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The quantitative determination of topically applied substances in the skin is severely limited and represents a challenging task. The porcine skin ex vivo was topically treated with a gel containing caffeine (CF) and propylene glycol (PG), and depth‐resolved Raman spectra were recorded with two confocal Raman microscopes. We applied a novel tailored multivariate curve resolution‐alternating least squares method to the selected spectral regions (512–604 and 778–1148 cm−1) of gel‐treated skin and quantitatively determined the concentrations of CF and PG in the stratum corneum (SC). The highest concentration of CF (181 mg/cm3) was found at the surface, while PG (384 mg/cm3) was found at 10% SC depth, indicating the formation of a reservoir at the superficial SC. The concentrations of CF and PG decreased monotonically and reached the detection limit at ≈60% and ≈80% SC depth, respectively, indicating that neither permeate the SC. [ABSTRACT FROM AUTHOR]

We analysed serum samples of 209 subjects immunized with yellow fever vaccine 17D by different assays: neutralization test, immunofluorescence assay, haemagglutination inhibition test and ELISA, for presence of 17D-specific antibodies. Serum samples were taken from a few weeks up to 35 years after vaccination. The neutralization test had the highest sensitivity. There was no correlation of results between the serological assays. Considering NT titres > 1:10 as indicating protection, we found that about 75% of subjects remained immune even 10 years after vaccination, with a median NT titre of 1:40 in reactive sera. [ABSTRACT FROM AUTHOR]

Skin moisturizing is important in dermatology and cosmetics. Raman microspectroscopy is a well‐suited method to determine water concentration profiles in the stratum corneum (SC) of untreated and formulation‐treated skin in vivo. Until now, the water in the SC was quantified using the ratio of water to proteins, and other SC components were neglected. Here, we apply the tailored multivariate curve resolution‐alternating least squares (tMCR‐ALS) method to improve the quantitative determination of water in the SC of cosmetic oil‐treated skin accounting Raman spectra of proteins, lipids, and oils in the high wavenumber region. We compared the water concentration profiles in the SC of petrolatum‐treated skin calculated using the tMCR‐ALS method and two existing conventional and extended methods, which are both based on the analysis of the water‐to‐protein‐ratio. The results show that in petrolatum‐treated skin, the conventional method calculates an incorrect water profile in the depth of 0–70% of the SC thickness; the extended method shows an incorrect profile in the depth of 0–10% of the SC thickness; the applied tMCR‐ALS method show results, which coincide well with the modern knowledge of the moisturizing effect of cosmetic oils on the SC. Almond, jojoba, and paraffin oils exhibit a similar moisturizing effect that manifests itself in an increase of water concentration in the intermediate SC depth. However, the effect of petrolatum is more pronounced. In the context of treated skin, the proposed method calculates water concentration profiles throughout the SC correctly and thus has a great potential in dermatology and cosmetics. [ABSTRACT FROM AUTHOR]

Reconstructed epidermal equivalents (REEs) consist of two distinct cell layers – the stratum corneum (SC) and the keratinocyte layer (KL). The interplay of these layers is particularly crucial in pruritic inflammatory disorders, like psoriasis, where a defective SC barrier is associated with immune dysregulation. However, independent evaluation of the skin barrier function of the SC and KL in REEs is highly challenging because of the lack of quantitative methodologies that do not disrupt the counter layer. Here, a non‐invasive impedance spectroscopy technique is introduced for dissecting the distinct contributions of the SC and KL to overall skin barrier function without disrupting the structure. These findings, inferred from the impedance spectra, highlight the individual barrier resistances and maturation levels of each layer. Using an equivalent circuit model, a correlation between impedance parameters and specific skin layers, offering insights beyond traditional impedance methods that address full‐thickness skin only is established. This approach successfully detects subtle changes, such as increased paracellular permeability due to mild irritants and the characterization of an immature SC in psoriatic models. This research has significant implications, paving the way for detailed mechanistic investigations and fostering the development of therapies for skin irritation and inflammatory disorders. [ABSTRACT FROM AUTHOR]

Background: Evidence for substance use‐related problems in individuals with mild intellectual disability is sparse and mainly limited to selected psychiatric populations. We evaluated the risk of substance use‐related problems in individuals with mild intellectual disability compared to the general population. Additionally, we have performed secondary sibling comparison analyses to account for familial confounding. Methods: We conducted a population‐based cohort study of individuals born in Sweden between 1973 and 2003. A total of 18,307 individuals with mild intellectual disability were compared to 915,350 reference individuals from the general population and 18,996 full siblings of individuals with mild intellectual disability. Information on mild intellectual disability and substance use‐related problems was obtained from several Swedish national and regional school and healthcare registers. Substance use‐related problems were measured via corresponding diagnostic and legal codes and included alcohol use disorder, drug use disorder, alcohol‐related somatic disease, conviction for a substance‐related crime, and substance‐related death. Results: Individuals with mild intellectual disability had a higher risk of any substance use‐related problem compared to the general population (HR, 1.81; 95% CI, 1.72–1.91), both in males (HR, 1.76; 95% CI, 1.65–1.89) and females (HR, 1.89; 95% CI, 1.74–2.05). The risks of substance use‐related problems were particularly elevated among individuals with mild intellectual disability and psychiatric comorbidities (HR, 2.21–8.24). The associations were attenuated in the sibling comparison models. Conclusions: Individuals with mild intellectual disability, especially those with psychiatric comorbidity, are at an elevated risk of substance use‐related problems. Familial factors shared by full siblings contribute considerably to the association between mild intellectual disability and substance use‐related problems. [ABSTRACT FROM AUTHOR]

The human stratum corneum (SC) contains an abundant amount of carotenoid antioxidants, quenching free radicals and thereby protecting the skin. For the precise measurements of the depth‐dependent carotenoid concentration, confocal Raman microscopy is a suitable method. The quantitative concentration can be determined by the carotenoid‐related peak intensity of a Gaussian function approached at ≈1524 cm−1 using non‐linear regression. Results show that the carotenoid concentration is higher at the superficial layers of the SC then decreases to a minimum at 20% SC depth and increases again towards the bottom of the SC. In the present work, two carotenoid penetration pathways into the SC are postulated. The first pathway is from the stratum granulosum to the bottom of the SC, while in the second pathway, the carotenoids are delivered to the skin surface by sweat and/or sebum secretion and penetrate from outside. The carotenoids are aggregated at the superficial layers, which are shown by high correlation between the aggregation states of carotenoids and the lateral organization of lipids. At the 30%‐40% SC depths, the ordered and dense lipid molecules intensify the lipid‐carotenoid interactions and weaken the carotenoid‐carotenoid interaction and thus exhibit the disaggregation of carotenoids. At 90%‐100% SC depths, the carotenoid‐lipid interaction is weakened and the carotenoids have a tendency to be aggregated. Thus, the molecular structural correlation of carotenoid and SC lipid might be reserved in the intercellular space of the SC and also serves as the skeleton of the intercellular lipids. [ABSTRACT FROM AUTHOR]

The quantitative determination of substance concentration in the stratum corneum (SC) is important for profiling of the skin barrier function‐related parameters and for investigating drug delivery through the SC. Hereby, confocal Raman microscopy (CRM) is a widely used method, which can be applied noninvasively and in vivo. Most analysis methods are based on the assumption that keratin is distributed homogeneously throughout the SC. In this study, the depth profiles of keratin‐related Raman peaks (1,003, 1,450, 1,650, and 2,935 cm−1) are investigated in detail. It was shown that each of these Raman peaks can be used for the precise determination of the skin surface position, which is important in case of overlapping of these with Raman bands associated to a formulation for treated skin. For correction of the depth‐dependent signal attenuation, that is, normalization, the 1,450, 1,650, and 2,935 cm−1 peaks can be used, whereas the 1,003 cm−1 peak cannot. Further analysis shows that the keratin concentration is nonhomogeneous throughout the SC and decreases towards its bottom due to water increase. Thus, the concentration of certain substances in the SC, such as urea, lipids, water, or natural moisturizing factor, determined using normalization on the keratin peak intensity, is overestimated in the deep SC layers starting from 30% SC depth. The correction coefficients were calculated for all four Raman peaks and for all SC depths with 10% increments. It was determined that at the bottom of the SC, the values obtained using keratin normalization should be multiplied by 0.88 (for 1,003 or 1,450 cm−1), 0.94 (for 1,650 cm−1), and 0.92 (for 2,935 cm−1) in order to compensate nonhomogeneous distribution of keratin in the SC. Thus, original values are overestimated at the SC bottom by 6–12%. The presented correction mechanism is proposed to be used for further correction. [ABSTRACT FROM AUTHOR]

Fibroblasts are among the most common cell types in the stroma responsible for creating and maintaining the structural organization of the extracellular matrix in the dermis, skin regeneration, and a range of immune responses. Until now, the processes of fibroblast adaptation and functioning in a varying environment have not been fully understood. Modern laser microscopes are capable of studying fibroblasts in vitro and ex vivo. One‐photon‐ and two‐photon‐excited fluorescence microscopy, Raman spectroscopy/microspectroscopy are well‐suited noninvasive optical methods for fibroblast imaging in vitro and ex vivo. In vivo staining‐free fibroblast imaging is not still implemented. The exception is fibroblast imaging in tattooed skin. Although in vivo noninvasive staining‐free imaging of fibroblasts in the skin has not yet been implemented, it is expected in the future. This review summarizes the state‐of‐the‐art in fibroblast visualization using optical methods and discusses the advantages, limitations, and prospects for future noninvasive imaging. [ABSTRACT FROM AUTHOR]

The study of aging and neurodegenerative processes in the human brain requires a comprehensive understanding of cytoarchitectonic, myeloarchitectonic, and vascular structures. Recent computational advances have enabled volumetric reconstruction of the human brain using thousands of stained slices, however, tissue distortions and loss resulting from standard histological processing have hindered deformation‐free reconstruction. Here, the authors describe an integrated serial sectioning polarization‐sensitive optical coherence tomography (PSOCT) and two photon microscopy (2PM) system to provide label‐free multi‐contrast imaging of intact brain structures, including scattering, birefringence, and autofluorescence of human brain tissue. The authors demonstrate high‐throughput reconstruction of 4 × 4 × 2cm3 sample blocks and simple registration between PSOCT and 2PM images that enable comprehensive analysis of myelin content, vascular structure, and cellular information. The high‐resolution 2PM images provide microscopic validation and enrichment of the cellular information provided by the PSOCT optical properties on the same sample, revealing the densely packed fibers, capillaries, and lipofuscin‐filled cell bodies in the cortex and white matter. It is shown that the imaging system enables quantitative characterization of various pathological features in aging process, including myelin degradation, lipofuscin accumulation, and microvascular changes, which opens up numerous opportunities in the study of neurodegenerative diseases in the future. [ABSTRACT FROM AUTHOR]

Ceramide NP (Cer‐NP) has favorable effects in treating dry skin and barrier damage; nevertheless, their efficacy is hindered by a relatively low skin permeability. The most common used method to evaluate drug permeability in cosmetic filed is Franz diffusion cell, which have limitations in terms of experimental materials and manipulation, making it difficult to reliably quantify drug permeability in vivo on the human skin. In contrast, confocal Raman spectroscopy (CRM) is regarded as a versatile tool for tracking of the penetration of active molecules through the skin, which is non‐invasive, non‐destructive, and real‐time and allows in vivo testing of ceramide permeability and efficacy as well. The goal of this study was to track the skin penetration of Cer‐NP nanoemulsions (NEs) into the inner forearm skin, and to assess the short‐term effects of Cer‐NP on stratum corneum (SC) thickness, hydration, and intercellular lipids (ICL) conformation order using the water content and lateral packing order Slat = I2880/I2850, which were obtained by CRM data. Cer‐NP penetrated into the SC and epidermis, and the amount of penetration reduced with depth and increased with duration and finally retained in the SC. The results also uncovered Cer‐NP‐promoted SC hydration and increased SC thickness and Slat. The research mentioned above demonstrated that Cer‐NP NEs successfully penetrated the skin and performed moisturizing and barrier restoration functions. [ABSTRACT FROM AUTHOR]

The presence of penetrated oils in the stratum corneum (SC), oil‐induced occlusion of the SC and formation of occluding homogeneous film on the skin surface are discussed in relation to their influence on results of water profile calculations using conventional and newly proposed extended methods. It is shown that the conventional method does not determine the water profiles in treated skin correctly due to the superposition of Raman bands of SC's proteins and penetrated and remnant oils. [ABSTRACT FROM AUTHOR]

Porcine skin is widely used as a human skin model in dermatology. For both, porcine stratum corneum (SC) ex vivo and human SC in vivo, the hydrogen bonding states of water, the secondary and tertiary structures of keratin, the natural moisturizing factor (NMF) concentrations and the intercellular lipids' (ICL) lateral organization are investigated depth‐dependently using confocal Raman microscopy. The SC depth profiles show that porcine SC ex vivo is characterized by lower hydrogen bonding states of water (10%‐30% SC depth), lower NMF concentration in the whole SC, more β‐sheet form of keratin (10%‐90% SC depth), more folded tertiary keratin structures (30%‐70% SC depth) and higher hexagonal lateral packing order of ICL (10%‐50% SC depth) compared to human SC in vivo. The results clearly show a higher value of skin barrier function of human SC in vivo than of porcine SC ex vivo. Thus, the human SC in vivo is less permeable for lipophilic and hydrophilic substances than porcine SC ex vivo. Considering the porcine SC as an ex vivo model of human SC in vivo, these findings should be taken into consideration. [ABSTRACT FROM AUTHOR]

Complex diseases are caused by a combination of genetic, lifestyle, and environmental factors and comprise common noncommunicable diseases, including allergies, cardiovascular disease, and psychiatric and metabolic disorders. More than 25% of Europeans suffer from a complex disease, and together these diseases account for 70% of all deaths. The use of genomic, molecular, or imaging data to develop accurate diagnostic tools for treatment recommendations and preventive strategies, and for disease prognosis and prediction, is an important step toward precision medicine. However, for complex diseases, precision medicine is associated with several challenges. There is a significant heterogeneity between patients of a specific disease—both with regards to symptoms and underlying causal mechanisms—and the number of underlying genetic and nongenetic risk factors is often high. Here, we summarize precision medicine approaches for complex diseases and highlight the current breakthroughs as well as the challenges. We conclude that genomic‐based precision medicine has been used mainly for patients with highly penetrant monogenic disease forms, such as cardiomyopathies. However, for most complex diseases—including psychiatric disorders and allergies—available polygenic risk scores are more probabilistic than deterministic and have not yet been validated for clinical utility. However, subclassifying patients of a specific disease into discrete homogenous subtypes based on molecular or phenotypic data is a promising strategy for improving diagnosis, prediction, treatment, prevention, and prognosis. The availability of high‐throughput molecular technologies, together with large collections of health data and novel data‐driven approaches, offers promise toward improved individual health through precision medicine. [ABSTRACT FROM AUTHOR]

Solar radiation and cigarette smoke are two environmental risk factors known to affect skin integrity. Although the toxic effects of these factors on skin have been widely studied separately, few studies have focused on their interaction. The objective of this study was to evaluate and understand the synergistic harmful effects of cigarette smoke and solar rays on human primary keratinocytes. The keratinocytes were exposed to cigarette smoke extract (CSE) and then irradiated with a solar simulator light (SSL). The viability, as determined by measuring metabolic activity of skin cells, and the levels of global reactive oxygen species (ROS) were evaluated after exposure to CSE and SSL. The combination of 3% CSE with 29 kJ m−2 UVA caused a decrease of 81% in cell viability, while with 10% to 20% CSE, the cell viability was null. This phototoxicity was accompanied by an increase in singlet oxygen but a decrease in type I ROS when CSE and SSL were combined in vitro. Surprisingly, an increase in the CSE's total antioxidant capacity was also observed. These results suggest a synergy between the two environmental factors in their effect on skin cells, and more precisely a phototoxicity causing a drastic decrease in cell viability. [ABSTRACT FROM AUTHOR]

The accelerated kinetic behaviour of charge carrier transfer and its unhindered surface reaction dynamic process involving oxygenated‐intermediate activation and conversion are urgently required in photocatalytic water (H2O) overall splitting, which has not been nevertheless resolved yet. Herein, localized CdS homojunctions with optimal collocation of high and low index facets to regulate d‐band center for chemically adsorbing and activating key intermediates (*‐OH and *‐O) have been achieved in H2O overall splitting into hydrogen. Density functional theory, hall effect, and in situ diffuse reflectance infrared Fourier transform spectroscopy confirm that, electrons and holes are kinetically transferred to reductive high index facet (002) and oxidative low index facet (110) of the localized CdS homojunction induced by facet Fermi level difference to dehydrogenate *‐OH and couple *‐O for hydrogen and oxygen evolution, respectively, along with a solar conversion into hydrogen (STH) of 2.20 % by Air Mass 1.5 Global filter irradiation. These findings contribute to solving the kinetic bottleneck issues of photocatalytic H2O splitting, which will further enhance STH. [ABSTRACT FROM AUTHOR]

This paper describes a methodology to differentiate morphea from lichen sclerosus based on examination with multiphoton microscopy (MPM) composed of two‐photon excited fluorescence (TPEF) and second harmonic generation (SHG). Subcellular‐resolution images were acquired by MPM from unstained lesion tissues then process spectral analysis to quantify the TPEF and SHG signals. Moreover, U‐Net was employed to segment elastic fiber in TPEF images to combine with collagen fiber in SHG images for precise fiber quantification. Predictions of segmentation showed excellent performance on several evaluation indicators. The mIoU, mPA, and F1 score reach 0.8516, 0.9281, and 0.941. The quantitative analysis demonstrated the increase of collagen fibers in morphea compared to that in lichen sclerosus cases. Meanwhile, the great diminution of elastic fiber in the dermis of lichen sclerosus was depicted based on MPM imaging. Thus, MPM was comparable to the histopathological examination and our experimental results accurately distinguish between morphea and lichen sclerosus. [ABSTRACT FROM AUTHOR]

This work aims at studying Raman spectroscopy in combination with chemometrics as an alternative fast noninvasive method to detect chronic heart failure (CHF) cases. Optical analysis is focused on the changes in the spectral features associated with the biochemical composition changes of skin tissues. A portable spectroscopy setup with the 785 nm excitation wavelength was used to record skin Raman features. In this in vivo study, 127 patients and 57 healthy volunteers were involved in measuring skin spectral features by Raman spectroscopy. The spectral data were analyzed with a projection on the latent structures and discriminant analysis. 202 skin spectra of patients with CHF and 90 skin spectra of healthy volunteers were classified with 0.888 ROC AUC for the 10‐fold cross validated algorithm. To identify CHF cases, the performance of the proposed classifier was verified by means of a new test set that is equal to 0.917 ROC AUC. [ABSTRACT FROM AUTHOR]

Antioxidants exhibit a powerful defense mechanism against aging and chronic disease. The human skin reflects the overall antioxidant status of the body. The cutaneous carotenoid concentration is a biomarker for individual nutritional intake of antioxidants, as it correlates with the overall antioxidant status. The cutaneous carotenoid concentrations of 44 adults were measured using a multiple spatially resolved reflection spectroscopy. During the first phase of the study, measurements of carotenoid concentrations were performed without revealing the antioxidant status, followed by an intervention phase during which the volunteers were informed about their individual values by biofeedback. During the third phase, biofeedback was combined with an additional intake of fruit juices. Across time points, participants showed increasing levels of carotenoid status. Thus, biofeedback leads to an improvement of the carotenoid value of the skin. Providing a biofeedback measurement to monitor the individual antioxidative status may be an easy and cost‐effective way of primary prevention. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic inflammatory skin disease involved with both complex morphological changes of skin and immune processes. The clinical diagnostics and research of psoriasis often require invasive biopsy which lacks their real‐time dynamics in vivo. Here we report a noninvasive microscopic system developed by combining in vivo fluorescent microscopy, optical clearing, and immunolabeling to enable real‐time imaging of immune cells and cytokines in blood flow in psoriatic animal models. The vascular morphology and time‐lapse kinetics of interleukin (IL)‐23, IL‐17, tumor necrosis factor‐α, and CD4+ cells in blood are captured at submicron resolution through the thickening epidermis and opaque scales during the development of psoriasis in vivo. Our data suggest IL‐23 recruits CD4+ cells to release IL‐17 in blood that further leaks out in the psoriatic skin area. This optical system enables noninvasive and real‐time assessment of immune molecules and cells in vivo, providing good potential for medical researches on psoriasis. [ABSTRACT FROM AUTHOR]

While the intercellular lipid structure of the stratum corneum (SC) plays an important role in the skin barrier function, the depth-dependent profile of the intercellular lipids contributes decisively to deepen the understanding of the skin barrier function, drug penetration, development of skin diseases and their medication. The depth-dependent profile of the lipids' chemico-physical properties, such as the solid-fluid phase transition and the order-disorder transition, can exclusively be measured in human skin in vivo by means of confocal Raman microscopy. In the present paper, the lipid-keratin peak (2820-3030 cm−1) was investigated. The lipid-related Raman peaks centered at 2850 cm−1 and 2880 cm−1 were deconvoluted using Gaussian functions and investigated for their depth-dependent shape and positional changes. Different fitting procedures show that even an additional Gaussian function cannot be used to fully characterize the lipid's polymethylene chains around 2880 cm−1, which justifies the introduction of the sharpness of the peak centered near 2880 cm−1. The results show that the 2880 cm−1 peak sharpness might be used for determining the SC thickness. The concentration of the lipids with long-chain carbon backbone (free fatty acids and ceramides) semi-quantitatively decreases from 10 µm to 20 µm (SC thickness is 19.8 µm). The maximum position and broadness of the Gaussian peak centered at 2850 cm−1 show that near the surface and in the deeper layers of the SC, the state of the lipids is more fluid and disordered compared to the medium layers of the SC. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The main components of the stratum corneum (SC), water, lipids, and proteins, are non‐homogeneously distributed throughout the depth. The quantitative determination of their concentration profiles and penetration depth of topically applied substances are urgent topics of dermatological and cosmetic research. Confocal Raman micro‐spectroscopy has distinct advantages when determining semi‐quantitative concentrations of SC components and topically applied substances non‐invasively and in vivo. In this work, we applied a tailored multivariate curve resolution‐alternating least squares (tMCR‐ALS) method to analyze Raman spectra of the SC in the 2000–4000 cm−1 region for quantitatively determining the concentrations of water, lipids, proteins, and topically applied oils using substance‐related spectral loadings which were allowed to change depth‐dependently from the SC's surface toward its bottom. tMCR‐ALS makes matching of depth‐dependent signal attenuation, that is, the normalization on keratin, unnecessary and requires only a few additional experiments for calibration – Raman spectra of the pure materials and their densities. [ABSTRACT FROM AUTHOR]

Lipid peroxidation (LPO) is an oxidative deterioration when oxidants such as reactive oxygen species attack lipids that contain double bonds especially polyunsaturated fatty acids (PUFAs). The mechanism of LPO is composed of three steps: initiation, propagation, and termination. It can result from several reaction pathways: (1) auto‐oxidation, (2) enzymatic oxidation, or (3) photo‐oxidation. UV solar exposition is a major concern in skin research, dermatology, and cosmetic science. Skin surface lipids (SSLs) and stratum corneum (SC) lipids are among the first skin components exposed to external insults such as UV radiations. Fatty acids represent a major lipid class in SSLs and SC. The aim of this paper is to study the photo‐oxidation of fatty acids under UV solar radiations using Raman spectroscopy. Vibrational spectroscopies are useful techniques to follow the LPO in its different stages of oxidation: (1) the initiation step by following the CH2/CH3 stretching bands ratio that decreases due to the hydrogen abstraction in alpha position; (2) the propagation step where primary oxidation products are formed such as hydroperoxides, which was evaluated by following the 1165/1640 cm−1 ((δ(OH) and ν(CO))/ν(CO)) ratio that increases during oxidation process; and finally, (3) the termination step that is marked by the formation of aldehydes, alcohols, ketone, trans secondary oxidation products, and others, which was monitored by following the 1730/1640 cm−1 (ν(CO) (ald.)/ν(CO) (acid)) ratio and the trans ν(CC)/cis ν(CC) ratio that increase indicating the formation of secondary oxidation products. To our knowledge, this work is the first to put together different spectral descriptors enabling to follow, step by step, the different modifications of free fatty acids structures during the oxidation process. [ABSTRACT FROM AUTHOR]

This aim of this study was to evaluate the penetration depth, antioxidant capacity and the clinical efficacy of Melaleuca alternifolia pure essential oil and in a nanoemulsion to prevent skin photoaging. For this, 2% of pure essential oil or 2% of this essential oil in a nanoemulsion were vehiculated in a formulation. The skin penetration was evaluated using confocal Raman microspectroscopy. The radical protection factor was evaluated using electron paramagnetic resonance spectroscopy. For a clinical study, 40 male participants, aged 18–28 years, were enrolled, being divided into three groups: vehicle formulation, M. alternifolia pure essential oil and M. alternifolia Nanoemulsion. All the participants also received a sunscreen SPF 50 to use during the day. Before and after 90 days of study, skin hydrolipidics and morphological characteristics were performed by skin imaging and biophysical techniques. The nanoemulsion presented a lower antioxidant capacity and a higher penetration through the stratum corneum, reaching the viable epidermis, improving the stratum granulosum morphology. The groups presented an increase in the papillary depth, improving in the dermis echogenicity and the collagen fibers. Melaleuca alternifolia essential provides the potential to improve photoaged skin, being the application of nanoemulsion able to reach deeper skin layers. [ABSTRACT FROM AUTHOR]

The epidermal protective functions are closely associated with skin hydration homeostasis. The understanding of different states of water binding is a rising concept in assessing topically applied formulations and their interaction within the stratum corneum (SC). In addition to global water content, primary bound water, partially bound water, and unbound water and barrier‐related lipid lateral packing and protein secondary structure can be measured by Raman spectroscopy. This study aimed to establish an in vitro SC model to evaluate differences in the efficacy of a natural sugar‐derived complex in combination with glycerol and a botanical extract in modulating SC water binding and structural proteins and barrier lipids. These compounds were selected due to their water‐binding and soothing properties. The SC water profiles were assessed at the surface and in 8 μm SC depth. After a 12‐hour hyperhydration and subsequent product incubation the measurements were performed during a 6 hours desiccation phase. The maximal water caption and the time until reaching a steady state are measured as well as water retention and resistance against water loss. Global water content, partially bound, and unbound water, as well as lipid and protein structures were assessed with confocal Raman microspectroscopy. Both the natural sugar‐derived mixture and more pronounced, the same mixture with additional glycerol increased all three water‐binding parameters at the surface and in 8 μm SC depth at the beginning and during the desiccation phase. Further addition of botanical extract did not result in an additional increase of the water‐binding. All three formulations showed an increase in the lipid lateral packing values prevented the protein alteration as measured by β‐sheets signal compared to blank. The present model is suited for screening studies comparing the specific effects of different compounds on hydration states. The natural sugar‐derived mixture Aquaxyl showed evidence for an improvement of all SC hydration states, lipid and protein structure which was further enhanced by the addition of glycerol 5%. This improvement was evidenced at the surface and within the SC for all hydration‐related parameters, and the lipid as well the protein structures. The addition of botanical extract phytoessence blue daisy did not show further improvement. [ABSTRACT FROM AUTHOR]

The increase of tissue transparency through sequential optical immersion clearing treatments and treatment reversibility have high interest for clinical applications. To evaluate the clearing reversibility in a broad spectral range and the magnitude of the transparency created by a second treatment, the present study consisted on measuring the spectral collimated transmittance of lung tissues during a sequence of two treatments with electronic cigarette (e‐cig) fluid, which was intercalated with an immersion in saline. The saline immersion clearly reverted the clearing effect in the lung tissue in the spectral range between 220 and 1000 nm. By a later application of a second treatment with the e‐cig fluid, the magnitude of the optical clearing effect was observed to be about the double as the one observed in the first treatment, showing that the molecules of the optical clearing agent might have converted some bound water into mobile water during the first treatment. [ABSTRACT FROM AUTHOR]

Inflammatory fibrotic tissue remodeling can lead to severe morbidity. Histopathology grading requires extraction of biopsies and elaborate tissue processing. Label‐free optical technologies can provide diagnostic readout without preparation and artificial stainings and show potential for in vivo applications. Here, we present an integration of Raman spectroscopy (RS) and multiphoton microscopy for joint investigation of the bio‐chemical composition and morphological features related to cellular components and connective tissue. Both modalities show that collagen signatures were significantly increased in a murine fibrosis model. Furthermore, autofluorescence signatures assigned to immune cells show high correlation with disease severity. RS indicates increased levels of elastin and lipids. Further, we investigated the effect of joint data sets on prediction performance in machine learning models. Although binary classification did not benefit from adding more features, multi‐class classification was improved by integrated data sets. [ABSTRACT FROM AUTHOR]

Neutrophils are the most abundant circulating leukocytes in human peripheral blood. They are often the first cells to respond to an invading pathogen and might therefore play an important role in malaria. Malaria is a globally important disease caused by Plasmodium parasites, responsible for more than 400,000 deaths each year. Most of these deaths are caused by complications, including cerebral malaria, severe malarial anaemia, placental malaria, renal injury, metabolic problems and malaria‐associated acute respiratory distress syndrome. Neutrophils contribute in the immune defence against malaria, through clearance of parasites via phagocytosis, production of reactive oxygen species and release of neutrophil extracellular traps (NETs). However, Plasmodium parasites diminish antibacterial functions of neutrophils, making patients more susceptible to other infections. Neutrophils might also be involved in the development of malaria complications, for example via the release of toxic granules and NETs. However, technical pitfalls in the determination of the roles of neutrophils have caused contradicting results. Further investigations need to consider these pitfalls, in order to elucidate the role of neutrophils in malaria complications. [ABSTRACT FROM AUTHOR]

The integration of silver nanoparticles (Ag NPs) with mesoporous silica nanoparticles (MSNs) protects the former from aggregation and promotes the controlled release of silver ions, resulting in therapeutic significance on cancer and infection. The unique size, shape, pore structure and silver distribution of silver mesoporous silica nanoparticles (Ag‐MSNs) embellish them with the potential to perform combined imaging and therapeutic actions via modulating optical and drug release properties. Here, we comprehensively review the recent progress in the fabrication and application of Ag‐MSNs for combination therapies for cancer and infection. We first elaborate on the fabrication of star‐shaped structure, core‐shell structure, and Janus structure Ag‐MSNs. We then highlight Ag‐MSNs as a multifunctional nanoplatform to surface‐enhanced Raman scattering‐based detection, non‐photo‐based cancer theranostics and photo‐based cancer theranostics. In addition, we detail Ag‐MSNs for combined antibacterial therapy via drug delivery and phototherapy. Overall, we summarize the challenges and future perspectives of Ag‐MSNs that make them promising for diagnosis and therapy of cancer and infection. [ABSTRACT FROM AUTHOR]

The effect of tissue optical clearing (TOC) to increase the probing depth and observe in‐depth structure of the ex vivo porcine dura mater was studied by confocal Raman microspectroscopy (CRM). Raman intensities were significantly increased at the depth of 250 μm for all collagen bands after treatment with glycerol. The influence of glycerol on collagen hydration was also investigated. The results indicate that the process of TOC can be divided into three main steps. The first one is a fast process of tissue dehydration accompanied by collagen shrinkage while the second relatively slow process is related to the glycerol penetration into the interfibrillar space of collagen combined with swelling of tissue. The third step is collagen dissociation caused by the high concentration of glycerol. To the best of our knowledge, this study is the first example to introduce the TOC technique in assisting CRM of ex vivo dura mater in‐depth probing. [ABSTRACT FROM AUTHOR]

An approach to significantly enhance spontaneous Raman sensitivity through the formation of a thin film via thermophoresis along with evaporation at the facet of a hollow‐core photonic crystal fiber is reported for the first time. Sensitivity of detection is increased by more than 6 orders of magnitude for both organic and inorganic nanoparticles, facilitating the search for trace analytes in solution. Detection of two nanoparticles, alumina and polystyrene, is demonstrated down to 392 nM without the use of surface‐enhanced Raman spectroscopy or other chemical‐based procedures. This new thin‐film deposition approach simplifies the simultaneous detection and analysis of small trace compounds, a previously arduous task using conventional spontaneous Raman. [ABSTRACT FROM AUTHOR]

Skin penetration of active molecules for treatment of diverse diseases is a major field of research owing to the advantages associated with the skin like easy accessibility, reduced systemic‐derived side effects, and increased therapeutic efficacy. Despite these advantages, dermal drug delivery is generally challenging due to the low skin permeability of therapeutics. Although various methods have been developed to improve skin penetration and permeation of therapeutics, they are usually aggressive and could lead to irreversible damage to the stratum corneum. Nanosized carrier systems represent an alternative approach for current technologies, with minimal damage to the natural barrier function of skin. In this Review, the use of nanoparticles to deliver drug molecules, genetic material, and vaccines into the skin is discussed. In addition, nanotoxicology studies and the recent clinical development of nanoparticles are highlighted to shed light on their potential to undergo market translation. [ABSTRACT FROM AUTHOR]

Quantitative noninvasive assessment of water content in tissues is important for biomedicine. Optical spectroscopy is potentially capable of solving this problem; however, its applicability for clinical diagnostics remains questionable. The presented study compares diffuse reflectance spectroscopy, Raman spectroscopy and multispectral imaging in the characterization of cutaneous edema. The source‐detector geometries for each method are selected based on Monte Carlo simulations results to detect the signal from the dermis. Then, the kinetics of the edema development is studied for two models. All methods demonstrate synchronous trends for histamine‐induced edema: The water content reaches a maximum of 1 hour after histamine application and then gradually decreases. For the venous occlusion, a 51% increase in water content is observed with Raman spectroscopy. The differences in water content estimation by three methods are explained based on the light propagation model. The obtained results are essential for introducing quantitative optical water measurement technology to the clinics. [ABSTRACT FROM AUTHOR]

We investigated for the first time zonal‐dependent water distribution in articular cartilage by Raman spectroscopy (RS). We further investigated the association of histopathologic score with RS‐ and magnetic resonance imaging (MRI)‐based water measurements. Cadaveric human cartilage plugs (N = 16) with different osteoarthritis (OA) severity were used. Water content distribution in cartilage zones was probed using RS‐ and MRI‐based techniques. Histopathologic scoring was performed by two independent observers blindly. Moderate associations existed between RS‐ and MRI‐based water measurements across all cartilage zones. RS‐based analysis of different water compartments helped assign the origin of the T2 signal collected from the various cartilage zones. RS‐based water parameters significantly correlated with OA‐severity score, whereas MRI‐based water measurements did not. RS can probe different water compartments in cartilage zones and predict up to 66% of the variation observed in the histopathologic score. RS‐based water measurement could be developed further to assess cartilage quality in the clinic. [ABSTRACT FROM AUTHOR]

The self‐assembly of peptides is a key direction for fabrication of advanced materials. Novel approaches for fine tuning of macroscopic and microscopic properties of peptide self‐assemblies are of a high demand for constructing biomaterials with desired properties. In this work, while studying the kinetics of the Fmoc‐Diphenylalanine (Fmoc‐FF) dipeptide self‐assembly using the Thioflavin T (ThT) dye, we observed that the presence of ThT strongly modifies structural and mechanical properties of the Fmoc‐FF hydrogel. Notably, the presence of ThT resulted in a tenfold increase of the gelation time and in the formation of short and dense fibers in the hydrogel. As a result of these morphological alteration higher thermal stability, and most important, tenfold increase of the hydrogel rigidity was achieved. Hence, ThT not only slowed the kinetics of the Fmoc‐FF hydrogel formation, but also strongly enhanced its mechanical properties. In this study, we provide a detailed description of the ThT effect on the hydrogel properties and suggest the mechanisms for this phenomenon, paving the way for the novel approach to the control of the peptide hydrogels' micro‐ and macroscale properties. [ABSTRACT FROM AUTHOR]

Bedside diagnosis of skin cancer remains a challenging task. The real‐time noninvasive technology of optical coherence tomography (OCT) masters a high diagnostic accuracy in basal cell carcinoma (BCC) but a lower specificity in recognizing imitators and other carcinomas. We investigate the delicate signal of papillary dermis using an in‐house developed ultrahigh resolution OCT (UHR‐OCT) system with shadow compensation and a commercial multi‐focus high resolution OCT (HR‐OCT) system for clinical BCC imaging. We find that the HR‐OCT system struggled to resolve the dark band signal of papillary dermis where the UHR‐OCT located this in all cases and detected changes in signal width. UHR‐OCT is able to monitor extension and position of papillary dermis suggesting a novel feature for delineating superficial BCCs in pursuit of a fast accurate diagnosis. Comprehensive studies involving more patients are imperative in order to corroborate results. [ABSTRACT FROM AUTHOR]

Skin aging is a multifactorial phenomenon that involves alterations at the molecular, cellular and tissue levels. Our aim was to carry out a multiparametric biophysical and Raman characterization of skin barrier between individuals of different age groups (<24 and >70 years old). Our results showed a significant decrease of lipids to proteins ratio overall the thickness of the stratum corneum and higher lateral packing in the outer part of the SC for elderly. This can explain the decrease in trans epidermal water loss measured values rather than only SC thickening. Both age groups showed similar water content at SC surface while elderly presented higher water content in deep SC and viable epidermis. Mechanical measurements showed a decrease in the elasticity and an increase in the fatigability with age and were correlated with partially bound water. Highest correlation and anti‐correlation values were observed for the deepest part of the SC and the viable epidermis. [ABSTRACT FROM AUTHOR]

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Water‐in‐salt electrolytes (WISE) have largely widened the electrochemical stability window (ESW) of aqueous electrolytes by formation of passivating solid electrolyte interphase (SEI) on anode and also absorption of the hydrophobic anion‐rich double layer on cathode. However, the cathodic limiting potential of WISE is still too high for most high‐capacity anodes in aqueous sodium‐ion batteries (ASIBs), and the cost of WISE is also too high for practical application. Herein, a low‐cost 19 m (m: mol kg−1) bi‐salts WISE with a wide ESW of 2.8 V was designed, where the low‐cost 17 m NaClO4 extends the anodic limiting potential to 4.4 V, while the fluorine‐containing salt (2 m NaOTF) extends the cathodic limiting potential to 1.6 V by forming the NaF–Na2O–NaOH SEI on anode. The 19 m NaClO4–NaOTF–H2O electrolyte enables a 1.75 V Na3V2(PO4)3∥Na3V2(PO4)3 full cell to deliver an appreciable energy density of 70 Wh kg−1 at 1 C with a capacity retention of 87.5 % after 100 cycles. [ABSTRACT FROM AUTHOR]

The current method for determining the sun protection factor (SPF) requires erythema formation. Noninvasive alternatives have recently been suggested by several groups. Our group previously developed a functional sensor based on diffuse reflectance measurements with one UVB LED, which was previously evaluated on pig ear skin. Here we present the results of a systematic in vivo study using 12 sunscreens on 10 volunteers (skin types [ST] I‐III). The relationship of the UVB‐LED reflectance of unprotected skin and melanin index was determined for each ST. The spatial variation of the reflectance signal of different positions was analyzed and seems to be mainly influenced by sample inhomogeneity except for high‐protection factors (PFs) where signal levels are close to detection noise. Despite the low‐signal levels, a correlation of the measured LED‐based UVB PF with SPF reference values from test institutes with R2 = 0.57 is obtained, suggesting a strong relationship of SPF and LED‐based UVB‐PF. Measured PFs tend to be lower for increasing skin pigmentation. The sensor design seems to be suitable for investigations where a fast measurement of relative changes of PFs, such as due to inhomogeneous application, bathing and sweating, is of interest. [ABSTRACT FROM AUTHOR]

The sun protection factor (SPF) values are currently determined using an invasive procedure, in which the volunteers are irradiated with ultraviolet (UV) light. Non‐invasive approaches based on hybrid diffuse reflectance spectroscopy (HDRS) have shown a good correlation with conventional SPF testing. Here, we present a novel compact and adjustable DRS test system. The in vivo measurements were performed using a multi‐lambda‐LED light source and an 84‐channel imaging spectrograph with a fiber optic probe for detection. A transmission spectrum was calculated based on the reflectance measured with sunscreen and the reflectance measured without sunscreen. The preexposure in vitro spectrum was fitted to the in vivo spectrum. Each of the 11 test products was investigated on 10 volunteers. The SPF and UVA‐PF values obtained by this new approach were compared with in vivo SPF results determined by certified test institutes. A correlation coefficient R2 = 0.86 for SPF, and R2 = 0.92 for UVA‐PF were calculated. Having examined various approaches to apply the HDRS principle, the method we present was found to produce valid and reproducible results, suggesting that the multi‐lambda‐LED device is suitable for in‐vivo SPF testing based on the HDRS principle as well as for in‐vivo UVA‐PF measurements. [ABSTRACT FROM AUTHOR]

This article is an overview of advances in Raman spectroscopy published in 2019 in the Journal of Raman Spectroscopy (JRS) and, in addition, trends over the past decade across journals that have published papers important to the field of Raman spectroscopy. The trends are based on statistical data of article counts obtained from Clarivate Analytic's Web of Science Core Collection by year and by subfield of Raman spectroscopy. Normally in this review, coverage would be provided for presentations involving Raman Spectroscopy at the following four international conferences previously scheduled for this year: the International Conference on Raman Spectroscopy (ICORS 2020) in Rome, Italy; SCIX 2020 organized by the Federation of Analytical Chemistry and Spectroscopy Societies (FACSS) in Reno, Nevada, USA, in October; the European Conference on Nonlinear Optical Spectroscopy (ECONOS 2020) in Karlsrue, Germany, in April; and the International Conference on the GeoRaman Spectroscopy (GeoRaman 2020) in Bilbao, Spain, in November (originally scheduled for Weihai, China, in June). Of these, the ICORS 2020 has been rescheduled for 2021 at the same location; ECONOS 2020 has been canceled, but instead, a special issue section is being organized by invitation to commemorate the passing of JRS Board member Marcus Motzkus; SCIX 2020 has been changed to a virtual online conference; GeoRaman 2020 has been canceled, but online submission of abstracts will be made available with selected invitations to submit papers for a special issue of JRS. Finally, papers published in JRS in 2019 are highlighted and arranged by topics at the frontier of Raman spectroscopy. Based on these data, presentations, and publications, it is clear that Raman spectroscopy continues as an expanding field of research across a wide range of novel disciplines and applications that provide sensitive photonic information at the molecular level. [ABSTRACT FROM AUTHOR]

The class of PEGylated emulsifiers finds broad application in the pharmaceutical and cosmetic industry. We target on one of the categories of polyethylene glycol (PEG) alkyl ethers with different lipophilic and hydrophilic chain length and aim to examine their effects on the skin comprehensively. In this study, we employed confocal Raman spectroscopy for skin depth profiling and imaging. A unique probe of heavy water (D2O) was incorporated, which can be tracked percutaneously and simultaneously monitor the effects caused by emulsifiers. According to the results, most of the PEGylated emulsifiers caused changes in skin lipid content/organization and induced the alteration in relative water content/hydrogen bonding structure. The results obtained from the depth profiling analysis provided the possibility to estimate the least penetration depth of emulsifiers. Among them, PEG‐20 ethers displayed the most penetration ability. Meanwhile, it is interesting to find that the treatment of emulsifiers also affected the spatial distribution of D2O whose differences were in line with the molecular skin variations. In particular, the isotopic H/D substitution in the skin was highlighted in detail. This result supports the possibility to use D2O as an excellent and cost‐effective probe to evaluate the skin barrier function. [ABSTRACT FROM AUTHOR]