The International journal of risk & safety in medicine
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Acetylcholinesterase (AChE) inhibitors are widely used in medicine for pharmacological correction of cholinergic neurotransmission pathologies such as myasthenia gravis (MG) and Alzheimer's disease [1, 2]. The efficacy of anti-AChE drugs is based on their ability to potentiate the effects of acetylcholine (ACh) due to a decrease in the rate of AChE-catalyzed hydrolysis of ACh. Crystallographic studies showed that the active site of AChE is located at the bottom of a deep gorge [3]. It was shown that, in addition to its catalytic center, AChE has other sites that are crucial for the proper functioning of the enzyme. In particular, the so-called peripheral anionic site (PAS) located at the entrance of the active site gorge is responsible for: 1) allosteric modulation of the catalytic center; 2) enzyme inhibition at high substrate concentration; 3) and non-catalytic functions such as enhancement of cell adhesion and neurite outgrowth. ⋯ In conclusion, it can be stated that pyrimidinophanes are promising lead scaffold structures for further design of specific ligands for the PAS of AChE. Also AChE inhibitors with a 6-methyluracil moiety may be considered as potential drugs for the treatment of pathological muscle weakness syndromes.
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The relevance of the problem of colorectal cancer (CRC) is evident because of extremely high morbidity and mortality rates, associated with this disease. CRC is mostly diagnosed only at very advanced stages. The reduction of mortality can be achieved by the popularization of screening-methods for early identification of CRC and adenomatous polyps of the colon, which are proved to be precancerous condition. Fecal occult blood test is a well-known method of screening for CRC. The advantages of this method when compared, for example, with colonoscopy are its simplicity and cost-effectiveness.Two techniques are usually used for detection of occult blood in the stool: Hemoccult (Guaiac) test and immunochemical test for hemoglobin. There is no consensus among researchers regarding the validity of these tests for the diagnosis of colorectal cancer. For example, J.S. Mandel (1996) notes 60% sensitivity of Guaiac-test for the detection of the early forms of colorectal cancer, while O.I. Kit (2014) suggets that it is not higher than 30%. There are also various opinions about specificity of these two tests. ⋯ 1. The sensitivity of the Guaiac test for occult blood in stool is lower than its specificity.2. Broad dispersion of the validity characteristics of the fecal occult blood tests was observed.3. The validity of tests for occult blood was higher when they were used for detection of colorectal cancer than of colon polyposis.4. The highest validity rate has been demonstrated for the immunochemical test when it was used for colon cancer screening.
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Ward rounds are the traditional process by which clinical information is interpreted and management plans made in the inpatient setting and the only time during which patient-doctor interaction can reliably occur. Efforts to improve quality and safety have started looking at the ward round but this has mainly been in the acute medical setting. ⋯ By starting a discussion about ward rounds we aim to align the process with the broader values of the organisation. Ward rounds can be the cornerstone of delivering safe, clean and personal care and measuring this process is vital to understanding efforts to improve them.
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Alzheimer's disease (AD) is the major age-related progressive neurodegenerative disorder. The brain of AD patients suffers from loss of cholinergic neurons and decreased number of synapses [1]. AD is caused by an imbalance between Aβ production and clearance, resulting in increased amount of Aβ in various forms [2]. Reduction of Aβ production and increasing clearance of Aβ pathogenic forms are key targets in the development of potential therapeutic agents for AD treatment. Unfortunately, only nosotropic approaches for treatment of AD are currently effective in humans. These approaches mainly focus on the inhibition of brain acetyl-cholinesterase (AChE) to increase lifetime of cerebral acetylcholine [3]. It is important to emphasize that AChE itself promotes the formation of Aβ fibrils in vitro and Aβ plaques in the cerebral cortex of transgenic mouse models of AD [4]. This property of AChE results from interaction between Aβ and the peripheral anionic site of the enzyme (PAS) [5]. Dual binding site inhibitors of both catalytic active site (CAS) and PAS can simultaneously improve cognition and slow down the rate of Aβ-induced neural degeneration. Unfortunately, the assortment of AChE PAS ligands is still extremely limited. ⋯ Experiments showed that the most potent AChE inhibitor compound 35 (6-methyluracil derivative) permeated the blood-brain barrier, improved working memory in the APP/PS1 transgenic mice and significantly reduced the number and area of Aβ plaques in the brain. Thus, compound 35 is a promising candidate as a bi-functional inhibitor of AChE for treatment of AD.
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Improving quality of care in many countries is one of the priorities of health systems. At the same time one of the most important methods of improving quality of care is the widespread use of methods and principles of evidence-based medicine (EBM) [1]. The implementation of EBM in public health practice provides for the optimization of quality of care in terms of safety, efficacy and cost, one way of which is the use of clinical guidelines. Clinical guidelines developed with the use of EBM, provide an opportunity to use the latest and accurate information to optimize or neutralize impact on physician decision-making of subjective factors such as intuition, expertise, opinion of respected colleagues, recommendations of popular manuals and handbooks, etc. ⋯ It is very important to ensure equal opportunities in access to medical interventions designed accordingly to the CGs and CPs at all health facilities that will prevent discrimination, depending on territorial distribution, administrative subordination, and other factors in the provision of health care. Implementation of CG and CP recommendations depends not only on the level of health care, knowledge and judgment of a clinician, but also on affordability of a particular diagnostic or therapeutic technologies for a patient. Cases when effective services are not unaffordable for patients should be considered from ethical perspective.