First Use of Optical Coherence Tomography on In Vivo Inflammatory Acne-Like Lesions: A Murine Model.

BACKGROUND AND OBJECTIVES: Successful outcomes of clinical studies for acne vulgaris depend greatly on achieving statistically significant reduction in acne lesion count and improvement in Investigator's Global Assessment score of the investigational drug product against its vehicle control. To date, there has not been a validated preclinical acne model to evaluate investigational drug products in order to improve the probability of clinical success. An inflammatory acne-like lesion mouse model developed in-house has previously been used for clinical guidance in our drug development program. In this study, we aim to implement and assess the adequacy of swept-source optical coherence tomography (SS-OCT) in quantifying the dynamic changes in inflammatory acne-like lesions. STUDY DESIGN/MATERIALS AND METHODS: Live Propionibacterium acnes bacteria were injected intradermally resulting in inflammatory acne-like lesions. Topical 1% and 2% minocycline gels were applied to the lesions in separate groups once daily for 2 weeks and compared with vehicle and untreated control groups. The growth of these lesions was monitored and measured with a ruler (height)/microcaliper (width)-an approach previously developed, and with SS-OCT. The reliability of the two methods were assessed. Acquired OCT images across the apex of these inflammatory lesions were statistically analyzed for lesion volume reduction from baseline as well as between the treatment groups and the control groups. RESULTS: The OCT technique allowed for reliable lesion volume analysis with varying conic profiles. After 14 days of topical minocycline treatments (1%, 2% minocycline), statistically significant reduction in lesion volume (P ≤ 0.05) based on OCT image analysis was observed compared with untreated and vehicle control groups as well as compared with baseline measurements. Under the right conditions, some morphological aspects of the P. acnes injection site were discernible within the skin in images captured with OCT. CONCLUSIONS: We demonstrated the first use of SS-OCT in evaluating in vivo inflammatory acne-like lesions in a murine model. Our findings support the use of OCT in assessing lesion size and evolution of P. acnes injection sites non-invasively in preclinical in vivo studies, which could potentially lead to more consistent and predictable outcomes in clinical development. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Oxytocin attenuates trust as a subset of more general reinforcement learning, with altered reward circuit functional connectivity in males.

Oxytocin (OT) is an endogenous neuropeptide that, while originally thought to promote trust, has more recently been found to be context-dependent. Here we extend experimental paradigms previously restricted to de novo decision-to-trust, to a more realistic environment in which social relationships evolve in response to iterative feedback over twenty interactions. In a randomized, double blind, placebo-controlled within-subject/crossover experiment of human adult males, we investigated the effects of a single dose of intranasal OT (40 IU) on Bayesian expectation updating and reinforcement learning within a social context, with associated brain circuit dynamics. Subjects participated in a neuroeconomic task (Iterative Trust Game) designed to probe iterative social learning while their brains were scanned using ultra-high field (7T) fMRI. We modeled each subject's behavior using Bayesian updating of belief-states ("willingness to trust") as well as canonical measures of reinforcement learning (learning rate, inverse temperature). Behavioral trajectories were then used as regressors within fMRI activation and connectivity analyses to identify corresponding brain network functionality affected by OT. Behaviorally, OT reduced feedback learning, without bias with respect to positive versus negative reward. Neurobiologically, reduced learning under OT was associated with muted communication between three key nodes within the reward circuit: the orbitofrontal cortex, amygdala, and lateral (limbic) habenula. Our data suggest that OT, rather than inspiring feelings of generosity, instead attenuates the brain's encoding of prediction error and therefore its ability to modulate pre-existing beliefs. This effect may underlie OT's putative role in promoting what has typically been reported as 'unjustified trust' in the face of information that suggests likely betrayal, while also resolving apparent contradictions with regard to OT's context-dependent behavioral effects.

[Urodynamic abnormalities in the kidneys of pancreonecrosis].

This paper presents experience in monitoring renal ultrasound data in patients with pancreatonecrosis from 20 to 60 years. It is also present two clinical cases of renal urodynamics in destructive forms of acute pancreatitis. Edematous form of acute pancreatitis and pancreatic cause violations not only secretion but also excretory function of the nephros. In patients with pancreatic necrosis accompanied by the formation of zones of limited fluid in the retroperitoneal space including retroperitoneal phlegmon may occur ureteral compression which is accompanied by appearance of urodynamic disorders in the nephros of varying severity. Ultrasound monitoring of renal care for patients with edematous form of acute pancreatitis, pancreatic necrosis helps to diagnose renal urodynamic disorders which allows timely corrected in the early stages of treatment activities in these patients and improve outcomes.

Preparatory study of feasibility for a vertical viewing electron cyclotron emission diagnostic for the JT-60SA tokamak.

A preparatory study is underway to investigate the feasibility study of high-energetic, non-thermal electron distribution function measurements using a vertical-viewing electron cyclotron emission (ECE) diagnostic on JT-60SA. The system is designed to detect broad ECE spectra (70-260 GHz) due to the second, third, and fourth harmonics using a focusing optics system with four quasi-optical mirrors in the upper port of JT-60SA. A Gaussian beam optics design is performed in vacuum, and ray tracing calculations are performed in plasma using the TRAVIS code to investigate density characteristics. A ceramic viewing dump is also designed to reduce the effects of multiple reflections from the opposing vacuum vessel surface.

Impact of avalanche type of transport on internal transport barrier formation in tokamak plasmas.

In magnetic fusion plasmas, a transport barrier is essential to improve the plasma confinement. The key physics behind the formation of a transport barrier is the suppression of the micro-scale turbulent transport. On the other hand, long-range transport events, such as avalanches, has been recognized to play significant roles for global profile formations. In this study, we observed the impact of the avalanche-type of transport on the formation of a transport barrier for the first time. The avalanches are found to inhibit the formation of the internal transport barrier (ITB) observed in JT-60U tokamak. We found that (1) ITBs do not form in the presence of avalanches but form under the disappearance of avalanches, (2) the surface integral of avalanche-driven heat fluxe is comparable to the time rate change of stored energy retained at the ITB onset, (3) the mean E × B flow shear is accelerated via the ion temperature gradient that is not sustained under the existence of avalanches, and (4) after the ITB formation, avalanches are damped inside the ITB, while they remain outside the ITB.

Characterization of a retroreflector array for 320-GHz interferometer system in Heliotron J.

A retroreflector array, composed of a cluster of small retroreflectors, is experimentally studied for application to a Michelson-type interferometer system in the fusion plasma experiment. Such a new-type reflector has the potential to be a vital and effective tool at a spatially limited location, such as on the vacuum chamber wall of plasma experimental devices. To investigate the effect of retroreflector array on the reflected beam properties, a tabletop experiment is performed with the retroreflector array composed of 4 mm corner-cube retroreflectors and with a 320-GHz (λ ∼ 0.937 mm) submillimeter wave source. An imaging camera is utilized to measure the submillimeter wave beam profile and is scanned perpendicularly to the beam propagation direction if necessary. The experimental result exhibits a diffraction effect on the reflected beam, resulting in the emergence of discrete peaks on the reflected beam profile, as predicted in the past numerical study; however, the most reflected beam power converges on the one reflected into the incident direction, resulting from a property as a retroreflector. Furthermore, the dependence of the reflected beam on the incident beam angle is characterized while fixing the detector position, and the retroreflection beam intensity is found to vary due to the diffraction effect. Such an undesired variation of beam intensity induced by the diffraction can be suppressed with a focusing lens placed in front of the detector in the practical application to an interferometer.

Clinical Experience of a Novel Optical Coherence Tomography-Guided Coronary Chronic Total Occlusion Re-Entry Device.

We demonstrated a first-in-human case of successful antegrade dissection and re-entry using an image-guided re-entry catheter that enables real-time high-resolution visualization with graphical augmentation, and precision steering and advancement of a guidewire. The total time from over-the-wire deployment in the proximity of the distal cap to successful re-entry was <20 minutes. (Level of Difficulty: Advanced.).

Experiment-Based Validation of Corneal Lenticule Banking in a Health Authority-Licensed Facility.

With the expected rise in patients undergoing refractive lenticule extraction worldwide, the number of discarded corneal stromal lenticules will increase. Therefore, establishing a lenticule bank to collect, catalog, process, cryopreserve, and distribute the lenticules (for future therapeutic needs) could be advantageous. In this study, we validated the safety of lenticule banking that involved the collection of human lenticules from our eye clinic, transportation of the lenticules to a Singapore Ministry of Health-licensed lenticule bank, processing, and cryopreservation of the lenticules, which, after 3 months or, a longer term, 12 months, were retrieved and transported to our laboratory for implantation in rabbit corneas. The lenticule collection was approved by the SingHealth Centralised Institutional Review Board (CIRB). Both short-term and long-term cryopreserved lenticules, although not as transparent as fresh lenticules due to an altered collagen fibrillar packing, did not show any sign of rejection and cytotoxicity, and did not induce haze or neovascularization for 16 weeks even when antibiotic and steroidal administration were withdrawn after 8 weeks. The lenticular transparency progressively improved and was mostly clear after 4 weeks, the same period when we observed the stabilization of corneal hydration. We showed that the equalization of the collagen fibrillar packing of the lenticules with that of the host corneal stroma contributed to the lenticular haze clearance. Most importantly, no active wound healing and inflammatory reactions were seen after 16 weeks. Our study suggests that long-term lenticule banking is a feasible approach for the storage of stromal lenticules after refractive surgery. Impact statement Since 2011, close to 3 million refractive lenticule extraction procedures have been performed. The majority of the extracted lenticules are discarded. The lenticules could have been cryopreserved and retrieved at a later date for therapeutic or refractive applications. Therefore, establishing a lenticule bank to collect, catalog, process, cryopreserve, and distribute the lenticules could be advantageous. In this study, we simulated a lenticule banking service in a validated health authority-licensed facility and showed that long-term cryopreservation of the lenticules in the facility was safe and feasible in vivo.

Methylphenidate actively induces emergence from general anesthesia.

BACKGROUND: Although accumulating evidence suggests that arousal pathways in the brain play important roles in emergence from general anesthesia, the roles of monoaminergic arousal circuits are unclear. In this study, the authors tested the hypothesis that methylphenidate (an inhibitor of dopamine and norepinephrine transporters) induces emergence from isoflurane general anesthesia. METHODS: Using adult rats, the authors tested the effect of intravenous methylphenidate on time to emergence from isoflurane general anesthesia. They then performed experiments to test separately for methylphenidate-induced changes in arousal and changes in minute ventilation. A dose-response study was performed to test for methylphenidate-induced restoration of righting during continuous isoflurane general anesthesia. Surface electroencephalogram recordings were performed to observe neurophysiological changes. Plethysmography recordings and arterial blood gas analysis were performed to assess methylphenidate-induced changes in respiratory function. Intravenous droperidol was administered to test for inhibition of methylphenidate's actions. RESULTS: Methylphenidate decreased median time to emergence from 280 to 91 s. The median difference in time to emergence without methylphenidate compared with administration of methylphenidate was 200 [155-331] s (median, [95% CI]). During continuous inhalation of isoflurane, methylphenidate induced return of righting in a dose-dependent manner, induced a shift in electroencephalogram power from delta (less than 4 Hz) to theta (4-8 Hz), and induced an increase in minute ventilation. Administration of intravenous droperidol (0.5 mg/kg) before intravenous methylphenidate (5 mg/kg) largely inhibited methylphenidate-induced emergence behavior, electroencephalogram changes, and changes in minute ventilation. CONCLUSIONS: Methylphenidate actively induces emergence from isoflurane general anesthesia by increasing arousal and respiratory drive, possibly through activation of dopaminergic and adrenergic arousal circuits. The authors' findings suggest that methylphenidate may be useful clinically as an agent to reverse general anesthetic-induced unconsciousness and respiratory depression at the end of surgery.

Prediction of a single Gaussian shape of spectral line measured with low-dispersion spectrometer by using machine learning.

We have developed a denoising autoencoder based neural network (NN) method to determine a spectral line intensity with an uncertainty lower than the uncertainty determined by fitting the spectral line. The NN method processes the measured raw spectral line shape, providing a single Gaussian shape based on the training dataset, which consists of synthetically prepared Doppler shift and broadening free spectral lines in the present work. It is found that the uncertainty reduction level significantly depends on the training dataset. Limitations originating from the training dataset are also discussed.

Infantile Hemangioma: An Updated Review.

BACKGROUND: Infantile hemangiomas are the most common vascular tumors of infancy, affecting up to 12% of infants by the first year of life. OBJECTIVE: To familiarize physicians with the natural history, clinical manifestations, diagnosis, and management of infantile hemangiomas. METHODS: A Pubmed search was conducted in November 2019 in Clinical Queries using the key term "infantile hemangioma". The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews published within the past 20 years. Only papers published in the English literature were included in this review. The information retrieved from the above search was used in the compilation of the present article. RESULTS: The majority of infantile hemangiomas are not present at birth. They often appear in the first few weeks of life as areas of pallor, followed by telangiectatic or faint red patches. Then, they grow rapidly in the first 3 to 6 months of life. Superficial lesions are bright red, protuberant, bosselated, or with a smooth surface, and sharply demarcated. Deep lesions are bluish and dome-shaped. Infantile hemangiomas continue to grow until 9 to 12 months of age, at which time the growth rate slows down to parallel the growth of the child. Involution typically begins by the time the child is a year old. Approximately 50% of infantile hemangiomas will show complete involution by the time a child reaches age 5; 70% will have disappeared by age 7; and 95% will have regressed by 10 to 12 years of age. The majority of infantile hemangiomas require no treatment. Treatment options include oral propranolol, topical timolol, and oral corticosteroids. Indications for active intervention include hemorrhage unresponsive to treatment, impending ulceration in areas where serious complications might ensue, interference with vital structures, life- or function-threatening complications, and significant disfigurement. CONCLUSION: Treatment should be individualized, depending upon the size, rate of growth, morphology, number, and location of the lesion (s), existing or potential complications, benefits and adverse events associated with the treatment, age of the patient, level of parental concern, and the physician's comfort level with the various treatment options. Currently, oral propranolol is the treatment of choice for high-risk and complicated infantile hemangiomas. Topical timolol may be considered for superficial infantile hemangiomas that need to be treated and for complicated infantile hemangiomas in patients at risk for severe adverse events from oral administration of propranolol.

Juvenile Dermatomyositis: Advances in Pathogenesis, Assessment, and Management.

BACKGROUND: Juvenile dermatomyositis is the most common inflammatory myopathy in the pediatric age group and a major cause of mortality and morbidity in individuals with childhood rheumatic diseases. Mounting evidence suggests that early diagnosis and timely aggressive treatment are associated with better outcomes. OBJECTIVE: The purpose of this article is to provide readers with an update on the evaluation, diagnosis, and the treatment of juvenile dermatomyositis. METHODS: A PubMed search was performed in Clinical Queries using the key term "juvenile dermatomyositis" in the search engine. The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. The search was restricted to English literature. The information retrieved from the above search was used in the compilation of the present article. RESULTS: Juvenile dermatomyositis is a chronic autoimmune inflammatory condition characterized by systemic capillary vasculopathy that primarily affects the skin and muscles with possible involvement of other organs. In 2017, the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) developed diagnostic criteria for juvenile idiopathic inflammatory myopathies and juvenile dermatomyositis. In the absence of muscle biopsies which are infrequently performed in children, scores (in brackets) are assigned to four variables related to muscle weakness, three variables related to skin manifestations, one variable related to other clinical manifestations, and two variables related to laboratory measurements to discriminate idiopathic inflammatory myopathies from non-idiopathic inflammatory myopathies as follows: objective symmetric weakness, usually progressive, of the proximal upper extremities (0.7); objective symmetric weakness, usually progressive, of the proximal lower extremities (0.8); neck flexors relatively weaker than neck extensors (1.9); leg proximal muscles relatively weaker than distal muscles (0.9); heliotrope rash (3.1); Gottron papules (2.1); Gottron sign (3.3); dysphagia or esophageal dysmotility (0.7); the presence of anti-Jo-1 autoantibody (3.9); and elevated serum levels of muscle enzymes (1.3). In the absence of muscle biopsy, a definite diagnosis of idiopathic inflammatory myopathy can be made if the total score is ≥7.5. Patients whose age at onset of symptoms is less than 18 years and who meet the above criteria for idiopathic inflammatory myopathy and have a heliotrope rash, Gottron papules or Gottron sign are deemed to have juvenile dermatomyositis. The mainstay of therapy at the time of diagnosis is a high-dose corticosteroid (oral or intravenous) in combination with methotrexate. CONCLUSION: For mild to moderate active muscle disease, early aggressive treatment with high-dose oral prednisone alone or in combination with methotrexate is the cornerstone of management. Pulse intravenous methylprednisolone is often preferred to oral prednisone in more severely affected patients, patients who respond poorly to oral prednisone, and those with gastrointestinal vasculopathy. Other steroid-sparing immunosuppressive agents such as cyclosporine and cyclophosphamide are reserved for patients with contraindications or intolerance to methotrexate and for refractory cases, as the use of these agents is associated with more adverse events. Various biological agents have been used in the treatment of juvenile dermatomyositis. Data on their efficacy are limited, and their use in the treatment of juvenile dermatomyositis is considered investigational.

Methylation of protocadherin 10, a novel tumor suppressor, is associated with poor prognosis in patients with gastric cancer.

BACKGROUND & AIMS: By using methylation-sensitive representational difference analysis, we identified protocadherin 10 (PCDH10), a gene that encodes a protocadherin and is silenced in a tumor-specific manner. We analyzed its epigenetic inactivation, biological effects, and prognostic significance in gastric cancer. METHODS: Methylation status was evaluated by combined bisulfite restriction analysis and bisulfite sequencing. The effects of PCDH10 re-expression were determined in growth, apoptosis, proliferation, and invasion assays. PCDH10 target genes were identified by complementary DNA microarray analysis. RESULTS: PCDH10 was silenced or down-regulated in 94% (16 of 17) of gastric cancer cell lines; expression levels were restored by exposure to demethylating agents. Re-expression of PCDH10 in MKN45 gastric cancer cells reduced colony formation in vitro and tumor growth in mice; it also inhibited cell proliferation (P < .01), induced cell apoptosis (P < .001), and repressed cell invasion (P < .05), up-regulating the pro-apoptosis genes Fas, Caspase 8, Jun, and CDKN1A; the antiproliferation gene FGFR; and the anti-invasion gene HTATIP2. PCDH10 methylation was detected in 82% (85 of 104) of gastric tumors compared with 37% (38 of 104) of paired nontumor tissues (P < .0001). In the latter, PCDH10 methylation was higher in precancerous lesions (27 of 45; 60%) than in chronic gastritis samples (11 of 59; 19%) (P < .0001). After a median follow-up period of 16.8 months, multivariate analysis revealed that patients with PCDH10 methylation in adjacent nontumor areas had a significant decrease in overall survival. Kaplan-Meier survival curves showed that PCDH10 methylation was associated significantly with shortened survival in stage I-III gastric cancer patients. CONCLUSIONS: PCDH10 is a gastric tumor suppressor; its methylation at early stages of gastric carcinogenesis is an independent prognostic factor.

Visualizing topical drug uptake with conventional fluorescence microscopy and deep learning.

Mapping the uptake of topical drugs and quantifying dermal pharmacokinetics (PK) presents numerous challenges. Though high resolution and high precision methods such as mass spectrometry offer the means to quantify drug concentration in tissue, these tools are complex and often expensive, limiting their use in routine experiments. For the many topical drugs that are naturally fluorescent, tracking fluorescence emission can be a means to gather critical PK parameters. However, skin autofluorescence can often overwhelm drug fluorescence signatures. Here we demonstrate the combination of standard epi-fluorescence imaging with deep learning for the visualization and quantification of fluorescent drugs in human skin. By training a U-Net convolutional neural network on a dataset of annotated images, drug uptake from both high "infinite" dose and daily clinical dose regimens can be measured and quantified. This approach has the potential to simplify routine topical product development in the laboratory.

Acute Hemorrhagic Edema of Infancy: A Diagnostic Challenge for the General Pediatrician.

BACKGROUND: Acute hemorrhagic edema of infancy (AHEI), a benign and self-limited disease, can be easily mistaken to be a number of diseases with similar dermatological manifestations but with potentially adverse outcomes. OBJECTIVE: This review aimed to familiarize pediatricians with the natural history, clinical manifestations, diagnosis, and management of AHEI. METHODS: A PubMed search was conducted in February 2020 in Clinical Queries using the key terms "acute hemorrhagic edema of infancy" OR "Finkelstein disease" OR "Seidlmayer disease". The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews published within the past 10 years. Only papers published in the English literature were included in this review. The information retrieved from the above search was used in the compilation of the present article. RESULTS: AHEI, a rare cutaneous leukocytoclastic small-vessel vasculitis, typically presents with palpable purpura, peripheral acral edema, and frequently with fever, most often in children between 4 and 24 months of age. A significant number of children experience prodromal symptoms of an upper respiratory infection. Fever is typically low grade and is present in approximately 50% of cases. The cutaneous lesions are characterized by rapid onset of small erythematous macules or papules that progress to well demarcated, annular, rosette, medallion-like, or targetoid purpuric plaques or ecchymosis in 24 to 48 hours. The skin lesions are typically palpable, nonpruritic, and symmetrically distributed. Sites of predilection include the face, auricles, and extremities. Edema is typically nonpitting and asymmetrical and occurs primarily on the dorsum of the hands and feet, the face, and the auricles. In spite of the acuteness and extent of the cutaneous findings, the child looks well and nontoxic. Systemic and/or visceral involvement are rare. The differential diagnosis is broad and includes, among others, Henoch-Schönlein purpura. It is crucial to distinguish AHEI from the other diseases since the management of these diseases is quite different. The clinical features of mimickers of AHEI are reviewed and clues to differentiate AHEI from these mimickers are highlighted..AHEI is a benign, self-limited disease with complete spontaneous recovery in one to three weeks in the majority of cases. CONCLUSION: Recognizing this rare disease is important for the pediatrician to rapidly differentiate AHEI from other potentially serious diseases that require prompt therapy and monitoring. With rapid recognition of AHEI, unnecessary investigations and inappropriate interventions can be prevented and parental anxiety can be avoided.

Scabies: A Neglected Global Disease.

BACKGROUND: Scabies is a skin disease caused by an obligate human parasite mite Sarcoptes scabiei var. hominis. Children under the age of two and elderly individuals are at the greatest risk. Knowledge of this condition is important for an early diagnosis to be made and treatment to be initiated. OBJECTIVE: The review aimed to familiarize physicians with the clinical manifestations, diagnosis, evaluation, and management of scabies. METHODS: A search was conducted using Pubmed with the built-in "Clinical Queries" tool. The search term "Scabies" was used. The categories of "epidemiology", "diagnosis", "therapy", "prevention" and "prognosis" had a limited scope for primary clinical studies. Meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews were included. Only papers published in the English language were included. A descriptive, narrative synthesis was provided of the retrieved articles. RESULTS: Worldwide, scabies affects 200 to 300 million individuals annually. The average prevalence is estimated to be 5 to 10% in children of developing countries. Transmission usually occurs after close prolonged skin-to-skin contact. Classic scabies is characterized by an erythematous papular eruption, serpiginous burrows, and intense pruritus. Sites of predilection include the webs of the fingers, volar wrists, lateral aspects of fingers, extensor surfaces of elbows and knees, waist, navel, abdomen, buttocks, groins, and, genitals. A clinical diagnosis of classic scabies can be made on the basis of the history and clinical findings. Other clinical variants include crusted scabies, nodular scabies, and bullous scabies. Finding the mite, ova, or fecal pellets on microscopic examination of scrapings taken from skin lesions confirms the diagnosis of scabies infestation. For eradication of scabies mites, the drugs of choice are topical permethrin and oral ivermectin. CONCLUSION: Scabies is a highly contagious parasitic cutaneous disease that is stigmatising and debilitating. Increased awareness, accurate diagnosis, and prompt treatment are essential for the effective control of scabies and for the prevention of the spread of the disease.

Time-resolved fluorescence microscopy with phasor analysis for visualizing multicomponent topical drug distribution within human skin.

Understanding a drug candidate's pharmacokinetic (PK) parameters is a challenging but essential aspect of drug development. Investigating the penetration and distribution of a topical drug's active pharmaceutical ingredient (API) allows for evaluating drug delivery and efficacy, which is necessary to ensure drug viability. A topical gel (BPX-05) was recently developed to treat moderate to severe acne vulgaris by directly delivering the combination of the topical antibiotic minocycline and the retinoid tazarotene to the pilosebaceous unit of the dermis. In order to evaluate the uptake of APIs within human facial skin and confirm accurate drug delivery, a selective visualization method to monitor and quantify local drug distributions within the skin was developed. This approach uses fluorescence lifetime imaging microscopy (FLIM) paired with a multicomponent phasor analysis algorithm to visualize drug localization. As minocycline and tazarotene have distinct fluorescence lifetimes from the lifetime of the skin's autofluorescence, these two APIs are viable targets for distinct visualization via FLIM. Here, we demonstrate that the analysis of the resulting FLIM output can be used to determine local distributions of minocycline and tazarotene within the skin. This approach is generalizable and can be applied to many multicomponent fluorescence lifetime imaging targets that require cellular resolution and molecular specificity.

Tinea Capitis: An Updated Review.

BACKGROUND: Tinea capitis is a common and, at times, difficult to treat, fungal infection of the scalp. OBJECTIVE: This article aimed to provide an update on the evaluation, diagnosis, and treatment of tinea capitis. METHODS: A PubMed search was performed in Clinical Queries using the key term "tinea capitis". The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. The search was restricted to English literature. The information retrieved from the above search was used in the compilation of the present article. Patents were searched using the key term "tinea capitis" at www.freepatentsonline.com. RESULTS: Tinea capitis is most often caused by Trichophyton tonsurans and Microsporum canis. The peak incidence is between 3 and 7 years of age. Non-inflammatory tinea capitis typically presents as fine scaling with single or multiple scaly patches of circular alopecia (grey patches); diffuse or patchy, fine, white, adherent scaling of the scalp resembling generalized dandruff with subtle hair loss; or single or multiple patches of well-demarcated area (s) of alopecia with fine-scale, studded with broken-off hairs at the scalp surface, resulting in the appearance of "black dots". Inflammatory variants of tinea capitis include kerion and favus. Dermoscopy is a highly sensitive tool for the diagnosis of tinea capitis. The diagnosis can be confirmed by direct microscopic examination with a potassium hydroxide wetmount preparation and fungal culture. It is desirable to have mycologic confirmation of tinea capitis before beginning a treatment regimen. Oral antifungal therapy (terbinafine, griseofulvin, itraconazole, and fluconazole) is considered the gold standard for tinea capitis. Recent patents related to the management of tinea capitis are also discussed. CONCLUSION: Tinea capitis requires systemic antifungal treatment. Although topical antifungal therapies have minimal adverse events, topical antifungal agents alone are not recommended for the treatment of tinea capitis because these agents do not penetrate the root of the hair follicles deep within the dermis. Topical antifungal therapy, however, can be used to reduce transmission of spores and can be used as adjuvant therapy to systemic antifungals. Combined therapy with topical and oral antifungals may increase the cure rate.

Imaging and quantifying drug delivery in skin - Part 1: Autoradiography and mass spectrometry imaging.

In this two-part review we present an up-to-date description of different imaging methods available to map the localization of drugs on skin as a complement of established ex-vivo absorption studies. This first part deals with invasive methods which are grouped in two classes according to their underlying principles: i) methods using radioactivity such as autoradiography and ii) mass spectrometry methods such as MALDI and SIMS. For each method, a description of the principle is given along with example applications of imaging and quantifying drug delivery in human skin. Thanks to these techniques a better assessment of the fate of drugs is obtained: its localization on a particular skin structure, its potential accumulation, etc. A critical comparison in terms of capabilities, sensitivity and practical applicability is included that will help the reader to select the most appropriate technique depending on the particular problem to be solved.

Onychomycosis: An Updated Review.

BACKGROUND: Onychomycosis is a common fungal infection of the nail. OBJECTIVE: The study aimed to provide an update on the evaluation, diagnosis, and treatment of onychomycosis. METHODS: A PubMed search was completed in Clinical Queries using the key term "onychomycosis". The search was conducted in May 2019. The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews published within the past 20 years. The search was restricted to English literature. Patents were searched using the key term "onychomycosis" in www.freepatentsonline.com. RESULTS: Onychomycosis is a fungal infection of the nail unit. Approximately 90% of toenail and 75% of fingernail onychomycosis are caused by dermatophytes, notably Trichophyton mentagrophytes and Trichophyton rubrum. Clinical manifestations include discoloration of the nail, subungual hyperkeratosis, onycholysis, and onychauxis. The diagnosis can be confirmed by direct microscopic examination with a potassium hydroxide wet-mount preparation, histopathologic examination of the trimmed affected nail plate with a periodic-acid-Schiff stain, fungal culture, or polymerase chain reaction assays. Laboratory confirmation of onychomycosis before beginning a treatment regimen should be considered. Currently, oral terbinafine is the treatment of choice, followed by oral itraconazole. In general, topical monotherapy can be considered for mild to moderate onychomycosis and is a therapeutic option when oral antifungal agents are contraindicated or cannot be tolerated. Recent patents related to the management of onychomycosis are also discussed. CONCLUSION: Oral antifungal therapies are effective, but significant adverse effects limit their use. Although topical antifungal therapies have minimal adverse events, they are less effective than oral antifungal therapies, due to poor nail penetration. Therefore, there is a need for exploring more effective and/or alternative treatment modalities for the treatment of onychomycosis which are safer and more effective.