PLOS ONE: [sortOrder=DATE_NEWEST_FIRST, filterJournals=PLoSONE, sort=Date, newest first, q=subject:"Sweat glands"]PLOShttps://journals.plos.org/plosone/webmaster@plos.orgaccelerating the publication of peer-reviewed sciencehttps://journals.plos.org/plosone/search/feed/atom?sortOrder=DATE_NEWEST_FIRST&filterJournals=PLoSONE&sort=Date,+newest+first&unformattedQuery=subject:%22Sweat+glands%22All PLOS articles are Open Access.https://journals.plos.org/plosone/resource/img/favicon.icohttps://journals.plos.org/plosone/resource/img/favicon.ico2024-03-29T14:51:47ZHarmonization of ICF Body Structures and ICD-11 Anatomic Detail: One foundation for multiple classificationsVincenzo Della MeaAnn-Helene AlmborgMichela MartinuzziSamson W. TuAndrea Martinuzzi10.1371/journal.pone.02801062023-07-27T14:00:00Z2023-07-27T14:00:00Z<p>by Vincenzo Della Mea, Ann-Helene Almborg, Michela Martinuzzi, Samson W. Tu, Andrea Martinuzzi</p>
The Family of International Classifications of the World Health Organization (WHO-FIC) currently includes three reference classifications, namely International Classification of Diseases (ICD), International Classification of Functioning, Disability, and Health (ICF), and International Classification of Health Interventions (ICHI). Recently, the three classifications have been incorporated into a single WHO-FIC Foundation that serves as the repository of all concepts in the classifications. Each classification serves a specific classification need. However, they share some common concepts that are present, in different forms, in two or all of them. For the WHO-FIC Foundation to be a logically consistent repository without duplicates, these common concepts must be reconciled. One important set of shared concepts is the representation of human anatomy entities, which are not always modeled in the same way and with the same level of detail. To understand the relationships among the three anatomical representations, an effort is needed to compare them, identifying common areas, gaps, and compatible and incompatible modeling. The work presented here contributes to this effort, focusing on the anatomy representations in ICF and ICD-11. For this aim, three experts were asked to identify, for each entity in the ICF Body Structures, one or more entities in the ICD-11 Anatomic Detail that could be considered identical, broader or narrower. To do this, they used a specifically developed web application, which also automatically identified the most obvious equivalences. A total of 631 maps were independently identified by the three mappers for 218 ICF Body Structures, with an interobserver agreement of 93.5%. Together with 113 maps identified by the software, they were then consolidated into 434 relations. The results highlight some differences between the two classifications: in general, ICF is less detailed than ICD-11; ICF favors lumping of structures; in very few cases, the two classifications follow different anatomic models. For these issues, solutions have to be found that are compliant with the WHO approach to classification modeling and maintenance.A <i>Hidradenitis Suppurativa</i> molecular disease signature derived from patient samples by high-throughput RNA sequencing and re-analysis of previously reported transcriptomic data setsJohannes M. FreudenbergZhi LiuJennifer SinghElizabeth ThomasChristopher TrainiDeepak K. RajpalChristopher J. Sayed10.1371/journal.pone.02840472023-04-06T14:00:00Z2023-04-06T14:00:00Z<p>by Johannes M. Freudenberg, Zhi Liu, Jennifer Singh, Elizabeth Thomas, Christopher Traini, Deepak K. Rajpal, Christopher J. Sayed</p>
Hidradenitis suppurativa (HS) is a common, debilitating inflammatory skin disease linked to immune dysregulation and abnormalities in follicular structure and function. Several studies have characterized the transcriptomic profile of affected and unaffected skin in small populations. In this study of 20 patients, RNA from lesional and matching non-lesional skin biopsies in 20 subjects were used to identify an expression-based HS disease signature. This was followed by differential expression and pathway enrichment analyses, as well as jointly reanalyzing our findings with previously published transcriptomic profiles. We establish an RNA-Seq based HS expression disease signature that is mostly consistent with previous reports. Bulk-RNA profiles from 104 subjects in 7 previously reported data sets identified a disease signature of 118 differentially regulated genes compared to three control data sets from non-lesional skin. We confirmed previously reported expression profiles and further characterized dysregulation in complement activation and host response to bacteria in disease pathogenesis. Changes in the transcriptome of lesional skin in this cohort of HS patients is consistent with smaller previously reported populations. The findings further support the significance of immune dysregulation, in particular with regard to bacterial response mechanisms. Joint analysis of this and previously reported cohorts indicate a remarkably consistent expression profile.Short-term heat acclimation protocols for an aging population: Systematic reviewEdward ColeKate J. DonnanAndrew J. SimpsonAndrew T. Garrett10.1371/journal.pone.02820382023-03-02T14:00:00Z2023-03-02T14:00:00Z<p>by Edward Cole, Kate J. Donnan, Andrew J. Simpson, Andrew T. Garrett</p>
Introduction <p>Elderly and sedentary individuals are particularly vulnerable to heat related illness. Short-term heat acclimation (STHA) can decrease both the physical and mental stress imposed on individuals performing tasks in the heat. However, the feasibility and efficacy of STHA protocols in an older population remains unclear despite this population being particularly vulnerable to heat illness. The aim of this systematic review was to investigate the feasibility and efficacy of STHA protocols (≤twelve days, ≥four days) undertaken by participants over fifty years of age.</p> Methods <p>Academic Search Premier, CINAHL Complete, MEDLINE, APA PsycInfo, and SPORTDiscus were searched for peer reviewed articles. The search terms were; (heat* or therm*) N3 (adapt* or acclimati*) AND old* or elder* or senior* or geriatric* or aging or ageing. Only studies using primary empirical data and which included participants ≥50 years of age were eligible. Extracted data includes participant demographics (sample size, gender, age, height, weight, BMI and V.O2max), acclimation protocol details (acclimation activity, frequency, duration and outcome measures taken) and feasibility and efficacy outcomes.</p> Results <p>Twelve eligible studies were included in the systematic review. A total of 179 participants took part in experimentation, 96 of which were over 50 years old. Age ranged from 50 to 76. All twelve of the studies involved exercise on a cycle ergometer. Ten out of twelve protocols used a percentage of V.O2max or V.O2peak to determine the target workload, which ranged from 30% to 70%. One study-controlled workload at 6METs and one implemented an incremental cycling protocol until T<sub>re</sub> was reached +0.9°C. Ten studies used an environmental chamber. One study compared hot water immersion (HWI) to an environmental chamber while the remaining study used a hot water perfused suit. Eight studies reported a decrease in core temperature following STHA. Five studies demonstrated post-exercise changes in sweat rates and four studies showed decreases in mean skin temperature. The differences reported in physiological markers suggest that STHA is viable in an older population.</p> Conclusion <p>There remains limited data on STHA in the elderly. However, the twelve studies examined suggest that STHA is feasible and efficacious in elderly individuals and may provide preventative protection to heat exposures. Current STHA protocols require specialised equipment and do not cater for individuals unable to exercise. Passive HWI may provide a pragmatic and affordable solution, however further information in this area is required.</p>Measurement of thermal sweating at rest and steady-state exercise in healthy adults: Inter-day reliability and relationships with components of partitional calorimetryJennifer S. PeelMelitta A. McNarryShane M. HeffernanVenturino R. NevolaLiam P. KilduffMark Waldron10.1371/journal.pone.02786522022-12-01T14:00:00Z2022-12-01T14:00:00Z<p>by Jennifer S. Peel, Melitta A. McNarry, Shane M. Heffernan, Venturino R. Nevola, Liam P. Kilduff, Mark Waldron</p>
Objective <p>Inter-day reliability of sweat measurements, including the absorbent patch and modified iodine-paper techniques, at rest and exercise were evaluated. We further evaluated the effect of iodine paper size and the method of establishing sweat gland activation (sweat gland counting or surface area covered) on reliability. Furthermore, the relationships between all measurement techniques and metabolic heat production [Ḣ<sub>prod</sub>] and evaporative requirement for heat balance [Ė<sub>req</sub>] were determined.</p> Method <p>Twelve participants were assessed for whole-body sweat loss (WBSL), local sweat rate (LSR; absorbent patch) and sweat gland activation (SGA; iodine-paper) during rest and sub-maximal cycling at ~200, ~250 and ~300 W/m<sup>2</sup> Ḣ<sub>prod</sub> in the heat. Variations in iodine paper (1 x 1 cm-9 x 9 cm) were used to quantify SGA by counting sweat glands or surface area covered. The ‘optimal’ area of SGA was also determined based on the highest density of recruited glands.</p> Results <p>All measures of the sweating response were positively related with Ḣ<sub>prod</sub> and Ė<sub>req</sub> (<i>r</i> = 0.53–0.84), with the 9 x 9 cm and 6 x 6 cm iodine paper sizes being the strongest (<i>r</i> = 0.66–0.84) for SGA. Superior inter-day reliability was found for all measures during exercise (CV% = 6–33.2) compared to rest (CV% = 33.5–77.9). The iodine-paper technique was most reliable at 9 x 9 cm (CV% = 15.9) or when the 1 x 1 cm (CV% = 17.6) and 3 x 3 cm (CV% = 15.5) optimal SGA was determined, particularly when measuring the sweat gland number.</p> Significance <p>WBSL, LSR and SGA measurement techniques are sufficiently reliable to detect changes in thermal sweating typically reported. We recommend 9 x 9 cm paper sizes or 1 x 1 cm-3 x 3 cm optimal areas, using either gland counting or surface area to determine SGA.</p>Chronic wasting disease prions in mule deer interdigital glandsAnthony NessDoris ZengAlsu KuznetsovaAlicia OteroChiye KimKelsey SaborakiSusan LingleMargo PybusJudd AikenSabine GilchDebbie McKenzie10.1371/journal.pone.02753752022-10-03T14:00:00Z2022-10-03T14:00:00Z<p>by Anthony Ness, Doris Zeng, Alsu Kuznetsova, Alicia Otero, Chiye Kim, Kelsey Saboraki, Susan Lingle, Margo Pybus, Judd Aiken, Sabine Gilch, Debbie McKenzie</p>
Chronic wasting disease (CWD) is a geographically expanding, fatal neurodegenerative disease in cervids. The disease can be transmitted directly (animal-animal) or indirectly via infectious prions shed into the environment. The precise mechanisms of indirect CWD transmission are unclear but known sources of the infectious prions that contaminate the environment include saliva, urine and feces. We have previously identified PrP<sup>C</sup> expression in deer interdigital glands, sac-like exocrine structures located between the digits of the hooves. In this study, we assayed for CWD prions within the interdigital glands of CWD infected deer to determine if they could serve as a source of prion shedding and potentially contribute to CWD transmission. Immunohistochemical analysis of interdigital glands from a CWD-infected female mule deer identified disease-associated PrP<sup>CWD</sup> within clusters of infiltrating leukocytes adjacent to sudoriferous and sebaceous glands, and within the acrosyringeal epidermis of a sudoriferous gland tubule. Proteinase K-resistant PrP<sup>CWD</sup> material was amplified by serial protein misfolding cyclic amplification (sPMCA) from soil retrieved from between the hoof digits of a clinically affected mule deer. Blinded testing of interdigital glands from 11 mule deer by real-time quake-induced conversion (RT-QuIC) accurately identified CWD-infected animals. The data described suggests that interdigital glands may play a role in the dissemination of CWD prions into the environment, warranting future investigation.Variation in CFTR-dependent ‘β-sweating’ among healthy adultsLesje DeRoseJeeyeon KimMiesha FarahmandMeagan Y. ShinbashiNam Soo JooJeffrey J. Wine10.1371/journal.pone.02654322022-03-21T14:00:00Z2022-03-21T14:00:00Z<p>by Lesje DeRose, Jeeyeon Kim, Miesha Farahmand, Meagan Y. Shinbashi, Nam Soo Joo, Jeffrey J. Wine</p>
The genetic disease cystic fibrosis (CF) results when mutations in the gene for the anion channel CFTR reduce CFTR’s activity below a critical level. CFTR activity = N·P<sub>O</sub>·γ (number of channels x open probability x channel conductance). Small molecules are now available that partially restore CFTR function with dramatic improvements in health of CF subjects. Continued evaluation of these and other compounds in development will be aided by accurate assessments of CFTR function. However, measuring CFTR activity <i>in vivo</i> is challenging and estimates vary widely. The most accurate known measure of CFTR activity <i>in vivo</i> is the ‘β/M’ ratio of sweat rates, which is produced by stimulation with a β-adrenergic agonist cocktail referenced to the same individual’s methacholine-stimulated sweat rate. The most meaningful metric of CFTR activity is to express it as a percent of normal function, so it is critical to establish β/M carefully in a population of healthy control subjects. Here, we analyze β/M from a sample of 50 healthy adults in which sweat rates to cholinergic and β-adrenergic agonists were measured repeatedly (3 times) in multiple, (~50) identified sweat glands from each individual (giving ~20,000 measurements). The results show an approximately 7-fold range, 26–187% of the WT average set to 100%. These provide a benchmark against which other measures of CFTR activity can be compared. Factors contributing to β/M variation in healthy controls are discussed.The use of 33 MHz ultra-high-frequency ultrasonography for the evaluation of sweat glands in the axilla with osmidrosisAkira ShinaokaRyuichi NakaharaMasanori Saeki10.1371/journal.pone.02516002021-05-13T14:00:00Z2021-05-13T14:00:00Z<p>by Akira Shinaoka, Ryuichi Nakahara, Masanori Saeki</p>
Background <p>This study aimed to assess the use of 33 MHz ultra-high-frequency ultrasonography (33MHz-UHFUS) for evaluating axillary sweat glands with osmidrosis in comparison with histological techniques. Axillary osmidrosis is a common problem in Asian societies, and the number and size of apocrine sweat glands have a strong relationship with osmidrosis severity. Currently, there are no methods to evaluate sweat gland distribution non-invasively.</p> Methods <p>In this study, 35 skin specimens from 10 fresh human cadavers without osmidrosis and retrospective ultrasonographic images from 20 patients with osmidrosis were used. Skin specimens were embedded in paraffin, thinly sliced, and finally stained with hematoxylin and eosin. Histologically, the apocrine and eccrine glands were evaluated, and the top and bottom depths of follicles were measured from the skin surface. In 33 MHz ultrasonography images, the depths of sweat glands were measured, and the mean grey value was calculated using Image J.</p> Results <p>Compared to histological data, 33MHz-UHFUS could be used to identify sweat glands as a hyperechoic structure between the dermis and fat layer. Furthermore, it could evaluate sweat gland distribution but could not distinguish between types of sweat glands.</p> Conclusions <p>The distribution of sweat glands in the axilla can be non-invasively evaluated via 33MHz-UHFUS.</p>Absence of reliable physiological signature of illusory body ownership revealed by fine-grained autonomic measurement during the rubber hand illusionHugo D. CritchleyVanessa BotanJamie Ward10.1371/journal.pone.02372822021-04-01T14:00:00Z2021-04-01T14:00:00Z<p>by Hugo D. Critchley, Vanessa Botan, Jamie Ward</p>
The neural representation of a ‘biological self’ is linked theoretically to the control of bodily physiology. In an influential model, selfhood relates to internal agency and higher-order interoceptive representation, inferred from the predicted impact of efferent autonomic nervous activity on afferent viscerosensory feedback. Here we tested if an altered representation of physical self (illusory embodiment of an artificial hand) is accompanied by sustained shifts in autonomic activity. Participants (N = 37) underwent procedures for induction of the rubber hand illusion (synchronous stroking of own unseen hand and observed stroking of artificial hand) and a control condition (asychronous stroking). We recorded electrocardiography, electrodermal activity, and a non-invasive measure of multiunit skin sympathetic nerve activity (SKNA) from the chest. We compared these autonomic indices between task conditions, and between individuals who did and did not experience the illusion. Bayes factors quantified the strength of evidence for and against null hypotheses. Observed proprioceptive drift and subjective reports confirmed the efficacy of the synchronous (vs asynchronous) condition in inducing illusory hand ownership. Stringent discriminant analysis classified 24/37 individuals as experiencing the rubber hand illusion. Surprisingly, heart rate, heart rate variability, electrodermal activity, and SKNA measures revealed no autonomic differences between synchronous vs asynchronous conditions, nor between individuals who did or did not experience the rubber hand illusion. Bayes factors indicated substantial evidence for no physiological differences. In contrast to earlier reports, our autonomic data show the absence of a reliable change in physiological state during the rubber hand illusion. More encompassing perturbations of self-experience, for example in full body illusions, may nevertheless be coupled to, or facilitated by, changes in efferent autonomic activity and afferent viscerosensory feedback. Our findings suggest that such changes in bodily physiology are not sustained as an obligatory component of the rubber hand illusion.Relationships between electrolyte and amino acid compositions in sweat during exercise suggest a role for amino acids and K<sup>+</sup> in reabsorption of Na<sup>+</sup> and Cl<sup>-</sup> from sweatGrace R. MurphyR. Hugh DunstanMargaret M. MacdonaldNattai BorgesZoe RadfordDiane L. SparkesBenjamin J. DascombeTimothy K. Roberts10.1371/journal.pone.02233812019-10-03T14:00:00Z2019-10-03T14:00:00Z<p>by Grace R. Murphy, R. Hugh Dunstan, Margaret M. Macdonald, Nattai Borges, Zoe Radford, Diane L. Sparkes, Benjamin J. Dascombe, Timothy K. Roberts</p>
Concentrations of free amino acids and [K<sup>+</sup>] in human sweat can be many times higher than in plasma. Conversely, [Na<sup>+</sup>] and [Cl<sup>-</sup>] in sweat are hypotonic to plasma. It was hypothesised that the amino acids and K<sup>+</sup> were directly or indirectly associated with the resorption of Na<sup>+</sup> and Cl<sup>-</sup> in the sweat duct. The implication would be that, as resources of these components became limiting during prolonged exercise then the capacity to resorb [Na<sup>+</sup>] and [Cl<sup>-</sup>] would diminish, resulting in progressively higher levels in sweat. If this were the case, then [Na<sup>+</sup>] and [Cl<sup>-</sup>] in sweat would have inverse relationships with [K<sup>+</sup>] and the amino acids during exercise. Forearm sweat was collected from 11 recreational athletes at regular intervals during a prolonged period of cycling exercise after 15, 25, 35, 45, 55 and 65 minutes. The subjects also provided passive sweat samples via 15 minutes of thermal stimulation. The sweat samples were analysed for concentrations of amino acids, Na<sup>+</sup>, Cl<sup>-</sup>, K<sup>+</sup>, Mg<sup>2+</sup> and Ca<sup>2+</sup>. The exercise sweat had a total amino acid concentration of 6.4 ± 1.2mM after 15 minutes which was lower than the passive sweat concentration at 11.6 ± 0.8mM (<i>p</i><0.05) and showed an altered array of electrolytes, indicating that exercise stimulated a change in sweat composition. During the exercise period, [Na<sup>+</sup>] in sweat increased from 23.3 ± 3.0mM to 34.6 ± 2.4mM (<i>p</i><0.01) over 65 minutes whilst the total concentrations of amino acids in sweat decreased from 6.4 ± 1.2mM to 3.6 ± 0.5mM. [Na<sup>+</sup>] showed significant negative correlations with the concentrations of total amino acids (<i>r</i> = -0.97, <i>p</i><0.05), K<sup>+</sup> (<i>r</i> = -0.93, <i>p</i><0.05) and Ca<sup>2+</sup> (<i>r</i> = -0.83, <i>p</i><0.05) in sweat. The results supported the hypothesis that amino acids and K<sup>+</sup>, as well as Ca<sup>2+</sup>, were associated with resorption of Na<sup>+</sup> and Cl<sup>-</sup>.Primary hyperhidrosis prevalence and characteristics among medical students in Rio de JaneiroMaria Ribeiro Santos MorardRicardo Betanho MartinsAna Carolina Lopes RibeiroPedro Guimarães Rocha LimaBeatriz dos Santos CarvalhoJosé Carlos Baldelim Santiago Junior10.1371/journal.pone.02206642019-09-13T14:00:00Z2019-09-13T14:00:00Z<p>by Maria Ribeiro Santos Morard, Ricardo Betanho Martins, Ana Carolina Lopes Ribeiro, Pedro Guimarães Rocha Lima, Beatriz dos Santos Carvalho, José Carlos Baldelim Santiago Junior</p>
Background <p>Hyperhidrosis is a pathological condition defined by excessive sweating beyond thermoregulatory physiological needs, which can cause substantial psychological impact and impairment of daily activities. Studies regarding its prevalence, however, are scarce and vary widely in their findings. The population of medical students is a particularly interesting subset for its recurring demand of physical contact during patient examination or procedures, and the potential for professional adversity. We aimed at furthering the comprehension of this disease prevalence and characteristics among medical students.</p> Methods <p>Questionnaires inquiring about the presence and characteristics of Primary Hyperhidrosis (PH) were applied through either written or digital means to all eligible medical students enrolled in three Medical Schools in the State of Rio de Janeiro who agreed to take part in the study. Demographic data regarding gender, ethnicity, current age, weight and height was collected in addition to clinical data (sweat site, age of onset, familial history, severity and previous treatments). Severity was evaluated through the Hyperhidrosis Disease Severity Scale (HDSS) and a symptoms survey.</p> Findings <p>Our response rate was roughly 1/3 of all eligible students (900/2700). PH prevalence was 20.56% (185/900). It was similar between men and women (23.08% and 19.41%, respectively) and strongly associated with family history of the disease (Prevalence Ratio of 4.27). Regarding ethnicity, of the total sample 73.78% (664/900) self-declared white, among which 19.28% (128/664) had PH. Mixed-race and other ethnicities encompassed 26.22% (236/900) of the sample, among which 24.15% (57/236) had PH. Most positive subjects (64.32%) presented associated forms of PH. Overall involvement of each site (both associated and isolated) was: 63.78% axillary, 50.81% palmar, 43.24% plantar, 20.54% craniofacial, 18.38% facial flushing and 2.16% gustatory sweating. Mean current age was 23.11(±4.04) years for PH patients, and age of onset was ≤18 years in 93.94% of cases. Regarding body mass index (BMI), 71.09% of PH patients had BMI<25kg/m<sup>2</sup> and only 4.69% presented BMI≥30kg/m<sup>2</sup>, none ≥35kg/m<sup>2</sup>. Some degree of life quality impairment was reported by 89.20% of PH patients, and 23.89% had HDSS 3 or 4 (moderate to severe).</p> Conclusions <p>PH prevalence among Rio de Janeiro medical students was 20.56%, similar between men and women, predominating associated presentations, axillary, palmar and plantar sites, strong familial history, age of onset before 18 years, and some degree of life impairment.</p>The evolution and multi-molecular properties of NF1 cutaneous neurofibromas originating from C-fiber sensory endings and terminal Schwann cells at normal sites of sensory terminations in the skinFrank L. RiceGeorge HoukJames P. WymerSara J. C. GoslineJustin GuinneyJianqiang WuNancy RatnerMichael P. JankowskiSalvo La RosaMarilyn DockumJames R. StoreySteven L. CarrollPhillip J. AlbrechtVincent M. Riccardi10.1371/journal.pone.02165272019-05-20T14:00:00Z2019-05-20T14:00:00Z<p>by Frank L. Rice, George Houk, James P. Wymer, Sara J. C. Gosline, Justin Guinney, Jianqiang Wu, Nancy Ratner, Michael P. Jankowski, Salvo La Rosa, Marilyn Dockum, James R. Storey, Steven L. Carroll, Phillip J. Albrecht, Vincent M. Riccardi</p>
In addition to large plexiform neurofibromas (pNF), NF1 patients are frequently disfigured by cutaneous neurofibromas (cNF) and are often afflicted with chronic pain and itch even from seemingly normal skin areas. Both pNFs and cNF consist primarily of benign hyperproliferating nonmyelinating Schwann cells (nSC). While pNF clearly arise within deep nerves and plexuses, the role of cutaneous innervation in the origin of cNF and in chronic itch and pain is unknown. First, we conducted a comprehensive, multi-molecular, immunofluorescence (IF) analyses on 3mm punch biopsies from three separate locations in normal appearing, cNF-free skin in 19 NF1 patients and skin of 16 normal subjects. At least one biopsy in 17 NF1 patients had previously undescribed micro-lesions consisting of a small, dense cluster of nonpeptidergic C-fiber endings and the affiliated nSC consistently adjoining adnexal structures—dermal papillae, hair follicles, sweat glands, sweat ducts, and arterioles—where C-fiber endings normally terminate. Similar micro-lesions were detected in hind paw skin of mice with conditionally-induced SC <i>Nf1</i><sup>-/-</sup> mutations. Hypothesizing that these microlesions were pre-cNF origins of cNF, we subsequently analyzed numerous overt, small cNF (s-cNF, 3–6 mm) and discovered that each had an adnexal structure at the epicenter of vastly increased nonpeptidergic C-fiber terminals, accompanied by excessive nSC. The IF and functional genomics assays indicated that neurturin (NTRN) and artemin (ARTN) signaling through cRET kinase and GFRα2 and GFRα3 co-receptors on the aberrant C-fiber endings and nSC may mutually promote the onset of pre-cNF and their evolution to s-cNF. Moreover, TrpA1 and TrpV1 receptors may, respectively, mediate symptoms of chronic itch and pain. These newly discovered molecular characteristics might be targeted to suppress the development of cNF and to treat chronic itch and pain symptoms in NF1 patients.The skin transcriptome in hidradenitis suppurativa uncovers an antimicrobial and sweat gland gene signature which has distinct overlap with wounded skinMargaret CoatesPaula MariottoniDavid L. CorcoranHélène Fradin KirshnerTarannum JaleelDavid A. BrownStephen R. BrooksJohn MurrayMaria I. MorassoAmanda S. MacLeod10.1371/journal.pone.02162492019-05-06T14:00:00Z2019-05-06T14:00:00Z<p>by Margaret Coates, Paula Mariottoni, David L. Corcoran, Hélène Fradin Kirshner, Tarannum Jaleel, David A. Brown, Stephen R. Brooks, John Murray, Maria I. Morasso, Amanda S. MacLeod</p>
Hidradenitis suppurativa (HS) is a debilitating chronic inflammatory skin disease resulting in non-healing wounds affecting body areas of high hair follicle and sweat gland density. The pathogenesis of HS is not well understood but appears to involve dysbiosis-driven aberrant activation of the innate immune system leading to excessive inflammation. Marked dysregulation of antimicrobial peptides and proteins (AMPs) in HS is observed, which may contribute to this sustained inflammation. Here, we analyzed HS skin transcriptomes from previously published studies and integrated these findings through a comparative analysis with a published wound healing data set and with immunofluorescence and qPCR analysis from new HS patient samples. Among the top differently expressed genes between lesional and non-lesional HS skin were members of the <i>S100</i> family as well as <i>dermcidin</i>, the latter known as a sweat gland-associated AMP and one of the most downregulated genes in HS lesions. Interestingly, many genes associated with sweat gland function, such as <i>secretoglobins</i> and <i>aquaporin 5</i>, were decreased in HS lesional skin and we discovered that these genes demonstrated opposite expression profiles in healing skin. Conversely, HS lesional and wounded skin shared a common gene signature including genes encoding for S100 proteins, defensins, and genes encoding antiviral proteins. Overall, our results suggest that the pathogenesis of HS may be driven by changes in AMP expression and altered sweat gland function, and may share a similar pathology with chronic wounds.A cardiac risk score based on sudomotor function to evaluate cardiovascular autonomic neuropathy in asymptomatic Chinese patients with diabetes mellitusTao YuanJiapei LiYong FuTao XuJuan LiXiangqing WangYing ZhouYingyue DongWeigang Zhao10.1371/journal.pone.02048042018-10-03T14:00:00Z2018-10-03T14:00:00Z<p>by Tao Yuan, Jiapei Li, Yong Fu, Tao Xu, Juan Li, Xiangqing Wang, Ying Zhou, Yingyue Dong, Weigang Zhao</p>
Backgrounds <p>Cardiac autonomic neuropathy is a common but always overlooked. More convenient diagnostic methods are needed.</p> Hypothesis <p>Cardiac autonomic neuropathy risk score evaluated by SUDOSCAN has a fine diagnostic efficacy detecting cardiac autonomic neuropathy.</p> Methods <p>This is a cross-sectional study among patients with diabetes mellitus. Subjects undertook SUDOSCAN tests and cardiac autonomic reflex tests, including heart rate variability due to Valsalva maneuver, heart rate response due to deep breathing and heart rate response due to standing up. Presenting 2 abnormal results was defined as cardiac autonomic neuropathy.</p> Results <p>Subjects with cardiac autonomic neuropathy has significantly higher cardiac autonomic neuropathy risk score (32.88±1.60 vs 27.64±1.24,P = 0.010). Cardiac autonomic neuropathy risk score was correlated significantly with the heart rate response due to deep breathing(P = 0.004). Multiple regression analysis including significant variables showed an independent association of cardiac autonomic neuropathy risk score and heart rate response due to deep breathing (P = 0.031) and age (P = 0.000). In receiver operating characteristic curve analysis evaluating the relationship between cardiac autonomic neuropathy risk score and cardiac autonomic neuropathy, The cut-off value was 20.5, with the sensitivity of 90.48%, the specificity of 29.5%, and the positive predictive value of 46.9%. In two-step diagnostic methods, Setting 20.5 as the cut-off value of cardiac autonomic neuropathy risk score and abnormal heart rate response due to standing up as the second diagnostic step’s positive result, and setting 16.5 as the cut-off value of cardiac autonomic neuropathy risk score and abnormal heart rate response due to deep breathing as the second diagnostic step’s positive result, both achieved good diagnostic efficacy.</p> Conclusion <p>Cardiac autonomic neuropathy risk score evaluated by SUDOSCAN is a good screening test for cardiac autonomic neuropathy. The two-step diagnostic methods could be considered as surrogate diagnostic methods.</p>Enhancing glucose flux into sweat by increasing paracellular permeability of the sweat glandAndrew JajackMichael BrothersGerald KastingJason Heikenfeld10.1371/journal.pone.02000092018-07-16T14:00:00Z2018-07-16T14:00:00Z<p>by Andrew Jajack, Michael Brothers, Gerald Kasting, Jason Heikenfeld</p>
Non-invasive wearable biosensors provide real-time, continuous, and actionable health information. However, difficulties detecting diluted biomarkers in excreted biofluids limit practical applications. Most biomarkers of interest are transported paracellularly into excreted biofluids from biomarker-rich blood and interstitial fluid during normal modulation of cellular tight junctions. Calcium chelators are reversible tight junction modulators that have been shown to increase absorption across the intestinal epithelium. However, calcium chelators have not yet been shown to improve the extraction of biomarkers. Here we show that for glucose, a paracellularly transported biomarker, the flux into sweat can be increased by >10x using citrate, a calcium chelator, in combination with electroosmosis. Our results demonstrate a method of increasing glucose flux through the sweat gland epithelium, thereby increasing the concentration in sweat. Future work should examine if this method enhances flux for other paracellularly transported biomarkers to make it possible to detect more biomarkers with currently available biosensors.Time-varying analysis of electrodermal activity during exerciseHugo F. Posada-QuinteroNatasa ReljinCraig MillsIan MillsJohn P. FlorianJaci L. VanHeestKi H. Chon10.1371/journal.pone.01983282018-06-01T14:00:00Z2018-06-01T14:00:00Z<p>by Hugo F. Posada-Quintero, Natasa Reljin, Craig Mills, Ian Mills, John P. Florian, Jaci L. VanHeest, Ki H. Chon</p>
The electrodermal activity (EDA) is a useful tool for assessing skin sympathetic nervous activity. Using spectral analysis of EDA data at rest, we have previously found that the spectral band which is the most sensitive to central sympathetic control is largely confined to 0.045 to 0.25 Hz. However, the frequency band associated with sympathetic control in EDA has not been studied for exercise conditions. Establishing the band limits more precisely is important to ensure the accuracy and sensitivity of the technique. As exercise intensity increases, it is intuitive that the frequencies associated with the autonomic dynamics should also increase accordingly. Hence, the aim of this study was to examine the appropriate frequency band associated with the sympathetic nervous system in the EDA signal during exercise. Eighteen healthy subjects underwent a sub-maximal exercise test, including a resting period, walking, and running, until achieving 85% of maximum heart rate. Both EDA and ECG data were measured simultaneously for all subjects. The ECG was used to monitor subjects’ instantaneous heart rate, which was used to set the experiment’s end point. We found that the upper bound of the frequency band (Fmax) containing the EDA spectral power significantly shifted to higher frequencies when subjects underwent prolonged low-intensity (Fmax ~ 0.28) and vigorous-intensity exercise (Fmax ~ 0.37 Hz) when compared to the resting condition. In summary, we have found shifting of the sympathetic dynamics to higher frequencies in the EDA signal when subjects undergo physical activity.