<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Death and explain in detail? [/INST] Death is the irreversible cessation of all biological functions that sustain an organism. For organisms with a brain, death can also be defined as the irreversible cessation of functioning of the whole brain, including brainstem, and brain death is sometimes used as a legal definition of death. The remains of a former organism normally begin to decompose shortly after death. Death is an inevitable process that eventually occurs in almost all organisms.
Death is generally applied to whole organisms; the similar process seen in individual components of an organism, such as cells or tissues, is necrosis. Something that is not considered an organism, such as a virus, can be physically destroyed but is not said to die. As of the early 21st century, over 150,000 humans die each day, with ageing being by far the most common cause of death.Many cultures and religions have the idea of an afterlife, and also may hold the idea of judgement of good and bad deeds in ones life (heaven, hell, karma).

Diagnosis
Problems of definition
The concept of death is a key to human understanding of the phenomenon. There are many scientific approaches and various interpretations of the concept. Additionally, the advent of life-sustaining therapy and the numerous criteria for defining death from both a medical and legal standpoint, have made it difficult to create a single unifying definition.
One of the challenges in defining death is in distinguishing it from life. As a point in time, death would seem to refer to the moment at which life ends. Determining when death has occurred is difficult, as cessation of life functions is often not simultaneous across organ systems. Such determination, therefore, requires drawing precise conceptual boundaries between life and death. This is difficult, due to there being little consensus on how to define life.
It is possible to define life in terms of consciousness. When consciousness ceases, an organism can be said to have died. One of the flaws in this approach is that there are many organisms that are alive but probably not conscious (for example, single-celled organisms). Another problem is in defining consciousness, which has many different definitions given by modern scientists, psychologists and philosophers. Additionally, many religious traditions, including Abrahamic and Dharmic traditions, hold that death does not (or may not) entail the end of consciousness. In certain cultures, death is more of a process than a single event. It implies a slow shift from one spiritual state to another.
Other definitions for death focus on the character of cessation of organismic functioning and a human death which refers to irreversible loss of personhood. More specifically, death occurs when a living entity experiences irreversible cessation of all functioning. As it pertains to human life, death is an irreversible process where someone loses their existence as a person.Historically, attempts to define the exact moment of a humans death have been subjective, or imprecise. Death was once defined as the cessation of heartbeat (cardiac arrest) and of breathing, but the development of CPR and prompt defibrillation have rendered that definition inadequate because breathing and heartbeat can sometimes be restarted. This type of death where circulatory and respiratory arrest happens is known as the circulatory definition of death (DCDD). Proponents of the DCDD believe that this definition is reasonable because a person with permanent loss of circulatory and respiratory function should be considered dead. Critics of this definition state that while cessation of these functions may be permanent, it does not mean the situation is irreversible, because if CPR was applied, the person could be revived. Thus, the arguments for and against the DCDD boil down to a matter of defining the actual words "permanent" and "irreversible," which further complicates the challenge of defining death. Furthermore, events which were causally linked to death in the past no longer kill in all circumstances; without a functioning heart or lungs, life can sometimes be sustained with a combination of life support devices, organ transplants and artificial pacemakers.
Today, where a definition of the moment of death is required, doctors and coroners usually turn to "brain death" or "biological death" to define a person as being dead; people are considered dead when the electrical activity in their brain ceases. It is presumed that an end of electrical activity indicates the end of consciousness. Suspension of consciousness must be permanent, and not transient, as occurs during certain sleep stages, and especially a coma. In the case of sleep, EEGs can easily tell the difference.
The category of "brain death" is seen as problematic by some scholars. For instance, Dr. Franklin Miller, senior faculty member at the Department of Bioethics, National Institutes of Health, notes: "By the late 1990s... the equation of brain death with death of the human being was increasingly challenged by scholars, based on evidence regarding the array of biological functioning displayed by patients correctly diagnosed as having this condition who were maintained on mechanical ventilation for substantial periods of time. These patients maintained the ability to sustain circulation and respiration, control temperature, excrete wastes, heal wounds, fight infections and, most dramatically, to gestate fetuses (in the case of pregnant "brain-dead" women)."While "brain death" is viewed as problematic by some scholars, there are certainly proponents of it that believe this definition of death is the most reasonable for distinguishing life from death. The reasoning behind the support for this definition is that brain death has a set of criteria that is reliable and reproducible. Also, the brain is crucial in determining our identity or who we are as human beings. The distinction should be made that "brain death" cannot be equated with one who is in a vegetative state or coma, in that the former situation describes a state that is beyond recovery.Those people maintaining that only the neo-cortex of the brain is necessary for consciousness sometimes argue that only electrical activity should be considered when defining death. Eventually it is possible that the criterion for death will be the permanent and irreversible loss of cognitive function, as evidenced by the death of the cerebral cortex. All hope of recovering human thought and personality is then gone given current and foreseeable medical technology. At present, in most places the more conservative definition of death – irreversible cessation of electrical activity in the whole brain, as opposed to just in the neo-cortex – has been adopted (for example the Uniform Determination Of Death Act in the United States). In 2005, the Terri Schiavo case brought the question of brain death and artificial sustenance to the front of American politics.
Even by whole-brain criteria, the determination of brain death can be complicated. EEGs can detect spurious electrical impulses, while certain drugs, hypoglycemia, hypoxia, or hypothermia can suppress or even stop brain activity on a temporary basis. Because of this, hospitals have protocols for determining brain death involving EEGs at widely separated intervals under defined conditions.

In the past, adoption of this whole-brain definition was a conclusion of the Presidents Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research in 1980. They concluded that this approach to defining death sufficed in reaching a uniform definition nationwide. A multitude of reasons were presented to support this definition including: uniformity of standards in law for establishing death; consumption of a familys fiscal resources for artificial life support; and legal establishment for equating brain death with death in order to proceed with organ donation.Aside from the issue of support of or dispute against brain death, there is another inherent problem in this categorical definition: the variability of its application in medical practice. In 1995, the American Academy of Neurology (AAN), established a set of criteria that became the medical standard for diagnosing neurologic death. At that time, three clinical features had to be satisfied in order to determine "irreversible cessation" of the total brain including: coma with clear etiology, cessation of breathing, and lack of brainstem reflexes. This set of criteria was then updated again most recently in 2010, but substantial discrepancies still remain across hospitals and medical specialties.The problem of defining death is especially imperative as it pertains to the dead donor rule, which could be understood as one of the following interpretations of the rule: there must be an official declaration of death in a person before starting organ procurement or that organ procurement cannot result in death of the donor. A great deal of controversy has surrounded the definition of death and the dead donor rule. Advocates of the rule believe the rule is legitimate in protecting organ donors while also countering against any moral or legal objection to organ procurement. Critics, on the other hand, believe that the rule does not uphold the best interests of the donors and that the rule does not effectively promote organ donation.

Signs
Signs of death or strong indications that a warm-blooded animal is no longer alive are:

Respiratory arrest (no breathing)
Cardiac arrest (no pulse)
Brain death (no neuronal activity)The stages that follow after death are:

Pallor mortis, paleness which happens in 15–120 minutes after death
Algor mortis, the reduction in body temperature following death. This is generally a steady decline until matching ambient temperature
Rigor mortis, the limbs of the corpse become stiff (Latin rigor) and difficult to move or manipulate
Livor mortis, a settling of the blood in the lower (dependent) portion of the body
Putrefaction, the beginning signs of decomposition
Decomposition, the reduction into simpler forms of matter, accompanied by a strong, unpleasant odor.
Skeletonization, the end of decomposition, where all soft tissues have decomposed, leaving only the skeleton.
Fossilization, the natural preservation of the skeletal remains formed over a very long period

Legal
The death of a person has legal consequences that may vary between different jurisdictions.
A death certificate is issued in most jurisdictions, either by a doctor, or by an administrative office upon presentation of a doctors declaration of death.

Misdiagnosed
There are many anecdotal references to people being declared dead by physicians and then "coming back to life", sometimes days later in their own coffin, or when embalming procedures are about to begin. From the mid-18th century onwards, there was an upsurge in the publics fear of being mistakenly buried alive, and much debate about the uncertainty of the signs of death. Various suggestions were made to test for signs of life before burial, ranging from pouring vinegar and pepper into the corpses mouth to applying red hot pokers to the feet or into the rectum. Writing in 1895, the physician J.C. Ouseley claimed that as many as 2,700 people were buried prematurely each year in England and Wales, although others estimated the figure to be closer to 800.In cases of electric shock, cardiopulmonary resuscitation (CPR) for an hour or longer can allow stunned nerves to recover, allowing an apparently dead person to survive. People found unconscious under icy water may survive if their faces are kept continuously cold until they arrive at an emergency room. This "diving response", in which metabolic activity and oxygen requirements are minimal, is something humans share with cetaceans called the mammalian diving reflex.As medical technologies advance, ideas about when death occurs may have to be re-evaluated in light of the ability to restore a person to vitality after longer periods of apparent death (as happened when CPR and defibrillation showed that cessation of heartbeat is inadequate as a decisive indicator of death). The lack of electrical brain activity may not be enough to consider someone scientifically dead. Therefore, the concept of information-theoretic death has been suggested as a better means of defining when true death occurs, though the concept has few practical applications outside the field of cryonics.
There have been some scientific attempts to bring dead organisms back to life, but with limited success.

Causes
The leading cause of human death in developing countries is infectious disease. The leading causes in developed countries are atherosclerosis (heart disease and stroke), cancer, and other diseases related to obesity and aging. By an extremely wide margin, the largest unifying cause of death in the developed world is biological aging, leading to various complications known as aging-associated diseases. These conditions cause loss of homeostasis, leading to cardiac arrest, causing loss of oxygen and nutrient supply, causing irreversible deterioration of the brain and other tissues. Of the roughly 150,000 people who die each day across the globe, about two thirds die of age-related causes. In industrialized nations, the proportion is much higher, approaching 90%. With improved medical capability, dying has become a condition to be managed. Home deaths, once commonplace, are now rare in the developed world.

In developing nations, inferior sanitary conditions and lack of access to modern medical technology makes death from infectious diseases more common than in developed countries. One such disease is tuberculosis, a bacterial disease which killed 1.8M people in 2015. Malaria causes about 400–900M cases of fever and 1–3M deaths annually. AIDS death toll in Africa may reach 90–100M by 2025.According to Jean Ziegler (United Nations Special Reporter on the Right to Food, 2000 – Mar 2008), mortality due to malnutrition accounted for 58% of the total mortality rate in 2006. Ziegler says worldwide approximately 62M people died from all causes and of those deaths more than 36M died of hunger or diseases due to deficiencies in micronutrients.Tobacco smoking killed 100 million people worldwide in the 20th century and could kill 1 billion people around the world in the 21st century, a World Health Organization report warned.Many leading developed world causes of death can be postponed by diet and physical activity, but the accelerating incidence of disease with age still imposes limits on human longevity. The evolutionary cause of aging is, at best, only just beginning to be understood. It has been suggested that direct intervention in the aging process may now be the most effective intervention against major causes of death.

Selye proposed a unified non-specific approach to many causes of death. He demonstrated that stress decreases adaptability of an organism and proposed to describe the adaptability as a special resource, adaptation energy. The animal dies when this resource is exhausted. Selye assumed that the adaptability is a finite supply, presented at birth. Later on, Goldstone proposed the concept of a production or income of adaptation energy which may be stored (up to a limit), as a capital reserve of adaptation. In recent works, adaptation energy is considered as an internal coordinate on the "dominant path" in the model of adaptation. It is demonstrated that oscillations of well-being appear when the reserve of adaptability is almost exhausted.In 2012, suicide overtook car crashes for leading causes of human injury deaths in the U.S., followed by poisoning, falls, and murder. Causes of death are different in different parts of the world. In high-income and middle income countries nearly half up to more than two thirds of all people live beyond the age of 70 and predominantly die of chronic diseases. In low-income countries, where less than one in five of all people reach the age of 70, and more than a third of all deaths are among children under 15, people predominantly die of infectious diseases.

Autopsy
An autopsy, also known as a postmortem examination or an obduction, is a medical procedure that consists of a thorough examination of a human corpse to determine the cause and manner of a persons death and to evaluate any disease or injury that may be present. It is usually performed by a specialized medical doctor called a pathologist.
Autopsies are either performed for legal or medical purposes. A forensic autopsy is carried out when the cause of death may be a criminal matter, while a clinical or academic autopsy is performed to find the medical cause of death and is used in cases of unknown or uncertain death, or for research purposes. Autopsies can be further classified into cases where external examination suffices, and those where the body is dissected and an internal examination is conducted. Permission from next of kin may be required for internal autopsy in some cases. Once an internal autopsy is complete the body is generally reconstituted by sewing it back together. Autopsy is important in a medical environment and may shed light on mistakes and help improve practices.
A necropsy, which is not always a medical procedure, was a term previously used to describe an unregulated postmortem examination. In modern times, this term is more commonly associated with the corpses of animals.

Senescence
Senescence refers to a scenario when a living being is able to survive all calamities, but eventually dies due to causes relating to old age. Animal and plant cells normally reproduce and function during the whole period of natural existence, but the aging process derives from deterioration of cellular activity and ruination of regular functioning. Aptitude of cells for gradual deterioration and mortality means that cells are naturally sentenced to stable and long-term loss of living capacities, even despite continuing metabolic reactions and viability. In the United Kingdom, for example, nine out of ten of all the deaths that occur on a daily basis relates to senescence, while around the world it accounts for two-thirds of 150,000 deaths that take place daily.Almost all animals who survive external hazards to their biological functioning eventually die from biological aging, known in life sciences as "senescence". Some organisms experience negligible senescence, even exhibiting biological immortality. These include the jellyfish Turritopsis dohrnii, the hydra, and the planarian. Unnatural causes of death include suicide and predation. From all causes, roughly 150,000 people die around the world each day. Of these, two thirds die directly or indirectly due to senescence, but in industrialized countries – such as the United States, the United Kingdom, and Germany – the rate approaches 90% (i.e., nearly nine out of ten of all deaths are related to senescence).Physiological death is now seen as a process, more than an event: conditions once considered indicative of death are now reversible. Where in the process a dividing line is drawn between life and death depends on factors beyond the presence or absence of vital signs. In general, clinical death is neither necessary nor sufficient for a determination of legal death. A patient with working heart and lungs determined to be brain dead can be pronounced legally dead without clinical death occurring.

Cryonics
Cryonics (from Greek κρύος kryos- meaning icy cold) is the low-temperature preservation of animals and humans who cannot be sustained by contemporary medicine, with the hope that healing and resuscitation may be possible in the future.Cryopreservation of people or large animals is not reversible with current technology. The stated rationale for cryonics is that people who are considered dead by current legal or medical definitions may not necessarily be dead according to the more stringent information-theoretic definition of death.Some scientific literature is claimed to support the feasibility of cryonics. Medical science and cryobiologists generally regards cryonics with skepticism.

Life extension
Life extension refers to an increase in maximum or average lifespan, especially in humans, by slowing down or reversing the processes of aging through anti-aging measures. Despite the fact that aging is by far the most common cause of death worldwide, it is socially mostly ignored as such and seen as "necessary" and "inevitable" anyway, which is why little money is spent on research into anti-aging therapies, a phenomenon known as the pro-aging trance.Average lifespan is determined by vulnerability to accidents and age or lifestyle-related afflictions such as cancer, or cardiovascular disease. Extension of average lifespan can be achieved by good diet, exercise and avoidance of hazards such as smoking. Maximum lifespan is also determined by the rate of aging for a species inherent in its genes. Currently, the only widely recognized method of extending maximum lifespan is calorie restriction. Theoretically, extension of maximum lifespan can be achieved by reducing the rate of aging damage, by periodic replacement of damaged tissues, or by molecular repair or rejuvenation of deteriorated cells and tissues.
A United States poll found that religious people and irreligious people, as well as men and women and people of different economic classes have similar rates of support for life extension, while Africans and Hispanics have higher rates of support than white people. 38 percent of the polled said they would desire to have their aging process cured.
Researchers of life extension are a subclass of biogerontologists known as "biomedical gerontologists". They try to understand the nature of aging and they develop treatments to reverse aging processes or to at least slow them down, for the improvement of health and the maintenance of youthful vigor at every stage of life. Those who take advantage of life extension findings and seek to apply them upon themselves are called "life extensionists" or "longevists". The primary life extension strategy currently is to apply available anti-aging methods in the hope of living long enough to benefit from a complete cure to aging once it is developed.

Location
Before about 1930, most people in Western countries died in their own homes, surrounded by family, and comforted by clergy, neighbors, and doctors making house calls. By the mid-20th century, half of all Americans died in a hospital. By the start of the 21st century, only about 20–25% of people in developed countries died outside of a medical institution. The shift away from dying at home towards dying in a professional medical environment has been termed the "Invisible Death". This shift occurred gradually over the years, until most deaths now occur outside the home.

Psychology
Death studies is a field within psychology. Many people are afraid of dying. Discussing, thinking about, or planning for their own deaths causes them discomfort. This fear may cause them to put off financial planning, preparing a will and testament, or requesting help from a hospice organization.
Different people have different responses to the idea of their own deaths. Philosopher Galen Strawson writes that the death that many people wish for is an instant, painless, unexperienced annihilation. In this unlikely scenario, the person dies without realizing it and without being able to fear it. One moment the person is walking, eating, or sleeping, and the next moment, the person is dead. Strawson reasons that this type of death would not take anything away from the person, as he believes that a person cannot have a legitimate claim to ownership in the future.

Society and culture
In society, the nature of death and humanitys awareness of its own mortality has for millennia been a concern of the worlds religious traditions and of philosophical inquiry. This includes belief in resurrection or an afterlife (associated with Abrahamic religions), reincarnation or rebirth (associated with Dharmic religions), or that consciousness permanently ceases to exist, known as eternal oblivion (associated with Secular humanism).Commemoration ceremonies after death may include various mourning, funeral practices and ceremonies of honouring the deceased. The physical remains of a person, commonly known as a corpse or body, are usually interred whole or cremated, though among the worlds cultures there are a variety of other methods of mortuary disposal. In the English language, blessings directed towards a dead person include rest in peace (originally the Latin requiescat in pace), or its initialism RIP.
Death is the center of many traditions and organizations; customs relating to death are a feature of every culture around the world. Much of this revolves around the care of the dead, as well as the afterlife and the disposal of bodies upon the onset of death. The disposal of human corpses does, in general, begin with the last offices before significant time has passed, and ritualistic ceremonies often occur, most commonly interment or cremation. This is not a unified practice; in Tibet, for instance, the body is given a sky burial and left on a mountain top. Proper preparation for death and techniques and ceremonies for producing the ability to transfer ones spiritual attainments into another body (reincarnation) are subjects of detailed study in Tibet. Mummification or embalming is also prevalent in some cultures, to retard the rate of decay.
Legal aspects of death are also part of many cultures, particularly the settlement of the deceased estate and the issues of inheritance and in some countries, inheritance taxation.

Capital punishment is also a culturally divisive aspect of death. In most jurisdictions where capital punishment is carried out today, the death penalty is reserved for premeditated murder, espionage, treason, or as part of military justice. In some countries, sexual crimes, such as adultery and sodomy, carry the death penalty, as do religious crimes such as apostasy, the formal renunciation of ones religion. In many retentionist countries, drug trafficking is also a capital offense. In China, human trafficking and serious cases of corruption are also punished by the death penalty. In militaries around the world courts-martial have imposed death sentences for offenses such as cowardice, desertion, insubordination, and mutiny.Death in warfare and in suicide attack also have cultural links, and the ideas of dulce et decorum est pro patria mori, mutiny punishable by death, grieving relatives of dead soldiers and death notification are embedded in many cultures. Recently in the western world, with the increase in terrorism following the September 11 attacks, but also further back in time with suicide bombings, kamikaze missions in World War II and suicide missions in a host of other conflicts in history, death for a cause by way of suicide attack, and martyrdom have had significant cultural impacts.

Suicide in general, and particularly euthanasia, are also points of cultural debate. Both acts are understood very differently in different cultures. In Japan, for example, ending a life with honor by seppuku was considered a desirable death, whereas according to traditional Christian and Islamic cultures, suicide is viewed as a sin. Death is personified in many cultures, with such symbolic representations as the Grim Reaper, Azrael, the Hindu god Yama and Father Time.

In Brazil, a human death is counted officially when it is registered by existing family members at a cartório, a government-authorized registry. Before being able to file for an official death, the deceased must have been registered for an official birth at the cartório. Though a Public Registry Law guarantees all Brazilian citizens the right to register deaths, regardless of their financial means, of their family members (often children), the Brazilian government has not taken away the burden, the hidden costs and fees, of filing for a death. For many impoverished families, the indirect costs and burden of filing for a death lead to a more appealing, unofficial, local, cultural burial, which in turn raises the debate about inaccurate mortality rates.Talking about death and witnessing it is a difficult issue with most cultures. Western societies may like to treat the dead with the utmost material respect, with an official embalmer and associated rites. Eastern societies (like India) may be more open to accepting it as a fait accompli, with a funeral procession of the dead body ending in an open-air burning-to-ashes of the same.

Consciousness
Much interest and debate surround the question of what happens to ones consciousness as ones body dies. The belief in the permanent loss of consciousness after death is often called eternal oblivion. Belief that the stream of consciousness is preserved after physical death is described by the term afterlife. Neither are likely to ever be confirmed without the ponderer having to actually die.

In biology
After death, the remains of a former organism become part of the biogeochemical cycle, during which animals may be consumed by a predator or a scavenger. Organic material may then be further decomposed by detritivores, organisms which recycle detritus, returning it to the environment for reuse in the food chain, where these chemicals may eventually end up being consumed and assimilated into the cells of an organism. Examples of detritivores include earthworms, woodlice and dung beetles.
Microorganisms also play a vital role, raising the temperature of the decomposing matter as they break it down into yet simpler molecules. Not all materials need to be fully decomposed. Coal, a fossil fuel formed over vast tracts of time in swamp ecosystems, is one example.

Natural selection
Contemporary evolutionary theory sees death as an important part of the process of natural selection. It is considered that organisms less adapted to their environment are more likely to die having produced fewer offspring, thereby reducing their contribution to the gene pool. Their genes are thus eventually bred out of a population, leading at worst to extinction and, more positively, making the process possible, referred to as speciation. Frequency of reproduction plays an equally important role in determining species survival: an organism that dies young but leaves numerous offspring displays, according to Darwinian criteria, much greater fitness than a long-lived organism leaving only one.

Extinction
Extinction is the cessation of existence of a species or group of taxa, reducing biodiversity. The moment of extinction is generally considered to be the death of the last individual of that species (although the capacity to breed and recover may have been lost before this point). Because a species potential range may be very large, determining this moment is difficult, and is usually done retrospectively. This difficulty leads to phenomena such as Lazarus taxa, where species presumed extinct abruptly "reappear" (typically in the fossil record) after a period of apparent absence. New species arise through the process of speciation, an aspect of evolution. New varieties of organisms arise and thrive when they are able to find and exploit an ecological niche – and species become extinct when they are no longer able to survive in changing conditions or against superior competition.

Evolution of aging and mortality
Inquiry into the evolution of aging aims to explain why so many living things and the vast majority of animals weaken and die with age (exceptions include Hydra and the jellyfish Turritopsis dohrnii, which research shows to be biologically immortal). The evolutionary origin of senescence remains one of the fundamental puzzles of biology. Gerontology specializes in the science of human aging processes.
Organisms showing only asexual reproduction (e.g. bacteria, some protists, like the euglenoids and many amoebozoans) and unicellular organisms with sexual reproduction (colonial or not, like the volvocine algae Pandorina and Chlamydomonas) are "immortal" at some extent, dying only due to external hazards, like being eaten or meeting with a fatal accident. In multicellular organisms (and also in multinucleate ciliates), with a Weismannist development, that is, with a division of labor between mortal somatic (body) cells and "immortal" germ (reproductive) cells, death becomes an essential part of life, at least for the somatic line.The Volvox algae are among the simplest organisms to exhibit that division of labor between two completely different cell types, and as a consequence include death of somatic line as a regular, genetically regulated part of its life history.

Religious views
Buddhism
In Buddhist doctrine and practice, death plays an important role. Awareness of death was what motivated Prince Siddhartha to strive to find the "deathless" and finally to attain enlightenment. In Buddhist doctrine, death functions as a reminder of the value of having been born as a human being. Being reborn as a human being is considered the only state in which one can attain enlightenment. Therefore, death helps remind oneself that one should not take life for granted. The belief in rebirth among Buddhists does not necessarily remove death anxiety, since all existence in the cycle of rebirth is considered filled with suffering, and being reborn many times does not necessarily mean that one progresses.Death is part of several key Buddhist tenets, such as the Four Noble Truths and dependent origination.

Christianity
While there are different sects of Christianity with different branches of belief; the overarching ideology on death grows from the knowledge of afterlife. Meaning after death the individual will undergo a separation from mortality to immortality; their soul leaves the body entering a realm of spirits. Following this separation of body and spirit (i.e. death) resurrection will occur. Representing the same transformation Jesus Christ embodied after his body was placed in the tomb for three days. Like Him, each persons body will be resurrected reuniting the spirit and body in a perfect form. This process allows the individuals soul to withstand death and transform into life after death.

Hinduism
In Hindu texts, death is described as the individual eternal spiritual jiva-atma (soul or conscious self) exiting the current temporary material body. The soul exits this body when the body can no longer sustain the conscious self (life), which may be due to mental or physical reasons, or more accurately, the inability to act on ones kama (material desires). During conception, the soul enters a compatible new body based on the remaining merits and demerits of ones karma (good/bad material activities based on dharma) and the state of ones mind (impressions or last thoughts) at the time of death.
Usually the process of reincarnation (souls transmigration) makes one forget all memories of ones previous life. Because nothing really dies and the temporary material body is always changing, both in this life and the next, death means forgetfulness of ones previous experiences (previous material identity).
Material existence is described as being full of miseries arising from birth, disease, old age, death, mind, weather, etc. To conquer samsara (the cycle of death and rebirth) and become eligible for one of the different types of moksha (liberation), one has to first conquer kama (material desires) and become self-realized. The human form of life is most suitable for this spiritual journey, especially with the help of sadhu (self-realized saintly persons), sastra (revealed spiritual scriptures), and guru (self-realized spiritual masters), given all three are in agreement.

Islam
The Islamic view is that death is the separation of the soul from the body as well as the beginning of the afterlife. The afterlife or akhirah is one of the six main beliefs in Islam. Rather than seeing death as the end of life, Muslims consider death as a continuation of life in another form. In Islam, the life on earth right now is a short, temporary life and a testing period for every soul. The true life begins with the Day of Judgement, when all people will be divided into two groups. The righteous believers will be welcomed to janna (heaven) and the disbelievers and evildoers will be punished in jahannam (hellfire).Muslims believe death to be wholly natural and predetermined by God. Only God knows the exact time of a person’s death. The Quran emphasizes that death is inevitable, no matter how much people try to escape death, it will reach everyone. Life on earth is the one and only chance for people to prepare themselves for the life to come and choose to either believe or not believe in God, and death is the end of that learning opportunity.

Judaism
There are a variety of beliefs about the afterlife within Judaism, but none of them contradict the preference of life over death. This is partially because death puts a cessation to the possibility of fulfilling any commandments.

Language
The word "death" comes from Old English dēaþ, which in turn comes from Proto-Germanic *dauþuz (reconstructed by etymological analysis). This comes from the Proto-Indo-European stem *dheu- meaning the "process, act, condition of dying".The concept and symptoms of death, and varying degrees of delicacy used in discussion in public forums, have generated numerous scientific, legal, and socially acceptable terms or euphemisms. When a person has died, it is also said they have "passed away", "passed on", "expired", or "gone", among other socially accepted, religiously specific, slang, and irreverent terms.
As a formal reference to a dead person, it has become common practice to use the participle form of "decease", as in "the deceased"; another noun form is "decedent".
Bereft of life, the dead person is a "corpse", "cadaver", "body", "set of remains" or, when all flesh is gone, a "skeleton". The terms "carrion" and "carcass" are also used, usually for dead non-human animals. The ashes left after a cremation are lately called "cremains".

See also
References
Bibliography
Further reading
Cochem, Martin of (1899). "On Death" . The four last things: death, judgment, hell, heaven. Benziger Brothers.
Daughters of Charity of St. Vincent de Paul. (1856). "Considerations on Death" . St. Vincents Manual. John Murphy & Co.
Liguori, Alphonsus (1868). Preparation for Death . Rivingtons.
Marques, Susana Moreira (13 October 2015). Now and At the Hour of Our Death. Translated by Sanches, Julia. And Other Stories. ISBN 978-1-908276-62-9.
Massillon, Jean-Baptiste (1879). "On Death" . Sermons by John-Baptist Massillon. Thomas Tegg & Sons.
Rosenberg, David (17 August 2014). "How One Photographer Overcame His Fear of Death by Photographing It (Walter Schels Life Before Death)". Slate.
Sachs, Jessica Snyder (2001). Corpse: Nature, Forensics, and the Struggle to Pinpoint Time of Death (270 pages). Perseus Publishing. ISBN 978-0-7382-0336-2.
Warraich, Haider (2017). Modern Death: How Medicine Changed the End of Life. St. Martins Press. ISBN 978-1250104588.

External links

Death at Curlie
"Death". Stanford Encyclopedia of Philosophy. Metaphysics Research Lab, Stanford University. 2016.
"Death" . Encyclopædia Britannica. Vol. 7 (11th ed.). 1911. pp. 898–900.
Best, Ben. "Causes of Death". BenBest.com. Retrieved 10 June 2016.
Schels, Walter; Lakotta, Beate. "Before and After Death". LensCulture.com. Archived from the original on 11 October 2014. Retrieved 19 September 2016. Interviews with people dying in hospices, and portraits of them before, and shortly after, death.
U.S </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Melena and explain in detail? [/INST] Melena or melaena refers to the dark black, tarry feces that are associated with upper gastrointestinal bleeding. The black color and characteristic strong odor are caused by hemoglobin in the blood being altered by digestive enzymes and intestinal bacteria.Iron supplements may cause a grayish-black stool that should be distinguished from melena, as should black coloration caused by a number of medications, such as bismuth subsalicylate (the active ingredient in Pepto-Bismol), or by foods such as beetroot, black liquorice, or blueberries.

Causes
The most common cause of melena is peptic ulcer disease. However, any bleeding within the upper gastrointestinal tract or the ascending colon can lead to melena. Melena may also be a complication of anticoagulant medications, such as warfarin.Causes of upper gastrointestinal bleeding that may result in melena include malignant tumors affecting the esophagus, stomach or small intestine, hemorrhagic blood diseases, such as thrombocytopenia and hemophilia, gastritis, Stomach cancer, esophageal varices, Meckels diverticulum and Mallory-Weiss syndrome.Causes of "false" melena include iron supplements, Pepto-Bismol, Maalox, and lead, blood swallowed as a result of a nose bleed (epistaxis), and blood ingested as part of the diet, as with consumption of black pudding (blood sausage), or with the traditional African Maasai diet, which includes much blood drained from cattle.Melena is considered a medical emergency as it arises from a significant amount of bleeding. Urgent care is required to rule out serious causes and prevent potentially life-threatening emergencies.A less serious, self-limiting case of melena can occur in newborns two to three days after delivery, due to swallowed maternal blood.

Diagnosis
In acute cases, with a large amount of blood loss, patients may present with anemia or low blood pressure </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Myxedema coma and explain in detail? [/INST] Myxedema coma is an extreme or decompensated form of hypothyroidism and while uncommon, is potentially lethal. A person may have laboratory values identical to a "normal" hypothyroid state, but a stressful event (such as an infection, myocardial infarction, or stroke) precipitates the myxedema coma state, usually in the elderly. Primary symptoms of myxedema coma are altered mental status and low body temperature. Low blood sugar, low blood pressure, hyponatremia, hypercapnia, hypoxia, slowed heart rate, and hypoventilation may also occur. Myxedema, although included in the name, is not necessarily seen in myxedema coma. Coma is also not necessarily seen in myxedema coma.According to newer theories, myxedema coma could result from allostatic overload in a situation where the effects of hypothyroidism are amplified by nonthyroidal illness syndrome.

Causes
Myxedema coma represents an extreme or decompensated form of hypothyroidism. Most cases occur in patients who have been previously diagnosed with hypothyroidism, yet in some cases, hypothyroidism may not have been previously identified. Common precipitating factors of myxedema coma include:

Hypothermia, especially during winter months
Metabolic disruption including hypoglycemia, hyponatremia, acidosis, and hypercalcemia
Respiratory compromise including hypoxemia and hypercapnia
Infections including pneumonia, cellulitis, and urosepsis
Congestive heart failure
Cerebrovascular accidents
Gastrointestinal bleeding
Trauma, motor vehicle accidents, and fractures
Medications including anesthetics, sedatives, tranquilizers, narcotics, amiodarone, and lithium
Withdrawal of thyroid supplements, especially in relation to a hospitalizationOther precipitating factors include:

Other medications including beta-blockers, diuretics, phenothiazines, phenytoin, rifampin, anti-TNF therapy
Burns
Influenza
Surgery
Consumption of raw bok choy
Diabetic ketoacidosis after total thyroidectomy

Pathophysiology
The thyroid gland is responsible for regulating whole-body metabolism through the production of two major hormones: thyroxine (T4) and triiodothyronine (T3). Of the metabolically active thyroid hormones, 93% is T4 and 7% is T3 </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Site and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Hyperesthesia and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Acute myeloid leukemia and explain in detail? [/INST] Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may include feeling tired, shortness of breath, easy bruising and bleeding, and increased risk of infection. Occasionally, spread may occur to the brain, skin, or gums. As an acute leukemia, AML progresses rapidly, and is typically fatal within weeks or months if left untreated.Risk factors include smoking, previous chemotherapy or radiation therapy, myelodysplastic syndrome, and exposure to the chemical benzene. The underlying mechanism involves replacement of normal bone marrow with leukemia cells, which results in a drop in red blood cells, platelets, and normal white blood cells. Diagnosis is generally based on bone marrow aspiration and specific blood tests. AML has several subtypes for which treatments and outcomes may vary.The first-line treatment of AML is usually chemotherapy, with the aim of inducing remission. People may then go on to receive additional chemotherapy, radiation therapy, or a stem cell transplant. The specific genetic mutations present within the cancer cells may guide therapy, as well as determine how long that person is likely to survive.In 2015, AML affected about one million people, and resulted in 147,000 deaths globally. It most commonly occurs in older adults. Males are affected more often than females. The five-year survival rate is about 35% in people under 60 years old and 10% in people over 60 years old. Older people whose health is too poor for intensive chemotherapy have a typical survival of five to ten months. It accounts for roughly 1.1% of all cancer cases, and 1.9% of cancer deaths in the United States.

Signs and symptoms
Most signs and symptoms of AML are caused by the crowding out in bone marrow of space for normal blood cells to develop. A lack of normal white blood cell production makes people more susceptible to infections. A low red blood cell count (anemia) can cause fatigue, paleness, shortness of breath and palpitations. A lack of platelets can lead to easy bruising, bleeding from the nose (epistaxis), small blood vessels on the skin (petechiae) or gums, or bleeding with minor trauma. Other symptoms may include fever, fatigue worse than what can be attributed to anaemia alone, weight loss and loss of appetite.Enlargement of the spleen may occur in AML, but it is typically mild and asymptomatic. Lymph node swelling is rare in most types of AML, except for acute myelomonocytic leukemia (AMML). The skin can be involved in the form of leukemia cutis; Sweets syndrome; or non-specific findings: flat lesions (macules), raised lesion papules), pyoderma gangrenosum and vasculitis.Some people with AML may experience swelling of the gums because of infiltration of leukemic cells into the gum tissue. Involvement of other parts of the body such as the gastrointestinal tract, respiratory tract and other parts is possible but less common. One area which has particular importance for treatment is whether there is involvement of the meninges around the central nervous system.

Risk factors
Most cases of AML do not have exposure to any identified risk factors. However, a number of risk factors for developing AML have been identified. These include other blood disorders, chemical exposures, ionizing radiation, and genetic risk factors. Where a defined exposure to past chemotherapy, radiotherapy, toxin or hematologic malignancy is known, this is termed secondary AML.

Other blood disorders
Other blood disorders, particularly myelodysplastic syndrome (MDS) and less commonly myeloproliferative neoplasms (MPN), can evolve into AML; the exact risk depends on the type of MDS/MPN. The presence of asymptomatic clonal hematopoiesis also raises the risk of transformation into AML.

Chemical exposure
Exposure to anticancer chemotherapy, in particular alkylating agents, can increase the risk of subsequently developing AML. Other chemotherapy agents, including fludarabine, and topoisomerase II inhibitors are also associated with the development of AML; most commonly after 4–6 years and 1–3 years respectively. These are often associated with specific chromosomal abnormalities in the leukemic cells.Other chemical exposures associated with the development of AML include benzene, chloramphenicol and phenylbutazone.

Radiation
High amounts of ionizing radiation exposure, such as that used for radiotherapy used to treat some forms of cancer, can increase the risk of AML. People treated with ionizing radiation after treatment for prostate cancer, non-Hodgkin lymphoma, lung cancer, and breast cancer have the highest chance of acquiring AML, but this increased risk returns to the background risk observed in the general population after 12 years. Historically, survivors of the atomic bombings of Hiroshima and Nagasaki had an increased rate of AML, as did radiologists exposed to high levels of X-rays prior to the adoption of modern radiation safety practices.

Genetics
Most cases of AML arise spontaneously, however there are some genetic mutations associated with an increased risk. Several congenital conditions increase the risk of leukemia; the most common is Down syndrome, with other more rare conditions including Fanconi anemia, Bloom syndrome and ataxia-telangiectasia (all characterised by problems with DNA repair), and Kostmann syndrome.

Other factors
Being overweight and obese increase the risk of developing AML, as does any amount of active smoking. For reasons that may relate to substance or radiation exposure, certain occupations have a higher rate of AML; particularly work in the nuclear power industry, electronics or computer manufacturing, fishing and animal slaughtering and processing.

Pathophysiology
The malignant cell in AML is the myeloblast. In normal development of blood cells (hematopoiesis), the myeloblast is an immature precursor of myeloid white blood cells; a normal myeloblast will mature into a white blood cell such as an eosinophil, basophil, neutrophil or monocyte. In AML, though, a single myeloblast accumulates genetic changes which stop maturation, increase its proliferation, and protect it from programmed cell death (apoptosis). Much of the diversity and heterogeneity of AML is because leukemic transformation can occur at a number of different steps along the differentiation pathway. Genetic abnormalities or the stage at which differentiation was halted form part of modern classification systems.Specific cytogenetic abnormalities can be found in many people with AML; the types of chromosomal abnormalities often have prognostic significance. The chromosomal translocations encode abnormal fusion proteins, usually transcription factors whose altered properties may cause the "differentiation arrest". For example, in APL, the t(15;17) translocation produces a PML-RARA fusion protein which binds to the retinoic acid receptor element in the promoters of several myeloid-specific genes and inhibits myeloid differentiation.The clinical signs and symptoms of AML result from the growth of leukemic clone cells, which tends to interfere with the development of normal blood cells in the bone marrow. This leads to neutropenia, anemia, and thrombocytopenia. Other symptoms can arise from the infiltration of malignant cells into parts of the body, such as the gingiva and skin.Many cells develop mutations in genes that affect epigenetics, such as DNA methylation. When these mutations occur, it is likely in the early stages of AML. Such mutations include in the DNA demethylase TET2 and the metabolic enzymes IDH1 and IDH2, which lead to the generation of a novel oncometabolite, D-2-hydroxyglutarate, which inhibits the activity of epigenetic enzymes such as TET2. Epigenetic mutations may lead to the silencing of tumor suppressor genes and/or the activation of proto-oncogenes.

Diagnosis
A complete blood count, which is a blood test, is one of the initial steps in the diagnosis of AML. It may reveal both an excess of white blood cells (leukocytosis) or a decrease (leukopenia), and a low red blood cell count (anemia) and low platelets (thrombocytopenia) can also be commonly seen. A blood film may show leukemic blast cells. Inclusions within the cells called Auer rods, when seen, make the diagnosis highly likely. A definitive diagnosis requires a bone marrow aspiration and biopsy.Bone marrow is examined under light microscopy, as well as flow cytometry, to diagnose the presence of leukemia, to differentiate AML from other types of leukemia (e.g. acute lymphoblastic leukemia), and to provide information about how mature or immature the affected cells are that can assist in classifying the subtype of disease. A sample of marrow or blood is typically also tested for chromosomal abnormalities by routine cytogenetics or fluorescent in situ hybridization. Genetic studies may also be performed to look for specific mutations in genes such as FLT3, nucleophosmin, and KIT, which may influence the outcome of the disease.Cytochemical stains on blood and bone marrow smears are helpful in the distinction of AML from ALL, and in subclassification of AML. The combination of a myeloperoxidase or Sudan black stain and a nonspecific esterase stain will provide the desired information in most cases. The myeloperoxidase or Sudan black reactions are most useful in establishing the identity of AML and distinguishing it from ALL. The nonspecific esterase stain is used to identify a monocytic component in AMLs and to distinguish a poorly differentiated monoblastic leukemia from ALL.The standard classification scheme for AML is the World Health Organization (WHO) system. According to the WHO criteria, the diagnosis of AML is established by demonstrating involvement of more than 20% of the blood and/or bone marrow by leukemic myeloblasts, except  in three forms of acute myeloid leukemia with recurrent genetic abnormalities: t(8;21), inv(16) or t(16;16), and acute promyelocytic leukemia with PML-RARA, in which the presence of the genetic abnormality is diagnostic irrespective of blast percent. Myeloid sarcoma is also considered a subtype of AML independently of the blast count. The older French-American-British (FAB) classification, which is no longer widely used, is a bit more stringent, requiring a blast percentage of at least 30% in bone marrow or peripheral blood for the diagnosis of AML.Because acute promyelocytic leukemia has the highest curability and requires a unique form of treatment, it is important to quickly establish or exclude the diagnosis of this subtype of leukemia. Fluorescent in situ hybridization performed on blood or bone marrow is often used for this purpose, as it readily identifies the chromosomal translocation [t(15;17)(q22;q12);] that characterizes APL. There is also a need to molecularly detect the presence of PML/RARA fusion protein, which is an oncogenic product of that translocation.

World Health Organization
The WHO classification of AML attempts to be more clinically useful and to produce more meaningful prognostic information than the FAB criteria. Each of the WHO categories contains numerous descriptive subcategories of interest to the hematopathologist and oncologist; however, most of the clinically significant information in the WHO schema is communicated via categorization into one of the subtypes listed below.
The revised fourth edition of the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues was released in 2016. This classification, which is based on a combination of genetic and immunophenotypic markers and morphology, defines the subtypes of AML and related neoplasms as: In 2022 a new classification has been published.

Acute leukemias of ambiguous lineage (also known as mixed phenotype or biphenotypic acute leukemia) occur when the leukemic cells can not be classified as either myeloid or lymphoid cells, or where both types of cells are present.

French-American-British
The French-American-British (FAB) classification system provides terminology that is still sometimes used, and it remains a valuable diagnostic tool in areas without access to genetic testing, this system has largely become obsolete in favor of the WHO classification, which correlates more strongly with treatment outcomes.The FAB system divides AML into eight subtypes, M0 through to M7, based on the type of cell from which the leukemia developed and its degree of maturity. AML of types M0 to M2 may be called acute myeloblastic leukemia. Classification is done by examining the appearance of the malignant cells with light microscopy and/or by using cytogenetics to characterize any underlying chromosomal abnormalities. The subtypes have varying prognoses and responses to therapy.
Six FAB subtypes (M1 through to M6) were initially proposed in 1976, although later revisions added M7 in 1985 and M0 in 1987.
The morphologic subtypes of AML also include rare types not included in the FAB system, such as acute basophilic leukemia, which was proposed as a ninth subtype, M8, in 1999.

Treatment
First-line treatment of AML consists primarily of chemotherapy, and is divided into two phases: induction and consolidation. The goal of induction therapy is to achieve a complete remission by reducing the number of leukemic cells to an undetectable level; the goal of consolidation therapy is to eliminate any residual undetectable disease and achieve a cure. Hematopoietic stem cell transplantation is usually considered if induction chemotherapy fails or after a person relapses, although transplantation is also sometimes used as front-line therapy for people with high-risk disease. Efforts to use tyrosine kinase inhibitors in AML continue.

Induction
The goal of the induction phase is to reach a complete remission. Complete remission does not mean the disease has been cured; rather, it signifies no disease can be detected with available diagnostic methods. All subtypes except acute promyelocytic leukemia are usually given induction chemotherapy with cytarabine and an anthracycline such as daunorubicin or idarubicin. This induction chemotherapy regimen is known as "7+3" (or "3+7"), because the cytarabine is given as a continuous IV infusion for seven consecutive days while the anthracycline is given for three consecutive days as an IV push. Response to this treatment varies with age, with people aged less than 60 years having better remission rates between 60% and 80%, while older people having lower remission rates between 33% and 60%. Because of the toxic effects of therapy and a greater chance of AML resistance to this induction therapy, different treatment, such as that in clinical trials might be offered to people 60–65 years or older.Acute promyelocytic leukemia is treated with all-trans-retinoic acid (ATRA) and either arsenic trioxide (ATO) monotherapy or an anthracycline. A syndrome similar to disseminated intravascular coagulation can develop during the initial few days of treatment or at the time the leukemia is diagnosed, and treatment can be complicated by a differentiation syndrome characterised by fever, fluid overload and low oxygen levels. Acute promyelocytic leukemia is considered curable. There is insufficient evidence to determine if prescribing ATRA in addition to chemotherapy to adults who have other subtypes of acute myeloid leukaemia is helpful.

Consolidation
Even after complete remission is achieved, leukemic cells likely remain in numbers too small to be detected with current diagnostic techniques. If no consolidation therapy or further postremission is given, almost all people with AML will eventually relapse.The specific type of postremission therapy is individualized based on a persons prognostic factors (see above) and general health. For good-prognosis leukemias (i.e. inv(16), t(8;21), and t(15;17)), people will typically undergo an additional three to five courses of intensive chemotherapy, known as consolidation chemotherapy. This generally involves cytarabine, with the doses administered being higher in younger patients, who are less likely to develop toxicity related to this treatment.

Stem cell transplantation
Stem cell transplantation from a donor, called allogenic stem cell transplantation, is usually pursued if the prognosis is not considered favourable, a person can tolerate a transplant and has a suitable donor. The basis of allogenic stem cell transplantation is on a graft versus leukemia effect whereby graft cells stimulate an immune response against leukemia cells. Unfortunately this is accompanied by immune responses against other host organs, called a graft versus host disease.

Supportive treatment
Support is necessary throughout treatment because of problems associated with AML and also arising from treatment. Blood transfusions, including of red blood cells and platelets, are necessary to maintain health levels, preventing complications of anemia (from low red blood cells) and bleeding (from low platelets). AML leads to an increased risk of infections, particularly drug-resistant strains of bacteria and fungi. Antibiotics and antifungals can be used both to treat and to prevent these infections, particularly quinolones.Adding aerobic physical exercises to the standard of care may result in little to no difference in the mortality, in the quality of life and in the physical functioning. These exercises may result in a slight reduction in depression. Furthermore, aerobic physical exercises probably reduce fatigue.Recent research into the role that epigenetic regulators play in hematopoietic malignancies has yielded new insights in the development of targeted epigenetic therapies as a supportive treatment for AML. The FDA has approved certain epigenetic modifying drugs like ivosidenib and enasidenib, which are used in patients that can no longer receive intensive induction chemotherapy; specifically, they are involved in the therapy of IDH1 and IDH2 mutations. Further research must be done to prove the efficacy of epigenetic treatments, but the development of new epigenetic therapies along with immunotherapies holds potential in the future treatment of AML.

In pregnancy
AML is rare in pregnancy, affecting about 1 in 75,000 to 100,000 pregnant women. It is diagnosed and treated similarly to AML in non pregnancy, with a recommendation that it is treated urgently. However, treatment has significant implications for the pregnancy. First trimester pregnancy is considered unlikely to be viable; pregnancy during weeks 24 – 36 requires consideration of the benefits of chemotherapy to the mother against the risks to the foetus; and there is a recommendation to consider delaying chemotherapy in very late pregnancy (> 36 weeks). Some elements of supportive care, such as which antibiotics to prevent or treat infections, also change in pregnancy.

Medication
Olutasidenib (Rezlidhia) was approved for medical use in the United States in December 2022.

Prognosis
Multiple factors influence prognosis in AML, including the presence of specific mutations, and a person with AMLs age. In the United States between 2011 and 2016, the median survival of a person with AML was 8.5 months, with the 5 year survival being 24%. This declines with age, with the poorer prognosis being associated with an age greater than 65 years, and the poorest prognosis seen in those aged 75–84.As of 2001, cure rates in clinical trials have ranged from 20 to 45%; although clinical trials often include only younger people and those able to tolerate aggressive therapies. The overall cure rate for all people with AML (including the elderly and those unable to tolerate aggressive therapy) is likely lower. Cure rates for APL can be as high as 98%.

Subtypes
Secondary AML has a worse prognosis, as does treatment-related AML arising after chemotherapy for another previous malignancy. Both of these entities are associated with a high rate of unfavorable genetic mutations.

Cytogenetics
Different genetic mutations are associated with a difference in outcomes. Certain cytogenetic abnormalities are associated with very good outcomes (for example, the (15;17) translocation in APL). About half of people with AML have "normal" cytogenetics; they fall into an intermediate risk group. A number of other cytogenetic abnormalities are known to associate with a poor prognosis and a high risk of relapse after treatment.A large number of molecular alterations are under study for their prognostic impact in AML. However, only FLT3-ITD, NPM1, CEBPA and c-KIT are currently included in validated international risk stratification schema. These are expected to increase rapidly in the near future. FLT3 internal tandem duplications (ITDs) have been shown to confer a poorer prognosis in AML with normal cytogenetics. Several FLT3 inhibitors have undergone clinical trials, with mixed results. Two other mutations – NPM1 and biallelic CEBPA are associated with improved outcomes, especially in people with normal cytogenetics and are used in current risk stratification algorithms.Researchers are investigating the clinical significance of c-KIT mutations in AML. These are prevalent, and potentially clinically relevant because of the availability of tyrosine kinase inhibitors, such as imatinib and sunitinib that can block the activity of c-KIT pharmacologically. It is expected that additional markers (e.g., RUNX1, ASXL1, and TP53) that have consistently been associated with an inferior outcome will soon be included in these recommendations. The prognostic importance of other mutated genes (e.g., DNMT3A, IDH1, IDH2) is less clear.

Other prognostic factors
Elevated lactate dehydrogenase level were also associated with poorer outcomes. Use of tobacco is associated with a person having a poorer prognosis, and people who are married and live together have a better prognosis. People who are treated at place with a higher volume of AML have a better prognosis than those who are treated at those in the lowest quartile. As with most forms of cancer, performance status (i.e. the general physical condition and activity level of the person) plays a major role in prognosis as well.

Epidemiology
AML is a relatively rare cancer. There were 19,950 new cases in the United States in 2016. In 2018, AML accounted for 1.2% of all cancer deaths in the United States.The incidence of AML increases with age and varies between countries. The median age when AML is diagnosed ranges between 63 and 71 years in the UK, Canada, Australia and Sweden, compared with 40 to 45 years in India, Brazil and Algeria.AML accounts for about 90% of all acute leukemias in adults, but is rare in children. The rate of therapy-related AML (AML caused by previous chemotherapy) is expected to rise with an increase in the use of chemotherapy, an ageing population and more patients surviving their initial chemotherapy treatment; therapy-related disease accounts for just under 10% of all cases of AML. AML is slightly more common in men, with a male-to-female ratio of 1.3:1 to 1.4:1. Incidence is also seen to differ by ethnicity, with caucasians having higher recorded incidences and the lowest recorded incidences being in Pacific Islanders and native Alaksans.In the UK, AML accounts for 31% of all leukemia cases, and around 3,100 people were diagnosed with the disease each year in 2016–2018.

History
The first published description of a case of leukemia in medical literature dates to 1827 when French physician Alfred-Armand-Louis-Marie Velpeau described a 63-year-old florist who developed an illness characterized by fever, weakness, urinary stones, and substantial enlargement of the liver and spleen. Velpeau noted the blood of this person had a consistency "like gruel", and speculated the appearance of the blood was due to white corpuscles. In 1845, a series of people who died with enlarged spleens and changes in the "colors and consistencies of their blood" was reported by the Edinburgh-based pathologist J.H </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Aneuploidy and explain in detail? [/INST] Aneuploidy is the presence of an abnormal number of chromosomes in a cell, for example a human cell having 45 or 47 chromosomes instead of the usual 46. It does not include a difference of one or more complete sets of chromosomes. A cell with any number of complete chromosome sets is called a euploid cell.An extra or missing chromosome is a common cause of some genetic disorders. Some cancer cells also have abnormal numbers of chromosomes. About 68% of human solid tumors are aneuploid. Aneuploidy originates during cell division when the chromosomes do not separate properly between the two cells (nondisjunction). Most cases of aneuploidy in the autosomes result in miscarriage, and the most common extra autosomal chromosomes among live births are 21, 18 and 13. Chromosome abnormalities are detected in 1 of 160 live human births. Autosomal aneuploidy is more dangerous than sex chromosome aneuploidy, as autosomal aneuploidy is almost always lethal to embryos that cease developing because of it.

Chromosomes
Most cells in the human body have 23 pairs of chromosomes, or a total of 46 chromosomes. (The sperm and egg, or gametes, each have 23 unpaired chromosomes, and red blood cells at first in bone marrow have nucleus but those red blood cells that are active in blood lose their nucleus and thus they have no nucleus and no chromosomes.)One copy of each pair is inherited from the mother and the other copy is inherited from the father. The first 22 pairs of chromosomes (called autosomes) are numbered from 1 to 22, from largest to smallest. The 23rd pair of chromosomes are the sex chromosomes. Normal females have two X chromosomes, while normal males have one X chromosome and one Y chromosome. The characteristics of the chromosomes in a cell as they are seen under a light microscope are called the karyotype.
During meiosis, when germ cells divide to create sperm and egg (gametes), each half should have the same number of chromosomes. But sometimes, the whole pair of chromosomes will end up in one gamete, and the other gamete will not get that chromosome at all.
Most embryos cannot survive with a missing or extra autosome (numbered chromosome) and are spontaneously aborted. The most frequent aneuploidy in humans is trisomy 16 and fetuses affected with the full version of this chromosome abnormality do not survive to term, although it is possible for surviving individuals to have the mosaic form, where trisomy 16 exists in some cells but not all. The most common aneuploidy that infants can survive with is trisomy 21, which is found in Down syndrome, affecting 1 in 800 births. Trisomy 18 (Edwards syndrome) affects 1 in 6,000 births, and trisomy 13 (Patau syndrome) affects 1 in 10,000 births. 10% of infants with trisomy 18 or 13 reach 1 year of age.Changes in chromosome number may not necessarily be present in all cells in an individual. When aneuploidy is detected in a fraction of cells in an individual, it is called chromosomal mosaicism. In general, individuals who are mosaic for a chromosomal aneuploidy tend to have a less severe form of the syndrome compared to those with full trisomy. For many of the autosomal trisomies, only mosaic cases survive to term. However, mitotic aneuploidy may be more common than previously recognized in somatic tissues, and aneuploidy is a characteristic of many types of tumorigenesis (see below).

Mechanisms
Aneuploidy arises from errors in chromosome segregation, which can go wrong in several ways.Nondisjunction usually occurs as the result of a weakened mitotic checkpoint, as these checkpoints tend to arrest or delay cell division until all components of the cell are ready to enter the next phase. For example, if a checkpoint is weakened, the cell may fail to notice that a chromosome pair is not lined with the spindle apparatus. In such a case, most chromosomes would separate normally (with one chromatid ending up in each cell), while others could fail to separate at all. This would generate a daughter cell lacking a copy and a daughter cell with an extra copy.Completely inactive mitotic checkpoints may cause nondisjunction at multiple chromosomes, possibly all. Such a scenario could result in each daughter cell possessing a disjoint set of genetic material.Merotelic attachment occurs when one kinetochore is attached to both mitotic spindle poles. One daughter cell would have a normal complement of chromosomes; the second would lack one. A third daughter cell may end up with the missing chromosome.
Multipolar spindles: more than two spindle poles form. Such a mitotic division would result in one daughter cell for each spindle pole; each cell may possess an unpredictable complement of chromosomes.
Monopolar spindle: only a single spindle pole forms. This produces a single daughter cell with its copy number doubled.
A tetraploid intermediate may be produced as the end-result of the monopolar spindle mechanism. In such a case, the cell has double the copy number of a normal cell, and produces double the number of spindle poles as well. This results in four daughter cells with an unpredictable complement of chromosomes, but in the normal copy number.

Somatic mosaicism in the nervous system
Mosaicism for aneuploid chromosome content may be part of the constitutional make-up of the mammalian brain. In the normal human brain, brain samples from six individuals ranging from 2–86 years of age had mosaicism for chromosome 21 aneuploidy (average of 4% of neurons analyzed). This low-level aneuploidy appears to arise from chromosomal segregation defects during cell division in neuronal precursor cells, and neurons containing such aneuploid chromosome content reportedly integrate into normal circuits. However, recent research using single-cell sequencing has challenged these findings, and has suggested that aneuploidy in the brain is actually very rare.

Somatic mosaicism in cancer
Aneuploidy is consistently observed in virtually all cancers. The German biologist Theodor Boveri was first to propose a causative role for aneuploidy in cancer. However, the theory of Boveri was forgotten until the molecular biologist Peter Duesberg reappraised it. Understanding through what mechanisms it can affect tumor evolution is an important topic of current cancer research.Somatic mosaicism occurs in virtually all cancer cells, including trisomy 12 in chronic lymphocytic leukemia (CLL) and trisomy 8 in acute myeloid leukemia (AML). However, these forms of mosaic aneuploidy occur through mechanisms distinct from those typically associated with genetic syndromes involving complete or mosaic aneuploidy, such as chromosomal instability (due to mitotic segregation defects in cancer cells). Therefore, the molecular processes that lead to aneuploidy are targets for the development of cancer drugs. Both resveratrol and aspirin have been found in vivo (in mice) to selectively destroy tetraploid cells that may be precursors of aneuploid cells, and activate AMPK, which may be involved in the process.Alteration of normal mitotic checkpoints are also important tumorigenic events, and these may directly lead to aneuploidy.
Loss of tumor suppressor p53 gene often results in genomic instability, which could lead to the aneuploidy genotype.In addition, genetic syndromes in which an individual is predisposed to breakage of chromosomes (chromosome instability syndromes) are frequently associated with increased risk for various types of cancer, thus highlighting the role of somatic aneuploidy in carcinogenesis.The ability to evade the immune system appears to be enhanced in tumoral cells with strong aneuploidy. This has therefore suggested that the presence of an abnormal number of chromosomes might be an effective predictive biomarker for response to precise immunotherapy. For example, in melanoma patients, high somatic copy number alterations are associated with less effective response to immune checkpoint blockade anti–CTLA4 (cytotoxic T lymphocyte–associated protein 4) therapy.A research work published in 2008 focuses on the mechanisms involved in aneuploidy formation, specifically on the epigenetic origin of aneuploid cells. Epigenetic inheritance is defined as cellular information other than the DNA sequence itself, that is still heritable during cell division. DNA methylation and histone modifications comprise two of the main epigenetic modifications important for many physiological and pathological conditions, including cancer. Aberrant DNA methylation is the most common molecular lesion in cancer-cells, even more frequent than gene mutations. Tumor suppressor gene silencing by CpG island promoter hypermethylation is supposed to be the most frequent epigenetic modification in cancer cells. Epigenetic characteristics of cells may be modified by several factors including environmental exposure, deficiencies of certain nutrients, radiation, etc. Some of the alterations have been correlated with the formation of aneuploid cells in vivo. In this study it is suggested on a growing basis of evidence, that not only genetics but also epigenetics, contribute to aneuploid cell formation.

Partial aneuploidy
The terms "partial monosomy" and "partial trisomy" are used to describe an imbalance of genetic material caused by loss or gain of part of a chromosome. In particular, these terms would be used in the situation of an unbalanced translocation, where an individual carries a derivative chromosome formed through the breakage and fusion of two different chromosomes. In this situation, the individual would have three copies of part of one chromosome (two normal copies and the portion that exists on the derivative chromosome) and only one copy of part of the other chromosome involved in the derivative chromosome. Robertsonian translocations, for example, account for a very small minority of Down syndrome cases (<5%). The formation of one isochromosome results in partial trisomy of the genes present in the isochromosome and partial monosomy of the genes in the lost arm.

Aneugens
Agents capable of causing aneuploidy are called aneugens. Many mutagenic carcinogens are aneugens. X-rays, for example, may cause aneuploidy by fragmenting the chromosome; it may also target the spindle apparatus. Other chemicals such as colchicine can also produce aneuploidy by affecting microtubule polymerization.
Exposure of males to lifestyle, environmental and/or occupational hazards may increase the risk of spermatozoa aneuploidy. Tobacco smoke contains chemicals that cause DNA damage </s>