advice from health care professionals. Although they are generally designed to mimic traditional design features of custom-made orthotics used in clinical practice, the effects of prefabricated insoles on plantar pressure distribution are poorly understood. OBJECTIVE: This investigation aimed to evaluate and directly compare the effects of a range of 6 different commercially available prefabricated orthotic insole designs on plantar pressure in healthy individuals. METHODS: This was a single-center, randomized, open-label, crossover investigation. In-shoe dynamic pressure (F-scan) was investigated in 24 healthy subjects with normal foot posture, wearing standard shoes alone and in combination with 6 different orthotic insoles, consecutively, measured on a single day. The biomechanical impact of each insole was determined by the statistical significance of changes from baseline measurements (standard shoe alone). RESULTS: Insoles with heel cups and medial arch geometries consistently increased contact area at medial arch and whole-foot regions and reduced both plantar peak pressure (PP) and pressure time integral at medial arch and heel regions. CONCLUSIONS: This investigation has aided in further understanding the mode of action of prefabricated insoles in a healthy population. The insoles in this study redistributed plantar pressure at key regions of the foot, based on design features common to prefabricated insoles. Prefabricated orthotic insoles represent an easily accessible means of reducing lower-body musculoskeletal stress for those who spend prolonged periods of time on their feet.