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Skin cancers are growing in incidence worldwide and are primarily caused by exposures to ultraviolet (UV) wavelengths of sunlight. UV radiation induces the formation of photoproducts and other lesions in DNA that if not removed by DNA repair may lead to mutagenesis and carcinogenesis. Though the factors that cause skin carcinogenesis are reasonably well understood, studies over the past 10-15 years have linked the timing of UV exposure to DNA repair and skin carcinogenesis and implicate a role for the body's circadian clock in UV response and disease risk. Here we review what is known about the skin circadian clock, how it affects various aspects of skin physiology, and the factors that affect circadian rhythms in the skin. Furthermore, the molecular understanding of the circadian clock has led to the development of small molecules that target clock proteins; thus, we discuss the potential use of such compounds for manipulating circadian clock-controlled processes in the skin to modulate responses to UV radiation and mitigate cancer risk.

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Multiresistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) cause serious postoperative infections. A skin tolerant far-UVC (< 240 nm) irradiation system for their inactivation is presented here. It uses UVC LEDs in combination with a spectral filter and provides a peak wavelength of 233 nm, with a full width at half maximum of 12 nm, and an irradiance of 44 µW/cm2. MRSA bacteria in different concentrations on blood agar plates were inactivated with irradiation doses in the range of 15-40 mJ/cm2. Porcine skin irradiated with a dose of 40 mJ/cm2 at 233 nm showed only 3.7% CPD and 2.3% 6-4PP DNA damage. Corresponding irradiation at 254 nm caused 15-30 times higher damage. Thus, the skin damage caused by the disinfectant doses is so small that it can be expected to be compensated by the skin's natural repair mechanisms. LED-based far-UVC lamps could therefore soon be used in everyday clinical practice to eradicate multiresistant pathogens directly on humans.

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BACKGROUND: Microfocused ultrasound with visualization (MFU-V) is a well-established treatment modality for skin tightening. There is a paucity of evidence for its use in body treatments, such as the lower abdomen. OBJECTIVE: To investigate the effectiveness and safety of MFU-V in treating lower abdominal skin and soft-tissue laxity in postpartum women. METHODS: The lower abdomen of 20 female patients between 6 and 24 months postpartum are treated with MFU-V using 1.5-, 3.0-, and 4.5-mm transducers. Data are prospectively collected and analyzed at 3 and 6 months using subject-reported and investigator-reported outcome measures. One additional patient underwent planned abdominoplasty 6 weeks after MFU-V treatment with tissue assessed intraoperatively and histologically. RESULTS: There was a mean improvement of 1.0 and 1.3 grades at 6 months using the investigator-reported and patient-reported skin laxity scale, respectively (p < .001). Patient-reported outcomes and satisfaction survey showed consistent improvement at 6 months. Histological examination of pretreated tissue showed increased total collagen, increased number and thickness of fibrous septae, and no change in fat cells within pretreated tissue compared with the control. No significant adverse events were recorded. CONCLUSION: MFU-V is an effective and safe treatment modality for lower abdominal skin laxity in postpartum patients.

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BACKGROUND Tattoos are popular in modern times. Due to the occurance of adverse effects such as poor aesthetic value, scar hyperplasia, and abnormal pigments, there is a high demand for uniform operation standards as well as standards for tattoo technologies. In the present study we used Sprague-Dawley rats to assess the tattoo removal efficacy of use of a picosecond laser at various energy values. MATERIAL AND METHODS Tattoos were made on the backs of rats, then we used a picosecond laser set at various energy parameters to remove the tattoos. After performing the removal procedure in multiple groups, we selected the most suitable energy levels with corresponding parameters for the tattoo removal. We recruited human volunteers who wanted their tattoos removed and used the energy level found to perform best during tattoo removal experiments. The tattoo removal effects were evaluated and verified. Four tattoo volunteers were treated by using the optimal energy parameters for picosecond laser technology. RESULTS Through characterization observation and pathological staining results, it was demonstrated that the 1.9 mJ/µbeam energy laser had the best hollowing effect and the most complete pigment particle crushing effect in the rat skin, and had the best tattoo removal effect. CONCLUSIONS We leveraged the evaluation standard to choose the most suitable energy value of the picosecond laser, which had a good tattoo removal effect and could be employed as a reference for clinical removal of tattoos. This process provides criteria for tattoo removal evaluations as well as alternatives for tattoo removal in clinical practice.

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Background: The fractionated picosecond laser produces microscopic lesions in the epidermis and dermis, which are known as laser-induced optical breakdown (LIOB) and intra-dermal laser-induced cavitation (LIC). There have been multiple histological reports on these phenomena, although some have been challenged on the grounds of similarity to artifacts. Asian skins, with a higher melanin content, may react differently to this treatment, and present literature is also lacking in this area.Purpose: To observe and report the histological effect of different energy levels and parameters of the fractional 532 nm/1064 nm picosecond laser on Asian skin ex vivo.Methods: Six skin samples were taken from clinically normal-looking perilesional areas and treated with different energy levels and parameters of the fractional 532 nm/1064 nm picosecond laser. The specimens were then sent to the lab for H&E staining, and the slides were reviewed by a dermatopathologist.Results: Superficial, intra-epidermal LIOBs were seen in skin treating at higher laser energies; deep, intra-dermal LICs were seen in skin treated at lower energies. Lesion sizes and depths were consistent with previously reported values on Caucasian skins, and lesions were spaced in 600-µm intervals or its multiple.Conclusions: The histological findings are consistent with results from other ethnicities, and the spacing of lesions is a strong indication of their validity as LIOBs or LICs.

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BACKGROUND: The skin microbiome has been implicated in the pathophysiology of atopic dermatitis (AD). Although 308 nm excimer light treatment is an effective phototherapy for AD, its effects on the skin microbiome currently remain unclear. Therefore, we investigated the effects of the excimer light treatment on the skin bacterial and fungal microbiome of lesional skin of AD. METHODS: Swab samples were collected from 11 healthy controls, non-lesional and lesional skin of 11 AD patients. The excimer light treatment was administered to the lesional skin. The composition of the skin microbiome, the clinical score and skin barrier function of the lesional skin were examined before and after the treatment. The composition of the skin microbiome was determined by sequencing bacterial 16S and fungal internal transcribed spacer regions. RESULTS: The excimer light treatment significantly changed the composition of the bacterial microbiome in the lesional skin of AD, as well as improved the clinical score and skin barrier function. The treatment increased the relative abundance of the phylum Cyanobacteria and decreased that of the phylum Bacteroidetes in lesional skin. At the species level, the treatment significantly decreased the relative abundance of Staphylococcus aureus (S aureus) in lesional skin. There was also a significant correlation between the reduction of S aureus and improvement of the clinical outcomes. CONCLUSION: Our findings suggest that alterations of the skin microbiome with excimer light treatment, specifically the decrease in the abundance of S aureus, are partly involved in the improvement of AD lesions.

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NEW FINDINGS: What is the central question of this study? Are ultraviolet radiation (UVR)-induced increases in skin blood flow independent of skin erythema? Does broad-spectrum UVR exposure attenuate NO-mediated cutaneous vasodilatation, and does sunscreen or sweat modulate this response? What are the main findings and their importance? Erythema and vascular responses to UVR are temporally distinct, and sunscreen prevents both responses. Exposure to UVR attenuates NO-mediated vasodilatation in the cutaneous microvasculature; sunscreen or simulated sweat on the skin attenuates this response. Sun over-exposure may elicit deleterious effects on human skin that are separate from sunburn, and sunscreen or sweat on the skin may provide protection. ABSTRACT: Exposure to ultraviolet radiation (UVR) may result in cutaneous vascular dysfunction independent of erythema (skin reddening). Two studies were designed to differentiate changes in erythema from skin vasodilatation throughout the 8 h after acute broad-spectrum UVR exposure with (+SS) or without SPF-50 sunscreen (study 1) and to examine NO-mediated cutaneous vasodilatation after acute broad-spectrum UVR exposure with or without +SS or simulated sweat (+SW) on the skin (study 2). In both studies, laser-Doppler flowmetry was used to measure red cell flux, and cutaneous vascular conductance (CVC) was calculated (CVC = flux/mean arterial pressure). In study 1, in 14 healthy adults (24 ± 4 years old; seven men and seven women), the skin erythema index and CVC were measured over two forearm sites (UVR only and UVR+SS) before, immediately after and every 2 h for 8 h post-exposure (750 mJ cm-2 ). The erythema index began to increase immediately post-UVR (P < 0.05 at 4, 6 and 8 h), but CVC did not increase above baseline for the first 4-6 h (P ≤ 0.01 at 6 and 8 h); +SS prevented both responses. In study 2, in 13 healthy adults (24 ± 4 years old; six men and seven women), three intradermal microdialysis fibres were placed in the ventral skin of the forearm [randomly assigned to UVR (450 mJ cm-2 ), UVR+SS or UVR+SW], and one fibre (non-exposed control; CON) was placed in the contralateral forearm. After UVR, a standardized local heating (42°C) protocol quantified the percentage of NO-mediated vasodilatation (%NO). The UVR attenuated %NO compared with CON (P = 0.01). The diminished %NO was prevented by +SS (P < 0.01) and +SW (P < 0.01). Acute broad-spectrum UVR attenuates NO-dependent dilatation in the cutaneous microvasculature, independent of erythema. Sunscreen protects against both inflammatory and heating-induced endothelial dysfunction, and sweat might prevent UVR-induced reductions in NO-dependent dilatation.

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Exaggerated itch responses to pruritic chemical provocations and mechanical stimuli are evident in patients with chronic itch, for example, in atopic dermatitis. Currently used human models of itch do not account for such itch sensitization features, and the mechanisms underlying clinical itch sensitization are unknown. This study utilized two established human models of cutaneous nociceptive sensitization to explore how pre-established inflammatory hyperalgesia (ultraviolet-B-irradiation; "UVB") and non-inflammatory neurotrophic pain sensitization (nerve growth factor; "NGF") alter sensitivity to chemical and mechanically evoked itch. Twenty healthy volunteers participated in the UVB experiment. Six volar forearm areas (2 cm diameter) were UVB irradiated with ≤2 × minimal erythemal dose, and two non-irradiated areas were used as controls. Sixteen healthy volunteers participated in the NGF experiment and had 2 µg intradermally injected (4 × 50 µL in 2 cm diameter areas) into both volar forearms. Isotonic saline was applied as control. Pain sensitivity measurements (mechanical and heat pain thresholds) were conducted to validate the models. Subsequently, itch was evoked using histamine and cowhage spicules in the sensitized skin areas, and itch/pain was rated using visual analogue scales. Mechanical hyperknesis (increased itch to punctuate stimuli) was probed with von Frey filaments before/after each itch provocation. Both UVB- and NGF models induced robust primary mechanical hyperalgesia (P < .01) and hyperknesis (P < .05). Neither of the models augmented itch in response to chemical itch provocations but significant increases specifically for pain ratings were observed for both histamine and cowhage (P < .05). This suggests that these models are of limited value as proxies for itch sensitization to pruritogens observed, e.g., in inflammatory dermatoses.

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A new electron skin dosimetry model was developed for the VARSKIN 5 tissue dosimetry code. This model employs energy deposition kernels that provides for improved accuracy of energy deposition at the end of electron tracks. The Monte Carlo code EGSnrc was utilized to develop these energy deposition kernels such that scaling of electron energy loss is dependent on effective atomic number and density of the source material, electron range and conservation of energy. This work contrasts VARSKIN's electron dosimetry model to several existing deterministic and Monte Carlo dosimetry tools to determine the efficacy of these improvements. Comparison results are given for a wide range of scenarios that extend beyond the typical use of VARSKIN, including mono-energetic electrons and a homogenous water medium. For planar and point sources in contact with the skin, VARSKIN produces results equated to other dosimetry methods within 10%. However, it appears that VARSKIN is unable to account accurately for electron energy loss with the introduction of a cover material or an air gap. The comparisons herein confirm that VARSKIN provides accurate electron dose calculations for skin-contamination scenarios.

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Chameleons have a diagnostic thermal protection that enables them to live under various conditions. Our developed special radiative control therefore is inspired by the chameleon thermal protection ability by imitating its two superposed layers as two pigment particles in one coating layer. One particle imitates a chameleon superficial surface for color control (visible light), and another particle imitates a deep surface to reflect solar irradiation, especially in the near-infrared region. Optical modeling allows us to optimally design the particle size and volume fraction. Experimental evaluation shows that the desired spectral reflectance, i.e., low in the VIS region and high in NIR region, can be achieved. Comparison between the measured and calculated reflectances shows that control of the particle size and dispersion/aggregation of particle cloud is important in improving the thermal-protection performance of the coating. Using our developed coating, the interior temperature decreases and the cooling load is reduced while keeping the dark tone of the object.

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Radiofrequency-based electrophysical agents (EPA) have been used in therapy practice over several decades (e.g., shortwave therapies). Currently, there is insufficient evidence supporting such devices operating below shortwave frequencies. This laboratory-based study investigated the skin physiological effects of 448 kHz capacitive resistive monopolar radiofrequency (CRMRF) and compared them to pulsed shortwave therapy (PSWT). In a randomised crossover study, seventeen healthy volunteers received four treatment conditions - High, Low and Placebo dose conditions receiving 15-min CRMRF treatment and a Control condition receiving no intervention. Fifteen participants also received high dose PSWT for comparison. Treatment was applied to the right lower medial thigh. Pre, post and 20-min follow-up measurements of skin temperature (SKT), skin blood flow (SBF) and nerve conduction velocity (NCV) were obtained using Biopac MP150 system. Group data were compared using the ANOVA model. Statistical significance was set at p ≤ 0.05 (0.8P, 95%CI). Significant increase and sustenance of SKT with both high and low dose CRMRF was demonstrated over the other groups (p < 0.001). PSWT increased SKT significantly (p < 0.001) but failed to sustain it over the follow-up. However, among the five conditions, only high dose CRMRF significantly increased and sustained SBF (p < 0.001). Overall, the CRMRF physiological responses were significantly more pronounced than that of PSWT. No significant changes in NCV were noted for any condition. Physiological changes associated with CRMRF were more pronounced when compared to PSWT, placebo or control. Any potential stronger therapeutic benefits of CRMRF need to be confirmed by comparative clinical studies.

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BACKGROUND: Two international guidelines/standards for human protection from electromagnetic fields define the specific absorption rate (SAR) averaged over 10 g of tissue as a metric for protection against localized radio frequency field exposure due to portable devices operating below 3-10 GHz. Temperature elevation is suggested to be a dominant effect for exposure at frequencies higher than 100 kHz. No previous studies have evaluated temperature elevation in the human head for local exposure considering thermoregulation. This study aims to discuss the temperature elevation in a human head model considering vasodilation, to discuss the conservativeness of the current limit. METHODS: This study computes the temperature elevations in an anatomical human head model exposed to radiation from a dipole antenna and truncated plane waves at 300 MHz-10GHz. The SARs in the human model are first computed using a finite-difference time-domain method. The temperature elevation is calculated by solving the bioheat transfer equation by considering the thermoregulation that simulates the vasodilation. RESULTS: The maximum temperature elevation in the brain appeared around its periphery. At exposures with higher intensity, the temperature elevation became larger and reached around 40 °C at the peak SAR of 100 W/kg, and became lower at higher frequencies. The temperature elevation in the brain at the current limit of 10 W/kg is at most 0.93 °C. The effect of vasodilation became notable for tissue temperature elevations higher than 1-2 °C and for an SAR of 10 W/kg. The temperature at the periphery was below the basal brain temperature (37 °C). CONCLUSIONS: The temperature elevation under the current guideline for occupational exposure is within the ranges of brain temperature variability for environmental changes in daily life. The effect of vasodilation is significant, especially at higher frequencies where skin temperature elevation is dominant.

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The aim of this study was to analyze photo-dynamic and photo-pathology changes of different color light radiations on human adult skin cells. We used a real-time biophysical and biomechanics monitoring system for light-induced cellular changes in an in vitro model to find mechanisms of the initial and continuous degenerative process. Cells were exposed to intermittent, mild and intense (1-180 min) light with On/Off cycles, using blue, green, red and white light. Cellular ultra-structural changes, damages, and ECM impair function were evaluated by up/down-regulation of biophysical, biomechanical and biochemical properties. All cells exposed to different color light radiation showed significant changes in a time-dependent manner. Particularly, cell growth, stiffness, roughness, cytoskeletal integrity and ECM proteins of the human dermal fibroblasts-adult (HDF-a) cells showed highest alteration, followed by human epidermal keratinocytes-adult (HEK-a) cells and human epidermal melanocytes-adult (HEM-a) cells. Such changes might impede the normal cellular functions. Overall, the obtained results identify a new insight that may contribute to premature aging, and causes it to look aged in younger people. Moreover, these results advance our understanding of the different color light-induced degenerative process and help the development of new therapeutic strategies.

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Ultraviolet B (UVB) radiation induces regulatory T cells (Treg cells) and depletion of these Treg cells alleviates immunosuppression and inhibits photocarcinogenesis in mice. Here, we determined the effects of dietary grape seed proanthocyanidins (GSPs) on the development and activity of UVB-induced Treg cells. C3H/HeN mice fed a GSPs (0.5%, w/w)-supplemented or control diet were exposed to UVB (150 mJ/cm2) radiation, sensitized to 2,4-dinitrofluorobenzene (DNFB) and sacrificed 5 days later. FACS analysis indicated that dietary GSPs decrease the numbers of UVB-induced Treg cells. ELISA analysis of cultured sorted Treg cells indicated that secretion of immunosuppressive cytokines (interleukin-10, TGF-ß) was significantly lower in Treg cells from GSPs-fed mice. Dietary GSPs also enhanced the ability of Treg cells from wild-type mice to stimulate production of IFNγ by T cells. These effects of dietary GSPs on Treg cell function were not found in XPA-deficient mice, which are incapable of repairing UVB-induced DNA damage. Adoptive transfer experiments revealed that naïve recipients that received Treg cells from GSPs-fed UVB-irradiated wild-type donors that had been sensitized to DNFB exhibited a significantly higher contact hypersensitivity (CHS) response to DNFB than mice that received Treg cells from UVB-exposed mice fed the control diet. There was no significant difference in the CHS response between mice that received Treg cells from UVB-irradiated XPA-deficient donors fed GSPs or the control diet. Furthermore, dietary GSPs significantly inhibited UVB-induced skin tumor development in wild-type mice but not in XPA-deficient mice. These results suggest that GSPs inactivate Treg cells by promoting DNA repair in dendritic cells in UVB-exposed skin.

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The innumerable intricacies associated with chronic wounds have made the development of new painless, noninvasive, biophysical therapeutic interventions as the focus of current biomedical research. Red and near-infrared light-induced photobiomodulation therapy appears to emerge as a promising drug-free approach for promoting wound healing, reduction in inflammation, pain and restoration of function owing to penetration power in conjunction with their ability to positively modulate the biochemical and molecular responses. This review will describe the physical properties of red and near-infrared light and their interaction with skin and highlight their efficacy of wound repair and regeneration. Near-infrared (800-830 nm) was found to be the most effective and widely studied wavelength range followed by red (630-680 nm) and 904 nm superpulsed light exhibiting beneficial photobiomodulatory effects on impaired dermal wound healing.

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Beauty treatment for skin requires a high-intensity focused ultrasound (HIFU) transducer to generate coagulative necrosis in a small focal volume (e.g., 1 mm³) placed at a shallow depth (3-4.5 mm from the skin surface). For this, it is desirable to make the F-number as small as possible under the largest possible aperture in order to generate ultrasound energy high enough to induce tissue coagulation in such a small focal volume. However, satisfying both conditions at the same time is demanding. To meet the requirements, this paper, therefore, proposes a double-focusing technique, in which the aperture of an ultrasound transducer is spherically shaped for initial focusing and an acoustic lens is used to finally focus ultrasound on a target depth of treatment; it is possible to achieve the F-number of unity or less while keeping the aperture of a transducer as large as possible. In accordance with the proposed method, we designed and fabricated a 7-MHz double-focused ultrasound transducer. The experimental results demonstrated that the fabricated double-focused transducer had a focal length of 10.2 mm reduced from an initial focal length of 15.2 mm and, thus, the F-number changed from 1.52 to 1.02. Based on the results, we concluded that the proposed double-focusing method is suitable to decrease F-number while maintaining a large aperture size.

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OBJECTIVE: The purpose of the research was to evaluate skin elasticity and reduction in the aging eye area using a 1410-nm nonablative fractional laser treatment, cutometric measurements and photographic documentation. MATERIAL AND METHODS: This study included 24 patients (21 women, three men), aged 33-50 years (the average age was 44.6) with Fitzpatrick skin type II and III. They received five successive treatment sessions with a 1410-nm nonablative fractional laser in 2-week intervals. Biomechanical properties of the skin were measured by using Cutometer (Courage+Khazaka electronic). Measurements of skin elasticity were made in three places of the eye area. A photographic documentation was used to compare changes after the series of treatment sessions. Additionally, the patients filled in a survey in which they were asked to make a self-evaluation of the administered procedure. RESULTS: Cutometric analysis showed a significant improvement of skin elasticity. Changes in the measurements of R2 and R6 parameters indicate that the statistical significance level is mostly P < 0.0001 for the differences in the measurements. The analysis of clinical results of the therapy, using photographic documentation, showed a 47% decrease in the quantity and depth of wrinkles in the eye area. CONCLUSIONS: A 1410-nm nonablative fractional laser treatment seems to be an effective method aiming at reducing wrinkles in the eye area and improving tightness. Cutometric measurements provide invaluable help in the objective evaluation of the anti-aging treatment and the photographic documentation is an excellent addition to the clinical analysis.

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OBJECTIVE: The purpose of the research was to evaluate skin elasticity and reduction in the aging eye area after using a nonablative radiofrequency treatment. MATERIAL AND METHODS: This study included 23 patients, aged 34-58 years with Fitzpatrick skin type II and III. They received five treatment sessions with a nonablative radiofrequency in 1-week intervals. Biomechanical properties of the skin were measured using Cutometer. A photodocumentation was used to compare changes before and after the series of treatment sessions. Additionally, the patients filled in a questionnaire in which they were asked to make a self-evaluation of the procedure. RESULTS: Cutometrical analysis showed improvement of skin elasticity. Changes in the measurements of R2 and R6 parameters indicate that the statistical significance level is mostly P < 0.0001 for the differences in the measurements. The comparison of clinical changes in the therapy, based on photodocumentation, showed a 33.26% improvement. CONCLUSIONS: This treatment was used to improve skin tightness and decrease the amount and depth of wrinkles. It is a noninvasive treatment, with low risk of complications. The cutometrical measurements seem to be useful to assess improvement of elasticity of the skin after cosmetology or esthetic dermatology treatments.

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The reference levels and maximum permissible exposure values for magnetic fields that are currently used have been derived from basic restrictions under the assumption of upright standing body models in a standard posture, i.e. with arms laterally down and without contact with metallic objects. Moreover, if anatomical modelling of the body was used at all, the skin was represented as a single homogeneous tissue layer. In the present paper we addressed the possible impacts of posture and skin modelling in scenarios of exposure to a 50 Hz uniform magnetic field on the in situ electric field strength in peripheral tissues, which must be limited in order to avoid peripheral nerve stimulation. We considered different body postures including situations where body parts form large induction loops (e.g. clasped hands) with skin-to-skin and skin-to-metal contact spots and compared the results obtained with a homogeneous single-layer skin model to results obtained with a more realistic two-layer skin representation consisting of a low-conductivity stratum corneum layer on top of a combined layer for the cellular epidermis and dermis. Our results clearly indicated that postures with loops formed of body parts may lead to substantially higher maximum values of induced in situ electric field strengths than in the case of standard postures due to a highly concentrated current density and in situ electric field strength in the skin-to-skin and skin-to-metal contact regions. With a homogeneous single-layer skin, as is used for even the most recent anatomical body models in exposure assessment, the in situ electric field strength may exceed the basic restrictions in such situations, even when the reference levels and maximum permissible exposure values are not exceeded. However, when using the more realistic two-layer skin model the obtained in situ electric field strengths were substantially lower and no violations of the basic restrictions occurred, which can be explained by the current-limiting effect of the low-conductivity stratum corneum layer.

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