scholarly journals In-silico evaluation of Malawi essential medicines and reactive metabolites for potential drug-induced toxicities

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ibrahim Chikowe ◽  
Alfred Chipanda Phiri ◽  
Kirios Patrick Mbewe ◽  
Dunstan Matekenya
Keyword(s):  
In Silico ◽  
Well Being ◽  
Essential Medicines ◽  
Reactive Metabolites ◽  
Potential Drug ◽  
Drug Induced ◽  
Chemical Structures ◽  
The World ◽  
Screening Study ◽  
Structural Alerts

Abstract Background Drug-induced toxicity is one of the problems that have negatively impacted on the well-being of populations throughout the world, including Malawi. It results in unnecessary hospitalizations, retarding the development of the country. This study assessed the Malawi Essential Medicines List (MEML) for structural alerts and reactive metabolites with the potential for drug-induced toxicities. Methods This in-silico screening study used StopTox, ToxAlerts and LD-50 values toxicity models to assess the MEML drugs. A total of 296 drugs qualified for the analysis (those that had defined chemical structures) and were screened in each software programme. Each model had its own toxicity endpoints and the models were compared for consensus of their results. Results In the StopTox model, 86% of the drugs had potential to cause at least one toxicity including 55% that had the potential of causing eye irritation and corrosion. In ToxAlerts, 90% of the drugs had the potential of causing at least one toxicity and 72% were found to be potentially reactive, unstable and toxic. In LD-50, 70% of the drugs were potentially toxic. Model consensus evaluation results showed that the highest consensus was observed between ToxAlerts and StopTox (80%). The overall consensus amongst the three models was 57% and statistically significant (p < 0.05). Conclusions A large number of drugs had the potential to cause various systemic toxicities. But the results need to be interpreted cautiously since the clinical translation of QSAR-based predictions depends on many factors. In addition, inconsistencies have been reported between screening results amongst different models.

scholarly journals In Silico Prediction and Insights Into the Structural Basis of Drug Induced Nephrotoxicity

2022 ◽  
Vol 12 ◽  
Author(s):  
Yinping Shi ◽  
Yuqing Hua ◽  
Baobao Wang ◽  
Ruiqiu Zhang ◽  
Xiao Li
Keyword(s):  
Drug Development ◽  
In Silico ◽  
Molecular Properties ◽  
Structural Basis ◽  
Consensus Model ◽  
In Silico Prediction ◽  
Drug Induced ◽  
Data Set ◽  
Chemical Structures ◽  
Structural Alerts

Drug induced nephrotoxicity is a major clinical challenge, and it is always associated with higher costs for the pharmaceutical industry and due to detection during the late stages of drug development. It is desirable for improving the health outcomes for patients to distinguish nephrotoxic structures at an early stage of drug development. In this study, we focused on in silico prediction and insights into the structural basis of drug induced nephrotoxicity, based on reliable data on human nephrotoxicity. We collected 565 diverse chemical structures, including 287 nephrotoxic drugs on humans in the real world, and 278 non-nephrotoxic approved drugs. Several different machine learning and deep learning algorithms were employed for in silico model building. Then, a consensus model was developed based on three best individual models (RFR_QNPR, XGBOOST_QNPR, and CNF). The consensus model performed much better than individual models on internal validation and it achieved prediction accuracy of 86.24% external validation. The results of analysis of molecular properties differences between nephrotoxic and non-nephrotoxic structures indicated that several key molecular properties differ significantly, including molecular weight (MW), molecular polar surface area (MPSA), AlogP, number of hydrogen bond acceptors (nHBA), molecular solubility (LogS), the number of rotatable bonds (nRotB), and the number of aromatic rings (nAR). These molecular properties may be able to play an important part in the identification of nephrotoxic chemicals. Finally, 87 structural alerts for chemical nephrotoxicity were mined with f-score and positive rate analysis of substructures from Klekota-Roth fingerprint (KRFP). These structural alerts can well identify nephrotoxic drug structures in the data set. The in silico models and the structural alerts could be freely accessed via https://ochem.eu/article/140251 and http://www.sapredictor.cn, respectively. We hope the results should provide useful tools for early nephrotoxicity estimation in drug development.

Economic Profit vs. Social Benefit

2021 ◽  
pp. 24-44
Author(s):  
M. Mercedes Galán-Ladero ◽  
M. Ángeles Galán-Ladero
Keyword(s):  
Well Being ◽  
Social Benefit ◽  
Economic Benefits ◽  
Essential Medicines ◽  
World Health ◽  
Human Right ◽  
The Sustainable Development ◽  
The World ◽  
Health Organization ◽  
The Right

There is currently a wide-ranging debate on whether it is ethical for pharmaceutical companies to profit and obtain large economic benefits by patenting and controlling the sale of essential medicines that can save thousands of lives, or, on the contrary, whether these medicines should be considered social products and offered at low prices so that anyone, in any country in the world, regardless of their purchasing power, can have access to them. This debate has intensified since health was considered a fundamental human right by the World Health Organization (WHO) and was expressly included in the Sustainable Development Goals (SDGs) adopted by the United Nations (specifically, in Goal 3: “Health and Well-Being”). Consequently, the overall objective of this chapter is to reflect on these questions: Should economic interests prevail over social ones in the case of essential life-saving medicines? Should the fundamental right to health prevail over the right granted by a patent? How far should corporate social responsibility (CSR) go in the pharmaceutical industry?

In silico prediction of drug‐induced rhabdomyolysis with machine‐learning models and structural alerts

2019 ◽  
Vol 39 (8) ◽  
pp. 1224-1232 ◽  
Author(s):  
Xueyan Cui ◽  
Juan Liu ◽  
Jinfeng Zhang ◽  
Qiuyun Wu ◽  
Xiao Li
Keyword(s):  
Machine Learning ◽  
In Silico ◽  
In Silico Prediction ◽  
Learning Models ◽  
Drug Induced ◽  
Structural Alerts ◽  
Machine Learning Models

Russian Citizens' Representations of the Country's Position in the Geopolitical Space of the Commonwealth of Independent States, Europe, and the World

2003 ◽  
Vol 8 (4) ◽  
pp. 238-251
Author(s):  
Victor F. Petrenko ◽  
Olga V. Mitina ◽  
Kirill A. Bertnikov
Keyword(s):  
Well Being ◽  
Multidimensional Space ◽  
Commonwealth Of Independent States ◽  
Repertory Grids ◽  
Implicit Model ◽  
The World ◽  
Public Consciousness ◽  
Independent States ◽  
Invariant Factors

The aim of this research was the reconstruction of the system of categories through which Russians perceive the countries of the Commonwealth of Independent States (CIS), Europe, and the world as a whole; to study the implicit model of the geopolitical space; to analyze the stereotypes in the perception of different countries and the superposition of mental geopolitical representations onto the geographic map. The techniques of psychosemantics by Petrenko, originating in the semantic differential of Osgood and Kelly's “repertory grids,” were used as working tools. Multidimensional semantic spaces act as operational models of the structures of consciousness, and the positions of countries in multidimensional space reflect the geopolitical stereotypes of respondents about these countries. Because of the transformation of geopolitical reality representations in mass consciousness, the commonly used classification of countries as socialist, capitalist, and developing is being replaced by other structures. Four invariant factors of the countries' descriptions were identified. They are connected with Economic and Political Well-being, Military Might, Friendliness toward Russia, and Spirituality and the Level of Culture. It seems that the structure has not been explained in adequate detail and is not clearly realized by the individuals. There is an interrelationship between the democratic political structure of a country and its prosperity in the political mentality of Russian respondents. Russian public consciousness painfully strives for a new geopolitical identity and place in the commonwealth of states. It also signifies the country's interest and orientation toward the East in the search for geopolitical partners. The construct system of geopolitical perception also depends on the region of perception.

The essence and causes of the spiritual and moral decline of mankind in the XX century

1998 ◽  
pp. 124-127
Author(s):  
V. Tolkachenko
Keyword(s):  
Well Being ◽  
Religious Institutions ◽  
Social Force ◽  
The World ◽  
Role Of Religion

One of the most important reasons for such a clearly distressed state of society was the decline of religion as a social force, the external manifestation of which is the weakening of religious institutions. "Religion," Baha'u'llah writes, "is the greatest of all means of establishing order in the world to the universal satisfaction of those who live in it." The weakening of the foundations of religion strengthened the ranks of ignoramuses, gave them impudence and arrogance. "I truly say that everything that belittles the supreme role of religion opens way for the revelry of maliciousness, inevitably leading to anarchy. " In another Tablet, He says: "Religion is a radiant light and an impregnable fortress that ensures the safety and well-being of the peoples of the world, for God-fearing induces man to adhere to the good and to reject all evil." Blink the light of religion, and chaos and distemper will set in, the radiance of justice, justice, tranquility and peace. "

Policy Review: Dubai Health Authority’s COVID-19 Rapid Response

2020 ◽  
Vol 5 (Special) ◽  
Keyword(s):  
United Arab Emirates ◽  
Well Being ◽  
Healthcare Services ◽  
Rapid Response ◽  
Policy Implications ◽  
World Health ◽  
Healthcare Sector ◽  
Services Delivery ◽  
First Case ◽  
The World

Dubai Health Authority (DHA) is the entity regulating the healthcare sector in the Emirate of Dubai, ensuring high quality and safe healthcare services delivery to the population. The World Health Organization (WHO) declared COVID-19 a pandemic on the 11th of March 2020, indicating to the world that further infection spread is very likely, and alerting countries that they should be ready for possible widespread community transmission. The first case of COVID-19 in the United Arab Emirates was confirmed on 29th of January 2020; since then, the number of cases has continued to grow exponentially. As of 8th of July 2020 (end of the day), 53,045 cases of coronavirus have been confirmed with a death toll of 327 cases. The UAE has conducted over 3,720,000 COVID-19 tests among UAE citizens and residents over the past four months, in line with the government’s plans to strengthen virus screening to contain the spread of COVID-19. There were vital UAE policies, laws, regulations, and decrees that have been announced for immediate implementation to limit the spread of COVID- 19, to prevent panic and to ensure the overall food, nutrition, and well-being are provided. The UAE is amongst the World’s Top 10 for COVID-19 Treatment Efficiency and in the World’s Top 20 for the implementation of COVID-19 Safety measures. The UAE’s mission is to work towards resuming life after COVID-19 and enter into the recovery phases. This policy research paper will discuss the Dubai Health Authority’s rapid response initiatives towards combating the control and spread of COVID-19 and future policy implications and recommendations. The underlying factors and policy options will be discussed in terms of governance, finance, and delivery.

Eating NAFTA

2018 ◽  
Author(s):  
Alyshia Gálvez
Keyword(s):  
Public Health ◽  
Chronic Disease ◽  
Low Income ◽  
Food System ◽  
Dietary Habits ◽  
Trade Agreement ◽  
Well Being ◽  
Health Crisis ◽  
The North ◽  
The World

In the two decades since the North American Free Trade Agreement (NAFTA) went into effect, Mexico has seen an epidemic of diet-related illness. While globalization has been associated with an increase in chronic disease around the world, in Mexico, the speed and scope of the rise has been called a public health emergency. The shift in Mexican foodways is happening at a moment when the country’s ancestral cuisine is now more popular and appreciated around the world than ever. What does it mean for their health and well-being when many Mexicans eat fewer tortillas and more instant noodles, while global elites demand tacos made with handmade corn tortillas? This book examines the transformation of the Mexican food system since NAFTA and how it has made it harder for people to eat as they once did. The book contextualizes NAFTA within Mexico’s approach to economic development since the Revolution, noticing the role envisioned for rural and low-income people in the path to modernization. Examination of anti-poverty and public health policies in Mexico reveal how it has become easier for people to consume processed foods and beverages, even when to do so can be harmful to health. The book critiques Mexico’s strategy for addressing the public health crisis generated by rising rates of chronic disease for blaming the dietary habits of those whose lives have been upended by the economic and political shifts of NAFTA.

An Econometric Analysis on the Relationship between Globalisation and Inequality in South Africa

2020 ◽  
Vol 11 (1) ◽  
pp. 89-89
Author(s):  
Jacques de Jongh
Keyword(s):  
South Africa ◽  
Well Being ◽  
Causality Analysis ◽  
Global Integration ◽  
Development Indicators ◽  
Long Run ◽  
The World ◽  
Distribution Of Resources ◽  
Short Run ◽  
The Impact

Globalisation has had an unprecedented impact on the development and well-being of societies across the globe. Whilst the process has been lauded for bringing about greater trade specialisation and factor mobility many have also come to raise concerns on its impact in the distribution of resources. For South Africa in particular this has been somewhat of a contentious issue given the country's controversial past and idiosyncratic socio-economic structure. Since 1994 though, considerable progress towards its global integration has been made, however this has largely coincided with the establishment of, arguably, the highest levels of income inequality the world has ever seen. This all has raised several questions as to whether a more financially open and technologically integrated economy has induced greater within-country inequality (WCI). This study therefore has the objective to analyse the impact of the various dimensions of globalisation (economic, social and political) on inequality in South Africa. Secondary annual time series from 1990 to 2018 were used sourced from the World Bank Development indicators database, KOF Swiss Economic Institute and the World Inequality database. By using different measures of inequality (Palma ratios and distribution figures), the study employed two ARDL models to test the long-run relationships with the purpose to ensure the robustness of the results. Likewise, two error correction models (ECM) were used to analyse the short-run dynamics between the variables. As a means of identifying the casual effects between the variables, a Toda-Yamamoto granger causality analysis was utilised. Keywords: ARDL, Inequality, Economic Globalisation; Social Globalisation; South Africa

Front-line Healthcare Workers in COVID-19: The Way from Elbow-Bump Greeting to Closing Body Bags

2020 ◽  
Author(s):  
Stefan Bittmann
Keyword(s):  
Health Service ◽  
Healthcare Workers ◽  
Well Being ◽  
The United States ◽  
Angiotensin Ii Receptor ◽  
Front Line ◽  
Resource Center ◽  
Research Activities ◽  
The World ◽  
The Usa

COVID-19 is a serious coronavirus disease that is spreading all over the world. As of the date of this publication, 2.834.134 people have been infected with COVID-19 and 197.924 deaths have been recorded in 185 countries (John Hopkins Corona Resource Center, 25th April 2020) [1]. This overwhelming mortality rate requires intensive research activities around the world. To date, the number of deaths per day in the United States is still killing, indicating an uncontrollable state of infection spread. SARS-CoV-2 binds to the angiotensin II receptor in various tissues of the human body, particularly in the oral cavity and tongue. SARS-CoV-2 requires the cheerful TMPRSS2 to activate this inertia. SARS-CoV-2 uses the ACE2 receptor as a gateway to the lungs. The SARS-CoV-2 virus binds with the spike protein to the ACE2 receptor. COVID-19 is more common among African Americans in the USA (Science 10th April 2020). The comfort and the emotional loading capacity of the employees in the health service are key components for the maintenance of the essential health services during the outbreak of the COVID-19 virus (Coronavirus) [2,3]. Hence, it will be important to anticipate the charges linked with this work and to release support for employees in the health service. The supervision and assessment of the psychic health and the well-being of the employees in the health service will be important, just as the efforts to guarantee a successful reunion with colleagues if they are infected.

Gauging Reactive Metabolites in Drug-Induced Toxicity

2014 ◽  
Vol 22 (4) ◽  
pp. 465-489 ◽  
Author(s):  
Marsha Eno ◽  
Michael Cameron
Keyword(s):  
Reactive Metabolites ◽  
Drug Induced
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