A case report of terbinafine-induced acute generalized exanthematous pustulosis in a striking photodistributed pattern.

Acute generalized exanthematous pustulosis is a rare severe cutaneous adverse reaction that classically presents in intertriginous or flexural areas and subsequently spreads diffusely across the trunk and extremities. To date, few cases of acute generalized exanthematous pustulosis arising in a photodistributed pattern are documented. Herein, we describe the second known case of photodistributed generalized exanthematous pustulosis arising in association with oral terbinafine use, providing a summary of the previously documented cases along with exploration of the potential pathophysiological mechanisms for this cutaneous reaction.

Large area fractional laser treatment of mouse skin increases energy expenditure.

Fractional laser (FL) treatment is a common dermatologic procedure that generates arrays of microscopic treatment zones separated by intact tissue, promoting fast wound healing. Using a mouse model, we introduced a large area fractional laser treatment (LAFLT) method to study metabolic effects. Using two laser modalities, ablative FL (AFL) and non-ablative FL (NAFL), and exposing different percentages of mice's total body surface area (TBSA), we followed changes in metabolic parameters in real time using metabolic cages. Additionally, body composition, markers of inflammation, neurohormonal signaling, and browning of adipocytes were investigated. LAFLT, especially in high TBSA groups, had specific metabolic effects such as significantly increased average daily energy expenditure, increased fat mass loss, systemic browning of adipocytes, and inflammatory states, without compromising other organs. The ability of LAFLT to stimulate metabolism in a controlled way could develop into a promising therapeutic treatment to induce positive metabolic changes that replace or augment systemic drugs.

Photoprotective measures among adolescents stratified by region: An analysis utilizing the National College Health Assessment.

BACKGROUND/PURPOSE: Exposure to sunlight has been shown to cause pigmentary alterations, photoaging and photocarcinogenesis. Understanding photoprotective patterns in adolescent populations is beneficial to public health initiatives. We utilized data provided by the American College Health Association's National College Health Assessment to evaluate photoprotective behaviors among adolescent populations. METHODS: Behavioral questions related to photoprotection were analyzed from the American College Health Association (ACHA) National College Health Assessment (NCHA) (Version III). RESULTS: When comparing races, Black/African American respondents had the lowest association of practicing photoprotective behaviors in comparison to white respondents (p < .05). When comparing US geographic regions, the south had the lowest association of photoprotective measures (p < .05). LIMITATIONS: The response rate of each institution varied, although there was still a large quantity of respondents. Finally, we cannot discern the specific reasoning for adolescent populations not using sunscreen. CONCLUSION: These data identify demographics where efforts to enhance education on photoprotective behaviors, specifically among skin of color and southern population, to support public health initiatives.

Systematic Review of Photodynamic Therapy in Gliomas.

Over the last 20 years, gliomas have made up over 89% of malignant CNS tumor cases in the American population (NIH SEER). Within this, glioblastoma is the most common subtype, comprising 57% of all glioma cases. Being highly aggressive, this deadly disease is known for its high genetic and phenotypic heterogeneity, rendering a complicated disease course. The current standard of care consists of maximally safe tumor resection concurrent with chemoradiotherapy. However, despite advances in technology and therapeutic modalities, rates of disease recurrence are still high and survivability remains low. Given the delicate nature of the tumor location, remaining margins following resection often initiate disease recurrence. Photodynamic therapy (PDT) is a therapeutic modality that, following the administration of a non-toxic photosensitizer, induces tumor-specific anti-cancer effects after localized, wavelength-specific illumination. Its effect against malignant glioma has been studied extensively over the last 30 years, in pre-clinical and clinical trials. Here, we provide a comprehensive review of the three generations of photosensitizers alongside their mechanisms of action, limitations, and future directions.

5-Aminolevulinic acid photodynamic therapy versus minocycline for moderate-to-severe rosacea: A single-center, randomized, evaluator-blind controlled study.

BACKGROUND: 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) showed potential to treat rosacea according to recent studies; however, a lack of clinical evidence and unclear adverse effects limit its use. OBJECTIVE: To compare the effect of ALA-PDT vs minocycline on rosacea. METHODS: In this single-center, randomized, evaluator-blind, controlled study, patients with moderate-to-severe rosacea were allocated to receive 3 to 5 sessions of ALA-PDT or 8 weeks of 100 mg daily minocycline treatment, followed by a 24-week follow-up. RESULTS: Of all the 44 randomized patients, 41 received complete treatment (ALA-PDT: 20 and minocycline: 21 patients). At the end of treatment, ALA-PDT showed noninferior improvement of papulopustular lesions and Rosacea-specific Quality of Life compared with minocycline (median reduction of lesion count: 19 vs 22, median change of Rosacea-specific Quality of Life score: 0.48 vs 0.53). The Clinician's Erythema Assessment success of ALA-PDT was lower than that of minocycline's (35% vs 67%). Demodex density and relapse rate were comparable in both groups. Erythema, mild pain, and exudation were the most common adverse reactions of ALA-PDT. LIMITATIONS: Limited sample size restricted us from drawing further conclusions. CONCLUSION: As minocycline does, ALA-PDT can improve rosacea mainly in papulopustular lesions and patients' quality of life, indicating a new option for rosacea.

Photodynamic and Photothermal Therapies: Synergy Opportunities for Nanomedicine.

Tumoricidal photodynamic (PDT) and photothermal (PTT) therapies harness light to eliminate cancer cells with spatiotemporal precision by either generating reactive oxygen species or increasing temperature. Great strides have been made in understanding biological effects of PDT and PTT at the cellular, vascular and tumor microenvironmental levels, as well as translating both modalities in the clinic. Emerging evidence suggests that PDT and PTT may synergize due to their different mechanisms of action, and their nonoverlapping toxicity profiles make such combination potentially efficacious. Moreover, PDT/PTT combinations have gained momentum in recent years due to the development of multimodal nanoplatforms that simultaneously incorporate photodynamically- and photothermally active agents. In this review, we discuss how combining PDT and PTT can address the limitations of each modality alone and enhance treatment safety and efficacy. We provide an overview of recent literature featuring dual PDT/PTT nanoparticles and analyze the strengths and limitations of various nanoparticle design strategies. We also detail how treatment sequence and dose may affect cellular states, tumor pathophysiology and drug delivery, ultimately shaping the treatment response. Lastly, we analyze common experimental design pitfalls that complicate preclinical assessment of PDT/PTT combinations and propose rational guidelines to elucidate the mechanisms underlying PDT/PTT interactions.

All-natural-molecule, bioluminescent photodynamic therapy results in complete tumor regression and prevents metastasis.

Self-luminescent photodynamic therapy (PDT) has gained attention owing to its potential to enable effective phototherapy without the bottleneck of shallow light penetration into tissues. However, the biosafety concerns and low cytotoxic effect of self-luminescent reagents in vivo have been problems. Here, we demonstrate efficacious bioluminescence (BL)-PDT by using bioluminescence resonance energy transfer (BRET) conjugates of a clinically approved photosensitizer, Chlorin e6, and a luciferase, Renilla reniformis; both derived from biocompatible, natural molecules. With over 80% biophoton utilization efficiency and membrane-fusion liposome-assisted intracellular delivery, these conjugates produce effective, targeted cancer cell killing. Specifically, in an orthotopic mouse model of 4T1 triple-negative breast cancer, BL-PDT showed strong therapeutic effects on large primary tumors and a neoadjuvant outcome in invasive tumors. Furthermore, BL-PDT resulted in complete tumor remission and prevention of metastasis for early-stage tumors. Our results demonstrate the promise of molecularly-activated, clinically viable, depth-unlimited phototherapy.

Photobiomodulation in Alzheimer's Disease-A Complementary Method to State-of-the-Art Pharmaceutical Formulations and Nanomedicine?

Alzheimer's disease (AD), as a neurodegenerative disorder, usually develops slowly but gradually worsens. It accounts for approximately 70% of dementia cases worldwide, and is recognized by WHO as a public health priority. Being a multifactorial disease, the origins of AD are not satisfactorily understood. Despite huge medical expenditures and attempts to discover new pharmaceuticals or nanomedicines in recent years, there is no cure for AD and not many successful treatments are available. The current review supports introspection on the latest scientific results from the specialized literature regarding the molecular and cellular mechanisms of brain photobiomodulation, as a complementary method with implications in AD. State-of-the-art pharmaceutical formulations, development of new nanoscale materials, bionanoformulations in current applications and perspectives in AD are highlighted. Another goal of this review was to discover and to speed transition to completely new paradigms for the multi-target management of AD, to facilitate brain remodeling through new therapeutic models and high-tech medical applications with light or lasers in the integrative nanomedicine of the future. In conclusion, new insights from this interdisciplinary approach, including the latest results from photobiomodulation (PBM) applied in human clinical trials, combined with the latest nanoscale drug delivery systems to easily overcome protective brain barriers, could open new avenues to rejuvenate our central nervous system, the most fascinating and complex organ. Picosecond transcranial laser stimulation could be successfully used to cross the blood-brain barrier together with the latest nanotechnologies, nanomedicines and drug delivery systems in AD therapy. Original, smart and targeted multifunctional solutions and new nanodrugs may soon be developed to treat AD.

Fast inactivation of coronavirus in filtering-facepiece respirators in a reflective cylindrical UV-C chamber.

Objective: We report on the development and characterization of a UV-C (λ  =  200 - 280 nm, λpeak = 254 nm) chamber designed for the rapid disinfection of N95 class filtering-facepiece respirators contaminated with SARS-CoV-2 coronaviruses. The device was evaluated against Betacoronavirus strain MHV-3 and its virucidal capacity was evaluated as a function of different applied UV-C doses (UV-C exposure times of 60 s, 120 s, 180 s, and 240 s) using two types of respirators geometry (shell and two-panel shapes, 3M 8801 H and 9920 H, respectively), at eight points of the respirators. Background: Most chemical disinfection methods are not recommended for N95 masks. UV-C light provided by UVGI lamps (254 nm) is an effective physical agent against viruses and bacteria due to direct photochemical harming effect on DNA/RNA, and can provide rapid disinfection for personal protective equipment such as N95/PFF2 masks. Results: The device reached a mean elimination rate of 99.9999% of MHV-3 inoculated into all the assessed different points on the tested PFF2 respirator models in a UV-C cycle of just 60 s. Statistical analysis performed through Person´s chi-square test showed no correlation between the viral infectivity reduction and the viral inoculation point (p = 0.512) and the tested respirator models (p = 0.556). However, a correlation was found between the exposure time and the viral infectivity reduction (p = 0.000*), between UV-C and no UV-C exposure. All the tested UV-C exposure times (60 s, 120 s, 180 s, and 240 s) provided the same reduction in infection rates. Therefore, 60 s was confirmed as the minimum exposure time to achieve a 99.9999% or 6 Log reduction in MHV-3 coronavirus infection rates in the PFF2 samples tested in the device. Conclusions: We conclude that the assessed UV-C chamber for the inactivation of MHV-3 coronavirus in N95/PFF2 standard masks can be a promising tool for effective and rapid disinfection of coronaviruses, including SARS-CoV-2 virus.

Wearable Photomedicine for Neonatal Jaundice Treatment Using Blue Organic Light-Emitting Diodes (OLEDs): Toward Textile-Based Wearable Phototherapeutics.

Neonatal jaundice is a very common disease in newborns and can lead to brain damage or death in severe cases. Phototherapy with light-emitting diode (LED) arrays is widely used as the easiest and fastest way to relieve jaundice in newborns, but it has distinct disadvantages such as loss of water in the patient, damage to the retina, and separation from parents. In this paper, a novel light source-based phototherapy for neonatal jaundice is proposed using a textile-based wearable organic light-emitting diode (OLED) platform that can move flexibly and conform to the curvature of the human body. The soft and flexible textile-based blue OLED platform is designed to have a peak wavelength of 470 nm, suitable for jaundice treatment, and shows performance (>20 µW cm-2 nm- 1 ) suitable for intensive jaundice treatment even at low voltage (<4.0 V). The textile-based OLEDs fabricated in this study exhibit an operating reliability of over 100 h and low-temperature operation (<35 °C). The results of an in vitro jaundice treatment test using a large-area blue OLED confirm that the bilirubin level decreases to 12 mg dL-1 with 3 h of OLED irradiation.

Optical control of the ß2-adrenergic receptor with opto-prop-2: A cis-active azobenzene analog of propranolol.

In this study, we synthesized and evaluated new photoswitchable ligands for the beta-adrenergic receptors ß1-AR and ß2-AR, applying an azologization strategy to the first-generation beta-blocker propranolol. The resulting compounds (Opto-prop-1, -2, -3) have good photochemical properties with high levels of light-induced trans-cis isomerization (>94%) and good thermal stability (t 1/2 > 10 days) of the resulting cis-isomer in an aqueous buffer. Upon illumination with 360-nm light to PSS cis , large differences in binding affinities were observed for photoswitchable compounds at ß1-AR as well as ß2-AR. Notably, Opto-prop-2 (VUF17062) showed one of the largest optical shifts in binding affinities at the ß2-AR (587-fold, cis-active), as recorded so far for photoswitches of G protein-coupled receptors. We finally show the broad utility of Opto-prop-2 as a light-dependent competitive antagonist of the ß2-AR as shown with a conformational ß2-AR sensor, by the recruitment of downstream effector proteins and functional modulation of isolated adult rat cardiomyocytes.

Upconversion nanomaterials and delivery systems for smart photonic medicines and healthcare devices.

In the past decade, upconversion (UC) nanomaterials have been extensively investigated for the applications to photomedicines with their unique features including biocompatibility, near-infrared (NIR) to visible conversion, photostability, controllable emission bands, and facile multi-functionality. These characteristics of UC nanomaterials enable versatile light delivery for deep tissue biophotonic applications. Among various stimuli-responsive delivery systems, the light-responsive delivery process has been greatly advantageous to develop spatiotemporally controllable on-demand "smart" photonic medicines. UC nanomaterials are classified largely to two groups depending on the photon UC pathway and compositions: inorganic lanthanide-doped UC nanoparticles and organic triplet-triplet annihilation UC (TTA-UC) nanomaterials. Here, we review the current-state-of-art inorganic and organic UC nanomaterials for photo-medicinal applications including photothermal therapy (PTT), photodynamic therapy (PDT), photo-triggered chemo and gene therapy, multimodal immunotherapy, NIR mediated neuromodulations, and photochemical tissue bonding (PTB). We also discuss the future research direction of this field and the challenges for further clinical development.

Efficacy and hazards of 425 nm oral cavity light dosing to inactivate SARS-CoV-2.

OBJECTIVE: Using a battery of preclinical tests to support development of a light-based treatment for COVID-19, establish a range of 425 nm light doses that are non-hazardous to the tissues of the oral cavity and assess whether a 425 nm light dose in this non-hazardous range can inactivate SARS-CoV-2 in artificial saliva. METHODS: The potential hazards to oral tissues associated with a range of acute 425 nm light doses were assessed using a battery of four preclinical tests: (1) cytotoxicity, using well-differentiated human large airway and buccal epithelial models; (2) toxicity to commensal oral bacteria, using a panel of model organisms; (3) light-induced histopathological changes, using ex vivo porcine esophageal tissue, and (4) thermal damage, by dosing the oropharynx of intact porcine head specimens. Then, 425 nm light doses established as non-hazardous using these tests were evaluated for their potential to inactivate SARS-CoV-2 in artificial saliva. RESULTS: A dose range was established at which 425 nm light is not cytotoxic in well-differentiated human large airway or buccal epithelial models, is not cytotoxic to a panel of commensal oral bacteria, does not induce histopathological damage in ex vivo porcine esophageal tissue, and does not induce thermal damage to the oropharynx of intact porcine head specimens. Using these tests, no hazards were observed for 425 nm light doses less than 63 J/cm2 delivered at irradiance less than 200 mW/cm2. A non-hazardous 425 nm light dose in this range (30 J/cm2 at 50 mW/cm2) was shown to inactivate SARS-CoV-2 in vitro in artificial saliva. CONCLUSION: Preclinical hazard assessments and SARS-CoV-2 inactivation efficacy testing were combined to guide the development of a 425 nm light-based treatment for COVID-19. CLINICAL SIGNIFICANCE: The process used here to evaluate the potential hazards associated with 425 nm acute light dosing of the oral cavity to treat COVID-19 can be extended to other wavelengths, anatomical targets, and therapeutic applications to accelerate the development of novel photomedicine treatments.

Innovative light sources for phototherapy.

The use of light for therapeutic purposes dates back to ancient Egypt, where the sun itself was an innovative source, probably used for the first time to heal skin diseases. Since then, technical innovation and advancement in medical sciences have produced newer and more sophisticated solutions for light-emitting sources and their applications in medicine. Starting from a brief historical introduction, the concept of innovation in light sources is discussed and analysed, first from a technical point of view and then in the light of their fitness to improve existing therapeutic protocols or propose new ones. If it is true that a "pure" technical advancement is a good reason for innovation, only a sub-system of those advancements is innovative for phototherapy. To illustrate this concept, the most representative examples of innovative light sources are presented and discussed, both from a technical point of view and from the perspective of their diffusion and applications in the clinical field.

Photomedicine based on heme-derived compounds.

Photoimaging and phototherapy have become major platforms for the diagnosis and treatment of various health complications. These applications require a photosensitizer (PS) that is capable of absorbing light from a source and converting it into other energy forms for detection and therapy. While synthetic inorganic materials such as quantum dots and gold nanorods have been widely explored for their medical diagnosis and photodynamic (PDT) and photothermal (PTT) therapy capabilities, translation of these technologies has lagged, primarily owing to potential cytotoxicity and immunogenicity issues. Of the various photoreactive molecules, the naturally occurring endogenous compound heme, a constituent of red blood cells, and its derivatives, porphyrin, biliverdin and bilirubin, have shown immense potential as noteworthy candidates for clinically translatable photoreactive agents, as evidenced by previous reports. While porphyrin-based photomedicines have attracted significant attention and are well documented, research on photomedicines based on two other heme-derived compounds, biliverdin and bilirubin, has been relatively lacking. In this review, we summarize the unique photoproperties of heme-derived compounds and outline recent efforts to use them in biomedical imaging and phototherapy applications.

Photodynamic Therapy for Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal of human cancers. Clinical trials of various chemotherapy, radiotherapy, targeted agents and combination strategies have generally failed to provide meaningful improvement in survival for patients with unresectable disease. Photodynamic therapy (PDT) is a photochemistry-based approach that enables selective cell killing using tumor-localizing agents activated by visible or near-infrared light. In recent years, clinical studies have demonstrated the technical feasibility of PDT for patients with locally advanced PDAC while a growing body of preclinical literature has shown that PDT can overcome drug resistance and target problematic and aggressive disease. Emerging evidence also suggests the ability of PDT to target PDAC stroma, which is known to act as both a barrier to drug delivery and a tumor-promoting signaling partner. Here, we review the literature which indicates an emergent role of PDT in clinical management of PDAC, including the potential for combination with other targeted agents and RNA medicine.

Dynamic nanoassemblies of nanomaterials for cancer photomedicine.

Photomedicine has long been used for treating cancerous diseases. With advances in chemical and material sciences, various types of light-activated photosensitizers (PSs) have been developed for effective photodynamic therapy (PDT) and photothermal therapy (PTT). However, conventional organic/inorganic materials-based PSs lack disease recognition capability and show limited therapeutic effects in addition to side effects. Recently, intelligent dynamic nanoassemblies that are activated in a tumor environment have been extensively researched to target diseased tissues more effectively, for increasing therapeutic effectiveness while minimizing side effects. This paper presents the latest dynamic nanoassemblies for effective PDT or PTT and combination phototherapies, including immunotherapy and image-guided therapy. Dynamic self-assembly exhibits great potential for clinical translation in diagnosis and treatment through its integrated versatility. Nanoassemblies based on multidisciplinary technology are a promising technique for treating incurable cancerous diseases in the future.

Engineering Hydrogel-Based Biomedical Photonics: Design, Fabrication, and Applications.

Light guiding and manipulation in photonics have become ubiquitous in events ranging from everyday communications to complex robotics and nanomedicine. The speed and sensitivity of light-matter interactions offer unprecedented advantages in biomedical optics, data transmission, photomedicine, and detection of multi-scale phenomena. Recently, hydrogels have emerged as a promising candidate for interfacing photonics and bioengineering by combining their light-guiding properties with live tissue compatibility in optical, chemical, physiological, and mechanical dimensions. Herein, the latest progress over hydrogel photonics and its applications in guidance and manipulation of light is reviewed. Physics of guiding light through hydrogels and living tissues, and existing technical challenges in translating these tools into biomedical settings are discussed. A comprehensive and thorough overview of materials, fabrication protocols, and design architectures used in hydrogel photonics is provided. Finally, recent examples of applying structures such as hydrogel optical fibers, living photonic constructs, and their use as light-driven hydrogel robots, photomedicine tools, and organ-on-a-chip models are described. By providing a critical and selective evaluation of the field's status, this work sets a foundation for the next generation of hydrogel photonic research.

Optical Waveguides and Integrated Optical Devices for Medical Diagnosis, Health Monitoring and Light Therapies.

Optical waveguides and integrated optical devices are promising solutions for many applications, such as medical diagnosis, health monitoring and light therapies. Despite the many existing reviews focusing on the materials that these devices are made from, a systematic review that relates these devices to the various materials, fabrication processes, sensing methods and medical applications is still seldom seen. This work is intended to link these multidisciplinary fields, and to provide a comprehensive review of the recent advances of these devices. Firstly, the optical and mechanical properties of optical waveguides based on glass, polymers and heterogeneous materials and fabricated via various processes are thoroughly discussed, together with their applications for medical purposes. Then, the fabrication processes and medical implementations of integrated passive and active optical devices with sensing modules are introduced, which can be used in many medical fields such as drug delivery and cardiovascular healthcare. Thirdly, wearable optical sensing devices based on light sensing methods such as colorimetry, fluorescence and luminescence are discussed. Additionally, the wearable optical devices for light therapies are introduced. The review concludes with a comprehensive summary of these optical devices, in terms of their forms, materials, light sources and applications.

Development of Folic Acid-Conjugated and Methylene Blue-Adsorbed Au@TNA Nanoparticles for Enhanced Photodynamic Therapy of Bladder Cancer Cells.

Photodynamic therapy (PDT) is a promising treatment for malignancy. However, the low molecular solubility of photosensitizers (PSs) with a low accumulation at borderline malignant potential lesions results in the tardy and ineffective management of recurrent urothelial carcinoma. Herein, we used tannic acid (TNA), a green precursor, to reduce HAuCl4 in order to generate Au@TNA core-shell nanoparticles. The photosensitizer methylene blue (MB) was subsequently adsorbed onto the surface of the Au@TNA nanoparticles, leading to the incorporation of a PS within the organic shell of the Au nanoparticle nanosupport, denoted as Au@TNA@MB nanoparticles (NPs). By modifying the surface of the Au@TNA@MB NPs with the ligand folate acid (FA) using NH2-PEG-NH2 as a linker, we demonstrated that the targeted delivery strategy achieved a high accumulation of PSs in cancer cells. The cell viability of T24 cells decreased to 87.1%, 57.1%, and 26.6% upon treatment with 10 ppm[Au] Au@TNA/MB NPs after 45 min, 2 h, and 4 h of incubation, respectively. We also applied the same targeted PDT treatment to normal urothelial SV-HUC-1 cells and observed minor phototoxicity, indicating that this safe photomedicine shows promise for applications aiming to achieve the local depletion of cancer sites without side effects.