Real-world data confirm elexacftor/tezacaftor/ivacaftor modulators halves sweat chloride concentration in eligible people with cystic fibrosis.

Sweat chloride concentration, a diagnostic feature in cystic fibrosis (CF), reflects CF transmembrane conductance regulator (CFTR) activity. CFTR modulator therapies, especially elexacaftor/tezacaftor/ivacaftor (ETI), has improved CF outcomes. We report nationwide, real-world data on sweat chloride concentration in people with CF (pwCF) with and without modulator therapies. All Danish pwCF with a minimum of one F508del allele were included. Sweat chloride measurements were stratified by genotype and modulator treatment. Differences were assessed using mixed-effects models. We included 977 sweat chloride measurements from 430 pwCF, 71% of which were F508del homozygous. Heterozygous and homozygous ETI-treated pwCF had an estimated mean sweat chloride concentration of 43 mmol/L (95% confidence interval: 39; 48) and 43 mmol/L (39; 47), respectively-48% and 59% lower than those without treatment. High variation in concentrations remained regardless of treatment status. Despite ETI treatment, 27% heterozygous and 23% homozygous pwCF had elevated concentrations (≥60 mmol/L). These real-world data confirm a substantial decrease in sweat chloride concentration during modulator treatment, especially ETI, where mean concentrations halved. However, large variation remained, including persistently high concentrations. These findings emphasize the potential of sweat chloride concentration as a treatment response biomarker and the need to explore its heterogeneity and relationship with clinical outcomes.

Role of wearable electrochemical biosensors in monitoring renal function biomarkers in sweat: a review.

Real-time detection of renal biomarkers is crucial for immediate and continuous monitoring of kidney function, facilitating early diagnosis and intervention in kidney-related disorders. This proactive approach enables timely adjustments in treatment plans, particularly in critical situations, and enhances overall patient care. Wearable devices emerge as a promising solution, enabling non-invasive and real-time data collection. This comprehensive review investigates numerous types of wearable sensors designed to detect kidney biomarkers in body fluids such as sweat. It critically evaluates the precision, dependability, and user-friendliness of these devices, contemplating their seamless integration into daily life for continuous health tracking. The review highlights the potential influence of wearable technology on individualized renal healthcare and its role in preventative medicine while also addressing challenges and future directions. The review's goal is to provide guidance to academics, healthcare professionals, and technologists working on wearable solutions for renal biomarker detection by compiling the body of current knowledge and advancements.

Ontogeny of Skin Stem Cells and Molecular Underpinnings.

Skin stem cells (SCs) play a pivotal role in supporting tissue homeostasis. Several types of SCs are responsible for maintaining and regenerating skin tissue. These include bulge SCs and others residing in the interfollicular epidermis, infundibulum, isthmus, sebaceous glands, and sweat glands. The emergence of skin SCs commences during embryogenesis, where multipotent SCs arise from various precursor populations. These early events set the foundation for the diverse pool of SCs that will reside in the adult skin, ready to respond to tissue repair and regeneration demands. A network of molecular cues regulates skin SC behavior, balancing quiescence, self-renewal, and differentiation. The disruption of this delicate equilibrium can lead to SC exhaustion, impaired wound healing, and pathological conditions such as skin cancer. The present review explores the intricate mechanisms governing the development, activation, and differentiation of skin SCs, shedding light on the molecular signaling pathways that drive their fate decisions and skin homeostasis. Unraveling the complexities of these molecular drivers not only enhances our fundamental knowledge of skin biology but also holds promise for developing novel strategies to modulate skin SC fate for regenerative medicine applications, ultimately benefiting patients with skin disorders and injuries.

Skin Development and Disease: A Molecular Perspective.

Skin, the largest organ in the human body, is a crucial protective barrier that plays essential roles in thermoregulation, sensation, and immune defence. This complex organ undergoes intricate processes of development. Skin development initiates during the embryonic stage, orchestrated by molecular cues that control epidermal specification, commitment, stratification, terminal differentiation, and appendage growth. Key signalling pathways are integral in coordinating the development of the epidermis, hair follicles, and sweat glands. The complex interplay among these pathways is vital for the appropriate formation and functionality of the skin. Disruptions in multiple molecular pathways can give rise to a spectrum of skin diseases, from congenital skin disorders to cancers. By delving into the molecular mechanisms implicated in developmental processes, as well as in the pathogenesis of diseases, this narrative review aims to present a comprehensive understanding of these aspects. Such knowledge paves the way for developing innovative targeted therapies and personalised treatment approaches for various skin conditions.

Development of a 3D Hydrogel SERS Chip for Noninvasive, Real-Time pH and Glucose Monitoring in Sweat.

Traditional diagnostic methods, such as blood tests, are invasive and time-consuming, while sweat biomarkers offer a rapid physiological assessment. Surface-enhanced Raman spectroscopy (SERS) has garnered significant attention in sweat analysis because of its high sensitivity, label-free nature, and nondestructive properties. However, challenges related to substrate reproducibility and interference from the biological matrix persist with SERS. This study developed a novel ratio-based 3D hydrogel SERS chip, providing a noninvasive solution for real-time monitoring of pH and glucose levels in sweat. Encapsulating the probe molecule (4-MBN) in nanoscale gaps to form gold nanoflower-like nanotags with internal standards and integrating them into an agarose hydrogel to create a 3D flexible SERS substrate significantly enhances the reproducibility and stability of sweat analysis. Gap-Au nanopetals modified with probe molecules are uniformly dispersed throughout the porous hydrogel structure, facilitating the effective detection of the pH and glucose in sweat. The 3D hydrogel SERS chip demonstrates a strong linear relationship in pH and glucose detection, with a pH response range of 5.5-8.0 and a glucose detection range of 0.01-5 mM, with R2 values of 0.9973 and 0.9923, respectively. In actual sweat samples, the maximum error in pH detection accuracy is only 1.13%, with a lower glucose detection limit of 0.25 mM. This study suggests that the ratio-based 3D hydrogel SERS chip provides convenient, reliable, and rapid detection capabilities with substantial application potential for analyzing body fluid pH and glucose.

Hidradenocarcinoma of Nose: A Rare Case Report.

This report details the surgical management of a rare case of hidradenocarcinoma in a 70-year-old man presenting as a large multilobulated swelling on the dorsum of the nose. Following histopathological confirmation, the patient underwent wide complete excision of the tumour, coupled with sentinel lymph node dissection. Reconstruction involved the use of a paramedian forehead flap and cheek advancement flap. The successful outcome underscores the importance of early diagnosis and a comprehensive surgical approach for managing hidradenocarcinoma on the nasal dorsum.

Silk fibroin-based wearable SERS biosensor for simultaneous sweat monitoring of creatinine and uric acid.

Sweat biomarkers have the potential to offer valuable clinical insights into an individual's health and disease condition. Current sensors predominantly utilize enzymes and antibodies as biometric components to measure biomarkers present in sweat quantitatively. However, enzymes and antibodies are susceptible to interference by environmental factors, which may affect the performance of the sensor. Herein, we present a wearable microfluidic surface-enhanced Raman scattering (SERS) biosensor that enables the non-invasive and label-free detection of biomarkers in sweat. Concretely, we developed a bimetallic self-assembled anti-opal array structure with uniform hot spots, enhanced the Raman scattering effect, and integrated it into a silk fibroin-based sensing patch. Utilizing a silk fibroin substrate in the wearable SERS sensor imparts desirable properties such as softness, breathability, and biocompatibility, which enables the sensor to establish close contact with the skin without causing chemical or physical irritation. In addition, introducing microfluidic channels enables the controlled and high temporal resolution management of sweat, facilitating more efficient sweat collection. The proposed label-free SERS sensor can offer chemical 'fingerprint' information, enabling the identification of sweat analytes. As an illustration of the feasibility, we have effectively monitored the creatinine and uric acid levels in sweat. This study presents a versatile and highly sensitive approach for the simultaneous detection of biomarkers in human sweat, showcasing significant potential for application in point-of-care monitoring.

Integrated mental stress smartwatch based on sweat cortisol and HRV sensors.

Mental stress, a human's common emotion that is difficult to recognize and describe, can give rise to serious psychological disorders. Skin and sweat are easily accessible sources of biomarkers and bio-signals that contain information about mental stress. It is challenging for current wearable devices to monitor psychological stress in real-time with a non-invasive manner. Therefore, we have developed a smartwatch integrated with a sweat cortisol sensor and a heart rate variation (HRV) sensor. This smartwatch can simultaneously record the cortisol levels in sweat and HRV index in real time over a long period. The cortisol sensors based on organic electrochemical transistor (OECT) are fabricated by utilizing the Prussian-blue (PB) doped molecular imprinting polymer (MIP) modified gate electrode. The sensor signal current will decrease following the combination of sweat cortisol, due to the blocking of the PBMIP conductive path, demonstrating good sensitivity, selectivity, and stability. The HRV sensor is manufactured by a photoplethysmography method. We have integrated the two sensors into a wearable smartwatch that can match well with the mobile phone APP and the upper computer software. Through the use of this smartwatch, we have observed a negative correlation between cortisol levels in sweat and the HRV index in short-term stressful environments. Our research presents a great progress in real-time and non-invasive monitoring human's stress levels, which promotes not only the stress management, but also better psychological research.

Patterned Gold Nanoparticle Superlattice Film for Wearable Sweat Sensors.

Nanoparticle superlattices are beneficial in terms of providing strong and uniform signals in analysis owing to their closely packed uniform structures. However, nanoparticle superlattices are prone to cracking during physical activities because of stress concentrations, which hinders their detection performance and limits their analytical applications. In this work, template printing methods were used in this study to prepare a patterned gold nanoparticle (AuNP) superlattice film. By adjustment of the size of the AuNP superlattice domain below the critical size of fracture, the mechanical stability of the AuNP superlattice domain is improved. Thus, long-term sustainable high-performance signal output is achieved. The patterned AuNP superlattice film was used to construct a wearable sweat sensor based on surface-enhanced Raman scattering (SERS). The designed sensor showed promise for long-term reliable use in actual scenarios in terms of recommending water replenishment, monitoring hydration states, and tracking the intensity of activity.

Effects of individual characteristics and local body functions on sweating response: A review.

In this study, we conducted a literature review to deepen our understanding of the sweating response of the thermoregulatory system, focusing on the influence of individual characteristics and local body functions. Among the factors related to individual characteristics, improvement in aerobic fitness had a positive effect on the sweating response, whereas aging exerted an inhibitory effect. Short-term artificial acclimation and seasonal heat acclimatization promoted sweating, whereas long-term geographical acclimatization suppressed sweating. Male exhibited higher sweat rates than female when the metabolic heat production was high. Individuals with smaller surface area-to-mass ratios tended to have higher sweat rates than those with larger ratios. Regarding local body functions, sweat distribution in the resting state showed high regional sweat rates in the lower limbs and torso, with higher values in the lower limbs when in the supine position and higher values in the torso when in the seated position. During exercise, the regional sweat rates was high in the torso, whereas the limbs exhibited relatively low sweat rates. These differences in sweat distribution stem from the thermoregulatory potential of each body region, which aims to efficiently regulate body temperature. Local effects have only been examined in the thigh and forearm, with temperature coefficient Q10 ranging from 2 to 5. Only the forehead showed significantly high thermosensitivity among all body regions.

Sweat lactate sensor for detecting anaerobic threshold in heart failure: a prospective clinical trial (LacS-001).

A simple method for determining the anaerobic threshold in patients with heart failure (HF) is needed. This prospective clinical trial (LacS-001) aimed to investigate the safety of a sweat lactate-monitoring sensor and the correlation between lactate threshold in sweat (sLT) and ventilatory threshold (VT). To this end, we recruited 50 patients with HF and New York Heart Association functional classification I-II (mean age: 63.5 years, interquartile range: 58.0-72.0). Incremental exercise tests were conducted while monitoring sweat lactate levels using our sensor. sLT was defined as the first steep increase in lactate levels from baseline. Primary outcome measures were a correlation coefficient of ≥ 0.6 between sLT and VT, similarities as assessed by the Bland-Altman analysis, and standard deviation of the difference within 15 W. A correlation coefficient of 0.651 (95% confidence interval, 0.391-0.815) was achieved in 32/50 cases. The difference between sLT and VT was -4.9 ± 15.0 W. No comparative error was noted in the Bland-Altman plot. No device-related adverse events were reported among the registered patients. Our sweat lactate sensor is safe and accurate for detecting VT in patients with HF in clinical settings, thereby offering valuable additional information for treatment.

Molecularly Imprinted Wearable Sensor with Paper Microfluidics for Real-Time Sweat Biomarker Analysis.

The urgent need for real-time and noninvasive monitoring of health-associated biochemical parameters has motivated the development of wearable sweat sensors. Existing electrochemical sensors show promise in real-time analysis of various chemical biomarkers. These sensors often rely on labels and redox probes to generate and amplify the signals for the detection and quantification of analytes with limited sensitivity. In this study, we introduce a molecularly imprinted polymer (MIP)-based biochemical sensor to quantify a molecular biomarker in sweat using electrochemical impedance spectroscopy, which eliminates the need for labels or redox probes. The molecularly imprinted biosensor can achieve sensitive and specific detection of cortisol at concentrations as low as 1 pM, 1000-fold lower than previously reported MIP cortisol sensors. We integrated multimodal electrochemical sensors with an iontophoresis sweat extraction module and paper microfluidics for real-time sweat analysis. Several parameters can be simultaneously quantified, including sweat volume, secretion rate, sodium ion, and cortisol concentration. Paper microfluidic modules not only quantify sweat volume and secretion rate but also facilitate continuous sweat analysis without user intervention. While we focus on cortisol sensing as a proof-of-concept, the molecularly imprinted wearable sensors can be extended to real-time detection of other biochemicals, such as protein biomarkers and therapeutic drugs.

Antifouling and antimicrobial wearable electrochemical sweat sensors for accurate dopamine monitoring based on amyloid albumin composite hydrogels.

Wearable electrochemical sweat sensors are potentially promising for health monitoring in a continuous and non-invasive mode with high sensitivity. However, due to the complexity of sweat composition and the growth of skin bacteria, the wearable sweat sensors may gradually lose their sensitivity or even fail over time. To deal with this issue, herein, we proposed a new strategy to construct wearable sweat sensors with antifouling and antimicrobial capabilities. Amyloid albumin hydrogels (ABSAG) were doped with two-dimensional (2D) nanomaterial MXene and CeO2 nanorods to obtain the antifouling and antimicrobial amyloid albumin composite hydrogels (ABSACG, CeO2/MXene/ABSAG), and the wearable sensors were prepared by modifying flexible screen-printed electrodes with the ABSACG. Within this sensing system, the hydrophilic ABSAG possesses strong hydration capability, and it can form a hydration layer on the electrode surface to resist biofouling in sweat. The 2D nanomaterial MXene dispersed in the hydrogel endows the hydrogel with good conductivity and electrocatalytic capability, while the doping of CeO2 nanorods further improves the electrocatalytic performance of the hydrogel and also provides excellent antimicrobial capability. The designed wearable electrochemical sensors based on the ABSACG demonstrated satisfying antifouling and antimicrobial abilities, and they were capable of detecting dopamine accurately in human sweat. It is expected that wearable sensors utilizing the antifouling and antimicrobial ABSACG may find practical applications in human body fluids analysis and health monitoring.

A wearable nanozyme-enzyme electrochemical biosensor for sweat lactate monitoring.

In this study, we developed a wearable nanozyme-enzyme electrochemical biosensor that enablies sweat lactate monitoring. The biosensor comprises a flexible electrode system prepared on a polyimide (PI) film and the Janus textile for unidirectional sweat transport. We obtained favorable electrochemical activities for hydrogen peroxide reduction by modifying the laser-scribed graphene (LSG) electrode with cerium dioxide (CeO2)-molybdenum disulphide (MoS2) nanozyme and gold nanoparticles (AuNPs). By further immobilisation of lactate oxidase (LOx), the proposed biosensor achieves chronoamperometric lactate detection in artificial sweat within a range of 0.1-50.0 mM, a high sensitivity of 25.58 µA mM-1cm-2 and a limit of detection (LoD) down to 0.135 mM, which fully meets the requirements of clinical diagnostics. We demonstrated accurate lactate measurements in spiked artificial sweat, which is consistent with standard ELISA results. To monitor the sweat produced by volunteers while exercising, we conducted on-body tests, showcasing the wearable biosensor's ability to provide clinical sweat lactate diagnosis for medical treatment and sports management.

Skin-attachable Tb-MOF ratio fluorescent sensor for real-time detection of human sweat pH.

The pH of human sweat is highly related with a variety of diseases, whereas the monitoring of sweat pH still remains challenging for ordinary families. In this study, we developed a novel dual-emission Tb-MOF using DPA as the ligand and further designed and constructed a skin-attachable Tb-MOF ratio fluorescent sensor for real-time detection of human sweat pH. With the increased concentration of H+, the interaction of H+ with carbonyl organic ligand leads to the collapse of the Tb-MOF crystal structure, resulting in the interruption of antenna effect, and correspondingly increasing the emission of the ligand at 380 nm and decreasing the emission of the central ion Tb3+ at 544 nm. This Tb-MOF nanoprobe has a good linear response in the pH range of 4.12-7.05 (R2 = 0.9914) with excellent anti-interference ability. Based on the merits of fast pH response and high sensitivity, the nanoprobe was further used to prepare flexible wearable sensor. The wearable sensor can detect pH in the linear range of 3.50-6.70, which covers the pH range of normal human sweat (4.50-6.50). Subsequently, the storage stability and detection accuracy of the sensors were evaluated. Finally, the sensor has been successfully applied for the detection of pH in actual sweat samples from 21 volunteer and the real-time monitoring of pH variation during movement processing. This skin-attachable Tb-MOF sensor, with the advantages of low cost, visible color change and long shelf-life, is appealing for sweat pH monitoring especially for ordinary families.