The Influence of UV Varnishes on the Content of Cysteine and Methionine in Women Nail Plates-Chromatographic Studies.

The main purpose of this work was to determine if the use of hybrid nail polishes causes changes in concentration of the most important sulfur amino acids that build nail plate structures, cysteine and methionine. We found that the average contents of cysteine and methionine in studied samples before the use of hybrid manicure were 1275.3 ± 145.9 nmol mg-1 and 111.7 ± 23.8 nmol mg-1, respectively. After six months of hybrid manicure use, the average amount of these sulfur amino acids in studied samples were 22.1% and 36.5% lower in the case of cysteine and methionine, respectively. The average amounts of cysteine and methionine in nail plate samples after the use of hybrid manicures were 992.4 ± 96.2 nmol mg-1 and 70.9 ± 14.8 nmol mg-1, respectively. We also confirmed that in studied women the application of UV light varnishes reduced the thickness of the nail plate, from 0.50 ± 0.12 mm before to 0.46 ± 0.12 mm after the use of the hybrid manicure.

Behavior of the electron spin resonance signals in X-ray irradiated human fingernails for the establishment of a dose reconstruction procedure.

The retrospective dosimetry that follows accidental X-ray exposure is becoming more significant for improving radiation diagnosis and treatment. We investigated the dosimetric properties of electron spin resonance (ESR) signals in X-ray irradiated fingernails under conditions that resemble realistic situations. We collected fingernails from 12 Japanese donors between the ages of 30 to 70. The sampled fingernails were utilized for X-ray irradiation, mechanical stimulation and background measurements. We also collected 10 toenails from one of the donors to evaluate their differences from fingernails. Additionally, we prepared 15 samples from two donors to compare the signals generated by γ-rays to those by X-rays. After observing the linear dose-response for both X- and γ-ray irradiated samples, we found that the sensitivity of the air-absorbed dose of γ-ray irradiated samples was identical to that of X-ray irradiated samples. The effect from secondary electrons seemed to be small in fingernails. The inter-individual variation in the sensitivity was no greater than the intra-individual variation. The signal intensities in each measurement fluctuated about the linear response curve, and the size of the fluctuation was dependent on the sample. The average fluctuation corresponded to 1.7 Gy, and the standard deviation was 1.3 Gy. The signal induced by X-rays could be erased by soaking the samples in water and subsequently drying them for four days, which allowed us to estimate the signal intensity prior to the exposure. These characteristics of the ESR signal induced by X-rays facilitate the development of a feasible protocol for fingernail dose reconstruction.

Treatment and management strategies of onychomycosis.

Onychomycosis is one of the most prevalent and severe nail fungal infections, which is affecting a wide population across the globe. It leads to variations like nail thickening, disintegration and hardening. Oral and topical drug delivery systems are the most desirable in treating onychomycosis, but the efficacy of the results is low, resulting in a relapse rate of 25-30%. Due to systemic toxicity and various other disadvantages associated with oral therapy like gastrointestinal, hepatotoxicity, topical therapy is commonly used. Topical therapy improves patient compliance and reduces the cost of treatment. However, due to poor penetration of topical therapy across the nail plate, research is focused on different chemical, mechanical and physical methods to improve drug delivery. Penetration enhancers like Thioglycolic acid, Hydroxypropyl-ß-cyclodextrin (HP-ß-CD), Sodium lauryl sulfate (SLS), carbocysteine, N-acetylcysteine etc. have shown results enhancing the drug penetration across the nail plate. Results with physical techniques such as iontophoresis, laser and Photodynamic therapy are quite promising, but the long-term suitability of these devices is in need to be determined. In this article, a brief analysis of the treatment procedures, factors affecting drug permeation across nail plate, chemical, mechanical and physical devices used to increase the drug delivery through nails for the onychomycosis management has been achieved.

Nailfold Capillaroscopic Findings in an Orthopedic Surgeon: Reversible Abnormalities after the Cessation of Radiation Exposure.

Interventional fluoroscopy is a leading source of occupational ionizing radiation exposure for medical personnel. For example, orthopedic surgeons represent one occupation where the risk of exposure is large. This occupational hazard is the result of a cumulative dose of radiation over time. Adverse health effects induced by low-dose radiation exposure can arise from daily procedures performed over an entire career. Many of the radiation-induced effects that may develop are transient erythema, permanent epilation, dry desquamation, dermal necrosis and telangiectasia; these effects have occurred on the skin of fingers of interventionalists. Nailfold videocapillaroscopy (NVC) is a non-invasive technique useful for early detection of radiation-induced effects on microcirculation of fingernails. Here we report on a case of an orthopedic surgeon exposed to radiation for 30 years during his professional career. He performed NVC before and after the end of his professional career, and regression of the microcirculatory abnormalities were documented after cessation of radiation exposure. To our knowledge, this is the first published work in which the regression of chronic low-dose radiation-induced alterations of finger microvessels have been described and documented.

Laser treatment for onychomycosis: A systematic review and meta-analysis.

BACKGROUND: Laser systems are a common treatment choice for onychomycosis. They exert their effects on inhibiting the growth of the fungus by selective photothermolysis but efficacy is dependent on the specific type of apparatus used. To systematically review the available published literature on the curative effects and safety of laser treatment for onychomycosis. METHODS: Databases including PubMed, web of science, China National Knowledge Internet (CNKI), WanFang Database and VIP were searched systematically to identify relevant articles published up to July 2018. Potentially relevant articles were sourced, assessed against eligibility criteria by 2 researchers independently and data were extracted from included studies. A meta-analysis was performed using R software. RESULTS: Thirty-five articles involving 1723 patients and 4278 infected nails were included. Meta-analysis of data extracted from these studies revealed that: the overall mycological cure rate was 63.0% (95%CI 0.53-0.73); the mycological cure rate associated with the 1064-nm Nd: YAG laser was 63.0% (95%CI 0.51-0.74); and that of CO2 lasers was 74.0% (95%CI 0.37-0.98). The published data indicate that laser treatment is relatively safe, but can cause tolerable pain and occasionally lead to bleeding after treatment. CONCLUSION: Laser treatment of onychomycosis is effective and safe. The cumulative cure rate of laser treatment was significantly higher for CO2 lasers than other types of laser. Laser practitioners should be made aware of potential adverse effects such as pain and bleeding.

Mechanism of human nail poration by high-repetition-rate, femtosecond laser ablation.

Optical poration, or drilling, of the human nail has the potential to drastically improve transungual drug delivery. However, this approach is accompanied by thermal damage to the nail tissue surrounding the laser radiation-created pore. In this paper, fluorescence microscopy has been employed to quantitatively evaluate thermal damage to the nail induced by laser ablation with 80 MHz, nanojoule, femtosecond pulses delivered via a hollow-core fibre. An empirical relation has been established between the intensity of the resulting fluorescence signal and temperature to which the nail was exposed. Using this relationship, detailed temperature maps have been created of the areas surrounding the pores, enabling the mechanism of poration to be better understood. It was deduced that plasma-mediated ablation is primarily responsible for nail tissue ablation at the centre of the pore, while cumulative photothermal processes dominate at the pore edges. It is concluded, furthermore, that temperature mapping represents a useful new tool with which to optimise the process of nail poration. The method is potentially generic and may be applicable to other biological materials.

AN ADVANCE IN EPR DOSIMETRY WITH NAILS.

Olive oil is proposed as a medium for storage of nails in the time between nail harvesting and electron paramagnetic resonance (EPR) measurements to minimise the decay of the radiation-induced EPR signals (RIS). The behaviours of three main EPR signals, namely, RIS, mechanically induced and the background signals (MIS and BG, respectively), were studied for storage in olive oil. The properties of the MIS and BG signals were very similar to those previously observed for the storage in a vacuum. The RIS singlet slightly increased during the first day of storage and then remained practically unchanged at least for 6 days. Dose recovery test revealed that doses at the level 2 Gy may be reconstructed with an accuracy of about ±20%.

The effect of sunlight and UV lamps on EPR signal in nails.

The effects of illumination of nail clippings by direct sunlight, UV lamps and fluorescent bulbs on native and radiation-induced electron paramagnetic resonance (EPR) signals in nails are presented. It is shown that a few minutes of exposure of the nail clippings to light including a UV component (sunlight and UV lamps) generates a strong EPR signal similar to the other EPR signals observable in nails: native background (BKG), mechanically induced (MIS) or radiation-induced (RIS). This effect was observed in clippings exposed and unexposed to ionizing radiation prior to the light illuminations. An exposure of the clippings to fluorescent light without a UV component generated, within the examined range of the light fluences (up to 240 kJ/m2), an EPR signal with considerably lower yield than UV light. The light-induced signal (LIS) decayed after 10 min of water treatment of the samples. In contrast, it was still observable 3 months after illumination in samples stored in air at room temperature, and 3 weeks in frozen samples, respectively. It is concluded that the LIS can considerably affect assessment of the dosimetric RIS components in irradiated nails, and of the background signals in unirradiated nails, thus contributing to errors in EPR dosimetry in nails.

A Dosimetry Study of Portable X-ray Fluorescence in Vivo Metal Measurements.

Portable x-ray fluorescence devices have grown in popularity for possible metal exposure assessment using in vivo measurements of bone and toenail. These measurements are accompanied by a small radiation dose, which is typically assessed by radiation safety committees to be minimal. However, an understanding of precise dose under different instrument conditions is still needed. This study set out to do a thorough investigation of the exact dose measurements using optically stimulated dosimeters, thermoluminescent dosimeters, and simulation with a Monte Carlo N-Particle transport code to assess the skin and total-body effective dose typical of portable x-ray fluorescence devices. We showed normal linear relationships between measurement time, x-ray tube current, and radiation dose with the device, and we showed a second order polynomial relationship with increasing voltage and radiation dose. Dose was quantified using thermoluminescent dosimeters, optically stimulated dosimeters, and simulations, which gave similar dose estimations. Skin dose for a standard 50-kV, 40-µA measurement for bone and toenail in vivo was 48.5 and 28.7 mSv, respectively, according to simulation results. Total-body effective dose was shown as 3.4 and 2.0 µSv for in vivo bone and toenail measurements, respectively, for adults using the portable x-ray fluorescence device.

Treatment of onychomycosis using a 1064-nm diode laser with or without topical antifungal therapy: a single-center, retrospective analysis in 56 patients.

BACKGROUND: Currently available treatment options for onychomycosis such as topical and systemic antifungals are often of limited efficacy, difficult to administer or associated with relevant side effects. Non-ablative laser therapy is proposed to represent a safe alternative without the disadvantages of drugs. Yet, to date, the efficacy of laser therapy for onychomycosis is discussed controversially. Against this background, we performed a systematic retrospective analysis of our clinical experience of 4 years of onychomycosis treatment applying a long-pulsed 1.064-nm diode laser. METHODS: We retrospectively evaluated the records of 56 patients with microscopic and culturally proven onychomycosis affecting a toenail of the hallux and other toes, who had been treated with a long-pulsed 1.064-nm diode laser (FOX, A.C.R. Laser GmbH, Nuremberg) during the time period of July 2013-December 2016 with or without concomitant topical antifungals. Thereof, 27 patients received laser treatment and 29 patients received laser treatment in combination with local antifungals. We conducted a mean of 3.9 laser treatments at 2-6-week intervals. The primary endpoint of our analysis was clinical improvement; secondary endpoints were complete remission of fungal pathogens in fungal culture and in microscopy. RESULTS: Clinical improvement was achieved in 56% of patients treated with laser only after a mean of 4.5 treatments and in 69% of patients treated with laser in combination with topical antifungals after a mean of 3.6 treatments. Cultural healing was detected in 63% of patients treated with laser only after a mean of 5.4 treatments, vs. 86% of patients treated with laser and concomitant topical antifungals after a mean of 4.8 treatments. Microscopic healing (complete healing) with the absence of fungal pathogens was achieved in 11% of patients after a mean of 4.7 treatments with laser only, vs. 21% of patients treated with laser and concomitant topical antifungals after a mean of 4 treatments. No relevant adverse effects were observed. CONCLUSIONS: The 1.064-nm diode laser is an effective and safe option for the treatment of onychomycosis. Of note, the combination with topical antifungals will increase overall treatment efficacy and reduce the time to healing. Particularly, patients with contraindications against systemic antifungals may benefit from this multimodal therapeutic approach. Our data, moreover, suggest that treatment efficacy is positively correlated with the total number of laser treatments.

Developments in Biodosimetry Methods for Triage With a Focus on X-band Electron Paramagnetic Resonance In Vivo Fingernail Dosimetry.

Instrumentation and application methodologies for rapidly and accurately estimating individual ionizing radiation dose are needed for on-site triage in a radiological/nuclear event. One such methodology is an in vivo X-band, electron paramagnetic resonance, physically based dosimetry method to directly measure the radiation-induced signal in fingernails. The primary components under development are key instrument features, such as resonators with unique geometries that allow for large sampling volumes but limit radiation-induced signal measurements to the nail plate, and methodological approaches for addressing interfering signals in the nail and for calibrating dose from radiation-induced signal measurements. One resonator development highlighted here is a surface resonator array designed to reduce signal detection losses due to the soft tissues underlying the nail plate. Several surface resonator array geometries, along with ergonomic features to stabilize fingernail placement, have been tested in tissue-equivalent nail models and in vivo nail measurements of healthy volunteers using simulated radiation-induced signals in their fingernails. These studies demonstrated radiation-induced signal detection sensitivities and quantitation limits approaching the clinically relevant range of ≤ 10 Gy. Studies of the capabilities of the current instrument suggest that a reduction in the variability in radiation-induced signal measurements can be obtained with refinements to the surface resonator array and ergonomic features of the human interface to the instrument. Additional studies are required before the quantitative limits of the assay can be determined for triage decisions in a field application of dosimetry. These include expanded in vivo nail studies and associated ex vivo nail studies to provide informed approaches to accommodate for a potential interfering native signal in the nails when calculating the radiation-induced signal from the nail plate spectral measurements and to provide a method for calibrating dose estimates from the radiation-induced signal measurements based on quantifying experiments in patients undergoing total-body irradiation or total-skin electron therapy.

Gel manicures and ultraviolet A light: A call for patient education.

Gel manicures have become a popular beauty trend in recent years. The specially formulated nail polish must undergo curing under light-based units. The majority of these curing lamps emit high-intensity ultraviolet A, which can cause skin damage and increase the risk for skin cancers. Incorporating relevant information in patient education endeavors can help them practice avoidance, apply broad-spectrum sunscreen prior, or use nitrile exam gloves in order to prevent photoaging and skin cancer resulting from these procedures.

Response of Fingernail Growth to Out-of-Field Low-Dose X ray in Cancer Patients Receiving Radiotherapy.

The entire body of a patient with cancer is exposed to low-dose levels of radiation (mGy) during radiation therapy. The safety and biological impact of such exposure to low-dose radiation on the human body are largely unknown. The fingernail is a highly proliferative tissue, and its growth can be monitored during radiation treatment to analyze early effects of low-dose radiation. The fingernails of 30 patients who received external beam radiotherapy (EBRT) were used in this study to investigate the change in nail growth during fractionated radiotherapy. Lead shields were applied to some fingers to create dose variance within individual patients. The absorbed dose was measured, and the relationship between the dose and change in nail growth rate was analyzed. Other factors, including serum albumin, hemoglobin level, body weight index, age, gender and chemotherapy, were also subjected to multivariate analysis. Fingernails from patients received an average of 0.96 mGy per treatment fraction. We observed a surprising decline in fingernail growth rate during radiotherapy, which was more prominent in the nonshielded fingernails with a relatively high-absorbed dose. Such growth delay could be observed as early as one week postirradiation and lasted the entire treatment course. Using fingernail growth as a novel marker for radioresponse, the current study showed that exposure to very low-dose ionizing radiation has previously unrecognized early effects on human tissue.

A review of the mechanism of action of lasers and photodynamic therapy for onychomycosis.

Onychomycosis is one of the most common diseases in the field of dermatology. It refers to the fungal infection of the nail plate or nail bed with high incidence in the general population. The available treatment options for onychomycosis have limited use due to side effects, drug interactions, and contraindications, which necessitates the application of an alternative treatment for onychomycosis. In the recent years, lasers and photodynamic therapy (PDT) have been recognized as alternative treatment options. Most of the previous studies have found them to be safe and effective treatment modalities in this indication; however, the results varied greatly and the in vitro and in vivo outcomes are contradictory. In the present review, studies related to the mechanism of action of lasers and PDT for the treatment of onychomycosis will be discussed, with a focus on to find explanation to the contradictory results.

Comparison of Continuous Wave and Rapid Scan X-band Electron Paramagnetic Resonance of Irradiated Clipped Fingernails.

X-band rapid scan electron paramagnetic resonance (EPR) measures the free radicals in irradiated clipped fingernails with higher signal-to-noise (S/N) and lower standard deviation of the signal amplitude for replicate measurements than does conventional continuous wave (CW) EPR in the same measurement time. For a clipped fingernail sample irradiated to 10 Gy and data acquisition time of 30 s with B1 = 8.5 µT, the S/N for rapid scan is >2000 for the absorption spectrum and 1200 for the corresponding first derivative. The standard deviation for replicate measurements of signal amplitude is ~1%. For CW spectra, the S/N depends on the modulation amplitude. The CW signal has a first derivative peak-to-peak linewidth of 0.95 mT. For 30 s of CW acquisition time, the S/N was 30 for a conservative modulation amplitude of 0.2 mT and B1 of 2.3 µT or 90 for a modulation amplitude of 0.4 mT and B1 of 3.2 µT, which resulted in standard deviations of replicate measurements of 5% or 2%, respectively.

POSSIBLE NATURE OF THE RADIATION-INDUCED SIGNAL IN NAILS: HIGH-FIELD EPR, CONFIRMING CHEMICAL SYNTHESIS, AND QUANTUM CHEMICAL CALCULATIONS.

Exposure of finger- and toe-nails to ionizing radiation generates an Electron Paramagnetic Resonance (EPR) signal whose intensity is dose dependent and stable at room temperature for several days. The dependency of the radiation-induced signal (RIS) on the received dose may be used as the basis for retrospective dosimetry of an individual's fortuitous exposure to ionizing radiation. Two radiation-induced signals, a quasi-stable (RIS2) and stable signal (RIS5), have been identified in nails irradiated up to a dose of 50 Gy. Using X-band EPR, both RIS signals exhibit a singlet line shape with a line width around 1.0 mT and an apparent g-value of 2.0044. In this work, we seek information on the exact chemical nature of the radiation-induced free radicals underlying the signal. This knowledge may provide insights into the reason for the discrepancy in the stabilities of the two RIS signals and help develop strategies for stabilizing the radicals in nails or devising methods for restoring the radicals after decay. In this work an analysis of high field (94 GHz and 240 GHz) EPR spectra of the RIS using quantum chemical calculations, the oxidation-reduction properties and the pH dependence of the signal intensities are used to show that spectroscopic and chemical properties of the RIS are consistent with a semiquinone-type radical underlying the RIS. It has been suggested that semiquinone radicals formed on trace amounts of melanin in nails are the basis for the RIS signals. However, based on the quantum chemical calculations and chemical properties of the RIS, it is likely that the radicals underlying this signal are generated from the radiolysis of L-3,4-dihydroxyphenylalanine (DOPA) amino acids in the keratin proteins. These DOPA amino acids are likely formed from the exogenous oxidation of tyrosine in keratin by the oxygen from the air prior to irradiation. We show that these DOPA amino acids can work as radical traps, capturing the highly reactive and unstable sulfur-based radicals and/or alkyl radicals generated during the radiation event and are converted to the more stable o-semiquinone anion-radicals. From this understanding of the oxidation-reduction properties of the RIS, it may be possible to regenerate the unstable RIS2 following its decay through treatment of nail clippings. However, the treatment used to recover the RIS2 also has the ability to recover an interfering, mechanically-induced signal (MIS) formed when the nail is clipped. Therefore, to use the recovered (regenerated) RIS2 to increase the detection limits and precision of the RIS measurements and, therefore, the dose estimates calculated from the RIS signal amplitudes, will require the application of methods to differentiate the RIS2 from the recovered MIS signal.

Dielectric-Backed Aperture Resonators for X-Band in vivo EPR Nail Dosimetry.

A new resonator for X-band in vivo EPR nail dosimetry, the dielectric-backed aperture resonator (DAR), is developed based on rectangular TE102 geometry. This novel geometry for surface spectroscopy improves at least a factor of 20 compared to a traditional non-backed aperture resonator. Such an increase in EPR sensitivity is achieved by using a non-resonant dielectric slab, placed on the aperture inside the cavity. The dielectric slab provides an increased magnetic field at the aperture and sample, while minimizing sensitive aperture resonance conditions. This work also introduces a DAR semi-spherical (SS)-TE011 geometry. The SS-TE011 geometry is attractive due to having twice the incident magnetic field at the aperture for a fixed input power. It has been shown that DAR provides sufficient sensitivity to make biologically relevant measurements both in vitro and in vivo Although in vivo tests have shown some effects of physiological motions that suggest the necessity of a more robust finger holder, equivalent dosimetry sensitivity of approximately 1.4 Gy has been demonstrated.

Effects of water on fingernail electron paramagnetic resonance dosimetry.

Electron paramagnetic resonance (EPR) is a promising biodosimetric method, and fingernails are sensitive biomaterials to ionizing radiation. Therefore, kinetic energy released per unit mass (kerma) can be estimated by measuring the level of free radicals within fingernails, using EPR. However, to date this dosimetry has been deficient and insufficiently accurate. In the sampling processes and measurements, water plays a significant role. This paper discusses many effects of water on fingernail EPR dosimetry, including disturbance to EPR measurements and two different effects on the production of free radicals. Water that is unable to contact free radicals can promote the production of free radicals due to indirect ionizing effects. Therefore, varying water content within fingernails can lead to varying growth rates in the free radical concentration after irradiation-these two variables have a linear relationship, with a slope of 1.8143. Thus, EPR dosimetry needs to be adjusted according to the water content of the fingernails of an individual. When the free radicals are exposed to water, the eliminating effect will appear. Therefore, soaking fingernail pieces in water before irradiation, as many researchers have previously done, can cause estimation errors. In addition, nails need to be dehydrated before making accurately quantitative EPR measurements.