Self-assembly of cascade nanoenzyme glucose oxidase encapsulated in copper benzenedicarboxylate for wearable sweat-glucose colorimetric sensors with smartphone readout.

BACKGROUND: With the advent of personalized medical approaches, precise and tailored treatments are expected to become widely accepted for the prevention and treatment of diabetes. Paper-based colorimetric sensors that function in combination with smartphones have been rapidly developed in recent years because it does not require additional equipment and is inexpensive and easy to perform. In this study, we developed a portable, low-cost, and wearable sweat-glucose detection device for in situ detection. RESULTS: The sensor adopted an integrated biomimetic nanoenzyme of glucose oxidase (GOx) encapsulated in copper 1, 4-benzenedicarboxylate (CuBDC) (GOx@CuBDC) through a biomimetic mineralization process. CuBDC exhibited a peroxide-like effect, cascade catalytic effect with the encapsulated GOx, and increased the enzyme stability. GOx@CuBDC and 3,3,5,5-tetramethylbenzidine were combined to form a hybrid membrane that achieved single-step paper-based glucose detection. SIGNIFICANCE AND NOVELTY: This GOx@CuBDC-based colorimetric glucose sensor was used to quantitatively analyze the sweat-glucose concentration with smartphone readings. The sensor exhibited a good linear relationship over the concentration range of 40-900 µM and a limit of detection of 20.7 µM (S/N = 3). Moreover, the sensor performed well in situ monitoring and in evaluating variations based on the consumption of foods with different glycemic indices. Therefore, the fabricated wearable sweat-glucose sensors exhibited optimal practical application performance.

CuxO decorated Ti3C2Tx MXene composites for non-enzymatic glucose sensing with large linear ranges.

Ti3C2Tx MXene/CuxO composites were prepared by acid etching combined with electrochemical technique. The abundant active sites on the surface of MXene greatly increase the loading of CuxO nanoparticles, and the synergistic effect between the different components of the composite can accelerate the oxidation reaction of glucose. The results indicate that at the working potential of 0.55 V (vs. Ag/AgCl), the glucose sensor based on Ti3C2Tx MXene/CuxO composite presents large linear concentration ranges from 1 µM to 4.655 mM (sensitivity of 361 µA mM-1 cm-2) and from 5.155 mM to 16.155 mM (sensitivity of 133 µA mM-1 cm-2). The limit of detection is 0.065 µM. In addition, the sensor effectively avoids the oxidative interference of common interfering species such as ascorbic acid, dopamine and uric acid. The sensor has good reproducibility, stability and acceptable recoveries for the detection of glucose in human sweat sample (97.5-103.3%) with RSD values less than 4%. Based on these excellent properties it has great potential for the detection of glucose in real samples.

Design of Cellulose Nanocrystal-Based Self-Healing Nanocomposite Hydrogels and Application in Motion Sensing and Sweat Detection.

Hydrogels, as flexible materials, have been widely used in the field of flexible sensors. Human sweat contains a variety of biomarkers that can reflect the physiological state of the human body. Therefore, it is of great practical significance and application value to realize the detection of sweat composition and combine it with human motion sensing through a hydrogel. Based on mussel-inspired chemistry, polydopamine (PDA) and gold nanoparticles (AuNPs) were coated on the surface of cellulose nanocrystals (CNCs) to obtain CNC-based nanocomposites (CNCs@PDA-Au), which could simultaneously enhance the mechanical, electrochemical, and self-healing properties of hydrogels. The CNCs@PDA-Au was composited with poly(vinyl alcohol) (PVA) hydrogel to obtain the nanocomposite hydrogel (PVA/CNCs@PDA-Au) by freeze-thaw cycles. The PVA/CNCs@PDA-Au has excellent mechanical strength (7.2 MPa) and self-healing properties (88.3%). The motion sensors designed with PVA/CNCs@PDA-Au exhibited a fast response time (122.9 ms), wide strain sensing range (0-600.0%), excellent stability, and fatigue resistance. With the unique electrochemical redox properties of uric acid, the designed hydrogel sensor successfully realized the detection of uric acid in sweat with a wide detection range (1.0-100.0 µmol/L) and low detection limit (0.42 µmol/L). In this study, the dual detection of human motion and uric acid in sweat was successfully realized by the designed PVA/CNCs@PDA-Au nanocomposite hydrogel.

Assessing the performance of a robust multiparametric wearable patch integrating silicon-based sensors for real-time continuous monitoring of sweat biomarkers.

The development of wearable devices for sweat analysis has experienced significant growth in the last two decades, being the main focus the monitoring of athletes health during workouts. One of the main challenges of these approaches has been to attain the continuous monitoring of sweat for time periods over 1 h. This is the main challenge addressed in this work by designing an analytical platform that combines the high performance of potentiometric sensors and a fluidic structure made of a plastic fabric into a multiplexed wearable device. The platform comprises Ion-Sensitive Field-Effect Transistors (ISFETs) manufactured on silicon, a tailor-made solid-state reference electrode, and a temperature sensor integrated into a patch-like polymeric substrate, together with the component that easily collects and drives samples under continuous capillary flow to the sensor areas. ISFET sensors for measuring pH, sodium, and potassium ions were fully characterized in artificial sweat solutions, providing reproducible and stable responses. Then, the real-time and continuous monitoring of the biomarkers in sweat with the wearable platform was assessed by comparing the ISFETs responses recorded during an 85-min continuous exercise session with the concentration values measured using commercial Ion-Selective Electrodes (ISEs) in samples collected at certain times during the session. The developed sensing platform enables the continuous monitoring of biomarkers and facilitates the study of the effects of various real working conditions, such as cycling power and skin temperature, on the target biomarker concentration levels.

A dried sweat spot paper (DSSP) method based on novel mass spectrometry probe labeling for detection and resolution of DL-lactate enantiomers as potential biomarkers for diabetes mellitus.

BACKGROUND: Human sweat can be collected non-invasively with low infectivity; however, its application as a determination method has been challenged due to the presence of trace amounts of chiral metabolites. Moreover, its application as a biological fluid for disease diagnosis has not been previously reported. In this study, the human dried sweat spot paper (DSSP) method was proposed for the derivatization of a novel mass spectrometric chiral probe, N-[1-Oxo-5-(triphenylphosphonium) pentyl]-(S)-3-aminopyrrolidine (OTPA), determination and resolution of DL-lactic acid (DL-LA) enantiomers in human elbow sweat. RESULTS: The methodological validation revealed the resolution (Rs) as 1.78, the limit of detection (S/N = 3) as 20.83 fmol, good linearity (R2 ≥ 0.9996), and the intra-day and intra-day stability with RSD ranging from 0.53 to 10.85 %, while the average recovery rate of D-LA and L-LA were 104.00 % ± 4.68 % and 107.41 % ± 8.34 %, respectively, with high accuracy. In addition, the method was applied for the determination of DL-LA in the sweat on elbow of 10 healthy volunteers and 30 diabetic patients. The results demonstrated that the D/L ratio and L/D ratio were significantly different (p < 0.0001). In addition, a moderate positive linear correlation between the D/L-LA ratio in human sweat and fasting blood glucose level (r = 0.7744, p < 0.0001) was observed, thereby suggesting that the D/L ratio of lactate in human sweat correlate the glucose level in human fasting blood. SIGNIFICANCE AND NOVELTY: The D/L lactate ratio in human sweat could be used as a potential biomarker for diabetes screening. The method can be used to screen for diabetes by providing a dry sweat paper to test equipment and has the potential to be a non-invasive early-warning diagnostic tool for diabetes.

Enhanced Sweat Biosensing with Thread-Embedded Microfluidic Devices.

BACKGROUND This study explored the integration of conductive threads into a microfluidic compact disc (CD), developed using the xurographic method, for a potential sweat biosensing platform. MATERIAL AND METHODS The microfluidic CD platform, fabricated using the xurographic method with PVC films, included venting channels and conductive threads linked to copper electrodes. With distinct microfluidic sets for load and metering, flow control, and measurement, the CD's operation involved spinning for sequential liquid movement. Impedance analysis using HIOKI IM3590 was conducted for saline and artificial sweat solutions on 4 identical CDs, ensuring reliable conductivity and measurements over a 1 kHz to 200 kHz frequency range. RESULTS Significant differences in |Z| values were observed between saline and artificial sweat treatments. 27.5 µL of saline differed significantly from 27.5 µL of artificial sweat, 72.5 µL of saline from 72.5 µL of artificial sweat, and 192.5 µL of saline from 192.5 µL of sweat. Significant disparities in |Z| values were observed between dry fibers and Groups 2, 3, and 4 (varying saline amounts). No significant differences emerged between dry fibers and Groups 6, 7, and 8 (distinct artificial sweat amounts). These findings underscore variations in fiber characteristics between equivalent exposures, emphasizing the nuanced response of the microfluidic CD platform to different liquid compositions. CONCLUSIONS This study shows the potential of integrating conductive threads in a microfluidic CD platform for sweat sensing. Challenges in volume control and thread coating degradation must be addressed for transformative biosensing devices in personalized healthcare.

Long-Term Detection of Glycemic Glucose/Hypoglycemia by Microfluidic Sweat Monitoring Patch.

A microfluidic sweat monitoring patch that collects human sweat for a long time is designed to achieve the effect of detecting the rise and fall of human sweat glucose over a long period of time by increasing the use time of a single patch. Five collection pools, four serpentine channels, and two different valves are provided. Among them, the three-dimensional valve has a large burst pressure as a balance between the internal and external air pressures of the patch. The bursting pressure of the two-dimensional diverter valve is smaller than that of the three-dimensional gas valve, and its role is to control the flow direction of the liquid. Through plasma hydrophilic treatment of different durations, the optimal hydrophilic duration is obtained. The embedded chromogenic disc detects the sweat glucose value at two adjacent time intervals and compares the information of the human body to increase or reduce glucose. The patch has good flexibility and can fit well with human skin, and because polydimethylsiloxane (PDMS) has good light transmission, it reduces the measurement error caused by the color-taking process and makes the detection results more accurate.

Development of a microfluidic wearable electrochemical sensor for the non-invasive monitoring of oxidative stress biomarkers in human sweat.

Oxidative stress is widely recognized as a pivotal factor contributing to numerous Central Nervous System (CNS) ailments. The concentrations of hydrogen peroxide (H2O2) and phosphorylated proteins within the human body serve as crucial indicators of oxidative stress. As such, the real-time monitoring of H2O2 and phosphorylated proteins in sweat is vital for the early identification, diagnosis, and management of diseases linked to oxidative stress. In this context, we present a novel microfluidic wearable electrochemical sensor by modifying the electrode with Prussian blue (PB) and loading sulfur-rich vacancy-containing molybdenum disulfide (MoS2-X) onto Multi-walled carbon nanotube (CNTs) to form coaxially layered CNTs/MoS2-X, which was then synthesized with highly dispersed titanium dioxide nanoparticles (TiO2) to synthesize CNTs/MoS2-X/TiO2 composites for the detection of human sweat H2O2 and phosphorylated proteins, respectively. This structure, with its sulfur vacancies and coaxial layering, significantly improved sensitivity of electrochemical sensors, allowing it to detect H2O2 in a range of 0.01-1 mM with a detection limit of 4.80 µM, and phosphoproteins in a range of 0.01-1 mg/mL with a threshold of 0.917 µg/mL. Furthermore, the miniature sensor demonstrates outstanding performance in detecting analytes in both simulated and real sweat. Comprehensive biosafety assessments have validated the compatibility of the electrode material, underscoring the potential of sensor as a reliable and non-invasive method for tracking biomarkers linked to CNS disorders. This microfluidic wearable electrochemical biosensor with high performance and biosafety features shows great promise for the development of cutting-edge wearable technology devices for tracking CNS disease indicators.

Preparation of Conductive Cellulose Coated with Conductive Polymer and Its Application in the Detection of pH and Characteristic Substances in Sweat.

Rich biological information in sweat provides great potential for health monitoring and management. However, due to the complexity of sweat, the development of environmentally friendly green electronic products is of great significance to the construction of ecological civilization. This study utilized a simple combination of polystyrene sulfonate sodium (PSS) and filter paper (FP) to prepare cellulose materials coated with conductive polymers, developing an electrochemical sensor based on the modified materials. The mechanical and electrochemical properties of the fabricated PSS/FP membrane were optimized by adjusting the feeding dosage of PSS. The realized PSS/FP composite containing 7% PSS displayed good conductivity (9.1 × 10-2 S/m), reducing electric resistance by 99.2% compared with the original FP membrane (6.7 × 10-4 S/m). The stable current of the membrane in simulated sweat under different pH environments is highly correlated with the pH values. Additionally, when the membrane is exposed to simulated sweat with varying ion concentrations, the current signal changes in real time with the concentration variations. The response time averages around 0.3 s.

Flexible Wearable Electrochemical Sensors Based on AuNR/PEDOT:PSS for Simultaneous Monitoring of Levodopa and Uric Acid in Sweat.

As a facile substitute for the invasive technique of blood testing, wearable electrochemical sensors exhibit high potential for the noninvasive and real-time monitoring of biomarkers in human sweat. However, owing to enzyme specificity, the simultaneous detection of multiple biomarkers by enzymatic analysis is challenging. Moreover, sweat accumulation under sensors causes sweat contamination, which hinders real-time biomarker detection from sweat. This study reports the design and fabrication of flexible wearable electrochemical sensors containing a composite comprising Au nanorods (AuNRs) and poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) for the nonenzymatic detection of levodopa (LD) and uric acid (UA) in sweat. Each sensor was integrated with a flexible three-electrode system and a microfluidic patch for sweat sampling. AuNRs immobilized by PEG-doped PEDOT:PSS showed excellent analytical performance for LD and UA at different potentials. Thus, the newly fabricated sensors could detect LD and UA over a broad detection range with high sensitivity and showed a low limit of detection for both species. On-body assessments confirmed the ability of these sensors to simultaneously detect LD and UA in real time. Therefore, this study could open new frontiers in the fabrication of wearable electrochemical sensors for the pharmacokinetic profile tracking of LD and gout management.

Dual-Function Wearable Hydrogel Optical Fiber for Monitoring Posture and Sweat pH.

In recent years, wearable devices have been widely used for human health monitoring. Such monitoring predominantly relies on the principles of optics and electronics. However, electronic detection is susceptible to electromagnetic interference, and traditional optical fiber detection is limited in functionality and unable to simultaneously detect both physical and chemical signals. Hence, a wearable, embedded asymmetric color-blocked optical fiber sensor based on a hydrogel has been developed. Its sensing principle is grounded in the total internal reflection within the optical fiber. The method for posture sensing involves changes in the light path due to fiber bending with color blocks providing wavelength-selective modulation by absorption changes. Sweat pH sensing is facilitated by variations in fluorescence intensity triggered by sweat-induced conformational changes in Rhodamine B. With just one fiber, it achieves both physical and chemical signal detection. Fabricated using a molding technique, this fiber boasts excellent biocompatibility and can accurately discern single and multiple bending points, with a recognition range of 0-90° for a single segment, a detection limit of 0.02 mm-1 and a sweat pH sensing linear regression R2 of 0.993, alongside great light propagation properties (-0.6 dB·cm-1). With its extensive capabilities, it holds promise for applications in medical monitoring.

Smartphone based wearable sweat glucose sensing device correlated with machine learning for real-time diabetes screening.

BACKGROUND: Diabetes is a significant health threat, with its prevalence and burden increasing worldwide indicating its challenge for global healthcare management. To decrease the disease severity, the diabetic patients are recommended to regularly check their blood glucose levels. The conventional finger-pricking test possesses some drawbacks, including painfulness and infection risk. Nowadays, smartphone has become a part of our lives offering an important benefit in self-health monitoring. Thus, non-invasive wearable sweat glucose sensor connected with a smartphone readout is of interest for real-time glucose detection. RESULTS: Wearable sweat glucose sensing device is fabricated for self-monitoring of diabetes. This device is designed as a body strap consisting of a sensing strip and a portable potentiostat connected with a smartphone readout via Bluetooth. The sensing strip is modified by carbon nanotubes (CNTs)-cellulose nanofibers (CNFs), followed by electrodeposition of Prussian blue. To preserve the activity of glucose oxidase (GOx) immobilized on the modified sensing strip, chitosan is coated on the top layer of the electrode strip. Herein, machine learning is implemented to correlate between the electrochemical results and the nanomaterial content along with deposition cycle of prussian blue, which provide the highest current response signal. The optimized regression models provide an insight, establishing a robust framework for design of high-performance glucose sensor. SIGNIFICANCE: This wearable glucose sensing device connected with a smartphone readout offers a user-friendly platform for real-time sweat glucose monitoring. This device provides a linear range of 0.1-1.5 mM with a detection limit of 0.1 mM that is sufficient enough for distinguishing between normal and diabetes patient with a cut-off level of 0.3 mM. This platform might be an alternative tool for improving health management for diabetes patients.

Sensing patches for biomarker identification in skin-derived biofluids.

In conventional clinical disease diagnosis and screening based on biomarker detection, most analysis samples are collected from serum, blood. However, these invasive collection methods require specific instruments, professionals, and may lead to infection risks. Additionally, the diagnosis process suffers from untimely results. The identification of skin-related biomarkers plays an unprecedented role in early disease diagnosis. More importantly, these skin-mediated approaches for collecting biomarker-containing biofluid samples are noninvasive or minimally invasive, which is more preferable for point-of-care testing (POCT). Therefore, skin-based biomarker detection patches have been promoted, owing to their unique advantages, such as simple fabrication, desirable transdermal properties and no requirements for professional medical staff. Currently, the skin biomarkers extracted from sweat, interstitial fluid (ISF) and wound exudate, are achieved with wearable sweat patches, transdermal MN patches, and wound patches, respectively. In this review, we detail these three types of skin patches in biofluids collection and diseases-related biomarkers identification. Patch classification and the corresponding manufacturing as well as detection strategies are also summarized. The remaining challenges in clinical applications and current issues in accurate detection are discussed for further advancement of this technology (Scheme 1).

Fully Integrated Multiplexed Wristwatch for Real-Time Monitoring of Electrolyte Ions in Sweat.

Considerable progress has already been made in sweat sensors based on electrochemical methods to realize real-time monitoring of biomarkers. However, realizing long-term monitoring of multiple targets at the atomic level remains extremely challenging, in terms of designing stable solid contact (SC) interfaces and fully integrating multiple modules for large-scale applications of sweat sensors. Herein, a fully integrated wristwatch was designed using mass-manufactured sensor arrays based on hierarchical multilayer-pore cross-linked N-doped porous carbon coated by reduced graphene oxide (NPCs@rGO-950) microspheres with high hydrophobicity as core SC, and highly selective monitoring simultaneously for K+, Na+, and Ca2+ ions in human sweat was achieved, exhibiting near-Nernst responses almost without forming an interfacial water layer. Combined with computed tomography, solid-solid interface potential diffusion simulation results reveal extremely low interface diffusion potential and high interface capacitance (598 µF), ensuring the excellent potential stability, reversibility, repeatability, and selectivity of sensor arrays. The developed highly integrated-multiplexed wristwatch with multiple modules, including SC, sensor array, microfluidic chip, signal transduction, signal processing, and data visualization, achieved reliable real-time monitoring for K+, Na+, and Ca2+ ion concentrations in sweat. Ingenious material design, scalable sensor fabrication, and electrical integration of multimodule wearables lay the foundation for developing reliable sweat-sensing systems for health monitoring.

Bio-inspired hierarchical wearable patch for fast sweat collection.

Sweat contains abundant physiological and metabolic data to evaluate an individual's physical health. Since the non-exercise sweat secretion rate is low, with an average value of 1-10 µl h-1 cm-2, sweat is generally collected during exercise for existing wearable sweat sensors. To expand their applications to include daily scenarios, these sensors developed for sports and fitness are challenged by the difficulty of collecting trace amounts of sweat. This study proposes a wearable patch inspired by the hierarchical structure of Sarracenia trichomes, allowing for the spontaneous and fast collection of a small amount of secreted sweat. The patch contains microfluidic channels featuring a 20 µm-wide rib structure, fully utilizing the capillary force, thereby eliminating the issue of sweat hysteresis. Furthermore, with only 0.5 µl of the sweat secreted at the collection site, it can converge on the detection medium located within the center reservoir. Volunteer verification demonstrated a twofold increase in sweat collection efficiency compared to traditional wearable patches. This patch serves as an efficient sweat-collection configuration, promising potential for diverse in situ sweat colorimetric analyses.

[Non-invasive glucose measurements : where do we stand?] / Mesures du glucose non invasives : où en est-on ?

The technologies used to measure blood glucose have significantly evolved the past few years, especially with the introduction of continuous interstitial glucose measurements, simplifying the management of the disease. More recently, there has been a lot of interest regarding some potential revolutionary methods, such as smartwatches, and glucose measurements in sweat, saliva, and even tears. In this article, we review the different technologies that are under development, and notice that although promising, they rest imprecise. False measurements can have fatal consequences for our patients. Nevertheless, these innovations are promising and have the potential to change the daily life of people with diabetes in the future.

Les technologies utilisées pour mesurer les glycémies des personnes présentant un diabète ont beaucoup évolué ces dernières années, avec notamment l'introduction des mesures interstitielles en continu, rendant le contrôle glycémique plus aisé. Depuis peu, il y a un intérêt croissant, notamment dans les médias, autour de potentielles méthodes révolutionnaires via des montres intelligentes, la sueur, la salive et même les larmes. Dans cet article, nous répertorions les différentes technologies en cours d'investigation et notons que plusieurs d'entre elles restent imprécises, empêchant leur utilisation pour nos patients diabétiques, chez qui des mesures incorrectes peuvent avoir de graves conséquences. Néanmoins, ces nouveautés sont prometteuses et ont le potentiel de changer le quotidien des personnes présentant un diabète dans le futur.

Recent advances in biosensors based on metal-oxide semiconductors system-integrated into bioelectronics.

Metal-oxide semiconductors (MOSs) have emerged as pivotal components in technology related to biosensors and bioelectronics. Detecting biomarkers in sweat provides a glimpse into an individual's metabolism without the need for sample preparation or collection steps. The distinctive attributes of this biosensing technology position it as an appealing option for biomedical applications beyond the scope of diagnosis and healthcare monitoring. This review encapsulates ongoing developments of cutting-edge biosensors based on MOSs. Recent advances in MOS-based biosensors for human sweat analyses are reviewed. Also discussed is the progress in sweat-based biosensing technologies to detect and monitor diseases. Next, system integration of biosensors is demonstrated ultimately to ensure the accurate and reliable detection and analysis of target biomarkers beyond individual devices. Finally, the challenges and opportunities related to advanced biosensors and bioelectronics for biomedical applications are discussed.

3D-Printed Flexible Microfluidic Health Monitor for In Situ Sweat Analysis and Biomarker Detection.

Wearable sweat biosensors have shown great progress in noninvasive, in situ, and continuous health monitoring to demonstrate individuals' physiological states. Advances in novel nanomaterials and fabrication methods promise to usher in a new era of wearable biosensors. Here, we introduce a three-dimensional (3D)-printed flexible wearable health monitor fabricated through a unique one-step continuous manufacturing process with self-supporting microfluidic channels and novel single-atom catalyst-based bioassays for measuring the sweat rate and concentration of three biomarkers. Direct ink writing is adapted to print the microfluidic device with self-supporting structures to harvest human sweat, which eliminates the need for removing sacrificial supporting materials and addresses the contamination and sweat evaporation issues associated with traditional sampling methods. Additionally, the pick-and-place strategy is employed during the printing process to accurately integrate the bioassays, improving manufacturing efficiency. A single-atom catalyst is developed and utilized in colorimetric bioassays to improve sensitivity and accuracy. A feasibility study on human skin successfully demonstrates the functionality and reliability of our health monitor, generating reliable and quantitative in situ results of sweat rate, glucose, lactate, and uric acid concentrations during physical exercise.

Personalized Hydration Strategy to Improve Fluid Balance and Intermittent Exercise Performance in the Heat.

Sweat rate and electrolyte losses have a large inter-individual variability. A personalized approach to hydration can overcome this issue to meet an individual's needs. This study aimed to investigate the effects of a personalized hydration strategy (PHS) on fluid balance and intermittent exercise performance. Twelve participants conducted 11 laboratory visits including a VO2max test and two 5-day trial arms under normothermic (NOR) or hyperthermic (HYP) environmental conditions. Each arm began with three days of familiarization exercise followed by two random exercise trials with either a PHS or a control (CON). Then, participants crossed over to the second arm for: NOR+PHS, NOR+CON, HYP+PHS, or HYP+CON. The PHS was prescribed according to the participants' fluid and sweat sodium losses. CON drank ad libitum of commercially-available electrolyte solution. Exercise trials consisted of two phases: (1) 45 min constant workload; (2) high-intensity intermittent exercise (HIIT) until exhaustion. Fluids were only provided in phase 1. PHS had a significantly greater fluid intake (HYP+PHS: 831.7 ± 166.4 g; NOR+PHS: 734.2 ± 144.9 g) compared to CON (HYP+CON: 369.8 ± 221.7 g; NOR+CON: 272.3 ± 143.0 g), regardless of environmental conditions (p < 0.001). HYP+CON produced the lowest sweat sodium concentration (56.2 ± 9.0 mmol/L) compared to other trials (p < 0.001). HYP+PHS had a slower elevated thirst perception and a longer HIIT (765 ± 452 s) compared to HYP+CON (548 ± 283 s, p = 0.04). Thus, PHS reinforces fluid intake and successfully optimizes hydration status, regardless of environmental conditions. PHS may be or is an important factor in preventing negative physiological consequences during high-intensity exercise in the heat.

Altered Sweat Composition Due to Changes in Tight Junction Expression of Sweat Glands in Cholinergic Urticaria Patients.

In cholinergic urticaria (CholU), small, itchy wheals are induced by exercise or passive warming and reduced sweating has been reported. Despite the described reduced muscarinic receptor expression, sweat duct obstruction, or sweat allergy, the underlying pathomechanisms are not well understood. To gain further insights, we collected skin biopsies before and after pulse-controlled ergometry and sweat after sauna provocation from CholU patients as well as healthy controls. CholU patients displayed partially severely reduced local sweating, yet total sweat volume was unaltered. However, sweat electrolyte composition was altered, with increased K+ concentration in CholU patients. Formalin-fixed, paraffin-embedded biopsies were stained to explore sweat leakage and tight junction protein expression. Dermcidin staining was not found outside the sweat glands. In the secretory coils of sweat glands, the distribution of claudin-3 and -10b as well as occludin was altered, but the zonula occludens-1 location was unchanged. In all, dermcidin and tight junction protein staining suggests an intact barrier with reduced sweat production capability in CholU patients. For future studies, an ex vivo skin model for quantification of sweat secretion was established, in which sweat secretion could be pharmacologically stimulated or blocked. This ex vivo model will be used to further investigate sweat gland function in CholU patients and decipher the underlying pathomechanism(s).