Wearable sweat chloride sensors: materials, fabrication and their applications.

Chloride is a crucial anion required for multiple functions in the human body including maintaining acid-base balance, fluid balance, electrical neutrality and supporting muscles and nerve cells. Low-chloride levels can cause nausea, diarrhoea, etc. Chloride levels are measured in different body fluids such as urine, serum, sweat and saliva. Sweat chloride measurements are used for multiple applications including disease diagnosis, sports monitoring, and geriatric care. For instance, a sweat chloride test is performed for cystic fibrosis screening. Further, sweat also offers continuous non-invasive access to body fluids for real-time monitoring of chloride that could be used for sports and geriatric care. This review focuses on wearable chloride sensors that are used for periodic and continuous chloride monitoring. The multiple sections in the paper discuss the clinical significance of chloride, detection methods, sensor fabrication methods and their application in cystic fibrosis screening, sports and geriatric care. Finally, the last section discusses the limitation of current sensors and future directions for wearable chloride sensors.

Menopausal vasomotor symptoms and plasma Alzheimer disease biomarkers.

BACKGROUND: Identifying risk factors for Alzheimer disease in women is important as women compose two-thirds of individuals with Alzheimer disease. Previous work links vasomotor symptoms, the cardinal menopausal symptom, with poor memory performance and alterations in brain structure, function, and connectivity. These associations are evident when vasomotor symptoms are monitored objectively with ambulatory skin conductance monitors. OBJECTIVE: This study aimed to determine whether vasomotor symptoms are associated with Alzheimer disease biomarkers. STUDY DESIGN: Between 2017 and 2020, the MsBrain study enrolled 274 community-dwelling women aged 45 to 67 years who had a uterus and at least 1 ovary and were late perimenopausal or postmenopausal status. The key exclusion criteria included neurologic disorder, surgical menopause, and recent use of hormonal or nonhormonal vasomotor symptom treatment. Women underwent 24 hours of ambulatory skin conductance monitoring to assess vasomotor symptoms. Plasma concentrations of Alzheimer disease biomarkers, including amyloid ß 42-to-amyloid ß 40 ratio, phosphorylated tau (181 and 231), glial fibrillary acidic protein, and neurofilament light, were measured using a single-molecule array (Simoa) technology. Associations between vasomotor symptoms and Alzheimer disease biomarkers were assessed via linear regression models adjusted for age, race and ethnicity, education, body mass index, and apolipoprotein E4 status. Additional models adjusted for estradiol and sleep. RESULTS: A total of 248 (mean age, 59.06 years; 81% White; 99% postmenopausal status) of enrolled MsBrain participants contributed data. Objectively assessed vasomotor symptoms occurring during sleep were associated with significantly lower amyloid ß 42/amyloid ß 40, (beta, -.0010 [standard error, .0004]; P=.018; multivariable), suggestive of greater brain amyloid ß pathology. The findings remained significant after additional adjustments for estradiol and sleep. CONCLUSION: Nighttime vasomotor symptoms may be a marker of women at risk of Alzheimer disease. It is yet unknown if these associations are causal.

Hydration and Performance in Young Triathletes During a Competition in Tropical Climate.

PURPOSE: We examined fluid intake, the relation between body mass (BM) loss and performance, and core temperature in young triathletes during a competition in tropical climate. METHODS: Fluid intake and pre and post BM were measured in 35 adolescent athletes, and core temperature was measured in one female and one male. RESULTS: Mean urine specific gravity (1.024 [0.007]) indicated that athletes were in suboptimal state of hydration upon waking. Race time was 73.2 (8.0) minutes. BM decreased by 0.6 (0.3) kg (P < .05). Fluid intake (528.5 [221.6] mL) replaced 47% of the fluid loss (1184.9 [256.4] mL) and was higher during run (11.5 [6.6] mL·min-1) compared to bike (7.3 [3.1] mL·min-1), P < .01. Loss in BM was ≥1.0% in 66% and ≥1.5% in 29% of the athletes. Males showed a moderate association between percentage loss in BM and finishing time (r = -.52), higher sweat rates (1.0 [0.3] L·h-1), and faster times (69.4 [7.5] min; P < .05). Core temperature rose to 40.1 °C in the female and 39.6 °C in the male. CONCLUSION: Young triathletes competing in a hot/humid climate became mildly to moderately dehydrated and hyperthermic even when water and sports drinks were available but did not show symptoms of heat illness.

Compensatory Hyperhidrosis After Non-Surgical Treatment of Primary Focal Hyperhidrosis: Two-Year Single-Centered Prospective Study From Jordan.

BACKGROUND: Primary focal hyperhidrosis (PH) can be managed by a wide range of medical and surgical modalities. Compensatory hyperhidrosis (CH) is a well-documented complication of surgical treatment. We aimed to investigate the occurrence of compensatory hyperhidrosis (CH) in PH patients after nonsurgical treatment with botulinum toxin A (BTX- A) or iontophoresis. METHODOLOGY: We carried out a unicentric prospective study on PH patients from King Abdullah University Hospital (KAUH) in Jordan. PH patients were evaluated after 1-month of nonsurgical treatment. Patients who developed CH were re-assessed after 3-6 months through a telephone-based interview. RESULTS: A total of 86 patients with PH who underwent nonsurgical treatment with iontophoresis or botulinum toxin were recruited. Twenty-four (27.9%) patients developed subjective CH. It was mild in (75%), moderate in (21%), and severe in (4%) of patients affected, it was self-limiting within a few months in all patients. Patients with CH did not differ significantly in demographic or clinical variables from patients who did not develop CH except at the site of PH (p value = .05). CONCLUSION: The findings of this study indicate that more than quarter (27.9%) of patients with PH may develop minor compensatory sweating, however this didn't affect satisfaction with treatment.

Development of a novel nomogram to predict the risk of severe compensatory sweating following endoscopic thoracic sympathectomy.

BACKGROUNDS: Endoscopic thoracic sympathectomy (ETS) is a permanent and effective treatment for primary hyperhidrosis and facial blushing; however, severe compensatory sweating (SCS) remains a devastating complication. We aimed to (i) construct a nomogram to predict the risk of SCS, and (ii) investigate factors associated with the level of satisfaction. METHODS: From Jan 2014 to Mar 2020, 347 patients underwent ETS by a single surgeon. These patients were asked to complete an online questionnaire regarding primary symptom resolution, level of satisfaction, and development of compensatory sweating. Multivariable analysis was conducted via logistic regression and ordinal regression to predict SCS and satisfaction level respectively. Nomogram was developed based on significant predictors. RESULTS: In total, 298 (85.9%) patients responded to the questionnaire with a mean follow up of 4.9 ± 1.8 years. Significant factors associated with SCS in the nomogram included older age (OR 1.05, 95% CI 1.02-1.09, P = 0.001), primary indication other than palmar hyperhidrosis (OR 2.30, 95% CI 1.03-5.12, P = 0.04), and current smoking (OR 5.91, 95% CI 2.46-14.20, P < 0.001). The area under receiver operating characteristic curve was 0.713. Multivariable analysis revealed that longer follow up (ß = -0.201 ± 0.078, P = 0.01), gustatory hyperhidrosis (ß = -0.781 ± 0.267, P = 0.003), primary indication other than palmar hyperhidrosis (ß = -1.524 ± 0.292, P < 0.001), and SCS (ß = -3.061 ± 0.404, P < 0.001) were independently associated with a lower degree of patient satisfaction. CONCLUSION: The novel nomogram can provide a personalized numerical risk estimate to assist both the clinician and patient weigh the pros and cons as part of the decision-making process, mitigating the chance of patient dissatisfaction.

Type 1 interferon signature and cytotoxic T lymphocyte activation targeted against sweat ducts in inflammatory acquired idiopathic generalized anhidrosis.

BACKGROUND: Acquired idiopathic generalized anhidrosis (AIGA) leads to heat intolerance due to the loss or reduction in thermoregulatory sweating over an extensive area of the body. The pathomechanism of AIGA is still unclear but is believed to be autoimmune. OBJECTIVES: We investigated the clinical and pathological features of inflammatory AIGA (InfAIGA) and noninflammatory AIGA (non-InfAIGA) within the skin. METHODS: We compared anhidrotic and normohidrotic skin samples from 30 patients with InfAIGA and non-InfAIGA, as well as skin samples of melanocytic nevus as a negative control. We conducted morphometric analysis and immunohistochemical analysis of cell types and expression of inflammatory molecules (TIA1, CXCR3 and MxA). MxA expression was used as a proxy for type 1 interferon activity. RESULTS: We found that tissue samples from patients with InfAIGA exhibited inflammation within the sweat duct and atrophy of the sweat coil, whereas patients with non-InfAIGA exhibited only atrophy of the sweat coil. Cytotoxic T lymphocyte infiltration and MxA expression were only observed in the sweat ducts of patients with InfAIGA. CONCLUSIONS: InfAIGA is associated with increased sweat duct inflammation and sweat coil atrophy, whereas non-InfAIGA is only associated with sweat coil atrophy. These data suggest that inflammation leads to epithelial destruction of sweat ducts associated with the sweat coil atrophy and subsequent loss of function. Non-InfAIGA may be regarded as a postinflammatory state of InfAIGA. These observations indicate the contribution of both type 1 and type 2 interferons to sweat gland injury. The mechanism involved is similar to the pathomechanism of alopecia areata (AA).

64-year-old woman • hot flashes, facial flushing, excessive sweating, and palpitations • daily headaches • history of hypertension • Dx?

► hot flashes, facial flushing, excessive sweating, and palpitations ► daily headaches ► history of hypertension.

Serum, interstitial and sweat ATP in humans exposed to heat stress: Insights into roles of ATP in the heat loss responses.

Hyperthermia increases intravascular adenosine triphosphate (ATP) and is associated with greater hyperthermia-induced cutaneous vasodilation. Hyperthermia may also increase skin interstitial fluid ATP thereby activating cutaneous vascular smooth muscle cells and sweat glands. We evaluated the hypothesis that whole-body heating would increase skin interstitial fluid ATP, and this response would be associated with an increase in cutaneous vasodilation and sweating. Nineteen (8 females) young adults underwent whole-body heating using a water-perfusion suit to increase core temperature by ~1°C during which time cutaneous vascular conductance (CVC, ratio of laser-Doppler blood flow to mean arterial pressure) and sweat rate (ventilated capsule technique) were measured at four forearm skin sites to minimize between-site variations. Dialysate from the skin sites were collected via intradermal microdialysis. Heating increased serum ATP, CVC, and sweat rate (all p ≤ 0.031). However, heating did not modulate dialysate ATP (median, baseline vs. end-heating: 2.38 vs. 2.70 nmol/ml) (p = 0.068), though the effect size was moderate (Cohen's d = 0.566). While the heating-induced increase in CVC was not correlated with changes in serum ATP (r = 0.439, p = 0.060), we observed a negative correlation (rs = -0.555, p = 0.017) between dialysate ATP and CVC. We did not observe a significant correlation between the heating-induced sweating and serum, dialysate, or sweat ATP (rs = 0.091 to -0.322, all p ≥ 0.222). Altogether, we showed that passive heating increases ATP in blood and possibly skin interstitial fluid, with the latter potentially blunting cutaneous vasodilation. However, ATP does not appear to modulate sweating.

A Causal Treatment for X-Linked Hypohidrotic Ectodermal Dysplasia: Long-Term Results of Short-Term Perinatal Ectodysplasin A1 Replacement.

X-linked hypohidrotic ectodermal dysplasia (XLHED), caused by a genetic deficiency of ectodysplasin A1 (EDA1), is a rare developmental disorder of ectodermal derivatives such as hair, sweat glands, and teeth. The absence of sweat glands and perspiration can evoke life-threatening hyperthermia. As molecular genetic findings are not always conclusive, the concentrations of circulating EDA1 may help to distinguish between total and partial EDA1 deficiencies. We previously treated nine male patients with obvious signs of XLHED with a recombinant EDA1 replacement protein, Fc-EDA, either shortly after birth (n = 3) or by prenatal administration in gestational week 26 and beyond (n = 6). Here, we present the long-term follow-up for up to six years. In patients who had received Fc-EDA after birth, neither sweat glands nor sweating ability were detected at the age of 12-60 months. In contrast, prenatal EDA1 replacement resulted in ample sweat gland development and pilocarpine-inducible sweating in all treated subjects, who also attained more permanent teeth than their untreated affected relatives. Normal perspiration has persisted for six years in the two oldest boys treated repeatedly with Fc-EDA in utero. When they had a sauna, adequate thermoregulation was evidenced. Lower sweat production after single prenatal dosing may indicate a dose-response relationship. The absence of circulating EDA1 in five prenatally treated subjects proved that these children would have been unable to perspire if they had been left untreated. The sixth infant was shown to produce an EDA1 molecule that, albeit interacting with its cognate receptor, cannot activate EDA1 signaling. In conclusion, a causal treatment of XLHED before birth is feasible.

Molecular and Physiological Functions of PACAP in Sweat Secretion.

Sweat plays a critical role in human body, including thermoregulation and the maintenance of the skin environment and health. Hyperhidrosis and anhidrosis are caused by abnormalities in sweat secretion, resulting in severe skin conditions (pruritus and erythema). Bioactive peptide and pituitary adenylate cyclase-activating polypeptide (PACAP) was isolated and identified to activate adenylate cyclase in pituitary cells. Recently, it was reported that PACAP increases sweat secretion via PAC1R in mice and promotes the translocation of AQP5 to the cell membrane through increasing intracellular [Ca2+] via PAC1R in NCL-SG3 cells. However, intracellular signaling mechanisms by PACAP are poorly clarified. Here, we used PAC1R knockout (KO) mice and wild-type (WT) mice to observe changes in AQP5 localization and gene expression in sweat glands by PACAP treatment. Immunohistochemistry revealed that PACAP promoted the translocation of AQP5 to the lumen side in the eccrine gland via PAC1R. Furthermore, PACAP up-regulated the expression of genes (Ptgs2, Kcnn2, Cacna1s) involved in sweat secretion in WT mice. Moreover, PACAP treatment was found to down-regulate the Chrna1 gene expression in PAC1R KO mice. These genes were found to be involved in multiple pathways related to sweating. Our data provide a solid basis for future research initiatives in order to develop new therapies to treat sweating disorders.

Potentiometric Chloride Ion Biosensor for Cystic Fibrosis Diagnosis and Management: Modeling and Design.

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.

Management of Menopausal Symptoms: A Review.

Importance: Menopause, due to loss of ovarian follicular activity without another pathological or physiological cause, typically occurs between the ages of 45 years and 56 years. During the menopausal transition, approximately 50% to 75% of women have hot flashes, night sweats, or both (vasomotor symptoms) and more than 50% have genitourinary symptoms (genitourinary syndrome of menopause [GSM]). Observations: Vasomotor symptoms typically last more than 7 years and GSM is often chronic. Efficacious treatments for women with bothersome vasomotor symptoms or GSM symptoms include hormonal and nonhormonal options. Systemic estrogen alone or combined with a progestogen reduces the frequency of vasomotor symptoms by approximately 75%. Oral and transdermal estrogen have similar efficacy. Conjugated equine estrogens (CEE) with or without medroxyprogesterone acetate (MPA) were the only hormonal treatments for which clinical trials were designed to examine cardiovascular events, venous thromboembolism, and breast cancer risk. Compared with placebo, the increased risk of stroke and venous thromboembolism associated with CEE (with or without MPA) and breast cancer (with use of CEE plus MPA) is approximately 1 excess event/1000 person-years. Low-dose CEE plus bazedoxifene is not associated with increased risk of breast cancer (0.25%/year vs 0.23%/year with placebo). Bioidentical estrogens approved by the US Food and Drug Administration (with identical chemical structure to naturally produced estrogens, and often administered transdermally) also are available to treat vasomotor symptoms. For women who are not candidates for hormonal treatments, nonhormonal approaches such as citalopram, desvenlafaxine, escitalopram, gabapentin, paroxetine, and venlafaxine are available and are associated with a reduction in frequency of vasomotor symptoms by approximately 40% to 65%. Low-dose vaginal estrogen is associated with subjective improvement in GSM symptom severity by approximately 60% to 80%, with improvement in severity by 40% to 80% for vaginal prasterone, and with improvement in severity by 30% to 50% for oral ospemifene. Conclusions and Relevance: During the menopausal transition, approximately 50% to 75% of women have vasomotor symptoms and GSM symptoms. Hormonal therapy with estrogen is the first-line therapy for bothersome vasomotor symptoms and GSM symptoms, but nonhormonal medications (such as paroxetine and venlafaxine) also can be effective. Hormone therapy is not indicated for the prevention of cardiovascular disease.

Cyclophosphamide exposure via sweat of patients receiving CHOP therapy.

INTRODUCTION: "Secondary exposure to anticancer drugs" refers to exposure to anticancer drugs after chemotherapy via the patient's urine and other excretions. The necessity of countermeasures against secondary exposure to anticancer drugs has been recently highlighted. Although anticancer drugs are also excreted through sweat, few studies have reported exposure to drug residues via this route. We investigated the amount of cyclophosphamide (CPA) excreted in the sweat of patients receiving CHOP therapy (cyclophosphamide, doxorubicin, vincristine, and prednisone). METHODS: The study population included eight patients with malignant lymphoma who received CHOP therapy between May and December 2021. The amount of CPA in their underwear (namely, cotton short-sleeved shirts) worn from the start of the CHOP therapy until 24 h after the end of CPA administration was measured, using liquid chromatography-mass spectrometry (LC-MS/MS). RESULTS: CPA was detected in the underwear of all the patients, with levels ranging between 7.38 and 160.77 ng/cm2. No subjective changes were observed in the sweating status of any patients during the study period. CONCLUSIONS: These results suggested that patients' sweat, as well as urine, is a potential route for exposure to anticancer drugs. Whether visibly contaminated or not, the clothing and linen worn directly by patients should be handled as a source of sweat-mediated exposure to anticancer drugs both in medical facilities and at home.

Prevalence and quality-of-life burden of vasomotor symptoms associated with menopause: A European cross-sectional survey.

OBJECTIVES: To determine, in a European cohort, the prevalence and health-related quality-of-life (QOL) burden of moderate-to-severe vasomotor symptoms (VMS) in postmenopausal women, and among subgroups of women not taking hormone therapy (HT). STUDY DESIGN: Screening surveys were sent to a random sample of women aged 40-65 years; those meeting the inclusion criteria completed the full questionnaire. Women with successfully treated VMS or breast cancer or who were receiving HT for medical conditions were excluded. MAIN OUTCOME MEASURES: Frequency and duration of VMS, perceptions of menopause, seeking advice from a healthcare professional, treatment for VMS symptoms, perceptions of HT use, out-of-pocket costs, and other approaches to coping with menopause. The Menopause-Specific QOL (MENQOL) questionnaire and Work Productivity and Activity Impairment (WPAI) questionnaire were included. RESULTS: Of 11,452 women who completed the screening survey, 5178 were postmenopausal and 2035 completed the full questionnaire. Prevalence of moderate-to-severe VMS ranged from 31 % in France to 52 % in Italy. The majority were in the HT-caution or HT-averse group, despite being eligible for HT. Most common menopausal symptoms reported in the MENQOL were "feeling tired or worn out," with aching in muscles and joints reported as the most common symptom in Spain. Weight gain was the most bothersome symptom in all countries, except for Spain, where low backache was more bothersome. Hot flashes and night sweats had a greater impact on daily than on working activities, as measured by the WPAI. CONCLUSIONS: A high proportion of European women reported experiencing moderate-to-severe VMS, with associated symptoms influencing QOL.

Case Reports of Transdermal Fentanyl Patch Administration Difficulties in Cancer Patients with Excess Sweating.

(Case 1) A 45-year-old male was diagnosed with prostate cancer. Treatment was administered using bicalutamide and leuprorelin acetate, while a transdermal fentanyl (TDF) was applied for pain relief. However, TDF continued to peel off owing to excessive sweating, even when reinforced by a protective layer. As such, TDF was discontinued and pain control was initiated using other medicines. Sweating occurred irregularly because of hot flashes, approximately four to five times per day. (Case 2) A 37-year-old male was diagnosed with a malignant thymoma and sacral metastasis. For analgesic control, etodolac tablets, carbamazepine tablets, and TDF were administered. Subsequently, the dose of the TDF was gradually increased, but the analgesic effect was low; thus, fentanyl blood concentration was measured. The measurements showed that even higher TDF doses did not increase fentanyl blood levels. During this period, full body sweating began to occur to a large extent due to unknown causes, and it was thought that the absorption of fentanyl decreased. When using a TDF, it is necessary to monitor patients for any sweating during treatment, while also considering changes in medication in some cases. This should promote the maintenance and improvement of the quality of life of the affected patients.

56-year-old man • increased heart rate • weakness • intense sweating • horseradish consumption • Dx?

► Increased heart rate ► Weakness ► Intense sweating ► Horseradish consumption.

When to investigate for secondary hyperhidrosis: data from a retrospective cohort of all causes of recurrent sweating.

Background: Identification of underlying diseases is crucial for secondary hyperhidrosis management, but data are lacking to guide appropriate investigation.Objective: To describe aetiologies of recurrent sweating in a hospital setting and the diagnostic performance parameters of their respective clinical/biological features.Patients and Methods: We performed a monocentric evaluative study in a tertiary care centre. Patients with recurrent generalised sweating were selected via the Clinical Data Warehouse (CDW) by screening all electronic hospital documents from the year 2018 using a keyword-based algorithm. All in and out-patients aged ≥ 18 years having reported recurrent sweating for at least 2 weeks in 2018 were included, with a minimum one-year follow-up after symptoms' onset.Results: A total of 420 patients were included. Over 130 different aetiologies were identified; 70 patients (16.7%) remained without diagnosis. Solid organ cancers (14.3% with 13 lung cancers), haematologic malignancies (14.0% with 35 non-Hodgkin's lymphomas) and Infectious Diseases (10.5% including 13 tuberculosis) were the most frequent diagnoses. Other aetiologies were gathered into inflammatory (16.9%) and non-inflammatory (27.6%) conditions. To distinguish non-inflammatory and undiagnosed hyperhidrosis from other causes, fever had a specificity of 94%, impaired general condition a sensitivity of 78%, and C-reactive protein (CRP) > 5.6 mg/l a positive predictive value of 0.86. Symptoms' duration over 1 year was in favour of non-infectious and non-malignant causes (94% specificity).Conclusions: We identified fever, impaired general condition, duration, and CRP as helpful orientation parameters to assess the need for complementary explorations for hyperhidrosis. The study provides a diagnostic algorithm for the investigation of recurrent sweating.KEY MESSAGESIn a hospital setting, malignancies and infections are the most frequently associated diseases, but 1/5 remain without diagnosis.Fever is a specific but not sensitive sign to distinguish inflammatory conditions.Over 1 year duration of symptoms significantly reduce the probability of malignancy or infection as the underlying diagnosis.