Fatal poisoning by dietary supplements accompanied by massive rhabdomyolysis and multiple organ failure. / Smiertelne zatrucie suplementami diety przebiegajace z masywna rabdomioliza i niewydolnoscia wielonarzadowa.

Obesity epidemic and prevailing standards of desired body shape encourage society to use weight loss aids. Thermogenics, which are dietary supplements aimed at increasing energy expenditure, are particularly gaining popularity. These preparations can be easily purchased without prescription and have a complex composition, which means they can interact with numerous substances. The article describes the case of a 31-year-old female patient who, in a suicide attempt, ingested significant amounts of the dietary supplements 'Blue Magic' and 'Purim'. Both supplements contain, among other ingredients: caffeine, yohimbine, reserpine, and synephrine. The patient developed multiple organ failure, which led to her death on the second day of hospitalization. Poisoning by dietary supplements, due to their diverse composition and the lack of correlation between the content and the composition declared by the manufacturer, can pose a significant threat to the health and life of consumers.

Deposition of Human-Serum-Albumin-Functionalized Spheroidal Particles on Abiotic Surfaces: Reference Kinetic Results for Bioparticles.

Human serum albumin (HSA) corona formation on polymer microparticles of a spheroidal shape was studied using dynamic light scattering and Laser Doppler Velocimetry (LDV). Physicochemical characteristics of the albumin comprising the zeta potential and the isoelectric point were determined as a function of pH for various ionic strengths. Analogous characteristics of the polymer particles were analyzed. The adsorption of albumin on the particles was in situ monitored by LDV. The stability of the HSA-functionalized particle suspensions under various pHs and their electrokinetic properties were also determined. The deposition kinetics of the particles on mica, silica and gold sensors were investigated by optical microscopy, AFM and quartz microbalance (QCM) under diffusion and flow conditions. The obtained results were interpreted in terms of the random sequential adsorption model that allowed to estimate the range of applicability of QCM for determining the deposition kinetics of viruses and bacteria at abiotic surfaces.

Kinetics of Human Serum Albumin Adsorption on Polycation Functionalized Silica.

The adsorption kinetics of human serum albumin (HSA) on bare and poly-L-arginine (PARG)-modified silica substrates were investigated using reflectometry and atomic force microscopy (AFM). Measurements were carried out at various pHs, flow rates and albumin concentrations in the 10 and 150 mM NaCl solutions. The mass transfer rate constants and the maximum protein coverages were determined for the bare silica at pH 4.0 and theoretically interpreted in terms of the hybrid random sequential adsorption model. These results were used as reference data for the analysis of adsorption kinetics at larger pHs. It was shown that the adsorption on bare silica rapidly decreased with pH and became negligible at pH 7.4. The albumin adsorption on PARG-functionalized silica showed an opposite trend, i.e., it was negligible at pH 4 and attained maximum values at pH 7.4 and 150 mM NaCl, the conditions corresponding to the blood serum environment. These results were interpreted as the evidence of a significant role of electrostatic interactions in the albumin adsorption on the bare and PARG-modified silica. It was also argued that our results can serve as useful reference data enabling a proper interpretation of protein adsorption on substrates functionalized by polyelectrolytes.

Anisotropic Particle Deposition Kinetics from Quartz Crystal Microbalance Measurements: Beyond the Sphere Paradigm.

Deposition kinetics of polymer particles characterized by a prolate spheroid shape on gold sensors modified by the adsorption of poly(allylamine) was investigated using a quartz crystal microbalance and atomic force microscopy. Reference measurements were also performed for polymer particles of a spherical shape and the same diameter as the spheroid shorter axis. Primarily, the frequency and dissipation shifts for various overtones were measured as a function of time. These kinetic data were transformed into the dependence of the complex impedance, scaled up by the inertia impedance, upon the particle size to the hydrodynamic boundary layer ratio. The results obtained for low particle coverage were interpolated, which enabled the derivation of Sauerbrey-like equations, yielding the real particle coverage using the experimental frequency or dissipation (bandwidth) shifts. Experiments carried out for a long deposition time confirmed that, for spheroids, the imaginary and real impedance components were equal to each other for all overtones and for a large range of particle coverage. This result was explained in terms of a hydrodynamic, lubrication-like contact of particles with the sensor, enabling their sliding motion. In contrast, the experimental data obtained for spheres, where the impedance ratio was a complicated function of overtones and particle coverage, showed that the contact was rather stiff, preventing their motion over the sensor. It was concluded that results obtained in this work can be exploited as useful reference systems for a quantitative interpretation of bioparticle, especially bacteria, deposition kinetics on macroion-modified surfaces.

The Relevance of Reperfusion Stroke Therapy for miR-9-3p and miR-9-5p Expression in Acute Stroke-A Preliminary Study.

Reperfusion stroke therapy is a modern treatment that involves thrombolysis and the mechanical removal of thrombus from the extracranial and/or cerebral arteries, thereby increasing penumbra reperfusion. After reperfusion therapy, 46% of patients are able to live independently 3 months after stroke onset. MicroRNAs (miRNAs) are essential regulators in the development of cerebral ischemia/reperfusion injury and the efficacy of the applied treatment. The first aim of this study was to examine the change in serum miRNA levels via next-generation sequencing (NGS) 10 days after the onset of acute stroke and reperfusion treatment. Next, the predictive values of the bioinformatics analysis of miRNA gene targets for the assessment of brain ischemic response to reperfusion treatment were explored. Human serum samples were collected from patients on days 1 and 10 after stroke onset and reperfusion treatment. The samples were subjected to NGS and then validated using qRT-PCR. Differentially expressed miRNAs (DEmiRNAs) were used for enrichment analysis. Hsa-miR-9-3p and hsa-miR-9-5p expression were downregulated on day 10 compared to reperfusion treatment on day 1 after stroke. The functional analysis of miRNA target genes revealed a strong association between the identified miRNA and stroke-related biological processes related to neuroregeneration signaling pathways. Hsa-miR-9-3p and hsa-miR-9-5p are potential candidates for the further exploration of reperfusion treatment efficacy in stroke patients.

Tetraacetyl riboflavin derivative mediates caspase 3/7 activation via MAPK in A431 cells upon blue light influence.

An acetylated riboflavin derivative, 3-methyl-tetraacetyl riboflavin (3MeTARF), is a compound with high photostability and photophysical properties similar to riboflavin, including the ability to photogenerate singlet oxygen. In the present study, we compared the effects of irradiation on A431 cancer cells with blue LED light (438 nm) in the presence of 3MeTARF and riboflavin on MAPK phosphorylation, apoptosis, caspase 3/7 activation and PARP cleavage. We observed that photogenerated oxidative stress in this reaction activates MAPK by increasing phosphorylation of p38 and JNK proteins. Preincubation of cells with inhibitors specific for phosphorylation of p38 and JNK proteins (SB203580, SP600125), respectively, results in decreased caspase 3/7 activation and PARP cleavage. We showed that the tetraacetyl derivative more effectively activates MAPK and skin cancer cell death compared to riboflavin. These data, together with results of our previous study, support the hypothesis that 3MeTARF, of riboflavin, might be more useful and desirable as a compound for use in photodynamic oxidation processes, including its therapeutic potential.

The use of CytoSorb in acute oral mercuric chloride poisoning at a potentially lethal dose.

INTRODUCTION: The study aims to present a case of acute mercuric chloride poisoning treated successfully with continuous renal replacement therapy using the CytoSorb filter. CASE DESCRIPTION: A 21-year-old female patient after a suicide attempt by intentional ingestion of mercuric chloride, was admitted to the hospital with features of multiple organ damage for specific treatment. The performed laboratory tests confirmed high levels of mercury in the blood (1051 µg/L) and urine (22,960 µg/L). Due to acute renal failure, continuous renal replacement therapy (CRRT) CVVHD Ci-Ca was initiated; the procedure was then converted to CVVHDF Ci-Ca with ultrafiltration to optimise therapy, and CytoSorb was added to the artificial kidney system on day 3. Specific antidote therapy (DMPS) was administered concurrently. The ongoing treatment resulted in a reduction in subjective complaints, a decrease in blood mercury levels to 580 µg/L, and an improvement in parenchymal organ function. CONCLUSION: In the event of poisoning with inorganic mercury compounds (mercuric chloride), continuous renal replacement therapy using the CytoSorb filter as an extracorporeal blood purification method may be considered.

Quantifying Nanoparticle Layer Topography: Theoretical Modeling and Atomic Force Microscopy Investigations.

A comprehensive method consisting of theoretical modeling and experimental atomic force microscopy (AFM) measurements was developed for the quantitative analysis of nanoparticle layer topography. Analytical results were derived for particles of various shapes such as cylinders (rods), disks, ellipsoids, hemispheres (caps), etc. It was shown that for all particles, their root-mean-square (rms) parameter exhibited a maximum at the coverage about 0.5, whereas the skewness was a monotonically decreasing function of the coverage. This enabled a facile determination of the particle coverage in the layer, even if the shape and size were not known. The validity of the analytical results was confirmed by computer modeling and experimental data acquired by AFM measurements for polymer nanoparticle deposition on mica and silica. The topographical analysis developed in this work can be exploited for a quantitative characterization of self-assembled layers of nano- and bioparticles, e.g., carbon nanotubes, silica and noble metal particles, DNA fragments, proteins, vesicles, viruses, and bacteria at solid surfaces. The acquired results also enabled a proper calibration, in particular the determination of the measurement precision, of various electron and scanning probe microscopies, such as AFM.

The Role of the Gravitational Field in Generating Electric Potentials in a Double-Membrane System for Concentration Polarization Conditions.

Electric potentials referred to as the gravielectric effect (∆ΨS) are generated in a double-membrane system containing identical polymer membranes set in horizontal planes and separating non-homogenous electrolyte solutions. The gravielectric effect depends on the concentration and composition of the solutions and is formed due to the gravitational field breaking the symmetry of membrane complexes/concentration boundary layers formed under concentration polarization conditions. As a part of the Kedem-Katchalsky formalism, a model of ion transport was developed, containing the transport parameters of membranes and solutions and taking into account hydrodynamic (convective) instabilities. The transition from non-convective to convective or vice versa can be controlled by a dimensionless concentration polarization factor or concentration Rayleigh number. Using the original measuring set, the time dependence of the membrane potentials was investigated. For steady states, the ∆ΨS was calculated and then the concentration characteristics of this effect were determined for aqueous solutions of NaCl and ethanol. The results obtained from the calculations based on the mathematical model of the gravitational effect are consistent with the experimental results within a 7% error range. It has been shown that a positive or negative gravielectric effect appeared when a density of the solution in the inter-membrane compartment was higher or lower than the density in the outer compartments. The values of the ∆ΨS were in a range from 0 to 27 mV. It was found that, the lower the concentration of solutions in the outer compartments of the two-membrane system (C0), for the same values of Cm/C0, the higher the ∆ΨS, which indicates control properties of the double-membrane system. The considered two-membrane electrochemical system is a source of electromotive force and functions as an electrochemical gravireceptor.

Riboflavin and Its Derivates as Potential Photosensitizers in the Photodynamic Treatment of Skin Cancers.

Riboflavin, a water-soluble vitamin B2, possesses unique biological and physicochemical properties. Its photosensitizing properties make it suitable for various biological applications, such as pathogen inactivation and photodynamic therapy. However, the effectiveness of riboflavin as a photosensitizer is hindered by its degradation upon exposure to light. The review aims to highlight the significance of riboflavin and its derivatives as potential photosensitizers for use in photodynamic therapy. Additionally, a concise overview of photodynamic therapy and utilization of blue light in dermatology is provided, as well as the photochemistry and photobiophysics of riboflavin and its derivatives. Particular emphasis is given to the latest findings on the use of acetylated 3-methyltetraacetyl-riboflavin derivative (3MeTARF) in photodynamic therapy.

Depletion of WFS1 compromises mitochondrial function in hiPSC-derived neuronal models of Wolfram syndrome.

Mitochondrial dysfunction involving mitochondria-associated ER membrane (MAM) dysregulation is implicated in the pathogenesis of late-onset neurodegenerative diseases, but understanding is limited for rare early-onset conditions. Loss of the MAM-resident protein WFS1 causes Wolfram syndrome (WS), a rare early-onset neurodegenerative disease that has been linked to mitochondrial abnormalities. Here we demonstrate mitochondrial dysfunction in human induced pluripotent stem cell-derived neuronal cells of WS patients. VDAC1 is identified to interact with WFS1, whereas loss of this interaction in WS cells could compromise mitochondrial function. Restoring WFS1 levels in WS cells reinstates WFS1-VDAC1 interaction, which correlates with an increase in MAMs and mitochondrial network that could positively affect mitochondrial function. Genetic rescue by WFS1 overexpression or pharmacological agents modulating mitochondrial function improves the viability and bioenergetics of WS neurons. Our data implicate a role of WFS1 in regulating mitochondrial functionality and highlight a therapeutic intervention for WS and related rare diseases with mitochondrial defects.

5-Deazaalloxazine as photosensitizer of singlet oxygen and potential redox-sensitive agent.

Flavins are a unique class of compounds that combine the features of singlet oxygen generators and redox-dependent fluorophores. From a broad family of flavin derivatives, deazaalloxazines are significantly underdeveloped from the point of view of photophysical properties. Herein, we report photophysics of 5-deazaalloxazine (1a) in water, acetonitrile, and some other solvents. In particular, triplet excited states of 1a in water and in acetonitrile were investigated using ultraviolet-visible (UV-Vis) transient absorption spectroscopy. The measured triplet lifetimes for 1a were all on the microsecond time scale (≈ 60 µs) in deoxygenated solutions. The quantum yield of S1 → T1 intersystem crossing for 1a in water was 0.43 based on T1 energy transfer from 1a to indicaxanthin (5) acting as acceptor and on comparative actinometric measurements using benzophenone (6). 1a was an efficient photosensitizer for singlet oxygen in aerated solutions, with quantum yields of singlet oxygen in methanol of about 0.76, compared to acetonitrile ~ 0.74, dichloromethane ~ 0.64 and 1,2-dichloroethane ~ 0.54. Significantly lower singlet oxygen quantum yields were obtained in water and deuterated water (Ð¤Δ ~ 0.42 and 0.44, respectively). Human red blood cells (RBC) were used as a cell model to study the antioxidant capacity in vitro and cytotoxic activity of 1a. Fluorescence-lifetime imaging microscopy (FLIM) data were analyzed by fluorescence lifetime parameters and distribution for different parts of the emission spectrum. Comparison of multidimensional fluorescent properties of RBC under physiological-like and oxidative-stress conditions in the presence and absence of 1a suggests its dual activity as probe and singlet-oxygen generator and opens up a pathway for using FLIM to analyze complex intracellular behavior of flavin-like compounds. These new data on structure-property relationship contribute to the body of information required for a rational design of flavin-based tools for future biological and biochemical applications.

Mimicking Pseudo-Virion Interactions with Abiotic Surfaces: Deposition of Polymer Nanoparticles with Albumin Corona.

Adsorption of human serum albumin (HSA) molecules on negatively charged polystyrene microparticles was studied using the dynamic light scattering, the electrophoretic and the solution depletion methods involving atomic force microscopy. Initially, the physicochemical characteristics of the albumin comprising the hydrodynamic diameter, the zeta potential and the isoelectric point were determined as a function of pH. Analogous characteristics of the polymer particles were acquired, including their size and zeta potential. The formation of albumin corona on the particles was investigated in situ by electrophoretic mobility measurements. The size, stability and electrokinetic properties of the particles with the corona were also determined. The particle diameter was equal to 125 nm, which coincides with the size of the SARS-CoV-2 virion. The isoelectric point of the particles appeared at a pH of 5. The deposition kinetics of the particles was determined by atomic force microscopy (AFM) under diffusion and by quartz microbalance (QCM) under flow conditions. It was shown that the deposition rate at a gold sensor abruptly vanished with pH following the decrease in the zeta potential of the particles. It is postulated that the acquired results can be used as useful reference systems mimicking virus adsorption on abiotic surfaces.

QCM-D Investigations of Anisotropic Particle Deposition Kinetics: Evidences of the Hydrodynamic Slip Mechanisms.

Deposition kinetics of positively charged polymer microparticles, characterized by prolate spheroid shape, at silica and gold sensors was investigated using the quartz microbalance (QCM) technique. Reference measurements were also performed for positively charged polymer particles of spherical shape and the same mass as the spheroids. Primarily, the frequency and bandwidth shifts for various overtones were measured as a function of time. It is shown that the ratio of these signals is close to unity for all overtones. These results were converted to the dependence of the frequency shift on the particle coverage, directly determined by atomic force microscopy and theoretically interpreted in terms of the hydrodynamic model. A quantitative agreement with experiments was attained considering particle slip relative to the ambient oscillating flow. In contrast, the theoretical results pertinent to the rigid contact model proved inadequate. The particle deposition kinetics derived from the QCM method was compared with theoretical modeling performed according to the random sequential adsorption approach. This allowed to assess the feasibility of the QCM technique to furnish proper deposition kinetics for anisotropic particles. It is argued that the hydrodynamic slip effect should be considered in the interpretation of QCM kinetic results acquired for bioparticles, especially viruses.

Succinate Dehydrogenase, Succinate, and Superoxides: A Genetic, Epigenetic, Metabolic, Environmental Explosive Crossroad.

Research focused on succinate dehydrogenase (SDH) and its substrate, succinate, culminated in the 1950s accompanying the rapid development of research dedicated to bioenergetics and intermediary metabolism. This allowed researchers to uncover the implication of SDH in both the mitochondrial respiratory chain and the Krebs cycle. Nowadays, this theme is experiencing a real revival following the discovery of the role of SDH and succinate in a subset of tumors and cancers in humans. The aim of this review is to enlighten the many questions yet unanswered, ranging from fundamental to clinically oriented aspects, up to the danger of the current use of SDH as a target for a subclass of pesticides.

Cyanide resistant respiration and the alternative oxidase pathway: A journey from plants to mammals.

In a large number of organisms covering all phyla, the mitochondrial respiratory chain harbors, in addition to the conventional elements, auxiliary proteins that confer adaptive metabolic plasticity. The alternative oxidase (AOX) represents one of the most studied auxiliary proteins, initially identified in plants. In contrast to the standard respiratory chain, the AOX mediates a thermogenic cyanide-resistant respiration; a phenomenon that has been of great interest for over 2 centuries in that energy is not conserved when electrons flow through it. Here we summarize centuries of studies starting from the early observations of thermogenicity in plants and the identification of cyanide resistant respiration, to the fascinating discovery of the AOX and its current applications in animals under normal and pathological conditions.

Nanoparticle and bioparticle deposition kinetics.

Mechanisms and kinetic of particle deposition at solid surfaces leading to the formation of self-assembled layers of controlled structure and density were reviewed. In the first part theoretical aspects were briefly discussed, comprising limiting analytical solutions for the linear transport under flow and diffusion. Methods of the deposition kinetics analysis for non-linear regimes affected by surface blocking were also considered. Characteristic monolayer formation times under diffusion and flow for the nanoparticle size range were calculated. In the second part illustrative experimental results obtained for micro- and nanoparticles were discussed. Deposition at planar substrates was analyzed with emphasis focused on the stability of layers and the release kinetics of silver particles. Applicability of the quartz microbalance measurements (QCM) for quantitative studies of nanoparticle deposition kinetic was also discussed. Except for noble metal and polymer particles, representative results for virus deposition at abiotic surfaces were analyzed. Final part of the review was devoted to nanoparticle corona formation at polymer carrier particles investigated by combination of the concentration depletion, AFM, SEM and the in situ electrokinetic method. It is argued that the results obtained for colloid particles can be used as reliable reference systems for interpretation of protein and other bioparticle deposition, confirming the thesis that simple is universal.

YouTube as a source of information on carbon monoxide poisoning: a content-quality analysis.

OBJECTIVES: The variety of clinical presentation on the topic of carbon monoxide (CO) intoxication ranges from slight headache to coma or death. YouTube allows patients to search not only for entertainment but also medical advice. Therefore, the aim of this study was to evaluate the content and quality of YouTube videos concerning CO poisoning as a source of knowledge for non-medical audience. MATERIAL AND METHODS: On the December 8, 2020 a YouTube search was conducted for the following phrases: "carbon monoxide poisoning," "carbon monoxide symptoms," "CO poisoning," "carbon monoxide asphyxiation," "carbon monoxide intoxication" using the "incognito mode" and without attachment to Google Account. The search results were set as: "default" in the YouTube browser. The first 50 results were taken into consideration. Two raters, a specialist in emergency medicine and a specialist in clinical toxicology rated videos with Quality Criteria for Consumer Health Information (DISCERN), Global Quality Score (GQS) and Journal of the American Medical Association (JAMA). "VidIQ Vision for YouTube" plug-in was used. RESULTS: Ninety-five videos were included. The interclass coefficient for DISCERN, GQS and JAMA scores were: 0.8, 0.74 and 0.62 reaching good and moderate reliability. The mean DISCERN/GQS/JAMA was 28.1 (SD 7.9), 2.5 (SD 0.8) and 1.1 (SD 0.7) respectively. Higher DISCERN/GQS/JAMA had videos providing information on: exposure time, treatment options, hyperbaric chamber indications as well as physician speaker (p < 0.05). Video Power Index was higher when the video contained animations and presented patients own history of CO exposure but not influenced the DISCERN/ GQS/JAMA scores. Videos providing misleading information had a higher like ratio. CONCLUSIONS: The overall video quality was poor indicating inappropriate educational and informative value for patients who search information about carbon monoxide poisoning. Int J Occup Med Environ Health. 2022;35(3):285-95.

Photophysical properties of alloxazine derivatives with extended aromaticity - Potential redox-sensitive fluorescent probe.

The spectral and photophysical properties of two four-ring alloxazine derivatives, naphtho[2,3-g]pteridine-2,4(1H,3H)-dione (1a) and 1,3-dimethylnaphtho[2,3-g]pteridine-2,4(1H,3H)-dione, (1b) were studied. The propensity of 1a for excited-state proton transfer reactions in the presence of acetic acid as a catalyst was also studied, showing no signature of the reaction occurring. In addition, quenching of 1a fluorescence by acetic acid was investigated. Singlet and triplet states and spectral data for 1a and 1b were calculated using density functional theory TD-DFT at B3LYP/6-31G(d) and UB3LYP levels. Finally, fluorescence lifetime imaging microscopy (FLIM) using 1a and 1b as fluorescence probes was applied to in vitro human red blood cells (RBCs) with and without tert-butyl hydroperoxide (TB) as an oxidising agent. To evaluate and compare the effects of 1a and 1b on the redox properties of RBCs, the fluorescence lifetime, amplitude and fractional intensities were calculated, and phasor plot analysis was performed. The results obtained show the appearance of a new proximal cluster in the phasor fingerprint of RBCs in the presence of 1b and a shorter fluorescence lifetime of RBCs in the presence of 1a.

Differences in Perceived Occupational Stress by Demographic Characteristics, of European Emergency Medical Services Personnel during the COVID-19 Virus Pandemic-An International Study.

OBJECTIVES: The outbreak of the COVID-19 pandemic has brought commercial, social, and economic consequences in every country that has experienced substantial SARS-CoV-2 infection rates. The complete change in the environment that took place due to the outbreak of the pandemic can lead to stressful situations, especially among healthcare personnel. MATERIAL AND METHODS: The research were conducted during the COVID-19 pandemic between the 27 March 2020 and the 20 April 2020. The research included 1984 employees of emergency medical systems in seven European countries. An internet-based questionnaire format was adopted for the study (ΩMc-Donald > 0.7). RESULTS: The highest level of stress was experienced by personnel in the United Kingdom M = 4.03, and the lowest by Norwegian employees M = 2.89. High levels of stress were also experienced by nurses from Spain and Poland. Women actively working in the healthcare system during the pandemic experienced higher stress levels than men. CONCLUSIONS: Women working in European emergency medical systems are more vulnerable to work-related stress, while carrying out emergency medical procedures during the pandemic. Differences in the level of stress experienced while carrying out duties in pre-hospital conditions were only found among Spanish emergency medical system personnel.