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The issues of practicality in using perfluorocarbon gas transport emulsions (or pure perfluorocarbons) in severe virus-associated pneumonia treatment were considered, including those caused by coronavirus infection. Perfluorocarbons are fully fluorinated carbon compounds, on the basis of which artificial blood substitutes have been developed gas transport perfluorocarbon emulsions for medical purposes. Perfluorocarbon emulsions were widely used in the treatment of patients in critical conditions of various genesis at the end of the lastthe beginning of this century, accompanied by hypoxia, disorders of rheological properties and microcirculation of blood, perfusion of organs and tissues, intoxication, and inflammation. Large-scale clinical trials have shown a domestic plasma substitute advantage based on perfluorocarbons (perfluoroan) over foreign analogues. It is quite obvious that the inclusion of perfluorocarbon emulsions in the treatment regimens of severe virus-associated pneumonia can significantly improve this categorys treatment results after analyzing the accumulated experience. A potentially useful area of therapy for acute respiratory distress syndrome is partial fluid ventilation with the use of perfluorocarbons as respiratory fluids as shown in the result of many studies on animal models and existing clinical experience. There is no gas-liquid boundary in the alveoli, as a result of which, there is an improvement in gas exchange in the lungs and a decrease in pressure in the respiratory tract when using this technique, due to the unique physicochemical properties of liquid perfluorocarbons. A promising strategy for improving liquid ventilation effectiveness using perfluorocarbon compounds is a combination with other therapeutic methods, particularly with moderate hypothermia. Antibiotics, anesthetics, vasoactive substances, or exogenous surfactant can be delivered to the lungs during liquid ventilation with perfluorocarbons, including to the affected areas, which will enhance the drugs accumulation in the lung tissues and minimize their systemic effects. However, the indications and the optimal technique for conducting liquid ventilation of the lungs in patients with acute respiratory distress syndrome have not been determined currently. Further research is needed to clarify the indications, select devices, and determine the optimal dosage regimens for perfluorocarbons, as well as search for new technical solutions for this technique.

This multilateral review provides current knowledge regarding pregnancy and infection with hepatitis B virus (HBV) and hepatitis C virus (HCV), as well as discusses modern methods to reduce mother-to-child transmission (MTCT) of these infections. Maternal HBV or HCV infection is associated with adverse outcomes of pregnancy and childbirth, including MTCT. In countries, including the United States, where postpartum HBV vaccination and immunoprophylaxis with hepatitis B immunoglobulin have been introduced, MTCT has generally decreased to approximately 5%. Unlike that for HBV infection, there is no available or recommended therapy to reduce the risk of MTCT of HBV infection, and the risk remains at 310%. MTCT of HCV can be minimized if do not use obstetric care and avoid birth injuries. Young women with HCV should be referred for treatment after childbirth, and newborns should be closely monitored to rule out infection. New, more affordable, and better tolerated HCV treatment regimens are now emerging that will help reduce the number of infected women and infants.

Чупрій Діана ЮріївнаОКРЕМІ ПРОБЛЕМИ СУБ’ЄКТНОГО СКЛАДУ ПРАВОНАСТУПНИЦТВА В АВТОРСЬКИХ ПРАВАХ У СКЛАДІВІДУМЕРЛОЇ СПАДЩИНИСтаття присвячена теоретичним і практичним проблемам інституту відумерлої спадщини за українським зако-нодавством, яку вже майже двадцять років може набувати територіальна громада. Центральне місце в дослі-дженні займають особливості набуття й подальшого здійснення нею авторських прав у складі такої спадщини,позаяк ці об’єкти вирізняються насамперед своєю потенційною значущістю не тільки для окремих суб’єктів, а йдля суспільства в цілому, незважаючи на смерть автора. Попри це, практика набуття територіальною громадоюдосі лишається бідною у зв’язку із, зокрема, досить поверховим нормативним урегулюванням цього питання,низькою культурою використання результатів чужої інтелектуальної творчості, необізнаністю щодо складу віду-мерлої спадщини, а також браком досвіду та механізмів щодо управління такими специфічними правами. Зазна-чене призводить до безсуб’єктності й унеможливлює законне використання громадянами результатів творчостіавтора, який помер без спадкоємців.У статті зазначається, що ефективність такого управління перебуває в прямій залежності від обсягу та специ-фіки правосуб’єктності, компетенції та наявності відповідного досвіду в правонаступника. У межах дослідженняпроведено огляд історії інституту відумерлої спадщини в Україні та проаналізовано законодавство деяких зару-біжних країн, на підставі чого автор дійшов висновку про доцільність повернення до практики набуття відумерлоїспадщини державою. У роботі обґрунтовується, що саме держава буде більш ефективним правонаступникомне тільки в правах інтелектуальної власності, а й у відумерлій спадщині в цілому. Перевага держави як право-наступника у відумерлій спадщині полягає в потенційно необмежених можливостях з управління таким майном,можливості централізованої реалізації державної політики у сфері інтелектуальної власності, а також у здатностіздійснення його розподілу між окремими установами й організаціями, тому необхідно дати державі можливістьспеціально наділяти компетентні державні органи відповідними повноваженнями щодо здійснення та захистутаких прав.Автор пропонує окремо врегулювати особливості такого правонаступництва в межах Закону України«Про авторське право і суміжні права», як це практикується в зарубіжному законодавстві, і визначити орган, якийбуде наділений повноваженнями з управління таким специфічним складником відумерлої спадщини.

Background Letermovir (LMV) is indicated for cytomegalovirus (CMV) prophylaxis in seropositive adults after allogeneic hematopoietic stem cell transplants (alloSCT). LMV is well tolerated compared to its alternatives. Our institution restricts LMV use to high-risk patient groups to maximize the cost/benefit of LMV. Despite these restrictions, LMV was in our institution’s top 50 drug expenditures, prompting a formal evaluation of its use. We describe a real-world experience with LMV at a 576-bed academic transplant center. Methods This was a single center, retrospective, descriptive study of LMV use at a transplant center. Any hospitalized patient who received ≥ 1 dose of LMV between August 2021 and January 2022 was eligible for analysis. Data collection included age, LMV administration data, length of stay, transplant status, Infectious Diseases (ID) consultation, documented rationale for non-criteria uses, and drug cost. The primary outcome was incidence of use not aligning with restriction criteria. The secondary outcome was institutional drug expenditure for non-criteria uses compared to approved uses. Results Over 6 months, 388 doses of LMV were administered to 31 unique patients during 41 admissions. LMV use during 12/41 admissions (31.7%) fell outside the institutional criteria. ID consult occurred in 58.3% (7/12) of cases. 27/31 (87%) were alloSCT patients, including 1 pediatric patient. There was also 1 liver and 1 heart transplant recipient. Reasons for non-criteria use were: primary prophylaxis in the heart transplant patient to avoid ganciclovir toxicity and in 2 alloSCT patients without high risk for CMV, pre-emptive therapy due to CMV reactivation (n=2), and step-down therapy for CMV viremia (n=4). LMV was used for extended periods ( > 100 days from transplant) in 2 cases. Non-criteria use of LMV accounted for $20 414 in drug cost over 6 months, 29% of total expenditure. Conclusion Our data suggest real world use of LMV often differs from the patient types enrolled in the phase 3 trials. Use of LMV as an alternative to available CMV therapies to avoid drug toxicities appears to drive much of this use. In addition, use outside of criteria was frequent and incurred a nontrivial cost. Modification of our criteria, such as requiring an ID consultation for off-label use, should be considered. Disclosures James S. Lewis, PharmD, FIDSA, Cidara: Advisor/Consultant|Merck: Advisor/Consultant|SeLux Diagnostics: Advisor/Consultant.

Background Coagulase-negative Staphylococci (CoNS), including mecA-positive Staphylococcus epidermidis (MRSE), are among the bacteria identified by BioFire blood culture identification (BCID2). After transition to BCID2 on 31 March 2021, our institution began providing a suggested empiric antimicrobial therapy (EAT) comment with rapid diagnostic results, whereas no suggestions were given with the prior platform. Limited data exist on the impact of EAT suggestions on antibiotic use when likely contaminants such as CoNS are identified. Methods This was a single center, observational, pre- and post-intervention study of patients aged ≥ 18 years with CoNS in the blood between 1 April 2020 and 30 September 2021. Patients with compromised immunity, intravenous drug use, polymicrobial cultures, or MRSE-active therapy use for a documented infection were excluded. Primary outcome was the rate of initiation or discontinuation of MRSE-active agent in response to the rapid diagnostic result. Secondary outcome was healthcare resource utilization such as Infectious Diseases consultation and delayed discharge. Results A total of 174 patients were included (pre-BCID2, n=93; post-BCID2, n=81). For all CoNS rapid diagnostic results, no significant difference was noted in MRSE-active agent initiation (33.3% vs. 37.0%, p=.90) and discontinuation (61.3% vs. 48.4%, p=.31). A subgroup analysis of S. epidermidis was performed with 64 and 46 patients in pre- and post-BCID2 groups, respectively; in the latter, BCID2 identified 31/46 (67.4%) as MRSE. In this subgroup, empiric MRSE-active agent was significantly less likely to be discontinued if EAT suggestion was reported with results (68.4% vs. 31.2%, p=.03). This change was not seen if Staphylococcus species were identified as the suggestion was to withhold EAT. There was no difference in healthcare resource utilization. Conclusion Providing EAT suggestion with BCID2 result for S. epidermidis unexpectedly encouraged continuing empiric MRSE-active agent for likely contaminants. In contrast, suggestion to withhold treatment had no impact on EAT use for other CoNS. The reason for this difference is unclear, but may be a result of the highlighted methicillin resistance in the BCID2 result reporting which is specific to S. epidermidis. Disclosures James S. Lewis, PharmD, FIDSA, Cidara: Advisor/Consultant|Merck: Advisor/Consultant|SeLux Diagnostics: Advisor/Consultant.

The purpose of this article is to provide a comprehensive overview of current knowledge about pregnancy and hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, and current methods to reduce mother-to-child transmission (MTCT). Maternal infection with HBV or HCV is associated with complicated pregnancy and childbirth outcomes, including MTCT. In countries, including the United States, which introduced postpartum HBV vaccination and immunization with hepatitis B immunoglobulin, MTCT overall decreased to about 5%. However, with maternal HBV levels greater than 200,000 IU/ml, the transmission rate of HBV to neonates is almost 30%. For these patients, there are new recommendations from the European Association for the Study of the Liver (EASL), which indicate that, in addition to vaccination of newborns and their immunization, treatment with antiviral drugs such as tenofovir disoproxil fumarate or telbivudine, used during pregnancy, starting from 32 weeks is necessary, that are safe and effective in preventing mother-to-child transmission. Unlike HBV, no therapy is yet available or recommended to further reduce the risk of mother-to-child transmission of HCV infection, which remains by 310%. MTCT of HCV can be minimized by avoiding obstetrics and birth trauma if possible. Young women with HCV should be sent for treatment after delivery, and newborns should be closely monitored to rule out infection. Newer, better tolerated HCV regimens have become more available and should reduce the number of women and babies infected.

Over the past 70 years, tourism has always been at the forefront of business transnationalization, as it has consistently used all the advantages of the transnational production and distribution system, thereby creating additional competitive advantages on a truly global scale. The purpose of this study is to analyze the evolution of the international travel market, as well as to identify a number of historical stages of its development, which the market has passed on the way to establishing strong international relations and interaction. In this article, transnationalization is defined as a modern form of organizing tourism and hotel business. It was proposed directly by entrepreneurs as one of the possible solutions to classic market problems (including limited demand and factors of production). These market problems intensified in the second half of the last century, and all of them directly influenced the development of tourism. The study analyzed the driving forces of transnationalization of the tourism and hospitality sectors, taking into account the economic effect of the synergy of transnationalization. Expansion of tourist activities of the sectoral transnational corporations along with their gradual transformation into influential subject of the world economy. All of the considered in the article synergy effects from tourist business transnationalization have nearly simultaneous impact on the process of tourist services’ production.

This study is aimed at identifying the best values for the parameters of energy efficient digital development of the petroleum and gas sector. Research methods - construction of a production function, regression analysis and linear programming. Based on the production function of Cobb-Douglas, the dependence of the sales volumes of the petroleum and gas sector of the economy on the costs of digitalization and labor costs was revealed; the regression analysis method provided the construction of a set of equations describing the impact of the costs of energy resources of petroleum and gas enterprises and the costs of digitalization on the total costs of enterprises for production and sales, the efficiency of using by-products from petroleum production and labor capital; the optimal values of energy-efficient digital resource-saving development of the petroleum and gas sector of the economy have been determined, the achievement of which will ensure a decrease in the energy consumption of processes at the enterprises of the petroleum and gas complex. Thus, connections have been established and the trajectories of energy efficient functioning of the petroleum and gas sector of the economy have been determined. The research results can be applied within the framework of strategies for socio-economic development, sustainable development, as well as digitalization of the petroleum and gas complex and industrial enterprises.Keywords: regression analysis, digitalization, resource conservation, energy efficiency, petroleum and gas sector, JEL Classifications: О14, D24, С41DOI: https://doi.org/10.32479/ijeep.11695

Osteosarcoma (OS) frequently metastasizes to lung where it greatly contributes to patient mortality. Frustratingly, OS treatment options have remained static due to a paucity of strong pre-clinical evidence to motivate clinical trials. To identify therapeutic targets, we assessed a number of FDA approved therapies for their cytotoxic effects. We found that histone deacetylase (HDAC) inhibitors (panobinostat and romidepsin) limited OS viability at low nM and were highly effective for the treatment of lung metastatic disease in vivo. Although clinically approved, HDAC inhibitors have noted toxicities. Therefore, we next examined the potential mechanisms through which HDAC controlled OS growth. Gene expression analyses on romidepsin treated OS cells revealed key up and downregulated targets. We found that SLC17A7, a vesicular glutamate transporter, was highly and consistently induced in response to romidepsin (greater than 100 fold more than base line) across multiple OS cell lines. Functionally, SLC17A7 traps glutamate in cytoplasmic synaptic vesicles that are then released via exocytosis. Our data show that HDAC inhibition reduces glutamate secretion from OS cells while SLC17A7 overexpression significantly impaired OS viability. Further, we showed that the glutamate export inhibitor, riluzole, significantly impairs the OS growth in vitro and is highly effective for the treatment of lung metastatic OS in vivo. Taken together, we conclude that HDAC1/2 suppression of SLC17A7 ensures high cytoplasmic glutamate levels that can be leveraged for OS growth. We posit that targeting glutamate usage by OS cells using FDA approved inhibitors such as riluzole will be highly effective for the treatment of lung metastatic OS. Citation Format: Niveditha Nerlakanti, Jeremy McGuire, Ryan T. Bishop, Diana Yu, Damon R. Reed, Conor C. Lynch. Delineating the role of vesicular glutamate transporter SLC17A7 in osteosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 276.

Arylamino derivatives of both the corresponding nitroquinolones and nitrosoquinolones were first obtained by direct nucleophilic substitution of hydrogen in the molecules of 1-methyl-5(6,7,8)-nitroquinolin-2(1Н)-ones.

OBJECTIVESTo characterize the voriconazole and posaconazole serum trough ordering practices in patients receiving prophylactic and treatment antifungal therapy.METHODSA retrospective chart review over a 6-year period of pediatric patients who received voriconazole and/or posaconazole for >24 hours.RESULTSA total of 113 patients were included in this study and of these patients, 105 received voriconazole and 16 received posaconazole during the study period. Additionally, 167 trough levels were assessed in this study. Only 50% and 54% of levels were considered within goal recommendations for voriconazole and posaconazole, respectively. The median dose required to achieve goal trough concentration was dependent on drug, indication, and dosage form. Lastly, the most common adverse drug reactions (ADRs) were hepatoxicity, QTc prolongation, and CNS changes, which were in concordance with ADRs documented in the clinical trials for voriconazole and posaconazole. Approximately 20% of patients receiving either voriconazole or posaconazole died during the study period and the median trough in both groups was subtherapeutic.CONCLUSIONSIncreased monitoring of trough concentrations may be warranted to prevent death or breakthrough invasive fungal infections. Further studies are warranted for assessing the relationship between trough concentrations and treatment outcomes as well as relationship between dosing and achieving goal trough concentrations.