Phenytoin enzyme induction for management of supratherapeutic tacrolimus levels due to drug-drug interaction with nirmatrelvir/ritonavir: Case series and discussion.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Nirmatrelvir/ritonavir is one of few options for outpatient treatment of COVID-19, but its use has been limited in transplant recipients due to significant drug interactions with immunosuppressants. Tacrolimus toxicity is possible when the drug is coadministered with nirmatrelvir/ritonavir and may require urgent reduction of tacrolimus levels. This case series describes the use of phenytoin for enzyme induction in 5 adult solid organ transplant recipients with supratherapeutic tacrolimus levels resulting from coadministration with nirmatrelvir/ritonavir. SUMMARY: Solid organ transplant recipients are at high risk for complications related to COVID-19. Outpatient treatment options are limited, and therapeutic drug monitoring is complex in patients requiring quarantine. The 5 solid organ transplant recipients described herein were initiated on nirmatrelvir/ritonavir in the outpatient setting and subsequently presented with supratherapeutic tacrolimus concentrations greater than 59 ng/mL and developed signs and symptoms of tacrolimus toxicity. In all patients, nirmatrelvir/ritonavir and tacrolimus were discontinued, and oral phenytoin (200-400 mg/day) was given for 2 to 4 days. Tacrolimus was resumed once tacrolimus levels decreased to appropriate levels. CONCLUSION: These observations demonstrate that metabolism induction using phenytoin may be a useful strategy in the setting of supratherapeutic tacrolimus levels resulting from concomitant administration with nirmatrelvir/ritonavir.

The Role of Polyphenolic Antioxidants from Tea and Rosemary in the Hydroxyl Radical Oxidation of N-Acetyl Alanine.

In dead biological tissues such as human hair, the ability of antioxidants to minimise autoxidation is determined by their chemical reactions with reactive oxygen species. In order to improve our understanding of factors determining such antioxidant properties, the mechanistic chemistry of four phenolic antioxidants found in tea and rosemary extracts (epicatechin, epigallocatechin gallate, rosmarinic and carnosic acids) has been investigated. The degradation of N-acetyl alanine by photochemically generated hydroxyl radicals was used as a model system. A relatively high concentration of the antioxidants (0.1 equivalent with respect to the substrate) tested the ability of the antioxidants to intercept both initiating hydroxyl radicals (preventive action) and propagating peroxyl radicals (chain-breaking action). LC-MS data showed the formation of hydroxylated derivatives, quinones and hydroperoxides of the antioxidants. The structure of the assignment was aided by deuterium exchange experiments. Tea polyphenolics (epicatechin and epigallocatechin gallate) outperformed the rosemary compounds in preventing substrate degradation and were particularly effective in capturing the initiating radicals. Carnosic acid was suggested to act mostly as a chain-breaking antioxidant. All of the antioxidants except for rosmarinic acid generated hydroperoxides which was tentatively ascribed to the insufficient lability of the benzylic C-H bond of rosmarinic acid.

The key phytochemistry of rosemary (Salvia rosmarinus) contributing to hair protection against UV.

Extracts from rosemary (Salvia Rosmarinus) are analysed for their phytochemistry using LC-MS and the phytochemistry identified. The same extracts were tested for their efficacy to act as antioxidants by both hydrogen-atom transfer (ORAC) and single electron transfer (FRAP). A correlation analysis was performed to identify the key phytochemistry responsible for antioxidant efficacy. The top performing extracts were then tested in a peptide model and in hair with the presence of UV to measure ability to protect against UV-induced peptide and protein damage. Polyphenols (e.g. rosmarinic acid, glycosides of selgin) and abietane diterpenes (e.g. carnosic acid) in rosemary were identified as the principal compounds which enables the extracts to protect hair from UV. OBJECTIVE: The objective of this work was to correlate the phytochemistry of rosemary (Salvia rosmarinus), a botanical with known antioxidant properties, to a UV protection benefit in hair. These data will give insights into mechanisms of UV damage, the ROS formed and their reactivity. METHODS: LC-MS was used to compare the compounds in 10 commercial extracts of rosemary. ORAC (oxygen radical antioxidant capacity) and FRAP (ferric reducing antioxidant power) were used to measure the antioxidant capacity of the rosemary extracts. The ORAC assay measures ability of an antioxidant to react with a peroxyl radical via hydrogen atom extraction and FRAP measures electron transfer through reduction of ferric iron (Fe3+ ) to ferrous iron (Fe2+ ) by antioxidants present in the samples. Correlation of extract composition with antioxidant measures was performed using principal component analysis. Selected extracts were assessed for their ability to protect hair from UV damage in a model peptide system and on hair. In addition, the same methods were used to test rosmarinic acid and carnosic acid, key phytochemistries in the rosemary extracts. The model system was a peptide and its decomposition on exposure to UV was monitored by LC-MS in the absence and presence of the rosemary extracts. Hair degradation in the presence of UV was measured by exposure of UV in an Atlas weatherometer followed by extraction of degraded protein in water. A fragment of the S100A3 protein was used as a marker of UV damage (m/z = 1278) and quantified via LC-MS. RESULTS: Ten rosemary extracts were assessed for antioxidant performance and correlated with their compositions. The phytochemistry in each extract varied widely with a total of 33 individual compounds identified. The differences were most likely driven by the solvent and extraction method used by the supplier with extracts varying in the proportion of polar or non-polar compounds. This did influence their reactivity in the ORAC and FRAP assays and their efficacy in preventing protein damage. Two of the key compounds identified were rosmarinic acid and carnosic acid, with rosmarinic acid dominating in extracts with mainly polar compounds and carnosic acid dominating in extracts with mainly nonpolar compounds. Extracts with higher rosmarinic acid correlated with ORAC and FRAP scores, with UV protection on hair and in the peptide model system. The extracts chosen for hair experiments showed hair protection. UV protection was also measured for rosmarinic and carnosic acid. CONCLUSIONS: Despite the variation in the profile of phytochemistries in the 10 rosemary extracts, likely driven by the chosen extraction method, all rosemary extracts had antioxidant activity measured. This study suggests that the polyphenols (e.g. rosmarinic acid, glycosides of selgin) and abietane diterpenes (e.g. carnosic acid) are the principal compounds which enables the extracts to protect hair from UV.

INTRODUCTION: Les extraits de romarin (Salvia Rosmarinus) sont analysés par LC-MS pour établir et identifier leur profil phytochimique. Les mêmes extraits ont été testés pour leur efficacité à agir comme antioxydants à la fois par transfert d'atome d'hydrogène (ORAC) et par transfert d'électrons uniques (FRAP). Une analyse de corrélation a été réalisée pour identifier les propriétés phytochimiques clés responsables de l'efficacité antioxydante. Les extraits les plus performants ont ensuite été testés dans un modèle peptidique et sur les cheveux en présences d'UV pour mesurer la capacité à protéger contre les dommages induits par les UV su les peptides et protéines. Les polyphénols (par ex. acide rosmarinique, glycosides de selgin) et les diterpènes d'abiétine (par ex. acide carnosique) dans le romarin ont été identifiés comme les principaux composés permettant aux extraits de protéger les cheveux des UV. OBJECTIF: L'objectif de ce travail était de mettre en corrélation la phytochimie du romarin (Salvia rosmarinus), une plante aux propriétés antioxydantes connues, et les bénéfices d'une protection contre les UV dans les cheveux. Ces données fourniront des informations sur les mécanismes des dommages causés par les UV, la formation du ROS et leur réactivité. MÉTHODES: La LC-MS a été utilisée pour comparer les composés de 10 extraits commerciaux de romarin. L'ORAC (Oxygen Radical Antioxidant Capacity/Capacité d'absorption des radicaux d'oxygène) et la FRAP (Ferric Reduction Antioxidant Power/Pouvoir antioxydant de réduction ferrique) ont été utilisés pour mesurer la capacité antioxydante des extraits de romarin. Le dosage ORAC mesure la capacité d'un antioxydant à réagir avec un radical peroxyl par extraction d'atome d'hydrogène et la FRAP mesure le transfert d'électrons par réduction du fer ferrique (Fe3+ ) en fer ferreux (Fe2+ ) par les antioxydants présents dans les échantillons. La corrélation entre la composition de l'extrait et les mesures des antioxydants a été effectuée en analysant les composants principaux. Les extraits sélectionnés ont été évalués pour leur capacité à protéger les cheveux des dommages causés par les UV dans un modèle de système peptidique et sur les cheveux. En outre, les mêmes méthodes ont été utilisées pour tester l'acide rosmarinique et l'acide carnosique, principales caractéristiques phytochimiques dans les extraits de romarin. Le système modèle était un peptide et sa décomposition à l'exposition aux UV a été suivie par LC-MS en l'absence et en présence des extraits de romarin. La dégradation des cheveux en présence d'UV a été mesurée par l'exposition aux UV dans un indicateur de désagrégation Atlas suivi de l'extraction de protéines dégradées dans l'eau. Un fragment de la protéine S100A3 a été utilisé comme marqueur de dommage UV (m/z = 1278) et quantifié par LC-MS. RÉSULTATS: Dix extraits de romarin ont été évalués en termes de performance antioxydante et mis en corrélation avec leurs compositions. La phytochimie de chaque extrait variait considérablement, avec un total de 33 composés individuels identifiés. Les différences étaient très probablement dues à la méthode du solvant et de l'extraction utilisée par le fournisseur avec des extraits variant dans la proportion de composés polaires ou non polaires. Cela a effectivement influencé leur réactivité dans les dosages ORAC et FRAP et leur efficacité dans la prévention des dommages protéiques. Deux des composés clés identifiés étaient l'acide rosmarinique et l'acide carnosique, l'acide rosmarinique dominant dans les extraits contenant principalement des composés polaires et l'acide carnosique dominant dans les extraits contenant principalement des composés non polaires. Les extraits avec un taux d'acide rosmarinique plus élevé étaient mis en corrélation avec les scores ORAC et FRAP, avec une protection UV sur les cheveux et dans le système de modèle peptidique. Les extraits choisis pour les expériences sur les cheveux ont montré une protection des cheveux. La protection contre les UV a également été mesurée pour l'acide rosmarinique et l'acide carnosique. CONCLUSIONS: Malgré la variation des profils phytochimiques dans les dix extraits de romarin, probablement induite par la méthode d'extraction choisie, l'activité antioxydante de tous les extraits de romarin a été mesurée. Les polyphénols (par ex. acide rosmarinique, glycosides de selgin) et les diterpènes d'abiétane (par ex. acide carnosique) dans le romarin ont été identifiés comme les principaux composés permettant aux extraits de protéger les cheveux contre les UV.

Hair surface interactions against different chemical functional groups as a function of environment and hair condition.

OBJECTIVE: The nature and magnitude of molecular interactions on hair surfaces underpin the design of formulated products, of which the application involves a competitive adsorption process between cationic surfactants, fatty alcohols and surface actives such as silicone. The knowledge of molecular interaction with hair surface will not only provide insight on the surface binding affinity but also offer an effective methodology in characterizing surface deposits. METHODS: Untreated and chemically treated hair samples were treated with either conditioner chassis alone (gel network) or conditioner chassis plus silicone (chassis/TAS). Hair surface interactions against four different chemical functional groups, namely methyl (-CH3 ), acid (-COOH), amine (-NH2 ) and hydroxyl (-OH), were quantified in both ambient and aqueous environment using Chemical Force Microscopy, a method based on atomic force microscopy (AFM). RESULTS: Surface adhesion on hair in ambient is dominated by capillary force that is determined by both the wettability of hair fibre (hydrophobic vs. hydrophilic), presence of any deposits and the chemical functionality of the AFM cantilever. Capillary force is diminished and replaced by electrostatic interaction when polar groups are present on both hair and AFM cantilever. A distinctively different force, hydrophobic interaction, plays a major role when virgin hair and hydrophobic functionalized AFM cantilever make contact in water. CONCLUSION: Results acquired by AFM cantilevers of different functional groups show that hydrophobic interaction is a key driver for deposition on virgin hair, whilst electrostatic interaction is the most important one for bleached hair. Interfacial conformation of chassis components upon deposition is determined by the hair surface properties. Our study highlights the possibility of a range of polar groups, not necessarily negatively charged, on the damaged hair. Unlike conventional surface chemical analysis method, it is possible to quantitatively evaluate the interfacial conformation of deposited surface actives on hair, which identifies the target moieties for conditioning products on different types of hair.

OBJECTIF: La nature et l'intensité des interactions moléculaires mesurables à la surface d'un cheveu, caractérisent l'effet de la formulation du produit initialement appliqué sur le cheveu. L'application du produit et son effet sur le cheveu repose sur un mécanisme d'adsorption complexe combinant l'effet de différents éléments tels que des surfactants cationiques, des alcools gras et des agents de surface tel que le silicone. L'étude et l'analyse des interactions moléculaires à la surface du cheveu permettent non seulement de déterminer l'affinité adhésive de surface, mais aussi d'offrir une méthode efficace pour caractériser les dépôts de surface. MÉTHODE: Des cheveux initialement traités et non-traités chimiquement, ont été analysés après l'application d'un après-shampoing chassis (structure en gel) ou d'un après-shampoing chassis avec du silicone (chassis/TAS). Les interactions entre la surface du cheveu et quatre groupes fonctionnels chimiques - méthyle (-CH3 ), acide (-COOH), amine (-NH2) et hydroxy (-OH) ont été quantifiées à l'air et en milieu aqueux par microscopie à force chimique, une méthode basée sur la microscopie à force atomique (AFM). RÉSULTATS: L'adhésion de surface sur cheveu à l'air est dominée par la force capillaire qui est déterminée par la mouillabilité de la fibre capillaire (hydrophobe vs. hydrophile), la présence de dépôts, et la fonction chimique du cantilever. La force capillaire diminue et est remplacée par des interactions électrostatiques quand des groupes polaires sont présents à la fois sur le cheveu et le cantilever. Une autre force - l'interaction hydrophobe, joue un rôle majeur quand un cheveu non-traité / vierge et un cantilever de fonction hydrophobe se rencontrent en milieu aqueux. CONCLUSIONS: Les résultats obtenus à partir de cantilevers de différentes fonctions chimiques, montrent que l'interaction hydrophobe joue un rôle clé dans l'application de produit capillaire sur cheveux non-traité tandis que les interactions électrostatiques sont prédominantes dans le cas de cheveux traités chimiquement. La conformation interfaciale des composés chassis avant déposition est déterminée par les propriétés de surface du cheveu. Notre étude souligne la présence potentielle de différents groupes polaires, pas nécessairement chargés négativement, sur la surface de cheveux endommagés. A l'inverse des méthodes conventionnelles d'analyse chimique de surface, il est possible d'évaluer quantitativement la conformation interfaciale de dépôts d'agents actifs présents à la surface du cheveu, ce qui permet d'identifier les zones cibles pour l'application d'après-shampoing sur différents types de cheveux.

UV and visible light exposure to hair leads to widespread changes in the hair lipidome.

OBJECTIVE: Scalp hair is among the most exposed parts of the human body, yet the impact of visible and UV light on hair lipids, an important structural component of hair, is poorly researched. We have used lipidomics, a broad-based approach to measure lipids in samples, which has hitherto not been applied to UV-exposed hair in the published literature, and could allow for a wider understanding of how UV light impacts on specific hair lipids. METHODS: Mixed blonde Caucasian hair switches were divided into two groups of five, with half of the hair switches exposed to UV and visible light mimicking normal daytime exposure and half left unexposed. LC-MS lipidomics was used to profile the lipids in the hair samples. RESULTS: A total of 791 lipids and 32 lipid classes with tentative identifications were detected in the hair samples. Nineteen lipid classes and 397 lipids differed between UV-treated and non-treated hair. The main lipid classes that differed were vitamin A fatty acid esters, sterol esters, several ceramides, mono-, di- and triglycerides, phosphatidylethanolamines (all decreased in UV-exposed hair) and bismonoacylglycerolphosphates, acylcarnitines and acylglycines (all increased in UV-exposed hair). Most detected lipids were decreased in UV-exposed hair, supporting earlier work that has found that UV exposure causes oxidation of lipids which would result in a decrease in most lipid classes. CONCLUSION: Light exposure to hair has a widespread impact on the hair lipidome. This study also adds to the emerging literature on the hair lipidome, broadening the range of lipid classes reported in hair.

OBJECTIF: Le cuir chevelu est l'une des parties les plus exposées de l'organisme. Cependant, l'impact de la lumière visible et des UV sur les lipides capillaires, un composant structurel important des cheveux, reste mal étudié. Nous avons utilisé la lipidomique, une approche large pour mesurer les lipides présents dans les échantillons de cheveux, qui n'a jusqu'ici pas été appliquée aux cheveux exposés aux UV dans la littérature publiée. Cette approche pourrait permettre de mieux comprendre l'impact de la lumière UV sur des lipides spécifiques des cheveux. MÉTHODES: Les mèches de cheveux caucasiens blonds mélangés ont été divisées en deux groupes de cinq, la moitié des mèches de cheveux étant exposées aux UV et à une lumière visible imitant l'exposition diurne normale tandis que l'autre moitié est restée non exposée. Le profil lipidique des échantillons de cheveux a été établi grâce à la lipidomique de la LC-MS. RÉSULTATS: Au total, 791 lipides et 32 classes de lipides avec des identifications provisoires ont été détectés dans les échantillons de cheveux. Entre les cheveux traités par UV et les cheveux non traités, dix-neuf classes de lipides et 397 lipides se sont avérés différents. Les principales classes de lipides qui différaient étaient les esters d'acides gras de la vitamine A, les esters de stérols, plusieurs céramides, les monoglycérides, diglycérides et triglycérides, les phosphatidyléthanolamines (tous diminués dans les cheveux exposés aux UV) et les bismonoacylglycérolphosphates, acylcarnitines et acylglycines (tous augmentés dans les cheveux exposés aux UV). La plupart des lipides détectés dans les cheveux exposés aux UV n'étaient présents qu'à taux réduit, soit un résultat cohérent avec une étude antérieure ayant montré que l'exposition aux UV provoque l'oxydation des lipides, ce qui entraînerait une diminution de la plupart des classes de lipides. CONCLUSION: L'exposition des cheveux à la lumière entraîne un impact généralisé sur leur lipidome. Cette étude vient également compléter la littérature émergente sur le lipidome capillaire, élargissant ainsi la gamme de classes lipidiques rapportées dans les cheveux.

Redox proteomics analysis of hair shaft proteins upon hydrothermal and alkaline insult.

OBJECTIVE: Human hair is regularly subjected to chemical and physical insults, such as heat, UV-irradiation and alkaline hair care products. These insults result in molecular modifications at the hair protein level that underpin mechanical and sensory property changes in the fibres. These changes can manifest itself in reduced hair quality and performance attributes observable to the consumer. In this work, changes in protein modification as a result of heat and alkaline treatments are determined. METHODS: Redox proteomic profiling using high-resolution mass spectrometry was applied to map and evaluate amino acid residue modifications in human hair exposed to a combination of thermal treatments and alkali exposure with the aim to understand the underlying chemical processes. RESULTS: Our results show that an increase in redox-related modifications is associated with exposure to higher levels of hydrothermal and alkaline insult. Post-translational modification profiling at the protein primary structural level delivered some further insights into the site-specificity of these modifications, with a clear increase in the number of cysteic acid modifications noticed in samples subjected to more extreme insults. CONCLUSION: Pinpointing modification sides within proteins and the hair shaft proteome can be used as a basis for employing mitigation or repair strategies of hair protein damage caused by environmental or hair treatment-related insults.

OBJECTIF: Les cheveux humains sont sujet à de nombreuses agressions physiques et chimiques telles que la chaleur, les radiations ultra-violettes et les produits alcalins d'entretien des cheveux. Ces agressions entrainent des modifications moléculaires dans les protéines constituant les cheveux et elles conduisent aussi à des changements mécaniques et sensoriels des fibres capillaires. Les manifestations possibles de ces transformations sont une baisse, visible pour le consommateur, de la qualité et des indicateurs de performance des cheveux. Lors de cette étude, nous mettons en évidence les changements au niveau protéique liés à la chaleur et aux traitements alcalins. MÉTHODES: Les méthodes de profilage d'oxydoréduction protéomique utilisant des spectromètres de masses à haute résolution ont été utilisées afin d'évaluer les modifications des amino-acides dans les cheveux humains après exposition à plusieurs combinaisons de traitements thermiques et alcalins dans le but de comprendre les processus chimiques impliqués. RÉSULTATS: Nos résultats montrent que l'augmentation des modifications d'oxydoréduction est associée à des niveaux élevés d'exposition aux traitements thermiques et/ou alcalins. Le profilage des modifications post-translationnelles des structures primaires des protéines ont permis de mieux comprendre les spécificités de ces modifications ; notamment une augmentation nette du nombre des modifications des acides cystéiques liée aux traitements les plus agressifs. CONCLUSION: Ce travail d'identification des modifications engendrées par les agressions liées aux traitements capillaires ou environnementales peut désormais servir de base pour évaluer et mettre en place des techniques de réduction des risques, protection et de réparation des protéines des cheveux.

Protection of hair from damage induced by ultraviolet irradiation using tea (Camellia sinensis) extracts.

BACKGROUND: Damage to hair by UV is relevant to most people, and for many, it is a major source of hair damage. Prevention of UV damage is of high interest to cosmetic companies. OBJECTIVES: Describe UV damage mechanisms and link these mechanisms to measurable changes in hair protein composition and color changes resulting from breakdown of yellow-colored kynurenines. Test the power of botanical antioxidants, specifically Camellia sinensis (tea) extracts to prevent this protein damage and color change. Link specific phytochemistry of extract samples to hair performance. METHODS: Camellia sinensis (tea) extracts were analyzed by LC-MS to identify the key composition chemistries. ORAC (Oxygen Radical Antioxidant Capacity) was used to measure ability of the extract to react with a peroxyl radical via a hydrogen abstraction mechanism. Hair protein structural damage was measured by quantification of a biomarker peptide that is specific to UV-induced damage and hair color changes were measured with a spectrophotometer. RESULTS: Levels of key phytochemistry in the extracts, specifically the catechins, correlated with prevention of UV-induced protein damage and prevention of color changes due to kynurenine breakdown. Extracts with higher phytochemistry levels also had higher ORAC scores indicating that they were more effective antioxidants. CONCLUSIONS: Camellia sinensis (tea) extracts can be used as effective protective treatments for hair protection but this efficacy is linked to extract concentrations of key chemistries (catechins).

Molecular interaction and partitioning in α-keratin using 1H NMR spin-lattice (T1) relaxation times.

The interactions between small molecules and keratins are poorly understood. In this paper, a nuclear magnetic resonance method is presented to measure changes in the 1H T1 relaxation times of small molecules in human hair keratin to quantify their interaction with the fibre. Two populations of small-molecule compounds were identified with distinct relaxation times, demonstrating the partitioning of the compounds into different keratin environments. The changes in relaxation time for solvent in hair compared with bulk solvent were shown to be related to the molecular weight (MW) and the partition coefficient, LogP, of the solvent investigated. Compounds with low MWs and high hydrophilicities had greater reductions in their T1 relaxation times and therefore experienced increased interactions with the hair fibre. The relative population sizes were also calculated. This is a significant step towards modelling the behaviour of small molecules in keratinous materials and other large insoluble fibrous proteins.

Role of Redox Metals in Color Formation in a Hair Colorant.

The objective of this work was to identify if low levels of redox metals such as copper would accelerate color formation on hair and to understand the consequent impact on initial color formation and color fade. Kinetics of color formation with oxidative dyes in solution in the presence of varying concentrations of copper ions were assessed via imaging and color measurements. Color uptake on hair and color fade were measured with a spectrophotometer, and copper levels in hair were measured with inductively coupled plasma atomic spectroscopy after hair digestion. In this work, the role of redox metal ions such as copper and iron on accelerating rates of oxidative dye formation was demonstrated. Kinetics of dye formation were measured in solution for three dye couples-p-phenylene diamine (PPD) plus resorcinol, PPD plus 5-amino-2-methylphenol (AHT), and 4,5-diamino-1-(2-hydroxyethyl) pyrazole sulfate (HDAP) plus AHT- in a solution that also contained ammonium hydroxide and hydrogen peroxide at pH 10. Low levels of copper were added at a concentration range from 0.01 µg/g to 0.1 µg/g and the rate of color formation measured over 2 h. All th ree dye couples showed signifi cant color acceleration that increased with increasing levels of copper. A mechanism where initial oxidation of primary intermediate PPD or HDAP is accelerated is proposed. This mechanism is demonstrated to become important when trace levels of copper are in hair and a hair colorant added. Color formation is accelerated outside versus inside hair, and ultimately, color uptake is reduced after the colorant is rinsed off hair. Noticeable color fade versus the starting hair color is also increased. This work provides evidence for the role of copper ions in color formation in hair and strategies to reduce copper levels in hair using a chelant such as histidine in a shampoo or conditioner before coloring.

Nanoscale Mass Spectrometry Multimodal Imaging via Tip-Enhanced Photothermal Desorption.

Materials ranging from adhesives, pharmaceuticals, lubricants, and personal care products are traditionally studied using macroscopic characterization techniques. However, their functionality is in reality defined by details of chemical organization on often noncrystalline matter with characteristic length scales on the order of microns to nanometers. Additionally, these materials are traditionally difficult to analyze using standard vacuum-based approaches that provide nanoscale chemical characterization due to their volatile and beam-sensitive nature. Therefore, approaches that operate under ambient conditions need to be developed that allow probing of nanoscale chemical phenomena and correlated functionality. Here, we demonstrate a tool for probing and visualizing local chemical environments and correlating them to material structure and functionality using advanced multimodal chemical imaging on a combined atomic force microscopy (AFM) and mass spectrometry (MS) system using tip-enhanced photothermal desorption with atmospheric pressure chemical ionization (APCI). We demonstrate enhanced performance metrics of the technique for correlated imaging and point sampling and illustrate the applicability for the analysis of trace chemicals on a human hair, additives in adhesives on paper, and pharmaceuticals samples notoriously difficult to analyze in a vacuum environment. Overall, this approach of correlating local chemical environments to structure and functionality is key to advancing research in many fields ranging from biology, to medicine, to material science.

Molecular environment and reactivity in gels and colloidal solutions under identical conditions.

A PEG-Tyr block copolymer forms a kinetically stable colloidal solution in water at room temperature which undergoes an irreversible conversion to a gel phase upon heating. A micellar solution and a gel can therefore be studied under identical experimental conditions. This made it possible to compare physical properties and chemical reactivity of micelles and gels in identical chemical environments and under identical conditions. EPR spectra of the spin-labelled copolymer showed that tyrosine mobility in gels was slightly reduced compared to micelles. Chemical reactivity was studied using photochemical degradation of tyrosine and tyrosine dimerization, in the absence and in the presence of an Fe(iii) salt. The reactivity trends were explained by reduced tyrosine mobility in the gel environment. The largest reactivity difference in gels and micelles was observed for bimolecular dityrosine formation which was also attributed to the reduction in molecular mobility.

Description and function of a difficult airway service.

The goal of the Pediatric Difficult Airway Service (DAS) is to improve the care of children with airway abnormalities primarily through identification of children at risk for failed airway management. The airway service encourages early recognition and provides consultation, a plan for airway management, expertise in airway management, and follow-up care for children who have a difficult airway. The service has improved the education of healthcare professionals and heightened awareness about the consequences of failed airway management.

Anomalous Fluorescence of White Hair Compared to Other Unpigmented Keratin Fibres.

OBJECTIVE: To demonstrate that the tryptophan (Trp) fluorescence of natural white hair is much weaker than other unpigmented keratin fibres such as wool, cashmere, rabbit hair and mink fur, and to explore possible reasons for this behaviour. The origin of the blue visible fluorescence (~450 nm) excited by UVA radiation in the range 360-380 nm, often associated with Trp degradation products, is also discussed and compared to other fibrous and globular proteins. METHODS: As the fluorescence spectrum of keratin fibres usually contains at least two major features, a visual comparison is more effectively demonstrated by creating a 3D contour plot of excitation versus emission wavelength, which is sometimes referred to as an excitation emission matrix (EEM). RESULTS: The Trp fluorescence from white hair is very much weaker than for wool, cashmere, rabbit hair and mink fur, but its visible fluorescence emission is stronger. Oxidation and reduction have little effect on the Trp intensity, which suggests quenching by cystine is not a major factor. Decuticulation of hair fibres had no effect on the Trp intensity showing that the increased number of cuticle scales surrounding the fibre cortex is not responsible. Trp fluorescence is very sensitive to exposure to UVB wavelengths, so possibly its low intensity in hair is due to greater levels of environmental exposure to sunlight than the other fibres examined. CONCLUSION: Trp fluorescence from natural white hair is either extremely weak or completely absent, in contrast to the four other keratin fibres examined. It is possible that environmental exposure to UV wavelengths present in sunlight contributes to a reduction in the Trp fluorescence intensity of white hair. However another explanation is that Trp is quenched, by either an unknown substance introduced into hair during keratinisation, or as a result of regular exposure to personal care products, which may interact with Trp or tyrosine residues and disrupt the energy transfer process involved in keratin fluorescence. Further studies will be required to definitively determine the cause.

High-resolution visualization of cosmetic active compounds in hair using nanoscale secondary ion mass spectrometry.

A wide range of small molecules are used in our daily hair products to improve the appearance of hair and to protect it from damage from the environment. In order to better design formulations of these products, an understanding of the partitioning and distributions of these small molecules in hair is critical. In this study, we used preferential extraction methods to measure the partitioning of active compounds commonly found in hair cosmetic products on the hair surface and inside hair, and investigated the use of stable isotope labelling, cryo-sample preparation and nanoscale secondary ion mass spectrometry (NanoSIMS) for high-resolution visualization of distributions of these compounds. With this approach, we quantified partitioning and directly visualized distributions at high-resolution of four molecules (e.g. resorcinol, salicylic acid, pentadecyl alcohol and pentadecanoic acid) in hair. This has not been achieved before and revealed distributions of high lipophilicity active compounds in the lipid-rich and hydrophobic cell membrane complex network in hair, while low lipophilicity ones distributed dispersedly.

Aqueous MEA and Ammonia Sorption-Induced Damage in Keratin Fibers.

The sorption of aqueous monoethanolamine (MEA) and ammonia solutions in keratin fibers and its subsequent effect on their mechanical performance has been investigated. The diffusion kinetics of MEA into keratin fibers for 0.1, 1.0, and 5 v/v % MEA in water at 30 and 50 °C were found to exhibit two clear regimes of absorption behavior: a linear Fickian diffusion regime for initial times up to 100 min, after which a second slower uptake process was observed. Single fiber tensile tests showed that the Young's modulus and the tensile failure stress for 5% MEA-treated fibers, compared to untreated fibers, were 25% lower after 1 h of treatment and 50% lower after 9 h of treatment. Aqueous treatments of 0.1 and 1% MEA, as well as 0.6 and 3% aqueous ammonia, had no measurable effect on either Young's modulus or tensile failure stress for the fibers. Scanning electron microscopy images and protein content analysis confirmed that keratin fibers exposed to 5% MEA solution exhibited significant surface damage as well as high levels of protein loss. This study confirms for the first time the important damage hair treatments containing 5% aqueous MEA can cause on keratin fibers.

Tertiary Care Referrals for Fractures in Children.

PURPOSE: With limited local access to pediatric subspecialty care outside major metropolitan areas, tertiary care hospitals treat many children originally seen at outside facilities for relatively brief but urgent surgical procedures. This referral-based care imposes significant financial and psychological stress on the families. DESIGN: Prospective, survey methodology was used. METHODS: Families of children aged 0-18 years admitted to the St. Louis Children's Hospital for surgical repair of fractures were surveyed. The questionnaire was developed by the research team and measured a variety of fields. FINDINGS: The operative procedure in the majority of these children was relatively brief in both groups, often less than one hour. The time of injury to their discharge from our hospital, however, extended to 36 hours. Families missed several days of work. Many children were kept NPO longer than needed. CONCLUSIONS: Our preliminary evaluation suggests that a relatively minor unexpected surgery of a child can impose significant financial, organizational, and psychological burden on the family.

Effect of humidity on photoinduced radicals in human hair.

EPR spectroscopy was used to monitor formation of free radicals in human hair upon UV irradiation. While the EPR spectra of brown hair were dominated by melanin signal, those of white hair were keratin-derived. The decay of UV induced keratin radicals was enhanced at increased ambient humidity. We argue that at higher humidity the swollen hair provides a more liquid-like environment, and higher molecular mobility in this environment leads to faster radical reactions. This interpretation is consistent with the increased UV-triggered protein damage in hair at high humidity as demonstrated by the protein loss, MALDI-TOF and FT-IR data.

Multimodal Evidence of Mesostructured Calcium Fatty Acid Deposits in Human Hair and Their Role on Hair Properties.

We provide the first conclusive evidence for the presence of exogenous calcium fatty acid deposits, which not only form in-between the cuticle layers in the lipid-rich cell membrane complex, but also grow to dimensions large enough to cause the structure to bulge, thereby impacting the optical and mechanical properties of the hair fiber. The composition and phase of these deposits were probed using a multimodal analytical approach with spatially resolved techniques including synchrotron micro X-ray fluorescence coupled with X-ray scattering, focused ion beam (FIB)-scanning electron microscopy (SEM), scanning transmission electron microscopy, X-ray energy dispersive spectroscopy, and Fourier transform infrared and Raman imaging where the collective analysis is consistent with a meso-phase composed of calcium C16/C18 saturated fatty acids from natural sources such as sebum. X-ray microtomography and serial "slice and view" FIB/SEM both reveal the location and volumetric shape of the deposits.

Role of Internal Lipids in Hair Health.

Saturated and unsaturated fatty acids make up 85% of the total hair lipid content and are found in the cuticle and cortical cell membrane complex. Although these lipids only make up 2-6% of the hair's overall weight, they play a crucial role in keeping hair healthy, influencing shine, feel, manageability, and strength. The objective of this work was to understand the mechanisms of how these lipids are lost on exposure to external stressors, such as chemical treatments, washing, and UV exposure and to understand how their loss impacts hair strength. The experimental approach was to measure these lipids and oxidation products, lipid peroxides (LPOs) and correlate their loss with fatigue strength measurements. The results show lipids are lost over time by washing, exposure to chemical treatments, such as coloring, and environmental insults, such as UV, and it was confirmed that a mechanism of degradation is via oxidation of unsaturated lipids to form LPOs. In addition, it was shown that replenishment of these lipids is possible by incorporating lipids, such as fatty alcohols (FaOHs), into a gel network with anionic surfactants to create a delivery system that can efficiently penetrate FaOHs into hair and increase internal strength as measured by fatigue.