bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiopulmonary Arrest Following a Single 25 mg Dose of Quetiapine: A Case Report
Authors: Chia Pamela , Chuan Poh Lim , Ong John , Ong Sharon
Published: November 2020

Introduction

Quetiapine is commonly used in intensive care units (ICU) to treat delirium. Cardiopulmonary arrest caused by low dose quetiapine is unreported. Only two cases in the literature have reported acute respiratory failure after single doses of 50mg and 100mg respectively. We report a case of cardiopulmonary arrest in a patient after the administration of a single 25mg dose of quetiapine.

Case presentation

A 72-year-old Chinese female with multiple cardiovascular co-morbidities was admitted to the ICU intubated, following complications from an elective endovascular repair of an infrarenal abdominal aortic aneurysm. She was alert and extubated the following day. She subsequently showed signs of delirium and was administered a single 25mg dose of oral quetiapine. Seven hours after ingestion, she developed type 2 respiratory failure and eventually cardiopulmonary arrest. She was successfully resuscitated and other causes for cardiopulmonary arrest were excluded. Twenty-four hours following her cardiopulmonary arrest, her respiratory failure had completely reversed and she was extubated uneventfully.

Conclusion

This case report demonstrates that a single dose of oral quetiapine 25mg is sufficient to cause respiratory failure and cardiopulmonary arrest. Caution is advised when prescribing quetiapine in the elderly, especially in those with impaired drug clearance.
Oestrus synchronisation with progesterone-containing sponge and equine chorionic gonadotropin in Pirlak ewes during the non-breeding season: can Toryum improve fertility parameters?
Authors: Kuru Mushap , Boga Kuru Buket , Sogukpinar Osman , Cebi Sen Cigdem , Oral Hasan , Kirmizibayrak Turgut
Published: November 2020

Introduction

The aim of the study was to determine the effect of the vitamins, omega-3 polyunsaturated fatty acid and minerals in the supplement Toryum administered before and during oestrus synchronisation on some fertility parameters of ewes during the non-breeding season.

Material and Methods

The experimental animals were clinically healthy Pirlak ewes, 55–75 days postpartum, aged 2–4 years and weighing 40–50 kg. A sponge was inserted into the vagina for 10 d (G1, n = 30; G2, n = 30) or 14 d (G3, n = 30; G4, n = 30) for oestrus synchronisation, and on the day of removal, 400 IU equine chorionic gonadotropin was injected. Toryum soft capsules were administered individually (1 capsule/ewe p.o.) to G1 and G3 ewes seven days before the sponge was inserted and on the day it was removed. Oestrus detection was started 12 h after sponge removal. Pregnancy was diagnosed by transrectal ultrasonography on the 30th day after mating.

Results

The pregnancy rate was statistically different between G1 and G4 (P < 0.05). The onset of oestrus was statistically different (P < 0.001) between the 10-d groups (G1 and G2) and the 14-d groups (G3 and G4). The litter size and oestrus, conception, lambing, multiple birth, and survival rates were not significantly different between the groups (P > 0.05).

Conclusion

Toryum administered to Pirlak ewes during progesterone-based oestrus synchronisation protocols during the non-breeding season may increase pregnancy rates. The relationship between Toryum and fertility parameters in ewes would be better understood by comprehensive studies.
Enhancement of color quality and luminous flux for remote-phosphor LEDs with red-emitting CaMgSi2O6:Eu2+,Mn2+
Authors: Luo Guo-Feng , Loan Nguyen Thi Phuong , Van Tho Le , Anh Nguyen Doan Quoc , Lee Hsiao-Yi
Published: November 2020

SiO2 particles and red-emitting CaMgSi2O6:Eu2+,Mn2+ phosphor have been added into a yellow phosphor compound YAG:Ce3+ to enhance the optical efficiency of white light LEDs whose average correlated color temperature (CCT) is in the range of 5600 K ÷ 8500 K. It was observed that altering CaMgSi2O6:Eu2+,Mn2+ concentration from 2 % to 30 % while maintaining 5 % of the SiO2 strongly influenced the color rendering index (CRI), color quality scale (CQS), and lumen efficiency of the compound. Besides, through the application of Monte Carlo simulation and Mie-scattering theory, it was possible to improve the optical properties by CaMgSi2O6:Eu2+,Mn2+ and SiO2 addition. The results provided a practical approach to achieve higher luminous efficiency and better color uniformity in remote-phosphor white LEDs (RP-WLEDs).
Density functional theory calculations and Hirshfeld surface analysis of propyl-para-hydroxybenzoate (PHB) for optoelectronic application
Authors: Mohankumar V. , Karunagaran N. , Pandian M. Senthil , Ramasamy P.
Published: November 2020

The geometries, electrostatic potential, Mulliken charge analysis, Natural Bond Orbital analysis and polarizabilities of propyl-para-hydroxybenzoate were calculated using B3LYP functional with 6-311++G(d,p) basis set. The calculated geometries are well matched with the experimental values. The Mullliken atomic charge analysis shows that the eventual charges are contained in the molecule. The NBO analysis explains the intramolecular charge transfer in the PHB molecule. The bonding features of the molecule were analyzed with the aid of Hirshfeld surface analysis. The frontier molecular orbital analysis showed the charge transfer obtained within the molecule. The calculated hyperpolarizability of the PHB molecule was 6.977E −30 esu and it was 8.9 times that of standard urea molecule.
Effects of acoustic warning signal intensity in the control of visuospatial interference
Authors: Cappucci Paola , Correa Ángel , Fischer Rico , Schubert Torsten , Lupiáñez Juan
Published: November 2020

Previous studies have reported increased interference when a task-irrelevant acoustic warning signal preceded the target presentation in cognitive tasks. However, the alerting-congruence interaction was mostly observed for tasks measuring Flanker and Simon interferences but not for Stroop conflict. These findings led to the assumption that warning signals widen the attentional focus and facilitate the processing of irrelevant spatial characteristics. However, it is not clear whether these effects are because of the temporal information provided by the warning signal or because of their alerting effects. Based on these findings, and on the open question about the nature of the warning signal intervention on visuospatial interferences, we decided to test the impact of the warning signal on the processing of irrelevant spatial features, by using a procedure suitable for measuring both Simon and spatial Stroop interferences. We also manipulated the intensity of the warning signal to study the effect of the task-irrelevant characteristics of warning signals in visuospatial interferences. For the Simon conflict, results demonstrated an increased interference provoked by the presence (Experiment 1) and intensity (Experiment 2) of warning signals. In contrast, neither the presence nor the intensity of warning signals affected the spatial Stroop interference. Overall, these findings suggest that the impact of warning signals primarily depends on the processing of irrelevant spatial attributes and on the type of conflict (e.g., spatial stimulus-response interference in Simon vs. stimulus-stimulus interference in spatial Stroop). In general, acoustic warning signals facilitate the automatic response activation, but their modulatory effect depends on the task setting involved.
Artificial intelligence in musculoskeletal oncological radiology
Authors: Vogrin Matjaz , Trojner Teodor , Kelc Robi
Published: November 2020

Background

Due to the rarity of primary bone tumors, precise radiologic diagnosis often requires an experienced musculoskeletal radiologist. In order to make the diagnosis more precise and to prevent the overlooking of potentially dangerous conditions, artificial intelligence has been continuously incorporated into medical practice in recent decades. This paper reviews some of the most promising systems developed, including those for diagnosis of primary and secondary bone tumors, breast, lung and colon neoplasms.

Conclusions

Although there is still a shortage of long-term studies confirming its benefits, there is probably a considerable potential for further development of computer-based expert systems aiming at a more efficient diagnosis of bone and soft tissue tumors.
Interleukin-10 (IL-10) 1082 promoter polymorphisms and plasma IL-10 levels in patients with bacterial sepsis
Authors: Vivas Monica Chavez , Villamarín-Guerrero Héctor Fabio , Sanchez Carlos Alberto
Published: November 2020

Background. Interleukin-10 (IL-10) is a multifunctional cytokine which has been seen to play a relevant role in the pathogenesis of sepsis. We examined the association between a single nucleotide polymorphism (SNP) in IL-10-1082G/A in patients with sepsis in Cali city.

Methods. A total of 100 patients with sepsis and 50 control subjects were enrolled in this study. Blood samples were collected from all patients in EDTA containing tubes. IL-10-1082G/A gene promoter polymorphism was analyzed by Sequence Specific Polymerase Chain Reaction (SS-PCR), while levels of serum IL-10 were measured by Enzyme Linked Immunoassay Assay (ELISA) in patients with sepsis and healthy controls.

Results. AA homozygous genotype was found more frequently in patients (32%), compared with controls (18%). AA homozygous patients showed an increased risk of developing infection by Gram-negative bacteria (OR = 2,875; 95% CI = 1.162-7.113; p = 0.020), and significantly high plasma levels of IL-10 (OR = 4.800, 95% CI 1.652–13.944; p = 0.002). AA homozygous patients high plasma IL-10 levels have greater risk of developing sepsis (63.6%; OR = 4,894; 95% CI: 1,337–17,909; p = 0.002). In this group, Afro-Colombian individuals were overrepresented among the sepsis patients with high plasma IL-10 levels (OR = 1.661; 95% CI: 1.408–1.959; p = 0.036).

Conclusion. Our study concluded that AA genotype of IL-10-1082G/A polymorphism is a risk factor for high IL-10 production and development of sepsis by Gram negative bacteria, especially in Afro-Colombian patients.
Predictors of disease severity and outcome of hospitalized renal transplant recipients with COVID-19 infection: a systematic review of a globally representative sample
Authors: Hasan Irtiza , Rashid Tasnuva , Suliman Sarah , Amer Hatem , Chirila Razvan M. , Mai Martin L. , Jarmi Tambi , Khouzam Samir , Franco Pablo Moreno , Heilig Charles W. , Wadei Hani M.
Published: November 2020

Introduction. COVID-19 presents a special challenge to the kidney transplant population.

Methods. A systematic review of articles that examined COVID-19 in kidney transplant recipients was performed. Patients’ demographics, clinical, laboratory and radiological presentations, immunosuppression modification, and COVID-19 specific management were abstracted and analyzed. COVID-19 severity was classified into mild, moderate, and severe. Disease outcome was classified by whether the patient was discharged, still hospitalized, or died.

Results. 44 articles reporting individual data and 13 articles reporting aggregated data on 149 and 561 kidney transplant recipients respectively with COVID-19 from Asia, Europe and America fulfilled all inclusion and exclusion criteria. Among studies reporting case specific data, 76% of cases had severe disease. Compared to patients with mild/moderate disease, patients with severe disease had higher CRP, LDH, Ferritin, D-dimer and were more likely to have bilateral lung involvement at presentation and longer time since transplantation (P < 0.05 for all). Recipients’ age, gender and comorbidities did not impact disease severity. Patients with severe disease had a more aggressive CNI reduction and more antiviral medications utilization. Outcome was reported on 145 cases, of those 34 (23%) died all with severe disease. Longer duration from transplant to disease diagnosis, hypoxia and higher LDH were associated with mortality (P < 0.05). Different immunosuppression reduction strategies, high dose parenteral corticosteroids use and various antiviral combinations did not demonstrate survival advantage. Similar finding was observed for studies reporting aggregated data.

Conclusion. COVID-19 in kidney transplant patients is associated with high rate of disease severity and fatality. Higher LDH and longer time since transplantation predicted both disease severity and mortality. None of the COVID-19 specific treatment correlated with, or improved disease outcome in kidney transplant recipients.
Collaborative Governance dalam Kebijakan Sertifikasi Produksi Pangan Industri Rumah Tangga Kopi Bubuk Koto Tuo Kabupaten Tanah Datar
Authors: Koeswara Hendri , Aromatica Desna , Yulivestra Malse , Kabullah Muhammad Ichsan , Liesmana Roza , Hidayat Enggi
Published: November 2020

The facilitation in the implementation of the Ground Coffee Home Food Industry (IRTP) certification policy by Tanah Datar District has not been optimal. This situation is counterproductive, with Nagari Koto Tuo being listed as one of the largest producers of ground coffee in Tanah Datar Regency. Nearly 75% of the Nagari Koto Tuo people live from processing coffee from generation to generation for more than two generations. A total of 160 Ground Coffee IRTPs with 177 coffee trademarks are registered in Nagari Koto Tuo, ironically only 14 have SPP-IRT. The policy issued by BPOM RI No. 22/2018 for the ease of providing the Home Industry Food Production Certificate (SPP-IRT) has not been able to respond in policy by the Regency Governments. The Nagari Koto Tuo government is also limited in advocating for Ground Coffee IRTP. And, since the launch of the Village Fund, there have not been many programs/and budgets allocated related to this Nagari, coupled with the existence of Nagari Owned Enterprises (BUMNag), which do not have a core business according to the village potential, namely coffee. Research using qualitative methods with a case study approach to collaborative governance was conducted by identifying the involvement of actors and policies in providing IRTP for Ground Coffee. The collaborative governance model removes the barriers of actors related to synergy and policies that have been blocked in their respective powers and duties and their respective functions that nullify the society's potential. Collaboration between actors has proven to be an important element in the success of providing SPP-IRTP for Ground Coffee by optimizing socio-economic capital in village development. This is where the obstacles that occur that cause a lack of IRT-P.
Insurance of economic security of registrars on the financial market: risk management techniques and allocation of resources (2001-2018). Part 2
Authors: Bekryashev Andrey
Published: November 2020

The subject of this research is the problems of allocation of resources associated with risk management of the registry of securities holders. The object of this research is the activity of the registrars on risk management. The author examines the peculiarities of risk management techniques of registrars, and dynamics of their application for the period from 2001 to 2018. The factors that contribute to selection of one or another technique are analyzed. Special attention is given to the market insurance and reservation as management techniques, as well as to price and institutional factors that affect the choice. The article employs the methods of retrospective research of economic indicators in accordance with sampling that covers Russia’s largest registrars (in 2001-2018), as well as methods of correlation and regression analysis. As a result of the conducted research, the author determines stages in the dynamics of using the key risk management techniques. The factors of dynamics are related to the parameters of risk and relative cost of implementation of particular techniques. The author's contribution consists in the empirical research on the basis of public data of factors and trends in allocation of resources associated with risk management of registrars on the financial market for the period from 2001 to 2018. The novelty of this work lies in outlining the factors and trends in allocation of resources related to risk management of registrars in fort the period from 2001 to2018, considering public data on the activity of Russia’s largest registrars, content analysis of publications, and case law of the  computer-based legal research system “ConsultantPlus”.
Socioeconomic relations between Kazakhstan and China after the dissolution of the Soviet Union
Authors: Ma Yifeng
Published: November 2020

The object of this research is the China – Kazakhstan relations in the XX-XXI centuries. The subject of this research is the socioeconomic ties between the two countries after the dissolution of the Soviet Union. Analysis is conducted on the general trend of socioeconomic ties between China and Kazakhstan, as well as socioeconomic cooperation between them during the 1990s and 2000s. The author examines such aspects as the advantages and difficulties with regards to trade, development of border trade, joint construction of railways, cooperation in the sphere of energy, etc. The main merit of the conducted research consists in the description of bilateral socioeconomic relations between the two countries, which are shifting to the next level and more diverse structure, due to the unique political coordination of Kazakhstan and China, benefits of geographical location and additional economic structure. The current China – Kazakhstan relations represent the model of mutual respect, equality and mutually advantageous cooperation. The novelty of this work lies in division of the China – Kazakhstan trade relations into different periods in accordance with the characteristics, as well as in determination of the priority vectors of cooperation. The article provides a general description of trade and economic cooperation between China and Kazakhstan.
Russia – China humanitarian cooperation in the area of youth cultural and educational projects between Amur Region and Heilongjiang Province (early XXI century)
Authors: Zalesskaia Olga , Yan Meiwei
Published: November 2020

The subject of this research is humanitarian cooperation between Russia and China in the area of youth cultural and educational projects between Amur Region and Heilongjiang Province in the early XXI century. The first two decades of the XXI century, these relations are characterized by active contacts in the area of culture and education, prominent education projects on intergovernmental and interregional levels. Within the framework of the National Years of Russia and China, a significant number of events were held to promote interaction between the youth of two countries and their familiarization with the culture of another country. Such events are of particular relevance in the Far Eastern border region – the intersection of Russia and China. The authors analyze the documentation on humanitarian cooperation between Russia and China, and give characteristics to the joint projects and programs in the sphere of education and science between Amur Region and Heilongjiang Province. The novelty of novelty of this work consists in the detailed analysis of specificity of youth education projects between the border regions of the Russian Far East and Northeast China in the early XXI century, which were implemented prior to the COVID-19 pandemic. The authors also considered the interaction between Russian and Chinese universities in the context of close humanitarian and youth cooperation. The article features the materials translated by the authors from Chinese language. The past two decades of the XXI century mark a substantial array of cultural and educational events dedicated to youth of Russia and China; thus, humanitarian cooperation between Russia and China in the sphere of youth education projects has become an integral element of interregional contacts between Amur Region and Heilongjiang Province. The accumulated historical experience with regards to cooperation between the two countries in this sphere directly impacts the development of Russia – China relations, and requires druthers research..
Activity of the Prosecutor's Office of the Khakas Autonomous Oblast during the Great Patriotic War
Authors: Chekushkina Ekaterina Olegovna , Tuguzhekova Valentina Nikolaevna
Published: November 2020

This article is dedicated to examination of the activity of the Prosecutor's Office of the Khakas Autonomous Oblast during the Great Patriotic War, with involvement of the archival sources. The object of this research is the Soviet Prosecutor's Office in Khakassia; while the subject is the activity of the Prosecutor's Office of the Khakas Autonomous Oblast during the Great Patriotic War. The goal consists in the analysis of work of the Prosecutor's Office of the Khakas Autonomous Oblast during the wartime. The scientific novelty lies in systematization, generalization of materials on the topic, examination of the activity of Prosecutor's Office on the example of a particular region (Khakas Autonomous Oblast), as well as involvement of archival sources. The conclusion is made on contribution of the employees of Prosecutor's Office in supporting and aiding the front. In the conditions of wartime, the Prosecutor's Office of the Khakas Autonomous Oblast alongside Prosecutor's Office of the USSR as a whole, had to transfer its work onto the “wartime footing”, as well as deal with such activities as the struggle against desertion, protection of the rights of military families. Ensuring law enforcement on the home front was the key task of the Prosecutor’s Office.
Modelling of multi-component droplet evaporation under cryogenic conditions
Authors: Xu Xiaochun , Privat Romain , Jaubert Jean-Noël , Qu Yongfeng , Bonnissel Marc
Published: November 2020

The vaporization of drops of highly vaporizable liquids falling inside a cryogenic environment is far from being a trivial matter as it assumes harnessing specialized thermodynamics and physical equations. In this paper, a multi-component falling droplet evaporation model was developed for simulating the spray cooling process. The falling speed of the sprayed droplets was calculated with the momentum equations considering three forces (gravity, buoyancy and drag) applied to a droplet. To evaluate the mass and heat transfer between the sprayed droplet and the surrounding gas phase, a gaseous boundary film of sufficient thinness was assumed to envelope the droplet, while the Peng-Robinson equation of state was used for estimating the phase equilibrium properties on the droplet’s surface. Based on the relevant conservation equations of mass and energy, the key properties (such as temperature, pressure and composition) of the liquid and gas phases in the tank during the spray process could be simulated. To conclude, the simulation algorithm is proposed.
Vulgar psoriasis and squamous cell carcinoma in a patient with discoid lupus erythematosus
Authors: Dubensky Valeriy V. , Nekrasova Elizaveta G. , Alexandrova Olga A. , Muraveva Ekaterina S.
Published: November 2020

A rare case of a combination of vulgar psoriasis and squamous cell carcinoma of the penis in a patient with discoid lupus erythematosus is described. The literature data on the comorbidity of dermatoses are given.
Physiological changes of the skin during pregnancy
Authors: Albanova Vera I.
Published: November 2020

The appearance of skin changes during pregnancy is inevitable and physiologically determined. This period is characterized by hormonal, immunological and metabolic changes and associated physiological changes in the skin. These include pigmentation (linea nigra, melasma, pseudoacanthosis, growth and appearance of pigmented nevi), changes in connective tissue (striae distensae, skin tags), blood vessels (stellate hemangiomas, erythema of the palms, vasodilatation, edema, cutis marmorata) and skin appendages (increased sebaceous and eccrine glands activity, reduced hair loss and increased hair density, onychodystrophy). It is important to inform women about possible changes, to recognize them in time to reduce the impact of their appearance on the health and course of pregnancy, as well as to avoid unnecessary tests and interventions.
Surgical oncology residents’ perspective in the COVID-19 pandemic: Standing at crossroads
Authors: Gundavda Kaival K. , Patkar Shraddha , Gulia Ashish
Published: November 2020

The COVID-19 pandemic has hampered health-care delivery, with non-emergent consultations and surgical procedures being brought to a standstill. However, a delay in comprehensive cancer care may result in disease progression and poorer outcomes. Surgical oncology residents often form the front line responders for cancer patients, but now also have to function outside of their specialty to serve in COVID-19 units. With the uncertainty and unpredictability of this pandemic, surgical oncology residents find themselves at a crossroads. The need to keep abreast with COVID-19 treatment guidelines and recommendations comes at the expense of their surgical training. There is also a rising concern about personal safety, wellness, psychosocial well-being, and burnout. We highlight various elements concerning residents and suggest strategies that may be undertaken to allay anxiety and fatigue and facilitate surgical education.
Molecular and biological characteristics of keratin intermediate filaments in intact skin under systemic inflammation
Authors: Демяшкин Г.А. , Шаповалова Е.Ю. , Маланичев М.Ю. , Погосян Д.А. , Батов М.А. , Зорин И.А. , Щекин В.И.
Published: November 2020

Введение. Несмотря на определенный прогресс в изучении патоморфологических механизмов сепсиса и усовершенствовании методов терапии критических состояний, летальность при сепсисе сохраняется на высоком уровне. При тяжелом системном воспалении нарушается морфофункциональное состояние кожного покрова, однако обусловливающие этот эффект механизмы описаны поверхностно. Нуждается в уточнении роль изменения экспрессии генов кератиноцитов цитоскелета, приводящая к нарушению их дифференцировки и миграции на фоне действия эндогенного фактора, индуцированного тяжелым системным воспалением. Цель работы - оценка молекулярно-генетического профиля дифференцировки и миграции кератиноцитов на фоне системного воспаления. Методика. Фрагменты интактной кожи пациентов с подтвержденным сепсисом (n=46) были изучены методом полимеразной цепной реакции в режиме реального времени для определения экспрессии генов промежуточных филаментов кератиноцитов KRT1, KRT10, KRT5, KRT14 и KRT16. Результаты. У пациентов в условии системного воспаления относительная экспрессия KRT1, KRT10, KRT5, KRT14 и KRT16 в интактной коже снижена, несмотря на сохранение уровня экспрессии генов, продукты которых поддерживают агрегацию филаментов и стабильность цитоскелета - FLG, IVL. Заключение. В интактной коже на фоне системного воспаления в отсутствие внешнего повреждающего фактора отмечается разобщение дифференцировки и пролиферации кератиноцитов, способное привести к нарушению барьерной функции кожи.

Introduction. Despite some progress in studying pathomorphological mechanisms of sepsis and improvement of therapy for critical conditions, mortality in sepsis remains high. In severe systemic inflammation, the morpho-functional state of skin is compromised; however, the mechanisms responsible for this effect are not completely understood. The role of mutations in keratinocyte cytoskeletal genes leading to disorders of keratinocyte differentiation and migration under the action of an endogenous factor induced by severe systemic inflammation, needs to be clarified. The aim of this work was to assess the molecular genetic profile of keratinocyte differentiation and migration under systemic inflammation. Methods. Fragments of intact skin from patients with confirmed sepsis (n=46) were studied with real-time polymerase chain reaction to determine the expression of keratin intermediate filament KRT1, KRT10, KRT5, KRT14, and KRT16 genes. Results. In patients with systemic inflammation, the relative expression of KRT1, KRT10, KRT5, KRT14, and KRT16 in intact skin was reduced, despite the normal expression of genes whose products support filament aggregation and cytoskeletal stability (FLG and IVL). Conclusion. In the intact skin under systemic inflammation in the absence of an external damaging factor, uncoupling of the keratinocyte differentiation from the keratinocyte proliferation was observed, which may lead to dysfunction of the skin barrier.
Review of properties and mechanisms of action of hepatoprotective drugs
Authors: Кардаш Е.В. , Григорьева Е.М. , Емельянова А.Г. , Тарасов С.А.
Published: November 2020

В медицинской практике достаточно часто возникает необходимость в одновременном приеме нескольких лекарственных средств. Иногда это оказывается невозможным в силу наличия у препаратов гепатотоксических свойств, поэтому актуальными задачами фармакологии являются как поиск и разработка новых препаратов, так и оптимизация уже существующих с целью уменьшения побочных эффектов при их приеме. В настоящем обзоре были проанализированы данные о фармакологических препаратах класса гепатопротекторов, разобраны механизмы их действия и потенциал поиска новых препаратов. В заключение отмечено, что в настоящее время в клинической практике наибольшей популярностью пользуются препараты, содержащие эссенциальные фосфолипиды и препараты, улучшающие рециркуляцию и выведение желчных кислот. Существуют теоретические обоснования механизмов действия этих препаратов и перспектива накопления доказательной базы для них в виде рандомизированных клинических исследований и мета-анализов.

Medical practice quite often requires simultaneous administration of several drugs. Sometimes it is impossible due to their hepatotoxicity; therefore, urgent tasks of pharmacology include searching for and developing new drugs as well as optimizing already existing products in order to reduce side effects during their administration. This review focused on pharmacological drugs of the hepatoprotector class and their mechanisms of action and evaluated the prospects of searching for new medicines. In conclusion, drugs containing essential phospholipids and those improving recirculation and removal of bile acids are currently the most popular agents in clinical practice. Mechanisms of action of these drugs are theoretically justified and there is a prospect for building an evidence base for them by randomized clinical trials and meta-analyses.
The current stage of neuroprotection: development of mitochondria-targeted approaches
Authors: Шакова Ф.М. , Кирова Ю.И. , Романова Г.А.
Published: November 2020

Обзор посвящен рассмотрению современных подходов к фармакологической модуляции структурно-функционального состояния митохондриального аппарата нейронов как перспективной стратегии терапии ишемического инсульта головного мозга, составляющего по современным оценкам до 85% всех случаев острого нарушения мозгового кровообращения. В обзоре проведен анализ классических представлений о нейропротекции как терапии, направленной на блокирование ключевых патогенетических звеньев «ишемического каскада», в контексте современного понимания приоритетной роли коррекции митохондриальной дисфункции в ограничении механизмов повреждения при церебральной ишемии. Обсуждаются возможности применения препаратов плейотропного нейропротекторного действия, реализующих митохондриально-направленные защитные эффекты через модуляцию активности транскрипционного коактиватора PGC-1α (peroxisome proliferator-activated receptor-1γ coactivator-1α), контролирующего процессы биогенеза митохондрий, ангиогенеза, ферментативное звено антиоксидантной системы.

The review addresses modern approaches to pharmacological modulation of structure and function of the neuronal mitochondrial apparatus. This is a promising strategy for therapy of ischemic stroke, which accounts for up to 85% of all cases of acute cerebrovascular disease. The review analyzes classical concepts of neuroprotection as a therapy aimed at blocking key pathogenetic components of the “ischemic cascade”. These concepts are based on current ideas about the importance of correcting mitochondrial dysfunction for alleviation of damage in cerebral ischemia. The authors discussed possibilities of using pleiotropic neuroprotectors that implement mitochondrial-targeted protective effects by modulating the activity of transcriptional coactivator, peroxisome proliferator-activated receptor-1γ coactivator-1α (PGC-1α), which controls mitochondrial biogenesis, angiogenesis, and the enzymatic antioxidant system.
Defects in the interventricular and atrial septa: the contribution of the transcription factor GATA6 and the signal molecule NOTCH1
Authors: Цепокина А.В. , Понасенко А.В. , Деева Н.С. , Шабалдин А.В.
Published: November 2020

Актуальность: Поиск биологических маркёров, вовлеченных в патогенез врожденных пороков сердца (ВПС), остается актуальным вопросом современной медицины и биологии. Врожденные пороки - мультифакторное заболевание, причинами развития которого является взаимовлияющее действие эндогенных и экзогенных факторов. В настоящее время показана роль генов семейства GATA и NOTCH1 в формировании предрасположенности к развитию врожденных пороков сердца. Материалы и методы: Группу исследования составили 58 детей с диагнозом дефекта межжелудочковой и межпредсердной перегородок, в контрольную группу включены 103 ребенка без данной патологии. Генотипирование проводили полимеразной цепной реакцией в режиме реального времени с использованием TaqMan-зондов. Результаты: Исследование встречаемости генотипов генов GATA6 и NOTCH1 в исследуемой и контрольной группах не показало статистически значимых различий. Однако, анализ межгенных взаимодействий при помощи программы MDR 3.0.2. позволил выделить ряд протективных и рисковых генотипов. Заключение: Несмотря на отсутствие статистически значимых различий по частоте встречаемости генотипов, полученные в ходе анализа межгенных связей сочетания генотипов могут быть связаны с предрасположенностью к развитию ВПС.

Background: The search for biological markers involved in the congenital heart diseases pathogenesis remains a topical problem in modern medicine and biology. Congenital heart diseases are a multifactorial disease caused by the mutually affecting effects of endogenous and exogenous factors. Currently, the role of GATA and NOTCH1 gene family in the predisposition to development of congenital heart diseases is shown. Materials and methods: 58 children with a diagnosis of congenital heart diseases (defects in the interventricular and atrial septa) and 103 children without this pathology were included in the study and the control groups, respectively. Genotyping was performed by real-time polymerase chain reaction using TaqMan probes Results: A study of the frequencies of the genotypes in the GATA6 and NOTCH1 genes in the study and control groups showed no statistically significant differences. At the same time, the analysis of gene-gene interactions using MDR 3.0.2 software allows to determine a number of protective and risk genotypes. Conclusion: Despite the absence of significant differences in the frequency of genotypes, combinations of genotypes obtained during the analysis of gene-gene interactions may be associated with a predisposition to the development of congenital heart diseases.
Elevated Lipocalin-2 Can Indicate the Vascular Inflammation in Patients with Ischemic Stroke
Authors:   Kaposi Mór Teaching Hospital Department of Hematology, Kaposvár, Hungary, P Rajnics , A Kellner ,   Kaposi Mór Teaching Hospital Department of Hematology, Kaposvár, Hungary, F Nagy ,   Kaposi Mór Teaching Hospital Department of Neurology, Kaposvár, Hungary, V Alföldi ,   Kaposi Mór Teaching Hospital Department of Neurology, Kaposvár, Hungary, C CsBödőr ,   MTA-SE Lendulet Molecular Oncohematology Research Group, 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, A Gángó ,   MTA-SE Lendulet Molecular Oncohematology Research Group, 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, M Moizs ,   Kaposi Mór Teaching Hospital Department of Hematology, Kaposvár, Hungary, M Egyed ,   Kaposi Mór Teaching Hospital Department of Hematology, Kaposvár, Hungary
Published: November 2020

Purpose: Elevated level of Lipocalin-2 (LCN2), a new acute phase adipokine, was described after ischemic stroke. A number of researchers feel as though that LCN2 originated from the infiltrating neutrophils and other cells in brain after stroke. Others measured elevated LCN2 expression in arteriosclerotic plaque. Therefore we have investigated LCN2 relative gene expression level of blood neutrophil granulocytes in patients with ischemic stroke to assess if elevated LCN2 is the cause or consequence of ischemic stroke. Methods: Laboratory and anamnestic data were collected, which could have a role in development of thrombo-embolic events in patients with ischemic stroke. RNA based method was used to evaluate the relative gene expression level of LCN2. We calculated Odds Ratio (OR) and Confidence Interval (CI) for the association between LCN2 and ischemic stroke. Results: 34 samples were available for evaluation. The LCN 2 relative gene expression level was decreased in 12 cases. In this group, 91% of patients have Atrial Fibrillation (AF) at the time of hospitalisation. The mean LCN2 relative gene expression value was 64.25% (ranges: 34%-115%) in patients with AF. It was significantly lower than in patients with normal sinus rhythm (409.2%; ranges: 127%-1127%; p=0.0003). The elevated LCN2 relative gene expression level significantly (p=0.012) increases the risk of stroke (OR: 12.6) independently from other factors. Conclusions: High LCN2 expression level seems to have strong positive predictive value on ischemic stroke, and may be useful in thrombotic risk stratification of plaque vulnerability in these patients.
Empecilhos e soluções para relação médico-enfermeiro: revisão narrativa / Obstacles and solutions for medical-nurse relationship: narrative review
Authors: Cespedes Mateus Da Silveira , Souza José Carlos Rosa Pires de , Borges Suellem Luzia Costa
Published: November 2020

Objetivos: Identificar e descrever os empecilhos e as soluções para a boa relação médico-enfermeiro. Métodos: trata-se de uma revisão narrativa da literatura com 10 estudos entre 2006 e 2018 que apresentavam como descritores “Relações Médico-Enfermeiro” e “Equipe de Assistência ao Paciente”, cuja pergunta norteadora foi quais os empecilhos e soluções para uma boa relação médico-enfermeiro? Resultados: encontraram-se como empecilhos: déficits na comunicação, pontos de vista conflitantes, alta rotatividade, pressões externas, funções ambíguas, conflito de tarefa, hierarquia, conhecimento técnico e hostilidade prévia. As soluções encontradas foram: redução da carga horária, melhora da estrutura, troca de informações frequentes e sucintas, estímulo às discussões de casos clínicos e propostas terapêuticas conjuntas, valorização dos profissionais mais antigos, delimitação clara da autoridade, responsabilidade e competência de cada profissional, manutenção de relação afetuosa extra-profissional, confiança e valorização dos profissionais. Conclusão: é necessário delimitar os fatores de piora na relação e pôr em prática as soluções oferecidas para desenvolver os profissionais e proporcioná-los melhor ambiente de trabalho.Palavras Chave: Relações médico-enfermeiro, Equipe de assistência ao paciente, Administração hospitalar, Corpo clínico hospitalar, Planejamento hospitalar ABSTRACT:Objectives: To identify and describe the obstacles and solutions for a good doctor-nurse relationship. Methods: it is a narrative review of the literature with 10 studies between 2006 and 2018 that presented as descriptors "Doctor-Nurse Relations" and "Patient Care Team", whose guiding question was what are the obstacles and solutions for a good relationship nurse-doctor? Results: found as impediments: deficits in communication, conflicting points of view, high turnover, external pressures, ambiguous functions, task conflict, hierarchy, technical knowledge and previous hostility. The solutions found were: reducing the workload, improving the structure, exchanging frequent and succinct information, encouraging discussions of clinical cases and joint therapeutic proposals, valuing the oldest professionals, clearly defining the authority, responsibility and competence of each professional, maintenance of an extra-professional affectionate relationship, trust and valorization of the professionals. Conclusion: it is necessary to delimit the factors that worsen the relationship and put into practice the solutions offered to develop professionals and provide them with a better work environment.Key words: Physician-nurse relations; Patient care team; Hospital administration; Teams, health care; Hospital organization and administration
Transcription Factor Allosteric Regulation Through Substrate Coordination to Zinc
Authors: Almeida Beatriz , Kaczmarek Jennifer , Figueiredo Pedro , Prather Kristala LJ , Carvalho Alexandra
Published: November 2020

The development of new synthetic biology circuits for biotechnology and medicine requires deeper mechanistic insight on allosteric transcription factors (aTFs). Here we studied the aTF UxuR, which is a dimer, with each monomer consisting of two structured domains connected by a highly flexible linker region. In order to explore how ligand binding to UxuR affects protein dynamics we performed molecular dynamics simulations in the free protein and the aTF bound to the inducer D-fructuronate or the structural isomer D-glucuronate. We then validated our results by constructing a sensor plasmid for D-fructuronate in E. coli and performed site-directed mutagenesis. Our results show that zinc coordination is necessary for UxuR function, since mutation to alanines prevents expression de-repression by D-fructuronate. Analyzing the different complexes, we found that the disordered linker regions allow the N-terminal domains to display fast and large movements. When the inducer is bound, UxuR is able to sample an open conformation with a more pronounced negative charge at the surface of the N-terminal DNA binding domains. In opposition, in the free and D-glucuronate bond forms the protein samples closed conformations, with a more positive character at the surface of the DNA binding regions. These molecular insights provide a new basis to better harness these systems for biological systems engineering.
Design, Synthesis, and Evaluation of Transition-State Analogs as Inhibitors of the Bacterial Quorum Sensing Autoinducer Synthase CepI
Authors: Higgins Erin , Kellner-Rogers Julian , Estanislau Alexandra , Esposito Alec , Vail Nora R. , Payne Sterling , Stockwell Julia , Ulrich Scott
Published: November 2020

Quorum sensing is a bacterial signaling system that involves the synthesis and detection of small signal molecules called autoinducers. A main class of autoinducers in Gram-negative bacteria are acylated homoserine lactones, produced by the LuxI family of autoinducer synthase enzymes and detected by the LuxR family of autoinducer receptors. Quorum sensing allows for changes in gene expression and bacterial behaviors in a coordinated, cell density dependent manner. Quorum sensing controls the expression of virulence factors in some human pathogens, making quorum sensing an antibacterial drug target. Here we describe the design and synthesis of transition-state analogs of the autoinducer synthase enzymatic reaction and evaluation of these compounds as inhibitors of the synthase CepI. One such compound potently inhibits CepI and constitutes a new type of inhibitor against this underdeveloped antibacterial target.
Operando Analysis of Semiconductor Junctions in Multi-Layered Photocathodes for Solar Water Splitting by Impedance Spectroscopy
Authors: Yang Wooseok , Moehl Thomas , Service Erin , Tilley David
Published: November 2020

Although electrochemical impedance spectroscopy (EIS) is a powerful technique for investigating optoelectronic devices, realistic equivalent circuit (EC) models suitable for multi-layered water splitting electrodes have rarely been reported due to their complex nature. In the present study, we demonstrate the utility of the EIS method for investigating multi-layered photocathodes for photoelectrochemical water splitting. By analyzing the EIS data of TiO2-coated Sb2Se3 photocathodes, we were able to obtain information about the constituent semiconductors and interfaces such as recombination processes, carrier lifetimes, doping densities, and flat band potentials under operando conditions. The charge transfer time to the electrolyte was also extracted from the EIS data and confirmed by transient photocurrent measurements. In addition, the method was successfully applied to other photocathodes with different classes of light absorber, such as metal oxides (Cu2O) and crystalline Si, to compare the device characteristics under real operational conditions. It is shown that the lifetime of photo-generated carriers in the Si photocathode under band bending conditions is much higher than those of the Sb2Se3 and Cu2O photocathodes. We believe that the EIS analysis method presented in this study has made significant progress in understanding the charge carrier behavior in multi-layered photoelectrodes and will become a powerful routine characterization technique for discovering the limiting factors in a wide range of photo-electrosynthetic devices.
Design of BET Inhibitor Prodrugs with Superior Efficacy and Devoid of Systemic Toxicities
Authors: Vohidov Farrukh , Andersen Jannik N. , Economides Kyriakos D. , Shipitsin Michail V. , Burenkova Olga , Ackley James C. , Vangamudi Bhavatarini , Gallagher Nolan M. , Shieh Peyton , Golder Matthew R. , Liu Jenny , Dahlberg William K. , Nguyen Hung V.-T. , Ehrlich Deborah J. C. , Kim Julie , Huh Sung Jin , Neenan Allison M. , Baddour Joelle , Paramasivan Sattanathan , de Stanchina Elisa , KC Gaurab , Turnquist David J. , K. Saucier-Sawyer Jennifer , Kopesky Paul W. , Brady Samantha W. , Jessel Michael J. , Reiter Lawrence A. , Chickering Donald E. , Johnson Jeremiah , Blume-Jensen Peter
Published: November 2020

Prodrugs engineered for preferential activation in diseased versus normal tissues offer immense potential to improve the therapeutic index of preclinical and clinical-stage active pharmaceutical ingredients that either cannot be developed otherwise or whose efficacy or tolerability it is highly desirable to improve. Such approaches, however, often suffer from trial-and-error design, precluding predictive design and optimization. Here, using BET bromodomain inhibitors (BETi)—a class of epigenetic regulators with proven anti-cancer activity but clinical development hindered by systemic adverse effects–– we introduce a platform that overcomes these challenges. Through tuning of traceless linkers appended to a “brush prodrug” scaffold, we demonstrate that it is possible to correlate in vitro prodrug activation kinetics with in vivo tumor pharmacokinetics, leading to novel BETi prodrugs with enhanced anti-tumor efficacy and devoid of dose-limiting toxicities. This work has immediate clinical implications, introducing principles for the predictive design of prodrugs and potentially overcoming hurdles in drug development.
Theoretical Study of a Derivative of Chlorophosphine with Aliphatic and Aromatic Grignard Reagents: SN2@P or the Novel SN2@Cl Followed by SN2@C?
Authors: Savoo Nandini , Rhyman Lydia , Ramasami Ponnadurai
Published: November 2020

The proposed SN2 reactions of a hindered organophosphorus reactant with aliphatic and aromatic nucleophiles [Ye et al., Org. Lett. 19, 5384–5387 (2017)] were studied theoretically in order to explain the observed stereochemistry of the products. Our computations indicate that the reaction with the aliphatic nucleophile occurs through a backside SN2@P pathway while the reaction with the aromatic nucleophile proceeds through a novel SN2@Cl mechanism, followed by a frontside SN2@C mechanism. To the best of our knowledge, this is the first time that a SN2@Cl mechanism is reported. We also found that on reducing the bulkiness of substituents around the phosphorus atom, the backside SN2@P mechanism is preferred. The conclusions made from investigating the steric effect should help experimentalists to decide for the organophosphorus reactant to achieve the products of desired stereochemistry.