Light Exposure Dose Research Articles

Exposure dose, light distribution and wavelength affect the fate of introduced bacterial biological control agents in the phyllosphere of greenhouse grown tomato

Societal Impact StatementThe use of chemical plant protection products must be reduced to promote sustainability in food production. One possible alternative is biological control agents (BCAs), but their efficacy under commercial conditions does not always reach the standard of chemical control agents. Previously, light has been found to induce mechanisms in bacterial BCAs that can affect their distribution and establishment. This could promote BCA efficacy. We looked into how monochromatic and polychromatic (which is what growers use) light treatments affected the occurrence of three BCAs post‐application. By combining two non‐chemical methods: a biological (BCA) and a cultural (light) control method, this offers a new integrated pest control strategy.Summary The dynamics and functionality of beneficial and non‐beneficial, non‐phototrophic bacteria can be influenced by light quality. We investigated if light could aid the survival of three bacterial biological control agents (BCAs; Bacillus amyloliquefaciens DSM7, Pseudomonas chlororaphis 50083 and Streptomyces griseoviridis CBS904.68) in the canopy of greenhouse‐grown tomatoes at four light treatments. Tomato plants were exposed to 50 μmol m−2 s−1 of either polychromatic light (white) or monochromatic light (blue: 420 nm, green: 530 nm and red: 660 nm) using DYNA LED lamps for a total of 48 h post foliar application of the BCAs. Leaves were harvested from two levels in the canopy at the top and middle of each plant at 0, 2, 4, 8, 12, 24 and 48 h post inoculation. The occurrences of the BCAs were quantified by plate count and droplet digital PCR (ddPCR). S. griseoviridis persisted under most treatments, whereas P. chlororaphis and B. amyloliquefaciens preferred the polychromatic and green light treatments as depicted by the viable count analyses. Significant differences between the DNA and cDNA concentrations were only noted for P. chlororaphis, with prominent wavelength effects. Light exposure dose, placement in the canopy and wavelength were found to be decisive factors for BCA re‐isolation, indicating that they have different optimal light environments.

Conjugated Polymer-Based Photo-Crosslinker for Efficient Photo-Patterning of Polymer Semiconductors.

Photo-patterning of polymer semiconductors using photo-crosslinkers has shown potential for organic circuit fabrication via solution processing techniques. However, the performance of patterning, including resolution (R), UV light exposure dose, sensitivity (S), and contrast (γ), remains unsatisfactory. In this study, a novel conjugated polymer based photo-crosslinker (PN3, Figure 1a) is reported for the first time, which entails phenyl-substituted azide groups in its side chains. Due to the potential π-π interactions between the conjugated backbone of PN3 and those of polymer semiconductors, PN3 exhibits superior miscibility with polymer semiconductors compared to the commonly used small molecule photo-crosslinker 4Bx (Figure 1a). Consequently, photo-patterning of polymer semiconductors with PN3 demonstrates improved performance with much lower UV light exposure dose, higher S and higher γ compared to 4Bx. By utilizing electron beam lithography, patterned arrays of polymer semiconductors with resolutions down to 500nm and clearer edges are successfully fabricated using PN3. Furthermore, patterned arrays of PDPP4T, the p-type semiconductor (Figure 1b), after being doped, can function as source-drain electrodes for fabricating field-effect transistors (FETs) with comparable charge mobility and significantly lower sub-threshold swing value compared to those with gold electrodes.

Evaluating the Potential of Green Light Exposure on Nociception-A Mini Review.

The capacity of animals to react to unpleasant stimuli that might endanger their integrity is known as nociception. Pharmacological treatments do not show satisfactory results in response to nociception. In the recent era, light therapy emerged as a potential non-pharmacological approach for treating various diseases, including seasonal affective disorders, migraine, pain, and others. Evaluating the potential of green light exposure on nociception involves studying its effects on different types of pain and pain-related conditions and determining the optimal exposure methods. This review provides the beneficial effects of green light on the reduction in the frequency of pain. The green light exposure on nociception changes the activity of pain-related genes and proteins in cells. This review could provide insights into the underlying mechanisms by which green light modulates pain. Overall, evaluating the potential of green light exposure on nociception requires a multidisciplinary approach and should consider the safety, efficacy, optimal dose, and duration of green light exposure and the type of pain. However, few studies have been reported so far; therefore, light therapy for treating migraines require more studies on animal models to provide precise results of light effects on nociception.

Photodegradation of poly(ether-b-amide) catalyzed by bismuth radiopaque additive

Bismuth compounds (e.g., bismuth subcarbonate and bismuth oxychloride) are often used as radiopaque additives in poly(ether-b-amide) (PEBA) for medical catheter applications to enhance the visibility of the catheter tips during fluoroscopy-guided minimally invasive surgeries. However, there is an increasing number of reports on bismuth-based photocatalysts in other fields; yet the impact of bismuth additives on the shelf life of PEBA has never been studied/reported. In this work, the stability of PEBA containing bismuth subcarbonate was tested against PEBA containing other radiopaque additives, barium sulfate and tungsten, in several real-life-relevant lighting conditions. It was found bismuth-containing PEBA degraded significantly faster than these counterpart materials under light exposure conditions including indoor fluorescent light, daylight-simulating xenon light and high-flux visible blue light. The extents of photodegradation of bismuth-containing PEBA were characterized by optical imaging, tensile test, FTIR analysis, Raman imaging and ESR radical analysis. The results showed material surface cracking, material hardening, surface oxidation and radical concentration increase over the course of light exposure. Various environmental factors were studied; it was found PEBA containing bismuth not only degraded under lights containing UV light but also degraded under high intensity visible blue light. Larger doses of light exposure and higher environmental temperatures led to more material degradation. Additional shelf aging studies on light-exposed samples were performed, which showed latent aging with continued degradation shortening the shelf life after the initial light exposure, due to the formation of persistent free radicals. Finally, several design and use considerations were discussed in the context of catheter material photodegradation.

O-006 Novel and scalable non-invasive metabolic imaging of early embryos using a lab-on-a-chip approach

Abstract Study question Is it feasible to safely determine metabolic imaging signatures to measure nicotinamide adenine dinucleotide (NADH) associated auto-fluorescence in early embryos using a scalable lab-on-a-chip approach? Summary answer We developed an optofluidic device capable of non-invasively obtain high-resolution 3D images of the metabolic activity of live mouse embryos using a lab-on-a-chip approach. What is known already Selecting the most suitable embryos for implantation and subsequent healthy live birth is crucial to the success rate of assisted reproduction and offspring health. Thus, developing non-invasive methods that are reliable to assess oocyte and embryo quality has been a significant aim for assisted reproduction. Besides morphological evaluation using optical microscopy, a promising alternative is the non-invasive imaging of live embryos to establish metabolic activity performance. However, metabolic imaging has been only achieved using highly complex advanced microscopy such as Fluorescence-lifetime imaging (FLIM) and hyperspectral microscopy, methods that are costly and challenging, limiting the potential for deployment in fertility clinics. Study design, size, duration The non-invasive nature of the system was investigated by assessing the development and viability of live embryos after embryo culture for 67hrs post metabolic imaging at the 2-cell embryo stage (n = 115), including a control for culture conditions and sham controls (system no-illuminated). Embryo quality of developed blastocysts was assessed by immunocytochemistry to quantify trophectoderm and inner mass cells (n = 75). Furthermore, inhibition of metabolic activity (FK866 inhibitor) during embryo culture was also assessed (n = 18). Participants/materials, setting, methods Optofluidic devices were manufactured by cast-moulding using a negative photoresist (SU8-2075; MicroChemicals GmbH, Ulm, Germany) by a standard UV-photolithography process. The microstructures fabricated of polydimethylsiloxane (PDSM) integrated Light Sheet Fluorescence Microscopy into a microfluidic system, including on-chip micro-lenses to generate a light sheet at the center of a microchannel. Super-ovulated F1 (CBA/C57Bl6) mice were used to produce 2-cell embryos and embryo culture experiments. Blastocyst formation rates and embryo quality (immunocytochemistry) were compared between study groups. Main results and the role of chance The optofluidic device was capable of non-invasively obtaining high-resolution 3D images of the metabolic activity in live mouse embryos. The system’s design allowed continuous tracking of the embryo location, including high control displacement through the light-sheet, fast imaging of the embryos (<2 second) and keeping a low dose of light exposure (16 J cm-2 and 8 J cm-2). Optimum settings for keeping sample viability showed that a modest light dosage was capable to obtain 30 times higher signal-noise-ratio images than images obtained with a confocal system (p < 0.00001; t-test). The results showed no significant differences between the control, illuminated and non-illuminated embryos (sham control) for embryo development as well as embryo quality at the blastocyst stage (p > 0.05; Yate’s chi squared test). Additionally, embryos with inhibited metabolic activity showed decreased blastocyst formation rates as well as 47% reduction in metabolic activity measured by non-invasive metabolic imaging (p < 0.0001; t-test). This study reports an optofluidic device capable of non-invasive metabolic imaging of live embryos using a similar concept as previously reported using FLIM technology and hyperspectral microscopy, but allowing a novel, scalable and affordable system with implementation potential in standard IVF laboratory equipment. Limitations, reasons for caution The study was conducted using a mouse model focused on early embryo development. Further safety studies are required to assess embryonic health by investigating the impact of the use of light during embryo development, live birth, embryo gene expression and epigenome stability. Wider implications of the findings This lab-on-a-chip is novel, scalable and has the potential to be used in fertility clinics as a technology platform to enable real-time monitoring of the metabolic function of embryos prior embryo transfer. Future applications include potential integration into existing IVF laboratory equipment such as bench and time-lapse incubators. Trial registration number N/A

0314 Late Evening Room Light and Sleep Restriction Reverses the Phase Advancing Effect of Bright Morning Light in Adolescents

Abstract Introduction Late bedtimes and sleep restriction are common during adolescence, particularly on school nights. We examined circadian phase advancing effects of bright morning light (ML) with increasing doses of evening room light exposure and sleep restriction due to late bedtimes. Methods Adolescents (n=38, 21 girls) aged 14.1 to 18.0 years completed a 14-day protocol during summer vacation. On days 1-7, they slept at home on individualized 10-h sleep/dark schedules. On days 8-14, they lived in the laboratory. On day 8, we measured their Dim Light Melatonin Onset (DLMO). On days 9 and 10, they were put to bed 1.5h (n=9), 3.0h (n=12), or 4.5h (n=8) later and kept awake in room light (104±11 lux at the angle of gaze). Wake time was unchanged; thus, sleep opportunity was shortened to 8.5h, 7h, and 5.5h, respectively. The fourth group (n=9) kept their baseline bedtime, were not exposed to any additional evening light (EL) and were not sleep restricted. On day 11, all groups were put to bed and awakened 1.5 h earlier and were exposed to intermittent bright ML (three 30-min exposures; 8599±885 lux). On each subsequent day (12 and 13), sleep and ML were advanced 1h. Thus, there were 3 days of a gradually advancing sleep schedule and bright ML. Final DLMO was measured on day 14. Results The 0h EL group showed a large DLMO advance (2.2±1.0 h), but the advance was reduced in the 1.5h EL group (0.5±0.6 h). DLMO delayed in the 3h EL group (-0.9±1.1 h). There was a large phase delay in the 4.5h EL group (-2.6±1.2 h). Phase shifts differed among all groups [F(3,34)=36.7, p<.001]. Conclusion Circadian rhythms of adolescents were advanced when they were exposed to bright ML and a gradually advancing sleep schedule, as shown in many studies of adults. However, when kept up later in ordinary room light, the same advancing sleep schedule and bright ML did not produce as much of an advance. Phase delay shifts occurred when bedtimes were 3h or 4.5h later. EL and sleep restriction can reverse the advancing effect of bright ML. Support (if any) R01 HL146772 (Crowley)

Effect of light exposure on growth rate of veterinary clinical dermatophyte isolates

Veterinary textbooks and literature suggest that exposure to light is inhibitory to growth of clinical dermatophyte isolates. We hypothesized that this idea was derived from experiments that examined the effect of high doses of ultraviolet and visible light exposure on dermatophyte growth, and that exposure to typical room lighting would not adversely affect dermatophyte growth rate. Isolates of common veterinary dermatophytes (three each of Microsporum canis, Nannizia gypsea and Trichophyton benhamiae) were exposed to typical fluorescent room lighting, incubated in a closed drawer, or exposed at close range to fluorescent wide-spectrum light. Dermatophytes were grown on Sabouraud Dextrose Agar (SAB) and Dermatophyte Test Medium (DTM). Colony diameter was measured and growth rate (expressed as colony diameter increase mm/day) calculated at the linear portion of the culture growth curve. Statistical analyses compared growth rates across the various incubation conditions and among dermatophyte isolates. There was little difference in growth rate between cultures incubated under typical fluorescent room lighting and those placed in the dark. Exposure to the close-range light increased growth rate as a consequence of the elevated incubation temperature created by the lamp. Significant differences in growth rate were noted among strains of the same dermatophyte species. Dermatophytes grew more rapidly on SAB than DTM agar. Exposure to typical lighting conditions in a clinical environment does not inhibit growth of dermatophyte colonies. Veterinary clinicians may conduct routine dermatophyte cultures without incubating them in the dark.

Global verification of a model for determining daylight photodynamic therapy dose.

Daylight photodynamic therapy is an effective treatment for actinic keratoses and relies on a minimum PpIX-effective light exposure dose being delivered during treatment. As such, daylight dosimetry is an important aspect of this treatment. Relatively simple measurements of illuminance may be converted to PpIX-effective irradiance, and subsequently exposure dose, via a conversion model (the O'Mahoney model). This model has been verified against spectral irradiance data from the UK, however the accuracy of the model has not been determined outside the UK. In this work, we test the O'Mahoney model against spectral irradiance measurements from several global locations to within bounds of a median deviation of ±10 %. The median percentage deviations are shown to be independent of location latitude and longitude. The model can be used confidently to determine PpIX-effective irradiance from illuminance measurements irrespective of location and can be widely implemented as an effective and low-cost means of accurately measuring effective light exposure for this important treatment.

Laser technologies in treatment of cervical intraepithelial neoplasia (review)

This review article discusses the key aspects of the use of laser technologies, namely, laser vaporization (LV) and photodynamic therapy (PDT), in the treatment of patients with cervical intraepithelial neoplasia (CIN). The authors analyzed and systematized the foreign experience of these methods of treatment, their indications and contraindications, as well as the advantages over traditional approaches to the treatment of this pathology. The main advantages of the LV are the possibility of complete evaporation of the pathological focus, visual control over the depth of tissue destruction, the absence of prolonged edema and cicatricial deformities, which allows maintaining the integrity of the cervix and its reproductive function. Despite the low trauma and low frequency of adverse reactions, the data on the effectiveness of LV are quite contradictory and, according to various authors, vary from 50% to 98%. To date, there is a significant amount of accumulated experience in the use of PDT with various photosensitizing agents (5-aminolevulinic acid (5-ALA), hematoporphyrin and chlorin and their derivatives) in the treatment of patients with CIN. The main advantages of the PDT are minimal toxicity to the surrounding normal tissues due to the selective accumulation of photosensitizer in pathological tissues, a low risk of severe pain syndrome, the absence of mechanisms of primary and acquired resistance, the possibility of an outpatient treatment session, the possibility of combining with other methods of therapeutic action, the absence of limiting cumulative doses of photosensitizers and light exposure, the possibility of multiple repetitions of the session, good cosmetic results and the possibility of implementing an organ-preserving method of treatment. The obtained results indicate good tolerability of the method (no severe adverse reactions) and a fairly high efficiency of PDT: the frequency of complete regressions varies from 30% to 67% - for application forms of 5-ALA and from 90% to 98.1% - for hematoporifirin and chlorin photosensitizers. Thus, LV and PDT can be considered safe and effective treatment options for patients with CIN.

Light-provoked skin symptoms on the hands of erythropoietic protoporphyria patients related to personal dosimeter measurements, skin symptoms, light protection and priming

Erythropoietic protoporphyria (EPP) is characterised by accumulation of protoporphyrin IX (PpIX) in erythrocytes. Upon illumination PpIX is released to the skin. Activation of the photoactive substance PpIX causes painful skin symptoms. This study aimed to objectively quantify individual light exposure of EPP patients in their everyday lives through spring and summer. We further aimed to establish the associations between daily symptoms and light exposure dose to photoprimed and non-photoprimed skin, use of gloves, and erythrocyte PpIX concentration. 14 Danish EPP patients participated from April through June, the period when symptoms are most frequent. Light exposure was measured using personal electronic dosimeters with sensor sensitivity comparable to the absorption spectrum of PpIX, measuring the biological effect of the light in this disease. Concurrently participants reported symptoms and use of protective gloves in a diary. Patients had a blood sample analysed for erythrocyte PpIX. The median patient was exposed to an average daily PpIX-weighted light dose of 3.8 J/cm2 corresponding to approximately 15 min in the midday sun during summer in Denmark. The median patient reported symptoms on 29% and wore gloves on 11% of study days. There was a significant positive correlation between erythrocyte PpIX concentration and percentage of days wearing gloves (r = 0.65, p = 0.011), and a significant negative correlation between erythrocyte PpIX concentration and mean daily light dose on days not wearing gloves (r = −0.53, p = 0.049). Photosensitivity was strongly dependent on photopriming.

A systematic study of light dependency of persistent photoconductivity in a-InGaZnO thin-film transistors* *Project supported in part by the National Natural Science Foundation of China (Grant Nos. 61974101 and 61971299), the State Key Laboratory of ASIC and System, Fudan University (Grant No. 2019KF007), the Natural Science Foundation of Jiangsu Province, China (Grant No. SBK2020021406), the Natural Science Foundation of the

Persistent photoconductivity (PPC) effect and its light-intensity dependence of both enhancement and depletion (E-/D-) mode amorphous InGaZnO (a-IGZO) thin-film transistors (TFTs) are systematically investigated. Density of oxygen vacancy (VO) defects of E-mode TFTs is relatively small, in which formation of the photo-induced metastable defects is thermally activated, and the activation energy (E a) decreases continuously with increasing light-intensity. Density of VO defects of D-mode TFTs is much larger, in which the formation of photo-induced metastable defects is found to be spontaneous instead of thermally activated. Furthermore, for the first time it is found that a threshold dose of light-exposure is required to form fully developed photo-induced metastable defects. Under low light-exposure below the threshold, only a low PPC barrier is formed and the PPC recovery is fast. With increasing the light-exposure to the threshold, the lattice relaxation of metal cations adjacent to the doubly ionized oxygen vacancies () is fully developed, and the PPC barrier increases to ∼ 0.25 eV, which remains basically unchanged under higher light-exposure. Based on the density of VO defects in the channel and the condition of light illumination, a unified model of formation of photo-induced metastable defects in a-IGZO TFTs is proposed to explain the experimental observations.

Strigea robusta causes polydactyly and severe forms of Rostand\u2019s anomaly P in water frogs

BackgroundCases of polydactyly in natural populations of amphibians have attracted great interest from biologists. At the end of the 1940s, the French biologist Jean Rostand discovered a polymorphic syndrome in some water frog (Anura: Pelophylax) populations that included polydactyly and some severe morphological anomalies (he called it ‘anomaly P’). The cause of this anomaly remains unknown for 70 years. In a previous study, we obtained anomaly P in the laboratory in tadpoles of water frogs that developed together with molluscs Planorbarius corneus (Mollusca: Gastropoda) collected in the field. We thus proposed the ‘trematode hypothesis’, according to which the infectious agent responsible for anomaly P is a trematode species.MethodsMetacercariae from tadpoles with anomaly P were identified using ITS2 gene sequencing as Strigea robusta (Trematoda: Strigeidae). To verify teratogenic features of the species, cercariae of S. robusta were tested for the possibility to cause anomalies. Identification of cercariae species was made using morphological and molecular methods (sequencing of ITS2 and 28S rRNA). The tadpoles were exposed to parasites at four doses of cercariae (control, low, medium and high) and divided into two groups: “early” (at 25–27 Gosner stages) and “late” (at 29–34 Gosner stages) exposure.ResultsA total of 58 (72.5%) tadpoles survived until metamorphosis under the dose-dependent experiment with the trematode S. robusta. Differences in the survival rates were observed between the exposed and unexposed tadpoles both in the group of “early” tadpoles and “late” tadpoles. The exposure of tadpoles to the cercariae of S. robusta induced anomaly P in 82% of surviving tadpoles. The severe forms developed only in “early” stages under all doses of cercariae exposure. Polydactyly predominantly developed in the “late” stages; under a light exposure dose, polydactyly also developed in “early” tadpoles. Laboratory-hatched tadpoles reared together with infected snails had different rates of survival and complexity of deformations associated with the period of coexistence.ConclusionsThe experiments with direct cercariae exposure provide compelling evidence that S. robusta leads to anomaly P in tadpoles of water frogs. The manifestation of anomaly P turned out to be dependent on the stage of development, cercariae dose, and the location of the cysts.

Mitigating Scattering Effects in Light-Based Three-Dimensional Printing Using Machine Learning

Abstract When using light-based three-dimensional (3D) printing methods to fabricate functional micro-devices, unwanted light scattering during the printing process is a significant challenge to achieve high-resolution fabrication. We report the use of a deep neural network (NN)-based machine learning (ML) technique to mitigate the scattering effect, where our NN was employed to study the highly sophisticated relationship between the input digital masks and their corresponding output 3D printed structures. Furthermore, the NN was used to model an inverse 3D printing process, where it took desired printed structures as inputs and subsequently generated grayscale digital masks that optimized the light exposure dose according to the desired structures’ local features. Verification results showed that using NN-generated digital masks yielded significant improvements in printing fidelity when compared with using masks identical to the desired structures.

A clinical evaluation of efficacy of photodynamic therapy in treatment of reticular oral lichen planus: A case series.

Background The aim of the study was to clinically evaluate the efficacy of photodynamic therapy in treatment of reticular oral lichen planus (OLP). Methods Fifty patients aged 26-84, with 124 OLP lesions in total, underwent photodynamic therapy (PDT) mediated with topically applied 5% 5-aminolevulinic acid. ALA was activated by a custom-made diode lamp with a high-power LED emitting light at 630 nm and 300 mW delivered through an optical fiber probe. A light exposure dose was 150 J/cm2. The therapy comprised of 10 weekly illumination sessions. The lesions' response was macroscopically measured in millimeters with a periodontal probe and clinically evaluated at each session, then on completion of the series and throughout the 12-month follow-up. Results The baseline mean size of lesions was 3.99 cm2±3.73. The lesions on the buccal mucosa and lips (lining mucosa) were larger than those on the gingiva and tongue (masticatory mucosa) - 4.58 cm2±4.01 and 2.93 cm2±2.91 respectively. On completion of the therapy 109 sites improved, including 46 in complete remission. The mean reduction in size was 62.91% (p = 0.000000). 12-month after therapy mean reduction of the lesions was 78.7% (p = 0.000000), specifically 79.48% (p = 0.000000) within the lining mucosa and 76.11% on the masticatory mucosa. Conclusions The results proved that ALA-mediated photodynamic therapy with a 630 nm light was effective and as such it can be used as an optional treatment for symptomatic OLP.

The effects of two different doses of ultraviolet-A light exposure on nitric oxide metabolites and cardiorespiratory outcomes

PurposeThe present study investigated different doses of ultraviolet-A (UV-A) light on plasma nitric oxide metabolites and cardiorespiratory variables.MethodsTen healthy male participants completed three experimental conditions, 7 days apart. Participants were exposed to no light (CON); 10 J cm2 (15 min) of UV-A light (UVA10) and 20 J cm2 (30 min) of UV-A light (UVA20) in a randomized order. Plasma nitrite [NO2−] and nitrate [NO3−] concentrations, blood pressure (BP), and heart rate (HR) were recorded before, immediately after exposure and 30 min post-exposure. Whole body oxygen utilization ({{dot{V}}}{rm O}_{2}), resting metabolic rate (RMR) and skin temperature were recorded continuously.ResultsNone of the measured parameters changed significantly during CON (all P > 0.05). {{dot{V}}}{rm O}_{2} and RMR were significantly reduced immediately after UVA10 (P < 0.05) despite no change in plasma [NO2−] (P > 0.05). Immediately after exposure to UVA20, plasma [NO2−] was higher (P = 0.014) and {{dot{V}}}{rm O}_{2} and RMR tended to be lower compared to baseline (P = 0.06). There were no differences in [NO2−] or {{dot{V}}}{rm O}_{2} at the 30 min time point in any condition. UV-A exposure did not alter systolic BP, diastolic BP or MAP (all P > 0.05). UV-A light did not alter plasma [NO3−] at any time point (all P > 0.05).ConclusionsThis study demonstrates that a UV-A dose of 20 J cm2 is necessary to increase plasma [NO2−] although a smaller dose is capable of reducing {{dot{V}}}{rm O}_{2} and RMR at rest. Exposure to UV-A did not significantly reduce BP in this cohort of healthy adults. These data suggest that exposure to sunlight has a meaningful acute impact on metabolic function.

Near-infrared photoimmunotherapy with galactosyl serum albumin in a model of diffuse peritoneal disseminated ovarian cancer.

Near-infrared photoimmunotherapy (NIR-PIT) is a highly cell-selective cancer therapy based on an armed antibody conjugated with a phthalocyanine-based photo-absorber, IRDye700DX (IR700). NIR-PIT can quickly kill target cells that express specific proteins on the cellular membrane but only when the antibody-IR700 conjugate binds to the cell membrane and is then exposed to NIR light. NIR-PIT is highly selective based on the specificity of the antibody. Galactosyl serum albumin (GSA) is composed of albumin decorated with galactose molecules conjugated to the carboxyl groups of albumin. GSA binds to beta-D-galactose receptors, a surface lectin, which are overexpressed on the cell surface of many cancers, including ovarian cancers and is quickly internalized after binding. Here, we demonstrate the feasibility of NIR-PIT in a model of disseminated peritoneal ovarian cancer (SHIN3 cells) using GSA-IR700 that binds to beta-D-galactose receptors. GSA-IR700 bound quickly to SHIN3 cells, then accumulated in the endo-lysosomes. Cell-specific killing was observed in vitro, yet a relatively large dose of NIR light exposure was required for cell killing compared to antibody-IR700 conjugates. To evaluate in vivo therapeutic effects of GSA-IR700 NIR-PIT, peritoneal disseminated SHIN3 tumor-bearing mice were separated into four groups: no treatment; NIR light only; GSA-IR700 only; and GSA-IR700 NIR-PIT. Repeated NIR-PIT showed significant suppression of tumor based on bioluminescence compared to the other groups (p < 0.05). Thus, repeated NIR-PIT using GSA-IR700 can achieve efficient antitumor effects, although GSA-IR700 NIR-PIT was less effective than antibody-IR700 NIR-PIT conjugates likely due to the rapid internalization of GSA-IR700.

Photodynamic therapy with photosensitizer photolon for oral leukoplakia

The objective – to assess tolerability, safety and immediate results of treatment of patients with oral leukoplakia using photodynamic therapy (PDT) with a photosensitizer photolon. The study included 40 patients (7 men, 33 women) with morphologically verified leukoplakia of the oral mucosa. The average age – 55±14 years. Number of treated foci – 109 (1 to 8). Photolon was administered intravenously at doses of 1.7-2.5 mg/kg. Photoirradiation («UPL PDT», Belarus, λ = 660±5 nm) was performed 2.5-3 h after administration: light exposure dose varied from 25 to 100 J/cm2, power density of 0.07 to 0.32 W/cm2, the duration of one field photoirradiation – from 2 to 13.5 min and according to its linear dimensions. The effectiveness of treatment was assessed 1-2 months after PDT by clinical data. Complete regression of foci recorded in 95% of cases (n=38), partial – in 5% (n=2).The follow-up period varied from 1 to 30 months. Full-epithelialization of the wound defect occurred within the period of 3-6 weeks after treatment. Photodynamic therapy may be recommended for patients with circumscribed or widespread oral leukoplakia as a simple, well-tolerated and effective option. Keywords: photodynamic therapy, photolon, oral leukoplakia.

Dose-response relationship between light exposure and cycling performance.

Light has a stimulating effect on physical performance if scheduled according to the chronotype, but dose-dependent effects on performance have not yet been examined. Three groups of healthy men (25.1 ± 3.1 years) were exposed to light for different durations in a parallel group design before a 40-min time-trial. In each group, subjects were exposed to either bright light (BL, 4420 lx) or moderate light (ML, 230 lx) in a randomized order in a crossover design. The durations of light exposure were 120 min prior to and during exercise (2HEX; n = 16), 60 min prior to and during exercise (1HEX; n = 10), or only for 60 min prior to exercise (1H; n = 15). Total work performed during the time-trial in kJ in the 2HEX group was significantly higher in the BL setting (527 kJ) than in ML (512 kJ) (P = 0.002), but not in 1HEX (BL: 485 kJ; ML: 498 kJ) or 1H (BL: 519 kJ; ML: 514 kJ) (P = 0.770; P = 0.485). There was a significant (P = 0.006) positive dose-response relationship between the duration of light exposure and the work performed over the three doses of light exposure. A long duration light exposure is an effective tool to increase total work in a medium length time-trial in subjects normalized for their individual chronotype.

Abstract 2484: IR700-conjugated anti-CD44 monoclonal antibody for phototherapy theranostics of triple-negative breast cancer

Abstract CD44 transmembrane glycoproteins are cell adhesion molecules that play a role in cancer cell proliferation, migration, and invasion.1 CD44 expression is associated with stem-like breast cancer cells1 and is upregulated under hypoxia2 making it a significant target. Monoclonal antibody (mAb)-linked to photosensitizers have achieved targeted phototherapy.3 We developed a CD44 mAb-targeted photosensitizer complex for combined fluorescent detection and phototherapy (PT) of CD44 expressing triple negative breast cancer cells. The mAb conjugate is activated by near-infrared (NIR) light, and demonstrates phototoxic effects selectively in CD44 expressing breast cancer cells following cell membrane binding. CD44 mAb was conjugated with a NIR phthalocyanine dye, IR700, to form CD44-IR700. MB-MDA-231 (CD44 positive), MCF-7 and BT-474 (CD44 negative) were selected for the cell studies. SDS-PAGE, UV spectroscopy and confocal fluorescence imaging were performed to determine purity, composition and cellular localization of the conjugate. Microscopic observation and cell viability tests were performed to study CD44-specific cell death. Tumor models were established by inoculating 2×106 MB-MDA-231 or BT-474 cells in the upper-right mammary fat pad of athymic female mice. In vivo fluorescence imaging was performed on a Li-Cor Pearl® Impulse scanner. Tumor bearing mice (n = 5 per group) injected with PBS, IR700, anti-CD44 mAb, IgG-IR700 and CD44-IR700 were monitored over a 3 week-period and sacrificed to harvest tumors. NIR light at a dose of 30 J/cm2 was applied on day 1 after injection. CD44-IR700 demonstrated preferential binding to the cell membrane of MB-MDA-231 but not MCF-7 or BT-474 cells. CD44-specific cell death was initiated by CD44-IR700-mediated PT (&amp;gt;90% of MB-MDA-231 cells were killed immediately, while 88% of MCF-7 cells and 90% of BT-474 cells were alive). Irradiation itself was harmless to cells and there was no cytotoxicity associated with IR700 and CD44 antibody or with CD44-IR700 in the absence of irradiation. In vivo fluorescence imaging verified the 3-fold increased retention of CD44-IR700 in MB-MDA-231 tumors compared to BT-474 tumors. CD44-IR700 injection together with a therapeutic dose of NIR light exposure resulted in significant growth delay in MB-MDA-231 tumors, but not BT-474 tumors. We did not observe tumor growth delay in separate groups of mice injected with PBS, IR700, anti-CD44 mAb, or IgG-IR700, irrespective of NIR light application. Histological studies confirmed a significant increase of necrosis in the treated MDA-MB-231 tumors. This novel PT theranostic strategy provides a promising opportunity for treating CD44 expressing primary and metastatic triple negative breast cancer.

Early changes in staurosporine-induced differentiated RGC-5 cells indicate cellular injury response to nonlethal blue light exposure.

Blue light has been previously demonstrated to induce injury of retinal cells. The cellular responses to nonlethal blue light exposure for each type of retinal cell are of particular interest but remain undetermined. Based on the doses of blue light reported in previous research to be nonlethal to retinal pigment epithelial cells, here we investigated whether and to what extent such doses of blue light are cytotoxic to staurosporine-differentiated RGC-5 cells. RGC-5 cells were differentiated for 24 hours using 200 nM staurosporine. The resulting cells were cultured and exposed to blue light at three different energy levels (1, 10, and 50 J cm(-2)). Cellular morphologies were investigated with an inverted microscope and cell viability was assessed with a Cell Counting Kit-8 (CCK-8) assay. The generation of intracellular reactive oxygen species (ROS) was evaluated by H2DCFDA. After loading of MitoTracker Green FM dye, the mitochondrial contents were analyzed using flow cytometry. The lactate dehydrogenase (LDH) activities in the media were also measured. The level of lipid peroxidation was determined by measuring the amount of malondialdehyde (MDA). Treatment of the cells for 24 hours with 200 nM staurosporine successfully induced the differentiation of RGC-5 cells. No morphological changes were observed in the ssdRGC-5 cells exposed to blue light at 50 J cm(-2), which was the highest energy level tested. Exposure of the ssdRGC-5 cells to this energy level of blue light did, however, decrease their numbers by approximately 72.1% compared to the numbers of such cells found after being left in the dark. Remarkably, the levels of ROS generation and mitochondrial contents were, respectively, increased to 142% and 118% of those of the control by a 10 J cm(-2) exposure of blue light. The LDH activities and MDA levels exhibited no obvious changes in the blue light-exposed ssdRGC-5 cells compared to the control cells. In vitro nonlethal blue light exposure led to cellular damage of staurosporine-differentiated RGC-5 cells. These increases in oxidative stress and mitochondrial content were the early steps of the cellular response to the exposure of relatively low doses (10 J cm(-2)) of blue light.