COVID-19 media fatigue: predictors of decreasing interest and avoidance of COVID-19-related news.

OBJECTIVES: COVID-19-related news is important for adherence to public health measures. We examined predictors of interest and avoidance of COVID-19 news in Lithuania. STUDY DESIGN: This is an online survey. METHODS: An online survey was conducted between October and December 2020 targeting the general population in Lithuania. Participants rated their interest and avoidance of news about the COVID-19 pandemic, with possible answers ranging from 'completely agree' to 'completely disagree'. The participants were also evaluated for symptoms of depression (Patient Health Questionnaire-8), anxiety (Generalized Anxiety Disorder-7), post-traumatic stress (Impact of Event Scale-Revised) and COVID-19 fear (COVID-19 Fears Questionnaire). RESULTS: In total, 1036 participants (83% women) completed the survey. The results indicated that 37% of participants were losing interest in COVID-19 news, 32% had started avoiding COVID-19 news and 26% had stopped following news about COVID-19. In the multivariate regression analyses, younger age, greater post-traumatic stress symptoms, less fear of COVID-19 and less frequent use of healthcare professionals for COVID-19 information were independent predictors of decreasing/diminished interest and avoidance of COVID-19 news (all P-values <0.005). More frequent use of friends/relatives for COVID-19 information was associated with increasing avoidance and diminished interest in news about COVID-19, while more frequent use of internet news portals for COVID-19 information predicted decreasing/diminished interest in news about COVID-19, independently from other factors considered in this study. CONCLUSIONS: Decreasing/diminished interest and avoidance of news about COVID-19 are common and are associated with younger age, greater post-traumatic stress symptoms, less fear of COVID-19 and less frequent use of healthcare professionals for COVID-19 information.

Spectroscopic studies of the human heart conduction system ex vivo: implication for optical visualization.

Fluorescence excitation and emission spectra of the heart tissues specimens have been measured ex vivo with the aim of finding out the optical differences characteristic for the human heart conduction system (the His bundle) and ventricular myocardium. The optimal conditions enhancing the spectral differences between the His bundle and myocardium were found by recording the fluorescence signal in the range from 420 nm to 465 nm under the excitation at wavelengths starting from 320 nm to 370 nm. In addition, the spectral differences between the His bundle and the connective tissue, which is often present in the heart, could be displayed by comparing the ratios of fluorescence intensities being measured at above 460 nm under the preferred excitation of elastin and collagen. The left and right branches of the His bundle were visualized ex vivo in the interventricular septum of the human heart under illumination at 366 nm.

The bystander effect in photodynamic inactivation of cells.

Treatment of MDCK II cells with the lipophilic photosensitizer tetra(3-hydroxyphenyl)porphyrin and light was found to induce a rapid apoptotic response in a large fraction of the cells. Furthermore, the distribution of apoptotic cells in microcolonies of eight cells was found to be different from the binomial distribution, indicating that the cells are not inactivated independently, but that a bystander effect is involved in cell killing by photodynamic treatment. The observation of a bystander effect disagrees with the common view that cells are inactivated only by direct damage and indicates that communication between cells in a colony plays a role in photosensitized induction of apoptosis. The degree of bystander effect was higher for cells dying by necrosis than for cell dying by apoptosis.

Electroporation of transplantable tumour for the enhanced accumulation of photosensitizers.

The aim of this study was to verify whether electroporation could increase the accumulation of the hydrophilic photosensitizers: aluminium phthalocyanine tetrasulphonate (AlPcS(4)) and chlorin e(6) (C e(6)) in tumour tissue. The experiment was performed in vivo using hybrid mice (C57Bl/CBA) bearing hepatoma A22 (MH-A22) tumours transplanted in the right haunch. The time dependence of the fluorescence intensity of administered photosensitizers was measured after the ordinary and electrically stimulated delivery. The obtained fluorescence spectroscopy results implied the tumour being affected by an electrical field in a way, which led to a higher accumulation of both photosensitizers (AlPcS(4) and C e(6)) in the periphery of the tumour and it superficial layer. Our pilot study suggests that electroporation could be considered as a useful procedure seeking for the more effective application of photodynamic tumour treatment.

Cooperative inactivation of cells in microcolonies treated with UVA radiation.

Microcolonies of Madison-Darby canine kidney cells (MDCK II) were exposed to UVA radiation, and the number of cells with membrane damage was determined by staining with propidium iodide and fluorescence microscopy. The cells were clearly damaged in a nonrandom manner: The distribution of damaged cells per microcolony was incompatible with the assumption that the cells were damaged independently. The data were accurately described by a so-called propagated damage model in which a damaged cell can influence its neighbors in a propagating manner. These findings do not agree with the common view that optical radiation interacts with cells in a way in which damage manifested in a cell is the result of absorption of light in the same cell.

Phototransformations of 5-aminolevulinic acid-induced protoporphyrin IX in vitro: a spectroscopic study.

Human adenocarcinoma cells of the line WiDr were incubated with 5-aminolevulinic acid to induce protoporphyrin IX (PpIX) and then exposed to laser light of wavelength 635 nm. The PpIX fluorescence decreased with increasing exposure. The decay rate was slightly dependent on the initial PpIX concentration. The PpIX fluorescence was halved by a fluence of about 40 J/cm2. Several fluorescing photoproducts were formed. The main one, supposedly the chlorine-type photoprotoporphyrin (Ppp), had a fluorescence excitation spectrum stretching out to about 680 nm with a maximum at around 668 nm. The formation kinetics of this product was dependent on the initial PpIX concentration. Moreover, it was selectively bleached by exposure to light at 670 nm. A photoproduct with an emission maximum at 652 nm, different from Ppp, remained after this exposure. Traces of a photoproduct(s) with fluorescence emission slightly blue-shifted compared with that of PpIX, supposedly water-soluble porphyrins, were also detected after light exposure.

Spectroscopic studies of photobleaching and photoproduct formation of porphyrins used in tumour therapy.

The illumination of haematoporphyrin, meso-tetraphenylporphyrin tetrasulphonate and haematoporphyrin derivative in aqueous solution causes two simultaneously occurring processes: photodegradation and the formation of stable photoproducts absorbing in the red spectral region. In the case of haematoporphyrin and its derivatives, these photoproducts have an absorption maximum around 640 nm (photoproduct 640). The former process, which is detected as the bleaching of the porphyrin absorption spectrum as well as a decrease in the fluorescence intensity, is slightly dependent on the solution pH and becomes dominant when the formation of the photoproduct reaches saturation. For the most part, the photodegradation can be explained as the opening of the porphyrin ring, leading to an increase in light absorbance in the UV region. The formation of photoproduct 640 is closely related to the aggregation state of the porphyrins, and shows a distinct dependence on the medium pH. The effectiveness of photoproduct 640 formation strongly increases in neutral and alkaline solutions, whereas the porphyrins are photostable below pH 5. The spectroscopic features of the photoproducts of haematoporphyrin and haematoporphyrin derivative, with absorption bands in the visible region, are similar to those of chlorin and/or porphyrin-chlorin linked systems. On the basis of these spectroscopic studies, it is suggested that photoproduct 640 is a chlorin-type molecule formed predominantly from the aggregates of porphyrins when photo-oxidation and photoreduction are in competition.

The photosensitizing effect of the photoproduct of protoporphyrin IX.

The photodynamic effect of a photoproduct of protoporphyrin IX (PpIX) induced by 5-aminolevulinic acid (ALA) was investigated in WiDr cells, a human adenocarcinoma cell line. The fluorescence excitation and emission spectra of PpIX and the photoproduct were measured. After 1, 3 or 5 min exposure of the ALA-incubated cells to 140 mW/cm(2) light at 635 nm, the photoproduct--the chlorin photoprotoporphyrin (Ppp), had an emission band around 670 nm. The Ppp excitation peak at 670 nm is well separated from the PpIX peak at 635 nm. The outcome of photodynamic therapy (PDT) was determined by measuring intracellular fluorescence intensity of propidium iodide (PI) 2 h following PDT and methylene blue (MB) staining 24 h following PDT. A significant increase in the fluorescence intensity of PI was noted when the ALA-loaded cells were exposed to 670 nm light after exposure to 635 nm, indicating enhanced cell membrane inactivation induced by the photodynamic action of the photoproduct. However, the fraction of the cells that survived following the same treatment as measured by MB staining was not significantly affected based on an analysis of variance. The fluorescence of PpIX decayed significantly during 635 nm light exposure. Exposure to light at 670 nm does not lead to any photodegradation of PpIX. The fluorescence of Ppp was bleached during 670 nm light exposure. Exposure of Ppp at 670 nm gives no PpIX back. Thus, the phototransformation of PpIX to Ppp is probably not a reversible process.

Fluorescence spectroscopy of normal mouse skin exposed to 5-aminolaevulinic acid and red light.

Photobleaching and phototransformation of protoporphyrin IX (PpIX) was investigated in normal mouse skin. The PpIX was induced by topical application of 5-aminolaevulinic acid (ALA). Exposure to laser light (635 nm) caused photobleaching of PpIX fluorescence and formation of fluorescent products. Analysis of the fluorescence spectra revealed appearance of new fluorescent photoproducts during light exposure. The main photoproduct, supposedly chlorin-type photoprotoporphyrin (PPp), exhibited fluorescence with an emission maximum at 675 nm. The other products exhibited main fluorescence peaks at around 588 and 623 nm that can presumably be attributed to an endogenous metallo-porphyrin and water-soluble porphyrin(s), respectively. Our results indicate that light exposure causes alterations in the enzymatic pathway of PpIX synthesis from ALA and leads to accumulation of intermediate water-soluble porphyrins. ALA-induced porphyrins are transported away from the treated area and partly deposited in remote skin sites.

Spectroscopic assessment of endogenous porphyrins in a rheumatoid arthritis rabbit model after the application of ALA and ALA-Me.

The sensitization of inflamed knee tissues with endogenous porphyrins was studied by means of fluorescence spectroscopy in an experimental model of rabbit rheumatoid monoarthritis after intraarticular (i.a.) or intravenous (i.v.) injections of 5-aminolevulinic acid (ALA) or ALA methyl ester (ALA-Me). Fluorescence measurements in vivo on the skin of the inflamed knee joint showed the dominance of protoporphyrin IX (PpIX). The highest fluorescence intensity was registered 2h after i.a. injection of ALA and ALA-Me. Comparative analysis of the PpIX fluorescence spectra ex vivo revealed that more PpIX accumulated in the tissues of the inflamed joint than in the tissues of the control joint, and that ALA-Me induced about five times more PpIX in the inflamed synovium than ALA. Meanwhile, the cartilages of the inflamed and control knee joints also accumulated water-soluble porphyrins. Thus, in vivo and ex vivo spectroscopic assessment of endogenous porphyrins in rabbit rheumatoid arthritis tissues implied that the injection of ALA is more appropriate for the diagnostics of inflammation due to the higher PpIX fluorescence intensity on the skin surface, while ALA-Me is more appropriate for the therapeutic applications due to the higher and more selective accumulation of PpIX in the inflamed synovium.

Photobleaching of protoporphyrin IX in cells incubated with 5-aminolevulinic acid.

Protoporphyrin IX (Pp IX) is the main photosensitizer in photochemotherapy with 5-aminolevulinic acid (ALA). Pp IX is photolabile and the present work shows that 70-95% of Pp IX in cells is degraded by clinically relevant light exposures (40-200 J cm(-2) at 630 nm). During light exposure a small yield of photoprotoporphyrin, which is also photolabile, is formed. A substantial fraction of Pp IX in cells incubated with ALA is bound to proteins. During light exposure these binding sites are destroyed, those close to tryptophan residues being the most sensitive. The rate of photodegradation of Pp IX in the cells is dependent on the initial concentration of Pp IX. The degradation mechanisms are therefore not only first order processes. Different degradation rates appear to be related to different types of binding sites. During light exposure, Pp IX molecules appear to move to different binding sites, evidently sites that are more vital for cell survival. Thus, the yield of photoinactivation of the cells, as measured per emitted photon of Pp IX fluorescence, increased during light exposure.

Phototransformation of sensitisers: 3. Implications for clinical dosimetry.

Spectroscopic studies of aqueous solutions of haematoporphyrin-type sensitisers reveal that photobleaching during eposure to light is followed by the formation of stable red-absorbing photoproducts. Experiments in model systems (sensitisers bound to human serum albumin or in a suspension of resealed erythrocyte 'ghosts') and in tumour tissue show that similar photomodification takes place in all investigated environments. Loss of total absorption and emission intensities is accompanied by an increase of absorption in the red spectral region (630-650 nm) which is used for the treatment of tumours because of the deeper penetration of light into tissues. This should be taken into account when the duration of illumination is chosen to reach an appropriate photodynamic dose using Hp-type sensitisers in the photodynamic treatment of tumours.