Search Results (20)

Cystic fibrosis (CF) is a chronic, autosomal-recessive disorder caused by mutations in the CFTR gene, leading to thickened secretions that affect multiple organ systems. This study examines the effectiveness of Georgia’s national CF screening program, which was initiated in 2012 and includes the measurement of immunoreactive trypsinogen (IRT) levels at birth. An analysis of data from 2022 and 2023 revealed a decrease in follow-up attendance for sweat chloride testing among newborns with elevated IRT levels, from 59.9% to 51.2%. The birth prevalence of cystic fibrosis in Georgia varied, suggesting a need to improve both the accessibility of free testing and the quality of follow-up care. Identified barriers include limited access to screening results for pediatricians and the cost of follow-up tests. Recommendations include incorporating free sweat chloride and genetic testing into the national program, as well as improving community education and coordination with social agencies. The identification of 29 CFTR mutations in patients underscores the importance of continued genetic counseling. Overall, while the screening program shows promise, addressing these barriers is essential to improve outcomes and ensure the timely diagnosis and management of cystic fibrosis in Georgia. Full article

Deodorants and antiperspirants available on the market are designed to reduce the discomfort associated with sweating. This study examined the types of active substances contained in deodorants and antiperspirants from international cosmetic brands available in Poland (part of the EU market) and the frequency of their use. Product compositions were analysed based on INCI (International Nomenclature of Cosmetic Ingredients) product labels. The investigation included the following 170 cosmetic products: 50 spray deodorants (from 50 different brands); 50 roll-on deodorants (from 50 brands); 20 stick deodorants (from 20 brands); 40 roll-on antiperspirants (from 40 brands); and 10 stick antiperspirants (from 10 brands). The most popular active components were Triethyl Citrate (51/120 formulations; 42.5%), followed by Alcohol (25.8%), Ethylhexylglycerin (25.0%), Caprylyl Glycol (12.5%), and Potassium Alum (10.0%). Antiperspirant products were dominated by aluminium-based compounds, with the most frequently used being the following aluminium-based salts: Aluminium Chlorohydrate (67.5%), Aluminium Sesquichlorohydrate (25.0%), and Aluminium Chloride (12.5%). In contrast, aluminium–zirconium complexes, such as Aluminum Zirconium Tri-, Penta-, and Octachlorohydrex Gly, were rarely used by cosmetic manufacturers. Additionally, composition complexity, i.e., the number of deodorizing and anti-sweating ingredients per single formulation, was examined for roll-on deodorants, stick deodorants, and roll-on antiperspirants. All tested antiperspirants and most deodorants contained fragrance-imparting ingredients; the most popular were Parfum/Fragrance, Limonene, Linalool, Citronellol, Citral, Benzyl Salicylate, Hexyl Cinnamal, and Geraniol. Full article

pH regulation in human biofluids is a crucial step for disease diagnosis and health monitoring. Traditional pH sensors are limited by their bulky size in wearable systems, and fragile glass tips require frequent calibration, thus limiting their use in continuous monitoring. Flexible sensors, particularly those utilizing microwires and thread-based substrates, present advantages for small sample analysis, including natural breathability and suitability for bandage or textile integration. This study examines iridium oxide and silver–silver chloride coated on thin gold wires, fabricated using sol–gel and dip-coating processes known for their simplicity. The flexible microwires demonstrated promising pH performance from a study of their pH characteristics, sensitivity, hysteresis, and potential drift. Electrodes tested in microwells allowed for small sample volumes and localized pH measurement in a controlled environment. Additional integration into fabrics for sweat sensing in wearables highlighted their potential for continuous, real-time health monitoring applications. Full article

The monitoring of potassium ion (K⁺) levels in human sweat can provide valuable insights into electrolyte balance and muscle fatigue non-invasively. However, existing laboratory techniques for sweat testing are complex, while wearable sensors face limitations like drift, fouling and interference from ions such as Na⁺. This work develops printed electrodes using β-cyclodextrin functionalized reduced graphene oxide (β-CD-RGO) for selective K⁺ quantification in sweat. The β-CD prevents the aggregation of RGO sheets while also providing selective binding sites for K⁺ capture. Electrodes were fabricated by screen printing the β-CD-RGO ink onto conductive carbon substrates. Material characterization confirmed the successful functionalization of RGO with β-CD. Cyclic voltammetry (CV) showed enhanced electrochemical behavior for β-CD-RGO-printed electrodes compared with bare carbon and RGO. Sensor optimization resulted in a formulation with 30% β-CD-RGO loading. The printed electrodes were drop-casted with an ion-selective polyvinyl chloride (PVC) membrane. A linear range from 10 μM to 100 mM was obtained along with a sensitivity of 54.7 mV/decade. The sensor showed good reproducibility over 10 cycles in 10 mM KCl. Minimal interference from 100 mM Na⁺ and other common sweat constituents validated the sensor’s selectivity. On-body trials were performed by mounting the printed electrodes on human subjects during exercise. The K⁺ levels measured in sweat were found to correlate well with serum analysis, demonstrating the sensor’s ability for non-invasive electrolyte monitoring. Overall, the facile synthesis of stable β-CD-RGO inks enables the scalable fabrication of wearable sensors for sweat potassium detection. Full article

CFTR modulator therapy with elexacaftor/tezacaftor/ivacaftor (ETI) has been approved for people with CF and at least one F508del allele in Europe. In the US, the ETI label has been expanded to 177 rare CFTR mutations responsive in Fischer rat thyroid cells, including G85E, but not N1303K. However, knowledge on the effect of ETI on G85E or N1303K CFTR function remains limited. In vitro effects of ETI were measured in primary human nasal epithelial cultures (pHNECs) of a G85E homozygous patient and an N1303K homozygous patient. Effects of ETI therapy in vivo in these patients were assessed using clinical outcomes, including multiple breath washout and lung MRI, and the CFTR biomarkers sweat chloride concentration (SCC), nasal potential difference (NPD) and intestinal current measurement (ICM), before and after initiation of ETI. ETI increased CFTR-mediated chloride transport in G85E/G85E and N1303K/N1303K pHNECs. In the G85E/G85E and the N1303K/N1303K patient, we observed an improvement in lung function, SCC, and CFTR function in the respiratory and rectal epithelium after initiation of ETI. The approach of combining preclinical in vitro testing with subsequent in vivo verification can facilitate access to CFTR modulator therapy and enhance precision medicine for patients carrying rare CFTR mutations. Full article

The sweat test (ST) is the current diagnostic gold standard for cystic fibrosis (CF). Many CF centres have switched from the Gibson–Cooke method to the Macroduct system-based method. We used these methods simultaneously to compare CF screening outcomes. STs using both methods were performed simultaneously between March and December 2022 at CF Centre in Florence. We included newborns who underwent newborn bloodspot screening (NBS), newborns undergoing transfusion immediately after birth, and children with CF screen-positive, inconclusive diagnosis (CFSPID). We assessed 72 subjects (median age 4.4 months; range 0–76.7): 30 (41.7%) NBS-positive, 18 (25.0%) newborns who underwent transfusion, and 24 (33.3%) children with CFSPID. No significant differences were found between valid sample numbers, by patient ages and groups (p = 0.10) and between chloride concentrations (p = 0.13), except for sweat chloride (SC) measured by the Gibson–Cooke and Macroduct methods in CFSPID group (29.0, IQR: 20.0–48.0 and 22.5, IQR: 15.5–30.8, respectively; p = 0.01). The Macroduct and Gibson–Cooke methods showed substantial agreement with the SC values, except for CFSPID, whose result may depend on the method of sweat collection. In case of invalid values with Macroduct, the test should be repeated with Gibson–Cooke method. Full article

The ion-sensitive field-effect transistor is a well-established electronic device typically used for pH sensing. The usability of the device for detecting other biomarkers in easily accessible biologic fluids, with dynamic range and resolution compliant with high-impact medical applications, is still an open research topic. Here, we report on an ion-sensitive field-effect transistor that is able to detect the presence of chloride ions in sweat with a limit-of-detection of 0.004 mol/m³. The device is intended for supporting the diagnosis of cystic fibrosis, and it has been designed considering two adjacent domains, namely the semiconductor and the electrolyte containing the ions of interest, by using the finite element method, which models the experimental reality with great accuracy. According to the literature explaining the chemical reactions that take place between the gate oxide and the electrolytic solution, we have concluded that anions directly interact with the hydroxyl surface groups and replace protons previously adsorbed from the surface. The achieved results confirm that such a device can be used to replace the traditional sweat test in the diagnosis and management of cystic fibrosis. In fact, the reported technology is easy-to-use, cost-effective, and non-invasive, leading to earlier and more accurate diagnoses. Full article

Wearable sensors for sweat biomarkers can provide facile analyte capability and monitoring for several diseases. In this work, a green wearable sensor for sweat absorption and chloride sensing is presented. In order to produce a sustainable device, polylactic acid (PLA) was used for both the substrate and the sweat absorption pad fabrication. The sensor material for chloride detection consisted of silver-based reference, working, and counter electrodes obtained from upcycled compact discs. The PLA substrates were prepared by thermal bonding of PLA sheets obtained via a flat die extruder, prototyped in single functional layers via CO₂ laser cutting, and bonded via hot-press. The effect of cold plasma treatment on the transparency and bonding strength of PLA sheets was investigated. The PLA membrane, to act as a sweat absorption pad, was directly deposited onto the membrane holder layer by means of an electrolyte-assisted electrospinning technique. The membrane adhesion capacity was investigated by indentation tests in both dry and wet modes. The integrated device made of PLA and silver-based electrodes was used to quantify chloride ions. The calibration tests revealed that the proposed sensor platform could quantify chloride ions in a sensitive and reproducible way. The chloride ions were also quantified in a real sweat sample collected from a healthy volunteer. Therefore, we demonstrated the feasibility of a green and integrated sweat sensor that can be applied directly on human skin to quantify chloride ions. Full article

In clinical routine, the diagnosis of cystic fibrosis (CF) is still challenging regardless of international consensus on diagnosis guidelines and tests. For decades, the classical Gibson and Cooke test measuring sweat chloride concentration has been a keystone, yet, it may provide normal or equivocal results. As of now, despite the combination of sweat testing, CFTR genotyping, and CFTR functional testing, a small fraction (1–2%) of inconclusive diagnoses are reported and justifies the search for new CF biomarkers. More importantly, in the context of precision medicine, with a view to early diagnosis, better prognosis, appropriate clinical follow-up, and new therapeutic development, discovering companion biomarkers of CF severity and phenotypic rescue are of utmost interest. To date, previous sweat proteomic studies have already documented disease-specific variations of sweat proteins (e.g., in schizophrenia and tuberculosis). In the current study, sweat samples from 28 healthy control subjects and 14 patients with CF were analyzed by nanoUHPLC-Q-Orbitrap-based shotgun proteomics, to look for CF-associated changes in sweat protein composition and abundance. A total of 1057 proteins were identified and quantified at an individual level, by a shotgun label-free approach. Notwithstanding similar proteome composition, enrichment, and functional annotations, control and CF samples featured distinct quantitative proteome profiles significantly correlated with CF, accounting for the respective inter-individual variabilities of control and CF sweat. All in all: (i) 402 sweat proteins were differentially abundant between controls and patients with CF, (ii) 68 proteins varied in abundance between F508del homozygous patients and patients with another genotype, (iii) 71 proteins were differentially abundant according to the pancreatic function, and iv) 54 proteins changed in abundance depending on the lung function. The functional annotation of pathophysiological biomarkers highlighted eccrine gland cell perturbations in: (i) protein biosynthesis and trafficking, (ii) CFTR proteostasis and membrane stability, and (iii) cell-cell adherence, membrane integrity, and cytoskeleton crosstalk. Cytoskeleton-related biomarkers were of utmost interest because of the consistency between variations observed here in CF sweat and variations previously documented in other CF tissues. From a clinical stance, nine candidate biomarkers of CF diagnosis (CUTA, ARG1, EZR, AGA, FLNA, MAN1A1, MIA3, LFNG, SIAE) and seven candidate biomarkers of CF severity (ARG1, GPT, MDH2, EML4 (F508del homozygous), MGAT1 (pancreatic insufficiency), IGJ, TOLLIP (lung function impairment)) were deemed suitable for further verification. Full article

An important goal to achieve sustainable development is to use raw materials that are easily recyclable and renewable, locally available, and eco-friendly. Sheep wool, composed of 60% animal protein fibers, 10% fat, 15% moisture, 10% sheep sweat, and 5% contaminants on average, is an easily recyclable, easily renewable, and environmentally friendly source of raw material. In this study, slump testing, compressive and flexural strengths, ultrasonic pulse velocity, sorptivity, and chloride penetration tests were investigated to assess the influence of wool fibers on the strength and transport properties of concrete composites. Ordinary Portland cement was used to make five concrete mixes incorporating conventional wool fibers (WFs) ranging from 0.5 to 2.5% and a length of 70 mm. The wool fibers were modified (MWFs) via a pre-treatment technique, resulting in five different concrete compositions with the same fiber content. The addition of WF and MWF to fresh concrete mixes resulted in a decrease in slump values. The compressive strength of concrete was reduced when wool fibers were added to the mix. The MWF mixes, however, achieved compressive strength values of more than 30 MPa after a 90-day curing period. Furthermore, by including both WF and MWF, the flexural strength was higher than that of plain concrete. In addition, adding fibers with volume fractions of up to 2% reduced the concrete composite’s sorptivity rate and chloride penetration depths for both WF and MWF content mixes. Consequently, biomass waste like sheep wool could be recycled and returned to the field following the circular economy and waste valorization principles. Full article

Cystic fibrosis, a multi-organ genetic disease, is characterized by abnormal function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, a chloride channel at the apical membrane of several epithelia. In recent years, therapeutic strategies have been developed to correct the CFTR defect. To evaluate CFTR function at baseline for diagnosis, or the efficacy of CFTR-restoring therapy, reliable tests are needed to measure CFTR function, in vitro, ex vivo and in vivo. In vitro techniques either directly or indirectly measure ion fluxes; direct measurement of ion fluxes and quenching of fluorescence in cell-based assays, change in transmembrane voltage or current in patch clamp or Ussing chamber, swelling of CFTR-containing organoids by secondary water influx upon CFTR activation. Several cell or tissue types can be used. Ex vivo and in vivo assays similarly evaluate current (intestinal current measurement) and membrane potential differences (nasal potential difference), on tissues from individual patients. In the sweat test, the most frequently used in vivo evaluation of CFTR function, chloride concentration or stimulated sweat rate can be directly measured. Here, we will describe the currently available bio-assays for quantitative evaluation of CFTR function, their indications, advantages and disadvantages, and correlation with clinical outcome measures. Full article

A new method for the determination of chloride anions in sweat is described. The novelty of the method relies on the different photochemical response of silver ions and silver chloride crystals when exposed to UV light. Silver ions undergo an intense colorimetric transition from colorless to dark grey-brown due to the formation of nanosized Ag while AgCl exhibits a less intense color change from white to slightly grey. The analytical signal is obtained as mean grey value of color intensity on the paper surface and is expressed as the absolute difference between the signal of the blank (i.e., in absence of chloride) and the sample (i.e., in the presence of chloride). The method is simple to perform (addition of sample, incubation in the absence of light, irradiation, and offline measurement in a flatbed scanner), does not require any special signal processing steps (the color intensity is directly measured from a constant window on the paper surface without any imager processing) and is performed with minimum sample volume (2 μL). The method operates within a large chloride concentration range (10–140 mM) with good detection limits (2.7 mM chloride), satisfactory recoveries (95.2–108.7%), and reproducibility (<9%). Based on these data the method could serve as a potential tool for the diagnosis of cystic fibrosis through the determination of chloride in human sweat. Full article

We evaluated the effectiveness and safety of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) in three subjects carrying the Phe508del/unknown CFTR genotype. An ex vivo analysis on nasal epithelial cells (NEC) indicated a significant improvement of CFTR gating activity after the treatment. Three patients were enrolled in an ELX/TEZ/IVA managed-access program, including subjects with the highest percent predicted Forced Expiratory Volume in the 1st second (ppFEV₁) < 40 in the preceding 3 months. Data were collected at baseline and after 8, 12 and 24 weeks of follow-up during treatment. All patients showed a considerable decrease of sweat chloride (i.e., meanly about 60 mmol/L as compared to baseline), relevant improvement of ppFEV₁ (i.e., >8) and six-minute walk test, and an increase in body mass index after the first 8 weeks of treatment. No pulmonary exacerbations occurred during the 24 weeks of treatment and all domains of the CF Questionnaire-Revised improved. No safety concerns related to the treatment occurred. This study demonstrates the benefit from the ELX/TEZ/IVA treatment in patients with CF with the Phe508del and one unidentified CFTR variant. The preliminary ex vivo analysis of the drug response on NEC helps to predict the in vivo therapeutic endpoints. Full article

With the advent of CFTR modulators, surrogate outcome parameters that accurately quantify the improvement in CFTR activity are needed. In vivo biomarkers that reflect CFTR ion transport and can serve as outcomes in the treatment of CFTR modulators are the sweat Cl⁻ test (SCT), the nasal potential difference (NPD) measurement or the intestinal current measurement (ICM). This review focus on the SCT and NPD. The SCT displays a low intra-patient variability in contrast to the NPD. It has been used extensively as a biomarker of CFTR function in clinical trials of CFTR modulator therapies and provides evidence for change in the short term. The level of functional rescue in the NPD increases up to 40% of normal CFTR in patients with a Gly551Asp treated with ivacaftor monotherapy, while in F508del homozygous patients treated with ivacaftor-lumacaftor, activity increased on average up to ~20% of normal activity. While both tests provide evidence of the effect on CFTR activity, they cannot be used at an individual level to predict the response to any CFTR modulators. Nevertheless, their rapid modification, reflecting electrophysiological properties, highlight their potential use in proof-of-concept studies for CFTR modulators. Full article

This work describes a multisensing wearable platform for monitoring biomarkers in sweat during the practice of exercise. Five electrochemical sensors for pH, potassium, sodium, chloride, and lactate were implemented in a flexible patch approach, together with a paper microfluidic component, to continuously measure sweat composition. The sensors are fabricated with silicon technologies: ion selective field effect transistors (ISFETs) for pH and ionic species; and a gold thin-film microelectrode for lactate. The latter includes a polymeric membrane based on an electropolymerized polypyrroled structure, where all the biocomponents required for carrying out the lactate analyses are entrapped. The flexible patch is fabricated using hybrid integration technologies, including printed pads defined on a polyimide (Kapton^®) substrate and wire bonding encapsulation of silicon chips. To fix and align the sensors to the flexible substrate, different laminated materials, such as polymethyl methacrylate (PMMA), polydimethylsiloxane (PDMS), and silicone-based adhesive, were used. The first results show good performance of the sensors—ISFETS sensitivity between 54–59 mV dec⁻¹ for ion ranges in sweat from 2 to 100 mM and lactate sensor sensitivity of −135 × 102 µA M⁻¹ cm⁻² for the range of 2–50 mM. The microfluidic platform has been tested in terms of adequate sensor wettability and rapid response during the time span of exercise activity (2 h) showing excellent results. Full article