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Добірка наукової літератури з теми "THERAPEUTICS ACTION"

Автор: Grafiati

Опубліковано: 11 вересня 2023

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Статті в журналах з теми "THERAPEUTICS ACTION"

Lenz, Kiersten D., Katja E. Klosterman, Harshini Mukundan, and Jessica Z. Kubicek-Sutherland. "Macrolides: From Toxins to Therapeutics." Toxins 13, no. 5 (May 12, 2021): 347. http://dx.doi.org/10.3390/toxins13050347.

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Macrolides are a diverse class of hydrophobic compounds characterized by a macrocyclic lactone ring and distinguished by variable side chains/groups. Some of the most well characterized macrolides are toxins produced by marine bacteria, sea sponges, and other species. Many marine macrolide toxins act as biomimetic molecules to natural actin-binding proteins, affecting actin polymerization, while other toxins act on different cytoskeletal components. The disruption of natural cytoskeletal processes affects cell motility and cytokinesis, and can result in cellular death. While many macrolides are toxic in nature, others have been shown to display therapeutic properties. Indeed, some of the most well known antibiotic compounds, including erythromycin, are macrolides. In addition to antibiotic properties, macrolides have been shown to display antiviral, antiparasitic, antifungal, and immunosuppressive actions. Here, we review each functional class of macrolides for their common structures, mechanisms of action, pharmacology, and human cellular targets.

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Cattley, Russell C., and Bert R. Radinsky. "Cancer Therapeutics: Understanding the Mechanism of Action." Toxicologic Pathology 32, no. 1_suppl (January 2004): 116–21. http://dx.doi.org/10.1080/01926230490426507.

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Cefalu, William T., and David Ribnicky. "Modulation of Insulin Action by Botanical Therapeutics." Obesity and Weight Management 5, no. 6 (December 2009): 277–81. http://dx.doi.org/10.1089/obe.2009.0604.

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Eidelman, Cristy, Tracy Sandritter, and Jennifer Lowry. "Individualized Pediatric Therapeutics Clinic: Action in Practice." Pediatrics 142, no. 1_MeetingAbstract (May 1, 2018): 798. http://dx.doi.org/10.1542/peds.142.1ma8.798.

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Cronstein, Bruce N. "Molecular therapeutics. Methotrexate and its mechanism of action." Arthritis & Rheumatism 39, no. 12 (December 1996): 1951–60. http://dx.doi.org/10.1002/art.1780391203.

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Alves de Souza, Stephanny Miranda, Blanca Hernández-Ledesma, and Theo Luiz Ferraz de Souza. "Lunasin as a Promising Plant-Derived Peptide for Cancer Therapy." International Journal of Molecular Sciences 23, no. 17 (August 23, 2022): 9548. http://dx.doi.org/10.3390/ijms23179548.

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Cancer has become one of the main public health problems worldwide, demanding the development of new therapeutic agents that can help reduce mortality. Lunasin is a soybean peptide that has emerged as an attractive option because its preventive and therapeutic actions against cancer. In this review, we evaluated available research on lunasin’s structure and mechanism of action, which should be useful for the development of lunasin-based therapeutic products. We described data on its primary, secondary, tertiary, and possible quaternary structure, susceptibility to post-translational modifications, and structural stability. These characteristics are important for understanding drug activity and characterizing lunasin products. We also provided an overview of research on lunasin pharmacokinetics and safety. Studies examining lunasin’s mechanisms of action against cancer were reviewed, highlighting reported activities, and known molecular partners. Finally, we briefly discussed commercially available lunasin products and potential combination therapeutics.

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Chaney, Sarah. "The action of the imagination." History of the Human Sciences 30, no. 2 (April 2017): 17–33. http://dx.doi.org/10.1177/0952695116687225.

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Histories of dynamic psychotherapy in the late 19th century have focused on practitioners in continental Europe, and interest in psychological therapies within British asylum psychiatry has been largely overlooked. Yet Daniel Hack Tuke (1827–95) is acknowledged as one of the earliest authors to use the term ‘psycho-therapeutics’, including a chapter on the topic in his 1872 volume, Illustrations of the Influence of the Mind upon the Body in Health and Disease. But what did Tuke mean by this concept, and what impact did his ideas have on the practice of asylum psychiatry? At present, there is little consensus on this topic. Through in-depth examination of what psycho-therapeutics meant to Tuke, this article argues that late-19th-century asylum psychiatry cannot be easily separated into somatic and psychological strands. Tuke’s understanding of psycho-therapeutics was extremely broad, encompassing the entire field of medical practice (not only psychiatry). The universal force that he adopted to explain psychological therapies, ‘the Imagination’, was purported to show the power of the mind over the body, implying that techniques like hypnotism and suggestion might have an effect on any kind of symptom or illness. Acknowledging this aspect of Tuke’s work, I conclude, can help us better understand late-19th-century psychiatry – and medicine more generally – by acknowledging the lack of distinction between psychological and somatic in ‘psychological’ therapies.

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Jerome, Christopher P., and Rogely Boyce. "Bone Therapeutics: Safety Considerations, Session Summary." Toxicologic Pathology 45, no. 7 (October 2017): 855–58. http://dx.doi.org/10.1177/0192623317737231.

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This session was a series of presentations focused on safety considerations for late stage or currently marketed bone therapeutic agents. The first presentation was an overview of a major regulatory requirement in the nonclinical filing package for bone therapeutics, studies designed to assess the impact of an agent on bone quality. Two presentations focused on safety issues associated with drugs whose primary mechanism of action is inhibition of bone resorption. Typical findings associated with this class of agents in general and reproductive toxicology studies were reviewed, highlighting INHAND (International Harmonization of Nomenclature and Diagnostic Criteria) nomenclature. This was followed by an overview of safety issues that have been identified largely through clinical experience. Similar presentations followed emphasizing safety and regulatory issues associated with classes of drugs whose primary mechanism of action is stimulation of bone formation known broadly as bone anabolic agents. The major focus of these discussions was carcinogenicity risk assessment. The final presentation was an introduction to a rapidly evolving area in bone therapeutics, treatment of rare genetic bone diseases, and the developmental challenges associated with these indications and novel therapeutic modalities.

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Kordus, Shannon L., Audrey K. Thomas, and D. Borden Lacy. "Clostridioides difficile toxins: mechanisms of action and antitoxin therapeutics." Nature Reviews Microbiology 20, no. 5 (November 26, 2021): 285–98. http://dx.doi.org/10.1038/s41579-021-00660-2.

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Guo, Haitao, Justin B. Callaway, and Jenny P.-Y. Ting. "Inflammasomes: mechanism of action, role in disease, and therapeutics." Nature Medicine 21, no. 7 (June 29, 2015): 677–87. http://dx.doi.org/10.1038/nm.3893.

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Дисертації з теми "THERAPEUTICS ACTION"

Crowley, John J. "Enabling carers to administer depot injections : an action research study." Thesis, University of Greenwich, 2014. http://gala.gre.ac.uk/11617/.

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This study has its origins in a question posed by a patient diagnosed with a psychotic illness, as to why her husband could not administer depot injection. Following local and national discussion the study aims were; - to explore the elements of risk management involved in enabling carers (supportive persons) to give depot injections - to develop a training package that may be useful for others to use should such a request be made - to establish whether enabling supportive persons to give depot injections would have an effect on the relationship between the user (recipient of the medication) and the supportive person (giver of medication) - to ascertain the views, concerns and attitudes of medical staff (prescribers) and mental health nurses (administrators of depot injections) about enabling carers/relatives (supportive persons) to give depot intramuscular injection medication. An action research study informed by empowerment theoretical perspectives and influenced by recovery philosophies was used to explore the issues about ‘supportive person’ depot administration. Methods used to collect data included case studies, interviews, observation, reflection and three validated evaluation tools. Data were analysed through thematic analysis, and alongside establishing data, relating to the study aims, additional themes i.e. stigma, disclosure, concealment and trust evolved from the data. The study has relevance for clinical practice, policy and service provision. Current government policies promote choice and collaborative working and health and social care staff are encouraged to be responsive to the views of mental health service users and carers in relation to their experiences and expectations of care. Mental health services are being asked to deliver and translate these policies into practice alongside expectations of gainful employment for service users.

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Romero-Canelón, Isolda. "Design and mechanism of action of organometallic anticancer complexes." Thesis, University of Warwick, 2012. http://wrap.warwick.ac.uk/55211/.

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Since the discovery of cisplatin, numerous attempts have been made to emulate its activity while reducing its collateral toxicity. Coordination complexes based on a wide number of transition metals have been developed in the search for improved bioavailability, selectivity and reduced adverse side-effects. Ruthenium(II) complexes have been widely developed in this field as a viable alternative to platinum chemotherapeutics. This thesis is concerned with the synthesis, characterization and biological evaluation of three series of novel half-sandwich complexes of the general formula [RuII(arene)(X)(YZ)]n+. These piano-stool RuII complexes have been designed as to allow the fine-tuning of their chemical and biological properties. In the first two series, the arene unit has been varied between p-cymene, biphenyl and terphenyl to investigate the correlation between hydrophobicity and antiproliferative activity, while the N,N-imino pyridine chelating ligand, YZ, has been modified to include either a higher number of aromatic units that could allow better DNA intercalation or substituent groups that could affect the overall charge distribution in the complex. Finally, the monodentate ligand, X, is either chloride or iodide. These compounds have been fully characterised by NMR, MS and elemental analysis. Their aqueous behaviour has been investigated together with the extent of 9-EtG binding, as an indication of the possible interaction with nucleobases. The antiproliferative activity of these novel RuII complexes was determined, several of them show promising IC50 values, in the low μM range, against ovarian, colon, lung and breast cancer cell lines, in many cases the activities observed are better than cisplatin. The pathways for cellular accumulation were investigated. Complexes with an I as the monodentate ligand, X, exhibit partial energy-independent uptake. Overall results indicate that the novel RuII complexes synthesised in this thesis are most likely to be multi-targeted and that their mechanism of action depends to a great extent on the nature of the monodentate ligand, X. Two particularly active complexes in these series include the impy-NMe2 ligand as YZ chelate. These have been compared to their isostructural azopyridine analogues and also to their OsII equivalents. In this case, experiments were designed to study the activation of landmark events that lead to apoptosis, allowing contrasting the effects of different metal centres (Ru vs Os), isoelectronic ligands (impy-NMe2 vs azpy-NMe2) and monodentate ligands (Cl vs I). Results indicate that the molecular pathway followed by the iodido complexes is p53-independent. In comparison, the chlorido analogues activate the intrinsic apoptotic pathway and their activity relies on the existence of this tumour suppressor. DNA intercalation was also evaluated as a possible mechanism of action. Finally, the third series includes inactive RuII complexes with tetrahydroquinoline derivatives, which were found to enhance the activity of platinum drugs in clinical use. These promising preliminary results in the use of RuII complexes in combination therapy open a world of possibilities for the dose-reduction of platinum-chemotherapeutics.

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Vieira, Goncalves Leonam. "Mechanisms of virucidal action of alcohol and metallic ions against nonenveloped viruses." Thesis, Cardiff University, 2018. http://orca.cf.ac.uk/111705/.

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Studying the mechanism of action (MoA) of biocides against pathogenic microorganisms is crucial to understand their efficacy and limitations, and to develop more efficient microbicidal formulations. Combining alcohol and zinc has been reported to enhance microbicidal activity, but the reasons for such activity are unknown. This study focuses on the impact of combining ethanol and zinc salt at pH 10.5 against nonenveloped viruses. The study is focused on three different aspects: i) virucidal activity screening of ethanol:zinc combinations against bacteriophages and human viruses; ii) impact of ethanol:zinc combinations on virus structure, particularly the viral capsid and nucleic acid, using Transmission Electron Microscopy (TEM); Atomic Force Microscopy (AFM) and agarose gel DNA electrophoresis and iii) chemical speciation and stability of ethanol:zinc combinations over time. The combination of ethanol with zinc salt was found to be more effective against viruses than control formulations containing sole active ingredients and/or excipients only. Activity test of 40%(w/v) ethanol with 0.1% (w/v) zinc salt with excipients (RB- 002 formulation) against F116 and adenovirus type 2 (AdV2) at 60 min contact time yielded 0.68 ± 0.02 and 5.26 ± 0.10 log10 reduction, respectively. In comparison, 0.1% (w/v) zinc salt only with excipient (RB-002G formulation) showed no virucidal activity against bacteriophage F116 (0.14 ± 0.02 log10 reduction) and AdV2 (0.80 ± 0.12 log10 reduction) in suspension. Differences between activities against bacteriophage MS2 and poliovirus type 1 were similar as the ones found between F116 and AdV2. Formulation containing 40%(w/v) ethanol with 0.1% (w/v) zinc salt produced a range of structural damage to F116 and attP AdV5 indicating possible capsid alteration. Effect of the combined formulation on viral capsid was confirmed with AFM with a possible decreased in virus capsid stiffness and significant virus capsid height reduction over 10 min contact time. F116 DNA damage was detected upon exposure to 40%(w/v) ethanol with 0.1% (w/v) zinc salt with excipients, but no damage was detected on AdV2 DNA through electrophoresis analysis. The alcohol/zinc formulation system at pH 10.5 was shown to have promising virucidal activity against non-enveloped viruses at room temperature following an alteration of the viral capsid, and possible damage to the viral nucleic acid. This study also showed the limitations of using bacteriophage as surrogate for mammalian viruses.

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Crisford, Anna. "An investigaton into mode of action and selective toxicity of the novel antiparasitic emodepside." Thesis, University of Southampton, 2011. https://eprints.soton.ac.uk/338971/.

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Cooper, David L., Derek E. Murrell, David Roane, and Sam Harirforoosh. "Effects of Formulation Design on Niacin Therapeutics: Mechanism of Action, Metabolism, and Drug Delivery." Digital Commons @ East Tennessee State University, 2015. https://dc.etsu.edu/etsu-works/7166.

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Niacin is a highly effective, lipid regulating drug associated with a number of metabolically induced side effects such as prostaglandin (PG) mediated flushing and hepatic toxicity. In an attempt to reduce the development of these adverse effects, scientists have investigated differing methods of niacin delivery designed to control drug release and alter metabolism. However, despite successful formulation of various orally based capsule and tablet delivery systems, patient adherence to niacin therapy is still compromised by adverse events such as PG-induced flushing. While the primary advantage of orally dosed formulations is ease of use, alternative delivery options such as transdermal delivery or polymeric micro/nanoparticle encapsulation for oral administration have shown promise in niacin reformulation. However, the effectiveness of these alternative delivery options in reducing inimical effects of niacin and maintaining drug efficacy is still largely unknown and requires more in-depth investigation. In this paper, we present an overview of niacin applications, its metabolic pathways, and current drug delivery formulations. Focus is placed on oral immediate, sustained, and extended release niacin delivery as well as combined statin and/or prostaglandin antagonist niacin formulation. We also examine and discuss current findings involving transdermal niacin formulations and polymeric micro/nanoparticle encapsulated niacin delivery.

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Ullah, Imran. "A novel in vitro bioluminescence rate-of-kill (BRoK) assay to study the pharmacodynamic properties of antimalarial drug action in Plasmodium falciparum." Thesis, Keele University, 2016. http://eprints.keele.ac.uk/2411/.

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Massive screens of chemical libraries for antimalarial activity have identified thousands of compounds that exhibit sub-micromolar potency against the blood stage of the malaria parasite Plasmodium falciparum. Triaging these compounds to establish priorities to take forward for development requires additional information regarding their activity. Key amongst their pharmacodynamics (PD) properties is the rate of kill– with a rapid cytocidal effect specifically identified as a key requirement for a Single Exposure Radical Cure and Prophylaxis (SERCaP) product. Compounds that exert an immediate cytocidal effect rapidly reduce parasite burden to ameliorate the morbidity and mortality of disease. With the overall aim to accelerate drug screening by validating a rapid rate of kill, the validation of a novel, quick (6hr) and potentially scalable bioluminescence rate of kill (BroK) assay is described here that demonstrates a good correlation with in vitro recrudescence-based rate of kill data and available in vivo clinical findings. The BRoK assay was used to screen the Medicine for Malaria Venture Malaria Box to identify compounds with rapid cytocidal activity. Seventeen compounds have an initial rate of kill greater than artemisinins, with a further 39 compounds exhibiting a rate of kill between chloroquine and artemisinins. These compounds represent potential Target Candidate Profile, compounds for a SERCaP product. This work highlights the opportunity for the BRoK assay as a hit discovery tool. In addition, the potential for this assay in lead validation through structure activity relationship studies are highlighted.

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Wortley, Michael. "An investigation into the efficacy and mechanisms of action of novel therapeutics for chronic cough." Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/29125.

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Whilst cough is a defensive reflex, in respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD) the cough reflex may become exaggerated and unproductive, leading to presentation of chronic cough as a troublesome symptom. Chronic cough is the most common reason that patients seek ambulatory care in the UK, and cough medications are one of the largest segments of the global over-the-counter drugs market, yet there are no cough medications (prescription or OTC) available that are both efficacious AND safe, indicating a large unmet clinical need. β-adrenergic receptor (β-AR) agonists, methylxanthines (theophylline) and fatty acid amide hydrogenase inhibitors (FAAHi) are peripherally acting drugs with a proven safety profile in humans for other uses, but are not currently recognised as anti-tussive medications. This thesis aimed to examine whether these drugs possess anti-tussive activity, and if so, the mechanisms by which they inhibit cough. These drugs were all effective at blocking the in vivo cough response to tussive stimuli in naïve guinea pigs, and in addition β-AR agonists and theophylline inhibited tussive stimulus evoked cough in guinea pigs previously exposed to cigarette-smoke, which display a clinically relevant enhanced cough phenotype. In vitro and in vivo assays of guinea pig vagus nerve/neuron activation were used to show that these compounds inhibit depolarisation of airway-innervating peripheral sensory nerves. Pharmacological and genetic tools were used to investigate the receptors and signalling pathways activated by these drugs. Whilst β-AR agonists, theophylline and FAAHi had different mechanisms of action, a common component was that all three classes of compound act on various potassium channels, thereby reducing the excitability of sensory neurons. This work suggests that drugs that inhibit peripheral sensory nerve activity have the potential to be efficacious as anti-tussives. Specifically the compounds tested have improved clinical side-effect profiles over currently used anti-tussives, and therefore have potential as therapies for chronic cough.

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Sayce, Andrew Cameron. "Iminosugars as dengue virus therapeutics : molecular mechanisms of action of a drug entering clinical trials." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:8d4da0ce-bfa6-447d-a280-630479f898af.

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Iminosugars are a class of small molecules defined by substitution of a sugar’s ring oxygen with nitrogen. Various chemical modifications of these basic structures (e.g. alkyl chain addition off of the ring nitrogen) have been developed during the last several decades. These molecules have been considered as therapeutics for a number of pathologies including viral infection, congenital disorders of glycosylation (of both glycoproteins and glycolipids), and diabetes. This thesis focuses on the application of a small subset of iminosugars, known as deoxynojirimycin derivatives, as therapeutics against dengue virus induced pathology. Dengue virus infection predominates in tropical climates, but autochthonous infection has recently emerged in areas of both southern Europe and the southern United States. With 390 million people infected annually, dengue is the most prevalent arthropod-borne viral infection worldwide, and the possibility of severe pathology including haemorrhage, shock, and/or death, necessitates development of effective antiviral therapies. Although the molecular mechanisms responsible for progression to severe dengue disease are not completely understood, there is considerable evidence for the role of both the innate and the adaptive immune responses in development of life-threatening complications. Excessive activation of the innate immune response, a phenomenon known as cytokine storm, has been hypothesised to explain development of symptoms related to vascular permeability, whereas the adaptive immune response has been implicated in severe disease through two hypotheses – the antibody dependent enhancement and original antigenic sin hypotheses. The evidence regarding each of these potential mechanisms of severe pathology is discussed throughout this thesis principally with respect to how iminosugar treatment could alter any detrimental effects of the immune response to dengue virus infection. The principal aim of this thesis is to consider the potential of deoxynojirimycin iminosugars as antiviral therapeutics in dengue infection with a focus on how these molecules exert their antiviral effects in primary human cells. I first consider the contributions of glycoprotein inhibition and glycolipid inhibition on production of infectious dengue virus. These experiments suggest that inhibition of glycoprotein folding is responsible for inhibition of infectious dengue virus production. I next consider the impact of treatment of a promising clinical candidate iminosugar, N9-methoxynonyl-deoxynojirimycin (MON-DNJ), on the primary human macrophage transcriptome. In uninfected macrophages as well as macrophages infected with dengue virus or treated with lipopolysaccharide to model bacterial sepsis, iminosugar treatment results in activation of the unfolded protein response and inhibition of several elements of the inflammatory response including signalling by the cytokines IFN-γ and TNF-α, and the inflammatory cascade mediated by NF-κB. Activation of the unfolded protein response as a result of treatment with MON-DNJ can be confirmed by analysis of phosphorylated (activated) NFE2L2, a transcription factor that functions principally to control oxidative stress in response to ER stress signals. Modulation of the inflammatory response of macrophages to dengue infection and bacterial sepsis is confirmed by analysis of secreted cytokines. As predicted by my transcriptomic experiments, levels of TNF-α and IFN-γ produced in response to dengue or lipopolysaccharide are reduced by treatment with MON-DNJ. Finally, I attempted to extend these observations to an animal model of dengue infection with a particular focus on TNF receptor and ligand superfamily members. Unfortunately, heterogeneity of cells types from tissue samples as well as limitations of the animal model complicate interpretation of these findings. Nevertheless, this thesis demonstrates that MON-DNJ is an effective dengue antiviral therapeutic and that this therapeutic activity may be related to both reduction of infectious virus as a consequence of inhibition of glycoprotein processing and as a result of changes to the host’s response to the pathogen. These results have been used in part to justify recently initiated clinical trials of MON-DNJ as a dengue antiviral therapy.

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Al, Matrood W. A. A. "Factors that enhance the ability of Pseudomonas aeruginosa to resist the action of antibiotics." Thesis, Liverpool John Moores University, 2016. http://researchonline.ljmu.ac.uk/4727/.

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P.aeruginosa is one of the most important pathogens in nosocomial infections and fails to respond to standard treatment, particularly in the case of patients subjected to prolong antibiotic treatment. To generate a more comprehensive understanding of the failure of antimicrobial treatment, focusing especially on the adaptive resistance could be the key area that the bacterium develops in this phenomenon. Most studies on antibiotic resistance in P.aeruginosa have focused upon genotypic studies. This study set out to develop an in vitro model to examine the effect of continual exposure of P.aeruginosa PA01 to the antibiotics studied. Experiments were initially conducted to consider the factors that having a significant influence on antibiotic susceptibility using a novel fluorescence based assay (OxoPlate® system). P.aeruginosa was subjected to the action of tobramycin, amikacin and colistin under various environmental factors. The results of the in vitro analysis showed that, from among the three antibiotics used, amikacin was the antibiotic where resistance was most readily developed. From these results, chemostat studies were designed to examine prolonged exposure of the antibiotic to planktonic cells. Chemostat cultures were exposed to amikacin at sub-inhibitory concentrations using Evans defined synthetic medium at different dilution rates (D) under glucose limitation. Both cultures grown at 0.025h-1 and 0.06h-1 developed the following characteristics i. low-level amikacin resistance, which exhibited an increase in the MIC 4-fold. ii. a clear development of phenotypic resistance and this resistance was not acquired as evidenced by the loss of resistance on culture into fresh medium lacking antibiotic. iii. adaptive resistance to amikacin conferred low-level resistance to other aminoglycosides such as tobramycin and antibiotics with different modes of action such as colistin. Low oxygen availability was seen in the cultures grown at 0.099 h-1 and 0.125 h-1, which lead to i. the appearance of the so called “persister” phenotype. These persisters are sub populations of cells that showed a reduction in bacterial cell size as evidenced from the flow cytometry output as well as being slow growing and resistant ii. extracellular polymeric fibrils were produced in the cells derived after 72h incubation time. In all cases, continual exposure resulted in phenotypically distinct mucoid and non- mucoid colony morphotypes, which were clearly observed on amikacin-free nutrient agar. Some of these selected morphotypes showed from the MIC and MBC data a high-level resistance to the antibiotic when left without antibiotics. The biological responses resulting from these studies offer valuable clues underlying unsuccessful treatment. Conducting experiments using robust systems renders this project extremely novel in the field of microbiology and this will contribute to the development of viable treatment options and ultimately the reduction of the emergence of antibiotic resistance.

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Mubaraki, Murad. "Pharmacometabolomic study of the human malaria parasite, Plasmodium falciparum : new insights into parasite biology and mode of drug action." Thesis, University of Liverpool, 2013. http://livrepository.liverpool.ac.uk/12337/.

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Malaria is a vector-borne parasitic disease spread by a bite of an infected female Anopheles mosquito that accounts for high morbidity and mortality, mainly in sub-Saharan Africa. Of the five species that can cause malaria in humans, Plasmodium falciparum is regarded the most virulent species. Antimalarial drugs, unaltered for many decades, remain the mainstay for treating P. falciparum infection. In addition, despite intensive research there remain significant knowledge gaps in understanding of the biology of the malaria parasite P. falciparum. These deficiencies hinder the ability of scientists to identify new targets for drug discovery at a time when new targets are urgently required, such as in the case of newly emerging drug resistant parasite strains. Therefore, an understanding of the biology of P. falciparum is helpful in identifying new drug targets. Metabolomics, defined as the comprehensive analysis of all metabolites in a biological system, offers a feasible platform for highly sensitive and specific analysis of the metabolic pathways of P. falciparum. This is supported by the assumption that metabolites are important players in biological systems and that resistant parasite strains may operate or alter single or multiple metabolic pathways in order to adapt to the drugs being used. Therefore, a targeted metabolomics approach was developed and validated (Chapter 3) in order to better understand the metabolic roles of mitochondria and the digestive vacuole of P. falciparum. Metabolite detection and quantification were conducted using a targeted LC-MS/MS metabolomics approach (Chapter 3). It was shown that metabolic activities, particularly carbohydrate metabolism, in trophozoite stage P. falciparum-infected RBC were remarkably higher than that of non-infected RBC (Chapter 4). This lead the study to progress further, examining the metabolic role of two components of the P. falciparum; the mitochondria and the digestive vacuole. A number of mitochondrial inhibitors selective for specific electron transport chain complexes and mitochondrial transporters were used to assess mitochondrial function in asexually growing trophozoite stage P. falciparum (Chapter 5 and 6). Despite the differing modes of action of the inhibitors, the metabolic fingerprints, which were carbamoyl-l-aspartate and dihydroorotate, from these experiments were consistent with the parasite mitochondrion playing a key role in pyrimidine biosynthesis at the point of dihydroorotate dehydrogenase (DHODH) (Chapter 5 and 6). This metabolic fingerprint, leading to parasite death, was quite distinct from fingerprints obtained from biologically distinct inhibitors such as heme-binding drugs (quinoline-containing antimalarials drugs) which primarily affected the metabolism of amino acids, perhaps in the digestive vacuole and parasite cytosol (Chapter 7). In contrast to genomic and proteomic approaches, metabolomics appears to better represent the parasites’ phenotype in response to drug perturbation. Pharmacometabolomics will therefore have significant utility in understanding the biological function of parasite components; and the mode of action, efficacy and toxicity of pharmaceutical drugs.

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Книги з теми "THERAPEUTICS ACTION"

Group, Diagram, ed. The Parent's emergency guide: An action handbook for childhood illnesses and accidents. London: Corgi, 1986.

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Lee, Scout. Basic terminology for therapeutic recreation and other action therapies. 3rd ed. Champaign, Ill: Stipes Pub. Co., 1997.

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Diagnosis, breast cancer: The best action plan for navigating your journey. Rolling Meadows, IL: Windy City Publishers, 2012.

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1950-, Morstyn George, Foote MaryAnn, and Lieschke Graham J, eds. Hematopoietic growth factors in oncology: Basic science and clinical therapeutics. Totowa, N.J: Humana Press, 2004.

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E, Lifson Lawrence, ed. Understanding therapeutic action: Psychodynamic concepts of cure. Hillsdale, NJ: Analytic Press, 1996.

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Pelt, Annemarie C. Glucocorticoids: Effects, action mechanisms, and therapeutic uses. Hauppauge, N.Y: Nova Science, 2011.

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Catania, Anna, ed. Melanocortins: Multiple Actions and Therapeutic Potential. New York, NY: Springer New York, 2010. http://dx.doi.org/10.1007/978-1-4419-6354-3.

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Younus, Hina, ed. Molecular and Therapeutic actions of Thymoquinone. Singapore: Springer Singapore, 2018. http://dx.doi.org/10.1007/978-981-10-8800-1.

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Keppler, D., A. Stiehl, U. Beuers, and M. Trauner, eds. Bile Acid Biology and Therapeutic Actions. Dordrecht: Springer Netherlands, 2009. http://dx.doi.org/10.1007/978-1-4020-9644-0.

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Catania, Anna. Melanocortins: Multiple actions and therapeutic potential. New York: Springer Science+Business Media, 2010.

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Частини книг з теми "THERAPEUTICS ACTION"

Yang, Kun, Robert A. DeAngelis, Janet E. Reed, Daniel Ricklin, and John D. Lambris. "Complement in Action: An Analysis of Patent Trends from 1976 Through 2011." In Complement Therapeutics, 301–13. New York, NY: Springer US, 2012. http://dx.doi.org/10.1007/978-1-4614-4118-2_21.

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Strijack, Bradford, and Paul A. Keown. "Cyclosporine: Molecular Action to Clinical Therapeutics." In Immunotherapy in Transplantation, 197–223. Oxford, UK: Wiley-Blackwell, 2012. http://dx.doi.org/10.1002/9781444355628.ch15.

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Zipfel, Peter F., and Nadine Lauer. "Defective Complement Action and Control Defines Disease Pathology for Retinal and Renal Disorders and Provides a Basis for New Therapeutic Approaches." In Complement Therapeutics, 173–87. Boston, MA: Springer US, 2012. http://dx.doi.org/10.1007/978-1-4614-4118-2_11.

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Zhang, Zuo, and Gordon G. Carmichael. "Mechanism of Action of Antisense RNA in Eukaryotic Cells." In Nucleic Acid Therapeutics in Cancer, 89–104. Totowa, NJ: Humana Press, 2004. http://dx.doi.org/10.1007/978-1-59259-777-2_7.

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Takahama, K., T. Shirasaki, and F. Soeda. "Central Mechanisms III: Neuronal Mechanisms of Action of Centrally Acting Antitussives Using Electrophysiological and Neurochemical Study Approaches." In Pharmacology and Therapeutics of Cough, 219–40. Berlin, Heidelberg: Springer Berlin Heidelberg, 2009. http://dx.doi.org/10.1007/978-3-540-79842-2_11.

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Rainsford, K. D. "Mechanisms of Inflammation and Sites of Action of NSAIDs." In Ibuprofen: Pharmacology, Therapeutics and Side Effects, 43–57. Basel: Springer Basel, 2012. http://dx.doi.org/10.1007/978-3-0348-0496-7_3.

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Prabhakar, Pranav Kumar, Yachana Mishra, and Vijay Mishra. "Potential Preventive and Therapeutic Accountability of Probiotics in Cancer: An Insight of Mechanism of Action." In Probiotic Research in Therapeutics, 29–45. Singapore: Springer Singapore, 2020. http://dx.doi.org/10.1007/978-981-15-8214-1_2.

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Hsu, Jennifer L., and Mien-Chie Hung. "Mechanisms of Action and Resistance of Trastuzumab in Breast Cancer." In Resistance to Targeted Anti-Cancer Therapeutics, 51–66. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-67932-7_3.

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Arechavala-Gomeza, Virginia, and Alejandro Garanto. "Antisense RNA Therapeutics: A Brief Overview." In Methods in Molecular Biology, 33–49. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2010-6_2.

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AbstractNucleic acid therapeutics is a growing field aiming to treat human conditions that has gained special attention due to the successful development of mRNA vaccines against SARS-CoV-2. Another type of nucleic acid therapeutics is antisense oligonucleotides, versatile tools that can be used in multiple ways to target pre-mRNA and mRNA. While some years ago these molecules were just considered a useful research tool and a curiosity in the clinical market, this has rapidly changed. These molecules are promising strategies for personalized treatments for rare genetic diseases and they are in development for very common disorders too. In this chapter, we provide a brief description of the different mechanisms of action of these RNA therapeutic molecules, with clear examples at preclinical and clinical stages.

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Schmitt, Sara M., Rahul R. Deshmukh, and Q. Ping Dou. "Proteasome Inhibitors and Lessons Learned from Their Mechanisms of Action and Resistance in Human Cancer." In Resistance to Targeted Anti-Cancer Therapeutics, 1–46. Cham: Springer International Publishing, 2014. http://dx.doi.org/10.1007/978-3-319-06752-0_1.

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Тези доповідей конференцій з теми "THERAPEUTICS ACTION"

Papineni, Rao, and Amithava Adhikary. "Abstract 482: Multiple chemical action cancer therapeutics." In Proceedings: AACR Annual Meeting 2020; April 27-28, 2020 and June 22-24, 2020; Philadelphia, PA. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/1538-7445.am2020-482.

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Bakay, Emel, Hilal Er, Aysenur Pamukcu, Didem Sen Karaman, and Nermin Topaloglu. "Enhanced photodynamic action with chlorin e6 and indocyanine green incorporated mesoporous silica nanoparticles against prostate cancer cells." In Translational Biophotonics: Diagnostics and Therapeutics, edited by Lothar D. Lilge and Zhiwei Huang. SPIE, 2021. http://dx.doi.org/10.1117/12.2615066.

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Pei, Yi, Thomas Pohl, Ahmed Hassan, Anna Przybyla, Raymond Yu, Huarui Lu, Fangqiang Tang, et al. "Abstract 920: Harnessing multiple mechanisms of action to target Nectin-4 as anti-tumor therapeutics." In Proceedings: AACR Annual Meeting 2021; April 10-15, 2021 and May 17-21, 2021; Philadelphia, PA. American Association for Cancer Research, 2021. http://dx.doi.org/10.1158/1538-7445.am2021-920.

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Giandomenico, Silvana Di, Roberta Frapolli, Ezia Bello, Silvana Pilotti, Paolo Casali, Federica Grosso, Roberta Sanfilippo, Alessandro Gronchi, Carlos Galmarini, and Maurizio D'Incalci. "Abstract A17: Mode of action of trabectedin in myxoid liposarcomas." In Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Nov 12-16, 2011; San Francisco, CA. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1535-7163.targ-11-a17.

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Pandiella, Atanasio, Juan Carlos Montero, Lolin Cuenca-Lopez, Florencia Re-Louhau, Francisco Moris, and Alberto Ocana. "Abstract B39: Action of EC8042 in triple-negative breast cancer." In Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Nov 12-16, 2011; San Francisco, CA. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1535-7163.targ-11-b39.

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van der Kraan, A. Gabrielle J., Ryan R. Chai, Michelle M. Kouspou, Ben J. Lang, Preetinder P. Singh, Jiake Xu, Damien Eeles, Matthew T. Gillespie, Julian M. Quinn, and John T. Price. "Abstract 2933: HSP90 inhibiting anti-cancer therapeutics enhance bone loss by increasing osteoclast formation: Mechanism of action." In Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-2933.

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Matthews, Charles S., Andrew J. McCarroll, Malcolm FG Stevens, Anne Monks, and Tracey D. Bradshaw. "Abstract B164: Role of endoplasmic reticulum stress in mechanism of action of antitumor quinols." In Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Nov 15-19, 2009; Boston, MA. American Association for Cancer Research, 2009. http://dx.doi.org/10.1158/1535-7163.targ-09-b164.

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Martínez-Diez, Marta, Juan Fernando Martínez-Leal, Luis F. Garcia-Fernandez, and Carlos M. Galmarini. "Abstract A177: Mode of action of PM060184, a new interfacial microtubule inhibitor of marine origin." In Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Oct 19-23, 2013; Boston, MA. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1535-7163.targ-13-a177.

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Ferreira, Germano A., Carolina H. Thome, Guilherme A. dos Santos, Priscila S. Scheucher, Andreia M. Leopoldino, Ana M. Simão, Clarice Izume, et al. "Abstract A229: Mechanism of action of perifosine on the mantle cell lymphoma line, Granta-519." In Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Oct 19-23, 2013; Boston, MA. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1535-7163.targ-13-a229.

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Smaill, Jeff B., Jagdish Jaiswal, Maria Abbattista, Guo-Liang Lu, Robert F. Anderson, Amir Ashoorzadeh, William A. Denny, et al. "Abstract A247: Mechanism of action of the hypoxia-activated irreversible pan-HER inhibitor SN29966." In Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Nov 12-16, 2011; San Francisco, CA. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1535-7163.targ-11-a247.

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Звіти організацій з теми "THERAPEUTICS ACTION"

Arnold, Jonathon, David Allsop, Nicholas Lintzeris, and Iain McGregor. Pharmacological actions and associated therapeutic levels of phytocannabinoids Addendum 2021. The Sax Institute, January 2016. http://dx.doi.org/10.57022/ovds2305.

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Анотація:

This review examined the pharmacological and possible therapeutic effects of various plant-derived cannabinoids (phytocannabinoids) in adults and children. There is reasonably good evidence of the therapeutic effects of CBD, with no evidence of THC-like intoxication. Evidence relating to potential therapeutic effects of the remaining phytocannabinoids mostly comes from preclinical studies, with little evidence of intoxication. Additional human studies are required.

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Cabot, Myles C. A Dual-Action Approach to Multidrug-Resistant Breast Cancer: Prophylaxis to Ensure Therapeutic Effect. Fort Belvoir, VA: Defense Technical Information Center, February 2007. http://dx.doi.org/10.21236/ada469157.

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Davidson, Nancy E. Therapeutic and Chemopreventive Actions of a Novel Polywmine Analog Against Breast Cancer. Fort Belvoir, VA: Defense Technical Information Center, September 2001. http://dx.doi.org/10.21236/ada397040.

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Davidson, Nancy E. Therapeutic and Chemopreventive Actions of a Novel Polyamine Analog Against Breast Cancer. Fort Belvoir, VA: Defense Technical Information Center, September 2002. http://dx.doi.org/10.21236/ada409999.

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Elmann, Anat, Orly Lazarov, Joel Kashman, and Rivka Ofir. therapeutic potential of a desert plant and its active compounds for Alzheimer's Disease. United States Department of Agriculture, March 2015. http://dx.doi.org/10.32747/2015.7597913.bard.

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We chose to focus our investigations on the effect of the active forms, TTF and AcA, rather than the whole (crude) extract. 1. To establish cultivation program designed to develop lead cultivar/s (which will be selected from the different Af accessions) with the highest yield of the active compounds TTF and/or achillolide A (AcA). These cultivar/s will be the source for the purification of large amounts of the active compounds when needed in the future for functional foods/drug development. This task was completed. 2. To determine the effect of the Af extract, TTF and AcA on neuronal vulnerability to oxidative stress in cultured neurons expressing FAD-linked mutants.Compounds were tested in N2a neuroblastoma cell line. In addition, we have tested the effects of TTF and AcA on signaling events promoted by H₂O₂ in astrocytes and by β-amyloid in neuronal N2a cells. 3. To determine the effect of the Af extract, TTF and AcA on neuropathology (amyloidosis and tau phosphorylation) in cultured neurons expressing FAD-linked mutants. 4. To determine the effect of A¦ extract, AcA and TTF on FAD-linked neuropathology (amyloidosis, tau phosphorylation and inflammation) in transgenic mice. 5. To examine whether A¦ extract, TTF and AcA can reverse behavioral deficits in APPswe/PS1DE9 mice, and affect learning and memory and cognitive performance in these FAD-linked transgenic mice. Background to the topic.Neuroinflammation, oxidative stress, glutamate toxicity and amyloid beta (Ab) toxicity are involved in the pathogenesis of Alzheimer's diseases. We have previously purified from Achilleafragrantissimatwo active compounds: a protective flavonoid named 3,5,4’-trihydroxy-6,7,3’-trimethoxyflavone (TTF, Fl-72/2) and an anti-inflammatory sesquiterpenelactone named achillolide A (AcA). Major conclusions, solutions, achievements. In this study we could show that TTF and AcA protected cultured astrocytes from H₂O₂ –induced cell death via interference with cell signaling events. TTF inhibited SAPK/JNK, ERK1/2, MEK1 and CREBphosphorylation, while AcA inhibited only ERK1/2 and MEK1 phosphorylation. In addition to its protective activities, TTF had also anti-inflammatory activities, and inhibited the LPS-elicited secretion of the proinflammatorycytokinesInterleukin 6 (IL-6) and IL-1b from cultured microglial cells. Moreover, TTF and AcA protected neuronal cells from glutamate and Abcytotoxicity by reducing the glutamate and amyloid beta induced levels of intracellular reactive oxygen species (ROS) and via interference with cell signaling events induced by Ab. These compounds also reduced amyloid precursor protein net processing in vitro and in vivo in a mouse model for Alzheimer’s disease and improvedperformance in the novel object recognition learning and memory task. Conclusion: TTF and AcA are potential candidates to be developed as drugs or food additives to prevent, postpone or ameliorate Alzheimer’s disease. Implications, both scientific and agricultural.The synthesis ofAcA and TTF is very complicated. Thus, the plant itself will be the source for the isolation of these compounds or their precursors for synthesis. Therefore, Achilleafragrantissima could be developed into a new crop with industrial potential for the Arava-Negev area in Israel, and will generate more working places in this region.

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Vishwanath, Arundathi. Theatre and Art in Education for Young Women with a Focus on Theatre of the Oppressed Techniques and Embodied Therapeutic Practices. Indian Institute for Human Settlements, 2023. http://dx.doi.org/10.24943/tesf0105.2023.

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This project unfolded in Nanahar village in the Kangra district of Himachal Pradesh. The main objectives of this project were to spark critical thought and action amongst the participants of the programme, facilitate a process to reclaim one’s agency, equip the participants with theatre facilitation skills and equip the organisation with a theatre and art in education curriculum. The project timeline was September 2021–October 2022. A pilot workshop was initially conducted with 24 women enrolled in a skill development course, and consequently a longer 16-week workshop series was conducted for a group of 33 women.

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Shijani, Seyed Mohammad Malakooti, Sina Neshat, Hossein Shayestehyekta, and Milad Gorgani. Lance-Adams syndrome; what we know now. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, November 2022. http://dx.doi.org/10.37766/inplasy2022.11.0025.

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Review question / Objective: 1. In Lance-Adams syndrome, what is the effect of current therapeutic management on improving patients' condition compared with the control group? 2. Are EEG, Brain CT, MRI, and brain SPECT more accurate in diagnosing Lance-Adams syndrome? 3. Does Early diagnosis and treatment influence the quality of life in patients with Lance-Adams syndrome? 4. Are patients with abnormal cortical discharge or cerebellum brain stem and thalamus cortical circuit or neurotransmitter imbalance at higher risk for/of Lance-Adams syndrome compared with patients without these symptoms? Condition being studied: LAS is a group of clinical symptoms; The primary manifestation is action myoclonus which can occur as generalized, focal, or multifocal repeated myoclonic motor movement myoclonus. In some patients, sensory stimuli can trigger myoclonus. Furthermore, negative myoclonus can impair posture and cause falls in the lower extremities.

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Brown, George B. Development and Testing of an In Vitro Assay for Screening of Potential Therapeutic Agents Active against Na Channel Neurotoxins. Fort Belvoir, VA: Defense Technical Information Center, April 1991. http://dx.doi.org/10.21236/ada237159.

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