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Unedited Cataract Surgery 3

Cisplatin is in a class of drugs known as platinum-containing compounds used to treat various types of cancers including metastatic testicular and ovarian tumors. The molecule was first discovered in 1845, but did not receive FDA approval until 1978. Today it is known as the "penicillin of cancer drugs," because it is so effective for many different cancers. There are three key players involved in Cisplatin's mechanism: (1) Cisplatin, (2) DNA (3) and an HMG Protein. Most Cisplatin enters the body through active transport, but some molecules are passively defused through the cell membrane. Once in the nucleus, Cisplatin can form an adduct with two consecutive guanine bases within a strand of DNA. The molecule loses its chlorine atoms in exchange for the nitrogen atoms of the target guanines. Cisplatin can bond more tightly with nitrogen because nitrogen balances the platinum charge more effectively than chlorine. It is this adduct-induced DNA bend that allows binding of proteins which contain the high mobility group, HMG domain. Once the protein is bound to the DNA, it inserts a wedge-like phenyl group of phenylalanine 37 into the widened minor groove created by the bend. The tightly bound HMG protein causes destacking of the nucleotide bases, resulting in the DNA helix becoming kinked. In this way, Cisplatin can be thought of as a monkey wrench in the DNA repair system. With the HMG protein bound to the DNA, the modified strand is not repaired properly and so the cell dies. The success of Cisplatin depends on its ratio of efficacy between cancerous and healthy cells.

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M.Torabi Nami MD, PhDc Department of Neuroscience Institute for Cognitive Science Studies (ICSS), Tehran 15948 Iran Torabi_m@iricss.org Abstract Sleepiness, tiredness and fatigue are complaints which must be thoroughly analyzed to eliminate blur and ambiguity. Physiological sleepiness (“sleep pressure”) increases while being awake and additionally underlies the circadian rhythm with a lower threshold to fall asleep during night time. Excessive daytime sleepiness (EDS) is considered normal only after sleep deprivation. Clinically, EDS manifests by frequents daytime napping and/or reduced alertness with automatic behavior or - in its extreme form - in recurrent attacks of sudden, uncontrollable compulsion to sleep also in inappropriate situations (= “sleep attacks”). EDS is “objectively” addressed by measuring the mean sleep latency to four to five nap opportunities throughout the day using the multiple sleep latency test (MSLT) or the maintenance of wakefulness test (MWT). EDS denotes both, a ready entrance into sleep as well as difficulty in staying awake during daytime or accordingly in inappropriate situations. These two partially independent aspects of EDS are separately assessed by the “passive” MSLT and the “active” MWT respectively. For that reason the MSLT and MWT only weakly correlate with each other when tested over a broad range of patients with EDS. It is important to keep in mind, that these tests are importantly influenced by a great variety of factors such as mood, anxiety, and motivation. “Vigilance” comprises wakefulness, alertness and attention and therefore is more than just the reciprocal to sleepiness. Cognitive performance tasks such as Steer Clear Reaction Time Test (SCRTT) or driving simulators require the complete integrity of vigilance to achieve normal results. Hypersomnia is usually broadly defined as the combination of abnormally prolonged night-time sleep (regularly >10 h) with EDS during ≥1 months. On the other hand, the term hypersomnia has also been used in a narrower scene for the isolated abnormality of a prolonged night-time sleep need (>10 h). “Tiredness”, also in colloquial language often used for sleepiness, in a broader sense also describes the feeling of lack of energy, motivation and initiative. These patients seek rest rather than sleep. They often cannot fall asleep when given the opportunity in spite of feeling tired, and hence, in an MSLT, do not show an abnormally short sleep latency. Furthermore, tiredness (and fatigue) as opposed to sleepiness has a mental (“central”) and physiological (bodily or “peripheral”) component, which the patients can readily distinguish. Patients with insomnia, mild sleep apnea syndrome, or depression rather suffer from mental tiredness than sleepiness during the day. The simple subjective self-assessment using the Epworth Sleepiness Scale (ESS) quite reliably differentiates between sleepiness and mental tiredness (without sleepiness), which makes it a widely used test. The term “fatigue” is also heterogeneously used. In physiology the “fatigue” implied a “time on task performance decrement” to describe decreasing muscle force during a sustained physical effort. In clinical medicine one distinguishes physical (“peripheral”) from mental (“central”) fatigue and the term usually denotes a chronic and more abnormal situation than tiredness. In a broad sense “fatigue” implies a deficiency in coping satisfactorily with mental and physical work load. The chronic fatigue syndrome entails both mental as well as a physical fatigue (so called “leaden paralysis” of limbs). Depressive states are often associated with insomnia and fatigue, but there are also cases with hypersomnia rather than insomnia ( non organic hypersomnia , “atypical depression” or “hypersom

http://www.landging.com/nervous-system-animation.html Human body nervous system, 3D MOA (Mechanism of Action) animation, designed for Beijing Natural History Museum.

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