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Chlamydia pneumoniae (C. pneumoniae) is a specialized intracellular parasitic pathogen capable of causing pneumonia, sinusitis, bronchitis, and other respiratory diseases, which pose significant public health challenges. Therefore, rapid, accurate, and sensitive diagnosis is crucial for the prevention and treatment of respiratory diseases caused by C. pneumoniae. In this study, we combined enzymatic recombination amplification (ERA) with the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) 12a system (CRISPR/Cas12a) to develop a dual detection platform termed the Cpn-ERA-CRISPR/Cas12a dual system. This system integrates both the ERA-CRISPR/Cas12a fluorescence system and the ERA-CRISPR/Cas12a lateral flow system. Detection results can be measured using a fluorescence detector or observed with the naked eye on lateral flow strips. The fluorescence system and the lateral flow system detect C. pneumoniae in 30 minutes and 15 minutes, respectively. This dual system exhibits no cross-reactivity with the other seven pathogens, demonstrating high specificity, and achieves a sensitivity of 100 copies/µL. Additionally, the Cpn-ERA-CRISPR/Cas12a dual system was employed to analyze 39 clinical samples, comprising 19 positive and 20 negative samples. The detection rate for positive samples was 100%, with no positive results in the negative samples, indicating a high level of concordance with qPCR results. In summary, the Cpn-ERA-CRISPR/Cas12a dual system represents a novel tool for diagnosing C. pneumoniae and holds promising application potential in grassroots community hospitals. [ABSTRACT FROM AUTHOR]

Background: Acute fish toxicity test (AFT) is one of the cornerstones of environmental risk assessment (ERA) of chemicals for the aquatic environment. Despite many efforts to find an alternative able to fully replace the test, there is still lasting pressure from stakeholders for AFT results. Results: Here, we present the results of a case study with eight pharmaceuticals from various pharmaceutical groups with different levels of expected toxicity to fish. Selected compounds were tested in two validated alternative tests—fish embryo toxicity test with zebrafish (Danio rerio) (zFET) and in vitro RTgill-W1 assay according to their corresponding OECD guidelines TG 236 and TG 249, respectively. Data for AFT were collected from PubMed and ECOTOX knowledgebase databases, and acute toxicity to fish was further predicted in silico by the ECOSAR program. Predicted environmental risks (risk quotients, RQ, calculated using the exposure data from NORMAN) from both zFET and RTgill-W1 well correlated with the average RQs based on AFT LC50s. The strongest and most significant correlation was observed while comparing the AFT results with the median of combined alternative methods (zFET, RTgill-W1, ECOSAR). Conclusions: This proposed approach combining experimental data with modeling could serve as a reliable tool for predictions of environmental risks promoting the 3R alternatives to acute fish toxicity testing. [ABSTRACT FROM AUTHOR]

Purpose: The impact of COVID-19 on the educational systems across the globe was characterized by the shutdown of university education systems. In the post COVID-19 era, examining the prospect of on-line education becomes demanding with emphasis on promoting effective and uninterrupted university education sector in Nigeria. Design/methodology/approach: This study employed phenomenological and descriptive research design. The sample size for the study was 15, comprising university lecturers, students and school social workers. In-depth Interview (IDI) interview was the instrument for data collection. Findings: Findings revealed that university education in Nigeria was adversely disrupted by COVID-19 lockdown during the pandemic. Similarly, the study revealed that online education will facilitate effective and uninterrupted university education in post-COVID-19 era. Challenges such as lack of access to laptops, smartphones, reliable internet services, electricity etc. are major obstacles to an effective transition to online education in the post-COVID-19 University education era. The students lamented that poor knowledge of ICT by their lecturers and inclusivity of indigent/disabled students were major concerns. Originality/value: Revitalizing the education sector is a core concern for low-income countries. Online education presents the lasting solution to the constant interruption of university education in Africa. Promoting effective and uninterrupted university education is pegged on an adequate government education budgetary allocation targeted towards providing an enabling environment for online education to thrive. The study recommends that school social workers' engagement in the educational sector would help advocate for the availability of technological infrastructures and mainstreaming of the poor and disabled in the online education dispensation. [ABSTRACT FROM AUTHOR]

According to the current data, the endometrium acts as a "sensor" of embryo quality, which promotes the implantation of euploid embryos and prevents the implantation and/or subsequent development of genetically abnormal embryos. The present review addresses the nature of the "sensory function" of the endometrium and highlights the necessity for assessing its functional status. The first section examines the evolutionary origin of the "sensory" ability of the endometrium as a consequence of spontaneous decidualization that occurred in placental animals. The second section details the mechanisms for implementing this function at the cellular level. In particular, the recent findings of the appearance of different cell subpopulations during decidualization are described, and their role in implantation is discussed. The pathological consequences of an imbalance among these subpopulations are also discussed. Finally, the third section summarizes information on currently available clinical tools to assess endometrial functional status. The advantages and disadvantages of the approaches are emphasized, and possible options for developing more advanced technologies for assessing the "sensory" function of the endometrium are proposed. [ABSTRACT FROM AUTHOR]

Abstract Background Acute fish toxicity test (AFT) is one of the cornerstones of environmental risk assessment (ERA) of chemicals for the aquatic environment. Despite many efforts to find an alternative able to fully replace the test, there is still lasting pressure from stakeholders for AFT results. Results Here, we present the results of a case study with eight pharmaceuticals from various pharmaceutical groups with different levels of expected toxicity to fish. Selected compounds were tested in two validated alternative tests—fish embryo toxicity test with zebrafish (Danio rerio) (zFET) and in vitro RTgill-W1 assay according to their corresponding OECD guidelines TG 236 and TG 249, respectively. Data for AFT were collected from PubMed and ECOTOX knowledgebase databases, and acute toxicity to fish was further predicted in silico by the ECOSAR program. Predicted environmental risks (risk quotients, RQ, calculated using the exposure data from NORMAN) from both zFET and RTgill-W1 well correlated with the average RQs based on AFT LC50s. The strongest and most significant correlation was observed while comparing the AFT results with the median of combined alternative methods (zFET, RTgill-W1, ECOSAR). Conclusions This proposed approach combining experimental data with modeling could serve as a reliable tool for predictions of environmental risks promoting the 3R alternatives to acute fish toxicity testing.

Plotinus is the greatest Neoplatonic philosopher and one of the most prominent thinkers of ancient times, whose ideas have greatly influenced later philosophers. The issue of time is of great importance to philosophers and philosophical schools after Aristotle, especially in the thinking of Plotinus. One of the important aspects of time-related discussions is how temporal fluid entities are related to fixed and discrete entities. Regarding the issue of time, Plotin first criticized Aristotle's definition of time and then explained the eternal, eternal and fixedness of the order of ages. pay Plotin finally proves his innovative point of view about the time of the image or the appearance of the soul in the world of matter. In the current research, it has been stated with the analytical-comparative method that Plotin's problems with the definition of time are not correct from Mulla Sadra's point of view. Plotin's claim that time is the image of the soul also faces many problems according to Mulla Sadra's principles in transcendental wisdom.

Surgical aortic valve replacement (SAVR) was the only symptom relieving and life-prolonging treatment until transcatheter aortic valve implantation (TAVI) became available. This option was introduced to treat old and high-risk patients. In a series of 2500 consecutive patients referred for SAVR with a biologic heart valve (BHV) prosthesis, their age, comorbid conditions, the complexity of the procedure, postoperative outcome, need for resources, and long-term survival were compared in patients before versus after the introduction of TAVI. Although the Carpentier-Edwards valve was used in most patients, the outcomes with respect to several other BHV types were studied. Patients undergoing isolated SAVR (i-SAVR) were studied separately from those who underwent SAVR with a concomitant procedure (c-SAVR). The number of referrals increased over time until 2016, whereafter the reimbursement for TAVI broadened. Age, prior percutaneous coronary interventions, diabetes, and chronic renal disease increased over time in both groups, while atrial fibrillation, the need for emergent SAVR, and other comorbid conditions increased significantly only in the c-SAVR group. Postoperative acute renal injury, conduction defects, and bleeding increased over time in both groups. The need for renal replacement therapy increased in both surgical groups, but this was more pronounced in c-SAVR; the need for a pacemaker implant (p < 0.001), blood products, and reintervention increased only in the c-SAVR group. There was a moderate but non-significant increase in the 30-day mortality for both groups over time. Furthermore, the long-term survival of both groups did not change after the introduction of TAVI. The Carpentier-Edwards Perimount valve showed good long-term results for durability. The Perceval device was used in older patients and showed good hemodynamic results, but the need for a postoperative permanent pacemaker implant was high. The results seem to indicate that a broader reimbursement for TAVI was warranted after its introduction in 2008. Nevertheless, with the development of newer devices for SAVR, surgery will remain one of the major treatment options for aortic valve disease.

Surgical aortic valve replacement (SAVR) was the only symptom relieving and life-prolonging treatment until transcatheter aortic valve implantation (TAVI) became available. This option was introduced to treat old and high-risk patients. In a series of 2500 consecutive patients referred for SAVR with a biologic heart valve (BHV) prosthesis, their age, comorbid conditions, the complexity of the procedure, postoperative outcome, need for resources, and long-term survival were compared in patients before versus after the introduction of TAVI. Although the Carpentier-Edwards valve was used in most patients, the outcomes with respect to several other BHV types were studied. Patients undergoing isolated SAVR (i-SAVR) were studied separately from those who underwent SAVR with a concomitant procedure (c-SAVR). The number of referrals increased over time until 2016, whereafter the reimbursement for TAVI broadened. Age, prior percutaneous coronary interventions, diabetes, and chronic renal disease increased over time in both groups, while atrial fibrillation, the need for emergent SAVR, and other comorbid conditions increased significantly only in the c-SAVR group. Postoperative acute renal injury, conduction defects, and bleeding increased over time in both groups. The need for renal replacement therapy increased in both surgical groups, but this was more pronounced in c-SAVR; the need for a pacemaker implant (p < 0.001), blood products, and reintervention increased only in the c-SAVR group. There was a moderate but non-significant increase in the 30-day mortality for both groups over time. Furthermore, the long-term survival of both groups did not change after the introduction of TAVI. The Carpentier-Edwards Perimount valve showed good long-term results for durability. The Perceval device was used in older patients and showed good hemodynamic results, but the need for a postoperative permanent pacemaker implant was high. The results seem to indicate that a broader reimbursement for TAVI was warranted after its introduction in 2008. Nevertheless, with the development of newer devices for SAVR, surgery will remain one of the major treatment options for aortic valve disease. [ABSTRACT FROM AUTHOR]

In the era of transcriptomics, the role of epigenetics in the study of cancers in females has gained increasing recognition. This article explores the impact of epigenetic modifications, such as DNA methylation, histone modification, and non-coding RNA, on cancers in females, including breast, cervical, and ovarian cancers (1). Our findings suggest that these epigenetic markers not only influence tumor onset, progression, and metastasis but also present novel targets for therapeutic intervention. Detailed analyses of DNA methylation patterns have revealed aberrant events in cancer cells, particularly promoter region hypermethylation, which may lead to silencing of tumor suppressor genes. Furthermore, we examined the complex roles of histone modifications and long non-coding RNAs in regulating the expression of cancer-related genes, thereby providing a scientific basis for developing targeted epigenetic therapies. Our research emphasizes the importance of understanding the functions and mechanisms of epigenetics in cancers in females to develop effective treatment strategies. Future therapeutic approaches may include drugs targeting specific epigenetic markers, which could not only improve therapeutic outcomes but also enhance patient survival and quality of life. Through these efforts, we aim to offer new perspectives and hope for the prevention, diagnosis, and treatment of cancers in females.

Chlamydia pneumoniae (C. pneumoniae) is a specialized intracellular parasitic pathogen capable of causing pneumonia, sinusitis, bronchitis, and other respiratory diseases, which pose significant public health challenges. Therefore, rapid, accurate, and sensitive diagnosis is crucial for the prevention and treatment of respiratory diseases caused by C. pneumoniae. In this study, we combined enzymatic recombination amplification (ERA) with the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) 12a system (CRISPR/Cas12a) to develop a dual detection platform termed the Cpn-ERA-CRISPR/Cas12a dual system. This system integrates both the ERA-CRISPR/Cas12a fluorescence system and the ERA-CRISPR/Cas12a lateral flow system. Detection results can be measured using a fluorescence detector or observed with the naked eye on lateral flow strips. The fluorescence system and the lateral flow system detect C. pneumoniae in 30 minutes and 15 minutes, respectively. This dual system exhibits no cross-reactivity with the other seven pathogens, demonstrating high specificity, and achieves a sensitivity of 100 copies/µL. Additionally, the Cpn-ERA-CRISPR/Cas12a dual system was employed to analyze 39 clinical samples, comprising 19 positive and 20 negative samples. The detection rate for positive samples was 100%, with no positive results in the negative samples, indicating a high level of concordance with qPCR results. In summary, the Cpn-ERA-CRISPR/Cas12a dual system represents a novel tool for diagnosing C. pneumoniae and holds promising application potential in grassroots community hospitals.

In the year 2000, cancer research in Europe had the potential to make a difference as it had several unique strengths, such as a strong foundation in biomedical science, good patient registries, infrastructures that spanned from biological repositories to bioinformatic hubs as well as thriving Comprehensive Cancer Centers (CCCs) and basic/preclinical cancer research institutions of high international standing. Research, however, was fragmented and lacked coordination. As a result, Europe could not harness its potential for translating basic research discoveries into a clinical setting for the patients' benefit. What was needed was a paradigm shift in cancer research that addressed the translational research continuum. Along these lines, in 2000, European Union (EU) Commissioner Philippe Busquin established the European Research Area (ERA) and in 2002 the European Cancer Research Area (ECRA), and their political approval was a powerful catalyst for the increased involvement of scientists in science policy in the EU. In this report, we briefly describe the actions embraced by the cancer community and cancer organizations in response to Busquin's proposals that led to the creation of the EU Mission on Cancer (MoC) in Horizon 2020 in 2021.

Targeting IL-17A using Secukinumab, a humanized monoclonal immunoglobulin G1 (IgG1)/κ against IL-17A is a therapeutic option for immune-mediated disorders such as psoriasis and ankylosing spondylitis. The US Food and Drug Administration and the European Medicines Agency have approved it for the treatment of moderate to severe plaque psoriasis, active psoriatic arthritis, ankylosing spondylitis, and non-radiographic axial spondylarthritis. Recently it has also been approved for use in children with severe plaque psoriasis, active psoriatic arthritis, and enthesitis-related arthritis. This review focuses on the role of Secukinumab in the management of children and adolescents with enthesitis-related arthritis and psoriatic arthritis. We discuss the salient findings of pivotal RCTs and other studies supporting the use of Secukinumab in adults and children, in particular, focusing on its safety and efficacy. Secukinumab is a therapeutic target for psoriasis, psoriatic arthritis, and spondyloarthropathies in both adults and children. No major safety signals are observed with its use in short-term follow-up. Thus far, Secukinumab has not been found to significantly increase the risk of tuberculosis (TB). [ABSTRACT FROM AUTHOR]

In the year 2000, cancer research in Europe had the potential to make a difference as it had several unique strengths, such as a strong foundation in biomedical science, good patient registries, infrastructures that spanned from biological repositories to bioinformatic hubs as well as thriving Comprehensive Cancer Centers (CCCs) and basic/preclinical cancer research institutions of high international standing. Research, however, was fragmented and lacked coordination. As a result, Europe could not harness its potential for translating basic research discoveries into a clinical setting for the patients' benefit. What was needed was a paradigm shift in cancer research that addressed the translational research continuum. Along these lines, in 2000, European Union (EU) Commissioner Philippe Busquin established the European Research Area (ERA) and in 2002 the European Cancer Research Area (ECRA), and their political approval was a powerful catalyst for the increased involvement of scientists in science policy in the EU. In this report, we briefly describe the actions embraced by the cancer community and cancer organizations in response to Busquin's proposals that led to the creation of the EU Mission on Cancer (MoC) in Horizon 2020 in 2021. [ABSTRACT FROM AUTHOR]

Introduction: Estrogens are crucial regulators of ovarian function, mediating their signaling through binding to estrogen receptors. The disruption of the estrogen receptor 1 (Esr1) provokes infertility associated with a hemorrhagic, cystic phenotype similar to that seen in diseased or aged ovaries. Our previous study indicated the possibility of altered iron metabolism in Esr1-deficient ovaries showing massive expression of lipocalin 2, a regulator of iron homeostasis. Methods: Therefore, we examined the consequences of depleting Esr1 in mouse ovaries, focusing on iron metabolism. For that reason, we compared ovaries of adult Esr1-deficient animals and age-matched wild type littermates. Results and discussion: We found increased iron accumulation in Esr1-deficient animals by using laser ablation inductively coupled plasma mass spectrometry. Western blot analysis and RT-qPCR confirmed that iron overload alters iron transport, storage and regulation. In addition, trivalent iron deposits in form of hemosiderin were detected in Esr1-deficient ovarian stroma. The depletion of Esr1 was further associated with an aberrant immune cell landscape characterized by the appearance of macrophage-derived multinucleated giant cells (MNGCs) and increased quantities of macrophages, particularly M2-like macrophages. Similar to reproductively aged animals, MNGCs in Esr1-deficient ovaries were characterized by iron accumulation and strong autofluorescence. Finally, deletion of Esr1 led to a significant increase in ovarian mast cells, involved in iron-mediated foam cell formation. Given that these findings are characteristics of ovarian aging, our data suggest that Esr1 deficiency triggers mechanisms similar to those associated with aging. [ABSTRACT FROM AUTHOR]

Water pollution has been increased by the discharge of several polycyclic aromatic hydrocarbons including Benzo (a) pyrene (BaP), which may affect aquatic animal lives and threaten human health. Common sole, Solea solea was selected as a bioindicator benthic fish to monitor pollution from El-Maadeya (one of the industrially polluted areas in Egypt). Concentration of "BaP" in collected samples of water, sediments and some organs of sole was detected using HPLC. A detected level of 21 μg ″BaP″/L was reported in water samples from El-Maadeya. Analysis results of ″BaP″ in El-Maadeya water, sediment, and biota exceeded the permissible limits. In a new trial for water remediation from ″BaP″, chitosan (Cs) was experimentally applied. Moreover, the impact of ″BaP″ alone or in combination with Cs for two weeks on water quality, sole fish brooders and histopathological changes in their ovaries was studied. Fifteen fish/tank were randomly classified into five groups in triplicates exposed to: GI) sea water only, GII) sea water with "DMSO", GIII) 21 μg ″BaP″/L (equivalent to the level detected in El-Maadeya), GIV) 50 μg ″BaP″/L, GVa) 21 μg ″BaP″/L & 0.5 g ″Cs″/L for 24 hrs and GVb) 21 μg ″BaP″/L & 0.5 g ″Cs″/L for one week. Obtained results showed that ″BaP″ accumulated in the liver and ovary of fish resulting in a negative impact on the reproduction due to the alteration of the ovarian architecture, atresia, and gonadosomatic index. Western Blot analysis showed also that ″BaP″ disrupted steroidogenic enzymes, upregulated the expression of Hsp-70, and forced the degradation of ERα. The addition of 0.5 g Cs/L has showed its efficiency against BaP toxicity, since it plays a role in ″BaP″ elimination by fast adsorption from water and sediments in timedependent manner, improved fish health, restored reproductive characteristics, decreased the percentage of atretic oocytes and reduced fish mortality. [ABSTRACT FROM AUTHOR]

This case report describes a couple with nine years of primary infertility and three failed in vitro fertilization (IVF) attempts that showed no reproductive abnormality. Negative results were observed following the conventional IVF protocol. The couple then insisted on laser-assisted hatching (LAH) and endometrial receptivity analysis (ERA). The ERA results showed a specific window for embryo implantation, and accordingly, the treatment was carried out, which resulted in seven good-quality oocytes, leading to the formation of four blastocyst-stage embryos. These embryos were then frozen, single embryo transfer (ET) was performed following the ERA results, and the embryos were successfully implanted. The βhCG level was 245 mIU/mL, indicating that the female had successfully conceived. This case highlights the challenges of a thick zona pellucida and recurrent implantation failure (RIF), defining how a personalized method combining both LAH and ERA could lead to successful implantation.

As long as the United States perpetuates the unequal statuses of males and females in the Constitution, dignity will mean different things to each. While males automatically have the dignity and worth of fully enfranchised citizens, females must accept a version of dignity based upon the manner in which they acquiesce to their legally inferior position. In suing the United States Soccer Foundation for equal pay, The United States Women's Soccer team brought the issue of status and dignity into the open in a very public way, enacting the dignity of those accorded full Constitutional rights. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Babylon Center for Humanities Studies is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction. Disputes about the “uniqueness” of one’s era in comparison with the achievements of previous ones have always been a “cornerstone” in the perception of past concepts regarding the values of the achievements of predecessors. However, at one time, Confucius said his world-famous phrase that if you don’t look back, there is no way forward. But many people are not interested in their past. That is why the “Querelle des Anciens et des Modernes” in the form of a literary debate, centered on a comparison of the value of the contributions of ancient authors and French authors of the 17th century, and which was widespread at the time, is still relevant today. The purpose and objectives of the article. The purpose of the article is to highlight the perception of the values of previous eras in the paradigms of “non-contemporary” prominent philosophers and writers. The tasks of the article are to reveal the reasons for the primordial disputes about “ancient and new”, a natural return to ancient literature and ancient philosophy. Research methodology. The leading research methods were: content-comparative - to analyze the reliability of judgments of French writers of the 17th century; retrospective, which helps to investigate the phenomenon of the value of “the ancient in the new” in the century-old controversy, the method of personalization, which ensures the study and understanding of the works of S. Perrault and his contemporaries. The results. It’s no secret that the tasks of art in the Antiquity, Middle Ages and Modern times differed greatly. For Antiquity, every craftsman was an artist, while the activity of a painter and sculptor was a more complex craft. It is typical for that time that there was almost no idea about creativity and the creative act, but despite this, the ancient Greeks were able to create immortal examples of art. The art of the Middle Ages was supposed to embody a moralistic character and remind of the eternal, the art of romanticism saw godlike creativity as its goal. The art of the 20th century presented its ideal in the denial of everything that the previous era saw as its goal, periodically declaring the death of art. Based on the fact that today there are many different ideas about the goals and tasks of modern art, we cannot say with full confidence what is the common goal of the art of our days, and it is even more difficult for us to imagine how art will live, for example, through a hundred years. Conclusions. So, we can come to the conclusion that in the era of the early Enlightenment, the attitude to the ancient heritage, in particular in France and England, was not unambiguous even among the educated aristocracy or university professors who knew Greco-Roman works well enough. This is clearly evidenced by the century-old dispute “about ancient and new”, which caused a lot of auxiliary discussions. Undoubtedly, even today arguing and debating about the art of previous eras and our own has a place in philosophy and literature, and they continue to do this with success for more than one hundred years. But to prove the rightness of one of the sides of these disputes is a sufficiently dubious matter for science. [ABSTRACT FROM AUTHOR]

Copyright of Basrah Journal of Science / Magallat Al-Barat Li-L-ulum is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

La quête d’acceptabilité sociale comme nouvelle norme de l’action publique pour les grands projets implique une transformation des processus décisionnels et des instruments. Au coeur de la transition énergétique, la question du transport de l’électricité apparaît stratégique. Le rôle des ententes sur les retombées et les avantages (ERA) est de plus en plus important et permet de poser la question de la justice distributive. L’article propose d’étudier la question de l’évolution d’une ERA sur quatre décennies, le Programme de mise en valeur intégrée (PMVI) d’Hydro-Québec concernant une vingtaine de projets de lignes à haute tension. Une approche sociopolitique par les instruments est mobilisée à cette fin et permet de rendre compte des résistances, ajustements et changements à l’oeuvre en s’interrogeant sur les implications de cet instrument de type conventionnel et incitatif du point de vue de la justice distributive dans le cadre de la gouvernance énergétique. La méthodologie repose sur l’analyse de contenu des rapports du Bureau d’audiences publiques sur l’environnement (BAPE).

GTPase Era from Staphylococcus aureus belongs to the TRAFAC superfamily of the TrmE-Era-EngA-EngB-Septin-like GTPases class and plays a significant role in the vital activity of this pathogenic microorganism as a maturation factor of the 30S ribosome subunit. However, the functions of this protein are not fully understood, making it a promising object for further study. Here, the 2.76 Å resolution crystal structure of Staphylococcus aureus Era in complex with GDP is presented. Structural comparison with other GTP-bound and GDP-bound homologous proteins, GTPase domain and the KH domain revealed a mutual orientation in S. aureus which has not been described before. The GDP-bound Era structure presented here will facilitate efforts to elucidate its interactions with its regulators and lay the foundation for a structure-based search for specific inhibitors. • Crystal structure of Sa Era is solved in GDP-bound form. • GTPase and KH domain folds differ in Sa Era. • The C-terminal part of the KH domain of Era differs in S. aureus. [ABSTRACT FROM AUTHOR]

An environmental risk assessment (ERA) is mandatory for all applications for marketing authorisation of medicines in the European Union (EU). We investigated stakeholder perspectives on the role of the ERA in EU regulation of medicines for human use. We discuss the current position of the ERA and the current conduct and assessment of the ERA, such as the required expertise, data, and studies, its applicability to generic drugs, and its use in regulatory decision-making. We also discuss future perspectives, including extension of the ERA to cover antimicrobial resistance, improved risk mitigation, impact on 'over-the-counter' (OTC) status, and incorporation into reimbursement considerations., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Medical historians typically situate the origins of the antimicrobial era during the early germ period at the turn of the 20th century. They have regarded the development of chemical compounds designed to treat infectious diseases by killing their causative germ as the beginning of the antimicrobial era. Scholars, however, had been speculating about the causal relationship between germs and diseases for centuries beforehand. One of them also addressed the practical applications of this theory. The Italian physician Fracastoro proposed in 1546 that infectious diseases could be treated by administering substances to antagonize disease causing germs. He claimed that health could be restored to people who became ill with infections by nullifying the responsible germs at a time when investigators could not see germs or investigate their ability to cause disease. The long genealogy of antimicrobial therapy from its conception to its fruition took place over the span of several centuries., Competing Interests: Potential conflicts of interest. The author: No reported conflicts of interest. The author has submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Recently, the European Commission (EC) published a regulatory proposal on plants generated with new genomic techniques (NGTs) (5 July 2023). According to this proposal, NGT plant applications are categorized into category 1 NGT (NGT1) and category 2 NGT (NGT2) based on their molecular characteristics, which diverges from the current legislation centered around Directive 2001/18/EC. To demonstrate where the path of the proposal leads to in practice, we applied the proposed criteria for categorization to a list of NGT plant applications currently in the commercialization pipeline. Combining literature research and a descriptive statistical approach, we can show that 94% of the plant applications affected by the EC proposal, would be classified as NGT1 and thus would receive market approval without risk assessment, monitoring, and sufficient labeling provisions. The remaining 6% of applications would be classified as NGT2 plants, for which, in deviation from the current regulation, an adapted risk assessment is proposed. Screening of the intended traits in the pipeline highlights that certain NGT1 plants can pose similar environmental risks (e.g., invasiveness) to other genetically modified organisms (GMOs), as defined in Directive 2001/18/EC. For example, NGT1 applications based on RNA interference technology can exhibit insecticidal effects with potential side effects on non-target organisms (i.e., other insects). Our quantitative and case-specific elaboration of how the current EC regulatory proposal would affect the environment, health, and consumer protection will be informative for decision-makers and politicians., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bohle, Schneider, Mundorf, Zühl, Simon and Engelhard.)

Era, a widely known GTP binding protein found in many organisms including prokaryotes and eukaryotes and plays a significant role in many fundamental cellular processes like cell growth, differentiation and signaling. In Mycobacterium tuberculosis (Mtb) H 37 Rv, Era protein had been proved as a GTPase protein but its structural and functional insights are still lacking. Through comparative analysis, structural modeling, docking and using various bioinformatic tools, a detailed investigation of Era was carried out to deduce the structure, function and residues involved in the activity of the protein. Intriguingly, docking results revealed high binding affinity of Era not only with GTP but also with ATP. Myristoylation modifications and phosphorylations on Era were predicted to possibly aid in regulating Era activity and localization; and also the role of Era in translation regulation was foreseen by showing its association with 16s rRNA. Moreover, point mutation of Era residues revealed the effect of W288G and K19G in highly destabilizing the protein structure and activity. Additionally, Era protein was docked with 25 GTPase/ATPase inhibitors, where, Dynasore inhibitor showed the highest affinity for the protein's GTP binding sites and can be used for further drug trials to inhibit growth of mycobacteria.Communicated by Ramaswamy H. Sarma.

In this chapter, we will first consider the overall goal of nonclinical safety testing during drug development and have a brief overview of its regulatory background. We will then discuss some basic requirements of safety/toxicity testing before concentrating on the safety testing of RNA vaccines and developing a sample RNA vaccine safety testing program., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)