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Background: Sodium oxybate (SMO) has been shown to be effective in the maintenance of abstinence (MoA) in alcohol-dependent patients in a series of small randomized controlled trials (RCTs). These results needed to be confirmed by a large trial investigating the treatment effect and its sustainability after medication discontinuation. Aims: To confirm the SMO effect on (sustained) MoA in detoxified alcohol-dependent patients. Methods: Large double-blind, randomized, placebo-controlled trial in detoxified adult alcohol-dependent outpatients (80% men) from 11 sites in four European countries. Patients were randomized to 6 months SMO (3.3–3.9 g/day) or placebo followed by a 6-month medication-free period. Primary outcome was the cumulative abstinence duration (CAD) during the 6-month treatment period defined as the number of days with no alcohol use. Secondary outcomes included CAD during the 12-month study period. Results: Of the 314 alcohol-dependent patients randomized, 154 received SMO and 160 received placebo. Based on the pre-specified fixed-effect two-way analysis of variance including the treatment-by-site interaction, SMO showed efficacy in CAD during the 6-month treatment period: mean difference +43.1 days, 95% confidence interval (17.6–68.5; p = 0.001). Since significant heterogeneity of effect across sites and unequal sample sizes among sites ( n = 3–66) were identified, a site-level random meta-analysis was performed with results supporting the pre-specified analysis: mean difference +32.4 days, p = 0.014. The SMO effect was sustained during the medication-free follow-up period. SMO was well-tolerated. Conclusions: Results of this large RCT in alcohol-dependent patients demonstrated a significant and clinically relevant sustained effect of SMO on CAD. Trial registration: ClinicalTrials.gov Identifier: NCT04648423

Chronic ethanol consumption in high doses is associated with constitutively elevated activity of the serum alcohol dehydrogenase I (ADH I) isoform, which demonstrates a high affinity not only for ethanol but also for a number of bioamine metabolites. Such excessive ADH activity is probably associated with disruptions in the metabolism of neurotransmitters (dopamine, serotonin, and norepinephrine) and subsequent long-term changes in the activity of their receptors. Ultimately, a stable depressive-like condition contributes to the development of patients' craving for ethanol intake, frequent disruptions during therapy, and low efficacy of treatment. We applied active immunization against ADH to investigate its efficacy in the reduction of excessive serum ADH activity and regulation of ethanol consumption by chronically ethanol-fed Wistar rats (15% ethanol, 4 months, free-choice method), and we analyzed its ability to influence the levels of bioamines in the brain. Immunization (2 injections, 2-week intervals) was performed using a combination of recombinant horse ADH isozyme as an antigen and 2% aluminum hydroxide-based adjuvant. The efficacy of immunization was demonstrated by the production of high titers of ADH-specific antibodies, which was consistent with the significantly reduced ADH activity in the serum of chronically ethanol-fed rats. On the 26th day after the first vaccine injection, we registered significantly lower levels of alcohol consumption compared to ethanol-fed control animals, and the difference reached 16% on the 49th day of the experiment. These observations were accompanied by data that showed reduced levels of ethanol preference in immunized rats. Chronic alcohol drinking led to a decrease in dopamine and DOPAL (a direct dopamine metabolite and a high-affinity ADH substrate) levels in the striatum,while immunization neutralized this effect. Additionally, we observed that inhibition of serum ADH activity caused a decrease in peak dopamine levels during acute alcohol intake in chronically ethanol-fed rats during ethanol withdrawal that was associated with reduced tyrosine hydroxylase activity in the striatum. The obtained data suggest a significant contribution of ADH to the changes in neurotransmitter systems during chronic alcohol consumption and make available new prospects for developing innovative strategies for treatment of excessive alcohol intake.

Aspects of selecting the most effective refrigerating machine for air conditioning systems, taking into account the comparative analysis of the energy efficiency of the refrigerating machine are considered. The purpose of the work is to improve the regulatory framework governing the design, construction and operation of buildings and structures, to obtain sufficient theoretical and reliable calculated data to determine the standardized parameters and clarify the requirements for the design, construction and operation of buildings and structures. The requirements should be focused on ensuring safe for human health conditions of residence and stay in buildings and structures and the energy efficiency of buildings and structures in order to implement the requirements of the Federal Law of December 30, 2009 No. 384-FZ “Technical Regulations on the Safety of Buildings and Structures”. The aim of the study is to ensure the protection of the life and health of citizens, property of individuals and legal entities, state or municipal property, to bring methods for determining operational characteristics and assessment methods to the uniformity, to ensure mutual consistency of existing regulatory technical documents in the construction industry. The object of the study is the refrigeration and air conditioning systems of public buildings.

(1) Background: the purpose of this study was a preliminary analysis of current methods of online teaching at the Faculty of Medical Sciences, University of Kragujevac, Republic of Serbia, in order to define the attitudes of biomedical students about education during the COVID-19 pandemic and to validate of the education medical questionnaire (eMedQ), a new tool for the assessment of the students’ perceptions about digital education. (2) Methods: this was a qualitative cross-sectional observational study that used the originally developed 45-item questionnaire (eMedQ) as an assessment instrument conducted on biomedical students (n = 209) of all study years at the Faculty of Medical Sciences, University of Kragujevac (Republic of Serbia), during winter semester or between September 2021 and January 2022. (3) Results: In this study, a Cronbach’s alpha value of 0.904 was obtained, which indicated good internal consistency; the correlation matrix revealed many coefficients greater than 0.3, denoting high correlations between the items. The Kaiser–Meyer–Olkin measure of sampling adequacy was 0.866 and Bartlett’s test of sphericity was significant (p < 0.001). The PCA revealed the presence of seven components with characteristic values over one, while three factors explained the highest percentage of variance. (4) Conclusions: this research developed and validated a new tool for evaluation of biomedical student perceptions about digital education.

Alcohol intoxication has a dangerous effect on human health and is often associated with a risk of catastrophic injuries and alcohol-related crimes. A demand to address this problem adheres to the design of new sensor systems for the real-time monitoring of exhaled breath. We introduce a new sensor system based on a porous hydrophilic layer of submicron silica particles (SiO2 SMPs) placed on a one-dimensional photonic crystal made of Ta2O5/SiO2 dielectric layers whose operation relies on detecting changes in the position of surface wave resonance during capillary condensation in pores. To make the active layer of SiO2 SMPs, we examine the influence of electrostatic interactions of media, particles, and the surface of the crystal influenced by buoyancy, gravity force, and Stokes drag force in the frame of the dip-coating preparation method. We evaluate the sensing performance toward biomarkers such as acetone, ammonia, ethanol, and isopropanol and test sensor system capabilities for alcohol intoxication assessment. We have found this sensor to respond to all tested analytes in a broad range of concentrations. By processing the sensor signals by principal component analysis, we selectively determined the analytes. We demonstrated the excellent performance of our device for alcohol intoxication assessment in real-time.

This article is devoted to both theoretical and practical aspects of modern epidemiology of infectious diseases associated with the improvement of pre-epidemic diagnostics and the need for its implementation in the system of risk-based surveillance. The authors summarized and systematized the current data on the factors of epidemiological risk as well as suggested methodological approaches to identify and assess the prerequisites and precursors of complication of the epidemiological situation. In addition, they took into consideration the existing problems of pre-epidemic diagnosis and ways to solve them.

The range of the biochemical reactions which can be catalyzed by ADH I and ADH IV is extremely wide. The most characterized functions of these enzymes are protection against excess endogenous acetaldehyde, products of lipid peroxidation, exogenous alcohols and some xenobiotics. It was found also that ADH I and ADH IV are important members of the enzyme system synthesizing retinoic acid (especially during embryogenesis). They can oxidize some steroids and participate in bioamine and prostaglandin metabolism but so far the extent of their contribution to the latter processes is under discussion. Recent data suggest a correlation between the activity of ADH I in some organs and fine physiological processes including behavior regulation and craving for alcohol in albino rats.

The fluorescent protein KillerRed, a new type of biological photosensitizer, is considered as a promising substitute for current synthetic photosensitizes used in photodynamic therapy (PDT). However, broad application of this photosensitiser in treating deep-seated lesions is challenging due to the limited tissue penetration of the excitation light with the wavelength falling in the visible spectral range. To overcome this challenge, we employ upconversion nanoparticles (UCNPs) that are able to convert deep-penetrating near infrared (NIR) light to green light to excite KillerRed locally, followed by the generation of reactive oxygen species (ROS) to kill tumour cells under centimetre-thick tissue. The photosensitizing bio-nanohybrids, KillerRed-UCNPs, are fabricated through covalent conjugation of KillerRed and UCNPs. The resulting KillerRed-UCNPs exhibit excellent colloidal stability in biological buffers and low cytotoxicity in the dark. Cross-comparison between the conventional KillerRed and UCNP-mediated KillerRed PDT demonstrated superiority of KillerRed-UCNPs photosensitizing by NIR irradiation, manifested by the fact that ∼70% PDT efficacy was achieved at 1-cm tissue depth, whereas that of the conventional KillerRed dropped to ∼7%.KillerRed is a protein photosensitizer that holds promise as an alternative for the existing hydrophobic photosensitizers that are widely used in clinical photodynamic therapy (PDT). However, applications of KillerRed to deep-seated tumours are limited by the insufficient penetration depth of the excitation light in highly scattering and absorbing biological tissues. Herein, we reported the deployment of upconversion nanoparticles (UCNPs) to enhance the treatment depth of KillerRed by converting the deep-penetrating near-infrared (NIR) light to upconversion photoluminescence and activating the PDT effect of KillerRed under deep tissues. This work demonstrated clear potential of UCNPs as the NIR-to-visible light converter to overcome the light penetration limit that has plagued PDT application for many years.