Postganglionic Sudomotor Assessment in Early Stage of Multiple System Atrophy and Parkinson Disease: A Morpho-functional Study

Background and Objectives:Sudomotor impairment has been recognized as a key feature in differentiating Parkinson disease (PD) and multiple system atrophy-parkinsonian type (MSA-P) with the latter been characterized by diffuse anhidrosis in prospective study including patients in late stage of disease.We aimed to evaluate morphological and functional postganglionic sudomotor involvement in patients with new diagnosis MSA-P and PD to identify possible biomarkers that might be of help in differentiating the two conditions in early stage.Methods:One hundred patients with parkinsonism within 2 years from onset of motor symptoms were included in the study. At time of recruitment, questionnaires to assess non-motor, autonomic and small fiber symptoms were administered and patients underwent post-ganglionic sudomotor function assessment by the dynamic sweat test and punch skin biopsy from distal leg. Skin samples were processed for indirect immunofluorescence with a panel of antibodies including noradrenergic and cholinergic markers. The density of intraepidermal, sudomotor and pilomotor nerve fibers was measured on confocal images using dedicated software. A follow-up visit twelve months after recruitment was performed to confirm the diagnosis.Results:We recruited 57 patients with PD (M/F=36/21; age 63.5±9.4years) and 43 patients with MSA-P (M/F=27/16; age 62.3±9.0 years). Clinical scales and questionnaires showed a more severe clinical picture in MSA-P compared to PD patients. Sweating output and intraepidermal, pilomotor and sudomotor nerve densities, compared to controls, were lower in both groups but with a greater impairment in MSA-P patients. Pilomotor and sudomotor nerve density correlated with sweating function and with non-motor clinical symptoms. A composite sudomotor parameter defined as the arithmetic product of sweat production multiplied by the density of sudomotor fibers, efficiently separated the two populations, the receiver operating characteristics showing an area under the curve of 0.83.Discussion:Dynamic sweat test and the quantification of cutaneous autonomic nerves provided to be a sensitive morpho-functional approach to assess postganglionic component of the sudomotor pathway, revealing a more severe involvement in MSA-P than in PD early in the disease course. This approach can be applied to early differentiate the two conditions.Classification of Evidence:This study provides Class II evidence that post ganglionic sudomotor morpho-functional assessment accurately distinguish PD from MSA-P patients.

Heat Exposure and Physiological Changes among Cooks

Cooks who are exposed to heat produced from stoves when working in the kitchen are at risk of thermal stress and heat-related illness. Physiological changes such as increased heart rate, sweat production and blood pressure may also affect them. This study aimed to determine the area heat exposure levels and physiological changes including core body temperature, blood pressure and heart rate during pre-, mid- and post-shift among cooks and its association, and to compare the mean difference of physiological changes between the shifts. This cross-sectional study utilised the purposive sampling method and recruited 30 cooks from food stalls and cafeterias in Kelantan. Area heat measurements were collected from 14 sites (7 inside and 7 outside the USM Health Campus). Wet-bulb Globe Temperature (WBGT) monitor was mounted on a tripod at 1.1 m height near the source of heat for 8 hours. The core body temperature, blood pressure, and heart rate were taken three times per day during pre-, mid- and post-shift for physiological changes measurement. Respondents’ personal information, health history, work description, and symptoms of heat-related illness were collected using a questionnaire. The overall WBGT area levels at each sampling site were homogeneously distributed. There was significant increase in core body temperature and heart rate from pre-shift to post-shift. However, there was no significant correlation (p>0.05) between heat exposure (WBGT index) established with the physiological changes. This may suggest that the increase in core body temperature and heart rate might be attributed to other factors and needed further investigation.

Ion Channel and Ubiquitin Differential Expression during Erythromycin-Induced Anhidrosis in Foals

Macrolide drugs are the treatment of choice for Rhodococcus equi infections, despite severe side-effects temporary anhidrosis as a. To better understand the molecular biology leading to macrolide induced anhidrosis, we performed skin biopsies and Quantitative Intradermal Terbutaline Sweat Tests (QITSTs) in six healthy pony-cross foals for three different timepoints during erythromycin administration—pre-treatment (baseline), during anhidrosis and post-recovery. RNA sequencing of biopsies followed by differential gene expression analysis compared both pre and post normal sweating timepoints to the erythromycin induced anhidrosis episode. After Bonferroni correction for multiple testing, 132 gene transcripts were significantly differentially expressed during the anhidrotic timepoint. Gene ontology analysis of the full differentially expressed gene set identified over-represented biological functions for ubiquitination and ion-channel function, both biologically relevant to sweat production. These same mechanisms were previously implicated in heritable equine idiopathic anhidrosis and sweat gland function and their involvement in macrolide-induced temporary anhidrosis warrants further investigation.

Finger sweat analysis enables short interval metabolic biomonitoring in humans

Metabolic biomonitoring in humans is typically based on the sampling of blood, plasma or urine. Although established in the clinical routine, these sampling procedures are often associated with a variety of compliance issues, which are impeding time-course studies. Here, we show that the metabolic profiling of the minute amounts of sweat sampled from fingertips addresses this challenge. Sweat sampling from fingertips is non-invasive, robust and can be accomplished repeatedly by untrained personnel. The sweat matrix represents a rich source for metabolic phenotyping. We confirm the feasibility of short interval sampling of sweat from the fingertips in time-course studies involving the consumption of coffee or the ingestion of a caffeine capsule after a fasting interval, in which we successfully monitor all known caffeine metabolites as well as endogenous metabolic responses. Fluctuations in the rate of sweat production are accounted for by mathematical modelling to reveal individual rates of caffeine uptake, metabolism and clearance. To conclude, metabotyping using sweat from fingertips combined with mathematical network modelling shows promise for broad applications in precision medicine by enabling the assessment of dynamic metabolic patterns, which may overcome the limitations of purely compositional biomarkers.

Enhancing sweat rate using a novel device for the treatment of congestion in heart failure

Background Current treatment of fluid retention in heart failure (HF) relies primarily on diuretics. However, adequate decongestion is not achieved in many patients. Purpose To study the feasibility and short-term performance of a novel approach to remove fluids and sodium directly from the interstitial compartment by enhancing sweat rate. Methods We used a device designed to enhance fluid and salt loss via the eccrine sweat glands. Skin temperature in the lower body was increased to 35–38°, where the slope of the relationship between temperature and sweat production is linear. With this wearable device, the sweat evaporates instantaneously, thus avoiding the awareness of perspiration. The primary efficacy endpoint was the ability to increase skin temperature to the desired range without elevating the core temperature above normal range. A secondary efficacy endpoint was a clinically meaningful hourly sweat output, defined as ≥150 mL/h. The primary safety endpoint was any procedure-related adverse events. Results We studied 6 normal subjects and 10 HF patients with clinical evidence of congestion and median NT-proBNP of 602 pg/mL [interquartile range 427 to 1719 pg/mL]. Participants underwent 3 treatment sessions of up to 4h. Skin temperature increased to a median of 37.5°C (interquartile range 37.1–37.9°C) with the core temperature remaining unchanged. The median total weight loss during treatment was 219±67 g/h (Figure) with a range of 100–338 g/h. In 77% of cases, the average sweat rate was ≥150 mL/h. Systolic (P=0.25) and diastolic (P=0.48) blood pressure and heart rate (P=0.11) remained unchanged during the procedure. There were no significant changes in renal function and no procedure-related adverse events. Conclusion Enhancing sweat rate was safe and resulted in a clinically meaningful fluid removal and weight loss. Further evaluation of this concept is warranted. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): AquaPass Inc Weight loss due to sweat

Effectiveness of Photodynamic Therapy for Management of Primary Palmar Hyperhidrosis

Background Hyperhidorsis is a condition in which sweat production exceeds that which is needed for thermoregulation, and can affect the hands, feet, axiall, face, back, grain, and legs. It is adisabling condition that affect, both children and adults, with in audience rate of 1-3% and onset usually during childhood or adokscne. Although not a dangerous condition, hyperhidrosis can cause social and occupational impairment and emotional distress and facilitate the development of secondary morbidity. Objectives So our aim to study the efficacy and safety of photodynamic therapy in management of primary palmar hyperhidrosis using two photosensitizers [MB2% and eosin]. Patients and Methods Twenty patients with primary palmar hyperhidrosis were recruited from the outpatient clinic of the Dermatology and Venereology department, Faculty of Medicine – Ain Shams University during the period from 2017 to 2018. The protocol was approved by Faculty of Medicine, Ain Shams University ethical committee (FWA000017585). An informed written consent was obtained from all patients prior to enrolment in the study. It is a right-left controlled study which included 20 patients with primary palmar hyperhidrosis. Results Our study showed that the PDT had positive treatment outcome in palmar hyperhidrosis with sustainable efficacy for at least twelve weeks after treatment stoppage. Conclusion Photodynamic therapy is an effective, safe and cheap method for management of primary palmar hyperhidrosis. Both eosin and methylene blue 2% can be used effectively as photosensitizers for photodynamic therapy with good results for treatment of primary palmar hyperhidrosis with minimal tolerable side effects.

‘Excessive sweating is not a feminine thing’: A qualitative study of women’s experiences suffering from primary hyperhidrosis

Background Primary hyperhidrosis, excessive focal sweating is a common disease equally affecting men and women. Women tend to seek care more often and assess being more affected by hyperhidrosis in their daily life. The aim of this study was to explore experiences of living with primary hyperhidros in a sample of 15 women. Methods Individual, semi-structured interviews with a purposive sample of 15 women diagnosed with primary hyperhidrosis and analysed by qualitative content analysis utilising an inductive approach. Results The analysis resulted in a theme, constantly guarding the female image, based on three categories, misfitting the feminine norms, avoiding the attention of others and passing like any woman. Primary hyperhidrosis in women disrupted the ideal feminine appearance. Wearing clothes that concealed hyperhidrosis and distancing from social gatherings, in combination with negative remarks by others, created stress and anxiety and had a negative effect on self-esteem. Women felt poorly understood by others regarding the extent of their sweating and were misunderstood in intimate situations while trying to reduce the sweat production. Choices regarding education and career opportunities were affected, since being exposed and receiving attention due to primary hyperhidrosis was unwanted. Treatment with botulinum toxin liberated women from excessive sweating and removed a social handicap they described living with. Conclusion Primary hyperhidrosis in women disrupts the feminine appearance, lowers self-esteem and hinders social interactions. Clinicians assessing primary hyperhidrosis need to be aware that women may report the impairments from primary hyperhidrosis as being more associated with body image and appearance than with functional reductions in daily life. Educating patients, providing accurate information regarding the disease via media and cooperating with patient groups are important for increasing awareness and achieving progress in care for women with primary hyperhidrosis.

Skin Injuries Associated With Moisture: Dermatitis Associated With Incontinence (Iad)

Both the skin of newborns and the elderly have a structure and composition that makes it weaker and more susceptible to damage from friction and external aggressions. It is approximately 60% thinner than that of the adult and has a smaller amount of hair. In addition, the functions of the stratum corneum are diminished, there is less cohesion between the dermis and the epidermis, less sebaceous and sweat production, and the pH they present is neutra

Soft, skin-interfaced sweat stickers for cystic fibrosis diagnosis and management

The concentration of chloride in sweat remains the most robust biomarker for confirmatory diagnosis of cystic fibrosis (CF), a common life-shortening genetic disorder. Early diagnosis via quantitative assessment of sweat chloride allows prompt initiation of care and is critically important to extend life expectancy and improve quality of life. The collection and analysis of sweat using conventional wrist-strapped devices and iontophoresis can be cumbersome, particularly for infants with fragile skin, who often have insufficient sweat production. Here, we introduce a soft, epidermal microfluidic device (“sweat sticker”) designed for the simple and rapid collection and analysis of sweat. Intimate, conformal coupling with the skin supports nearly perfect efficiency in sweat collection without leakage. Real-time image analysis of chloride reagents allows for quantitative assessment of chloride concentrations using a smartphone camera, without requiring extraction of sweat or external analysis. Clinical validation studies involving patients with CF and healthy subjects, across a spectrum of age groups, support clinical equivalence compared to existing device platforms in terms of accuracy and demonstrate meaningful reductions in rates of leakage. The wearable microfluidic technologies and smartphone-based analytics reported here establish the foundation for diagnosis of CF outside of clinical settings.

Finger Sweat Analysis Enables Short Interval Metabolic Biomonitoring in Humans

Metabolic biomonitoring in humans is typically based on the sampling of blood, plasma or urine. Although established in the clinical routine, these sampling procedures are often associated with a variety of compliance issues and are impractical for performing time-course studies. The analysis of the minute amounts of sweat sampled from the fingertip enables a solution to this challenge. Sweat sampling from the fingertip is non-invasive and robust and can be accomplished repeatedly by untrained personnel. This matrix represents a rich source for metabolomic phenotyping, which is exemplified by the detection of roughly 50’000 features per sample. Moreover, the determined limits of detection demonstrate that the ingestion of 200 μg of a xenobiotic may be sufficient for its detection in sweat from the fingertip. The feasibility of short interval sampling of sweat from the fingertips was confirmed in three time-course studies after coffee consumption or ingestion of a caffeine capsule, successfully monitoring all known caffeine metabolites. Fluctuations in the rate of sweat production were accounted for by mathematical modelling to reveal individual rates of caffeine uptake, metabolism and clearance. Biomonitoring using sweat from the fingertip has far reaching implications for personalised medical diagnostics and biomarker discovery.