StemCell Therapy

Death is the termination of all biological functions that sustain an organism. Phenomena which commonly bring about death include biological aging (senescence), predation, malnutrition, disease, suicide, homicide, starvation, dehydration, and accidents or trauma resulting in terminal injury.[1] Bodies of living organisms begin to decompose shortly after death. Death has commonly been considered a sad or unpleasant occasion, particularly for humans, due to the affection for the being that has died and/or the termination of social and familial bonds with the deceased. Other concerns include fear of death, necrophobia, anxiety, sorrow, grief, emotional pain, depression, sympathy, compassion, solitude, or saudade. The potential for an afterlife is of concern for humans and the possibility of reward or judgement and punishment for past sin with people of certain religions.

The word death comes from Old English dea, which in turn comes from Proto-Germanic dauthuz (reconstructed by etymological analysis). This comes from the Proto-Indo-European stem dheu- meaning the "Process, act, condition of dying".[2]

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 for death. When a person has died, it is also said they have passed away, passed on, expired, or are gone, among numerous other socially accepted, religiously specific, slang, and irreverent terms. Bereft of life, the dead person is then a corpse, cadaver, a body, a set of remains, and when all flesh has rotted away, a skeleton. The terms carrion and carcass can also be used, though these more often connote the remains of non-human animals. As a polite 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. The ashes left after a cremation are sometimes referred to by the neologism cremains, a portmanteau of "cremation" and "remains".

Senescence refers to a scenario when a living being is able to survive all calamities, but eventually dies due to old age. Human, 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 (Hayflick & Moody, 2003).

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,[3] the hydra, and the planarian. Unnatural causes of death include suicide and homicide. From all causes, roughly 150,000 people die around the world each day.[4] Of these, two thirds die directly or indirectly due to senescence, but in industrialized countriessuch as the United States, the United Kingdom, and Germanythe rate approaches 90%, i.e., nearly nine out of ten of all deaths are related to senescence.[4]

Physiological death is now seen as a process, more than an event: conditions once considered indicative of death are now reversible.[5] 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. As scientific knowledge and medicine advance, a precise medical definition of death becomes more problematic.[6]

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

The concept of death is a key to human understanding of the phenomenon.[7] There are many scientific approaches to the concept. For example, brain death, as practiced in medical science, defines death as a point in time at which brain activity ceases.[7][8][9][10]

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 requires drawing precise conceptual boundaries between life and death. This is problematic because there is little consensus over how to define life. This general problem applies to the particular challenge of defining death in the context of medicine.

It is possible to define life in terms of consciousness. When consciousness ceases, a living organism can be said to have died. One of the flaws in this approach is that there are many organisms which 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.[11]

Other definitions for death focus on the character of cessation of something.[12][clarification needed] In this context "death" describes merely the state where something has ceased, for example, life. Thus, the definition of "life" simultaneously defines death.

Historically, attempts to define the exact moment of a human's death have been problematic. 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. 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 by some scholars to be problematic. 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)."[13]

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.

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 himself or by an administrative office upon presentation of a doctor's declaration of death.

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 public's fear of being mistakenly buried alive,[14] 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 corpse's mouth to applying red hot pokers to the feet or into the rectum.[15] Writing in 1895, the physician J.C. Ouseley claimed that as many as 2,700people were buried prematurely each year in England and Wales, although others estimated the figure to be closer to 800.[16]

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.[17] This "diving response", in which metabolic activity and oxygen requirements are minimal, is something humans share with cetaceans called the mammalian diving reflex.[17]

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[18] has been suggested as a better means of defining when true death occurs, though the concept has few practical applications outside of the field of cryonics.

There have been some scientific attempts to bring dead organisms back to life, but with limited success.[19] In science fiction scenarios where such technology is readily available, real death is distinguished from reversible death.

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,[4] 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.[4] In industrialized nations, the proportion is much higher, approaching 90%.[4] 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 1.7M people in 2004.[21]Malaria causes about 400900M cases of fever and 13M deaths annually.[22]AIDS death toll in Africa may reach 90100M by 2025.[23][24]

According to Jean Ziegler (United Nations Special Reporter on the Right to Food, 2000Mar 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.[25]

Tobacco smoking killed 100million people worldwide in the 20th century and could kill 1billion people around the world in the 21st century, a World Health Organization report warned.[20]

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.[26]

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.[27] 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.[28] 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.[29]

In 2012, suicide overtook car crashes for leading causes of human injury deaths in America, followed by poisoning, falls and murder.[30] 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.[31]

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 person's 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" is an older term for a postmortem examination, unregulated, and not always a medical procedure. In modern times the term is more often used in the postmortem examination of the corpses of animals.

Cryonics (from Greek '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.[32][33]

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.[18][34] It is proposed that cryopreserved people might someday be recovered by using highly advanced technology.[35][36]

Some scientific literature supports the feasibility of cryonics.[35][36][37] Many other scientists regard cryonics with skepticism.[38] By 2015, more than 300 people have undergone cryopreservation procedures since cryonics was first proposed in 1962.[39]

Life extension refers to an increase in maximum or average lifespan, especially in humans, by slowing down or reversing the processes of aging. 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.[40] 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.

"One of medicine's new frontiers: treating the dead", recognizes that cells that have been without oxygen for more than five minutes die,[41] not from lack of oxygen, but rather when their oxygen supply is resumed. Therefore, practitioners of this approach, e.g., at the Resuscitation Science institute at the University of Pennsylvania, "aim to reduce oxygen uptake, slow metabolism and adjust the blood chemistry for gradual and safe reperfusion."[42]

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.[43] By the mid-20th century, half of all Americans died in a hospital.[44] By the start of the 21st century, only about 20 to 25% of people in developed countries died outside a medical institution.[44][45][46] The shift away from dying at home, towards dying in a professionalized medical environment, has been termed the "Invisible Death."[44]

In society, the nature of death and humanity's awareness of its own mortality has for millennia been a concern of the world's 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 atheism).[47]

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 world's 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, 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 one's spiritual attainments into another body (reincarnation) are subjects of detailed study in Tibet.[48]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 one's 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.[49]

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 cartrio, 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 cartrio. 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.[50]

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.

Much interest and debate surround the question of what happens to one's consciousness as one's body dies. The belief in the permanent loss of consciousness after death is often called eternal oblivion. Belief that consciousness is preserved after physical death is described by the term afterlife.

After death the remains of an organism become part of the biogeochemical cycle. 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. 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 decomposed fully. Coal, a fossil fuel formed over vast tracts of time in swamp ecosystems, is one example.

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 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.

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 already cited 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),[52] 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.[53]

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.[53][54]

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Death - Wikipedia, the free encyclopedia

The Johns Hopkins Integrative Medicine & Digestive Center is part of The Johns Hopkins University School of Medicine, Division of Gastroenterology & Hepatology. The Center is located at Green Spring Station, 2360 W. Joppa Road, Suite 200, Lutherville, MD 21093.

Our team of practitioners, including board-certified physicians, licensed massage therapists, acupuncturists, psychotherapists, and nutritionists, works closely with our patients and their other healthcare providers to address a variety of chronic conditions using an individualized approach. These services are offered in conjunction with the best of Hopkins' cutting-edge research to provide our patients with all the latest treatment options.

We welcome patients with all types of health conditions, including those wishing to learn more about preventive health care and what constitutes a healthy lifestyle. Appointments can be made with any of the providers at our Center by calling the Center. For those patients who are unsure about what services would best help them, they are encouraged to first make an Integrative Health Visit with one of our staff who can guide them to the appropriate services and practitioners within the Center. If you are visiting from outside the Baltimore area, appointments can be coordinated if necessary so you can see more than one practitioner the same day or week.

At our Center, you will not be rushed through your visit so we may fully understand your concerns. We believe in being accessible to our patients and taking the time to address all your questions.

It is important we communicate with your other healthcare providers so your healthcare is unified. We encourage you to give us permission to share our recommendations with your other providers whenever possible.

Link:
Johns Hopkins Integrative Medicine and Digestive Center ...

Medicine (British English i; American English i) is the science and practice of the diagnosis, treatment, and prevention of disease.[1][2] The word medicine is derived from Latin medicus, meaning "a physician".[3][4] Medicine encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness. Contemporary medicine applies biomedical sciences, biomedical research, genetics, and medical technology to diagnose, treat, and prevent injury and disease, typically through pharmaceuticals or surgery, but also through therapies as diverse as psychotherapy, external splints and traction, medical devices, biologics, and ionizing radiation, amongst others.[5]

Medicine has existed for thousands of years, during most of which it was an art (an area of skill and knowledge) frequently having connections to the religious and philosophical beliefs of local culture. For example, a medicine man would apply herbs and say prayers for healing, or an ancient philosopher and physician would apply bloodletting according to the theories of humorism. In recent centuries, since the advent of modern science, most medicine has become a combination of art and science (both basic and applied, under the umbrella of medical science). While stitching technique for sutures is an art learned through practice, the knowledge of what happens at the cellular and molecular level in the tissues being stitched arises through science.

Prescientific forms of medicine are now known as traditional medicine and folk medicine. They remain commonly used with or instead of scientific medicine and are thus called alternative medicine. For example, evidence on the effectiveness of acupuncture is "variable and inconsistent" for any condition,[6] but is generally safe when done by an appropriately trained practitioner.[7] In contrast, treatments outside the bounds of safety and efficacy are termed quackery.

Medical availability and clinical practice varies across the world due to regional differences in culture and technology. Modern scientific medicine is highly developed in the Western world, while in developing countries such as parts of Africa or Asia, the population may rely more heavily on traditional medicine with limited evidence and efficacy and no required formal training for practitioners.[8] Even in the developed world however, evidence-based medicine is not universally used in clinical practice; for example, a 2007 survey of literature reviews found that about 49% of the interventions lacked sufficient evidence to support either benefit or harm.[9]

In modern clinical practice, doctors personally assess patients in order to diagnose, treat, and prevent disease using clinical judgment. The doctor-patient relationship typically begins an interaction with an examination of the patient's medical history and medical record, followed by a medical interview[10] and a physical examination. Basic diagnostic medical devices (e.g. stethoscope, tongue depressor) are typically used. After examination for signs and interviewing for symptoms, the doctor may order medical tests (e.g. blood tests), take a biopsy, or prescribe pharmaceutical drugs or other therapies. Differential diagnosis methods help to rule out conditions based on the information provided. During the encounter, properly informing the patient of all relevant facts is an important part of the relationship and the development of trust. The medical encounter is then documented in the medical record, which is a legal document in many jurisdictions.[11] Follow-ups may be shorter but follow the same general procedure, and specialists follow a similar process. The diagnosis and treatment may take only a few minutes or a few weeks depending upon the complexity of the issue.

The components of the medical interview[10] and encounter are:

The physical examination is the examination of the patient for medical signs of disease, which are objective and observable, in contrast to symptoms which are volunteered by the patient and not necessarily objectively observable.[12] The healthcare provider uses the senses of sight, hearing, touch, and sometimes smell (e.g., in infection, uremia, diabetic ketoacidosis). Four actions are the basis of physical examination: inspection, palpation (feel), percussion (tap to determine resonance characteristics), and auscultation (listen), generally in that order although auscultation occurs prior to percussion and palpation for abdominal assessments.[13]

The clinical examination involves the study of:

It is to likely focus on areas of interest highlighted in the medical history and may not include everything listed above.

The treatment plan may include ordering additional medical laboratory tests and medical imaging studies, starting therapy, referral to a specialist, or watchful observation. Follow-up may be advised. Depending upon the health insurance plan and the managed care system, various forms of "utilization review", such as prior authorization of tests, may place barriers on accessing expensive services.[14]

The medical decision-making (MDM) process involves analysis and synthesis of all the above data to come up with a list of possible diagnoses (the differential diagnoses), along with an idea of what needs to be done to obtain a definitive diagnosis that would explain the patient's problem.

On subsequent visits, the process may be repeated in an abbreviated manner to obtain any new history, symptoms, physical findings, and lab or imaging results or specialist consultations.

Contemporary medicine is in general conducted within health care systems. Legal, credentialing and financing frameworks are established by individual governments, augmented on occasion by international organizations, such as churches. The characteristics of any given health care system have significant impact on the way medical care is provided.

From ancient times, Christian emphasis on practical charity gave rise to the development of systematic nursing and hospitals and the Catholic Church today remains the largest non-government provider of medical services in the world.[15] Advanced industrial countries (with the exception of the United States)[16][17] and many developing countries provide medical services through a system of universal health care that aims to guarantee care for all through a single-payer health care system, or compulsory private or co-operative health insurance. This is intended to ensure that the entire population has access to medical care on the basis of need rather than ability to pay. Delivery may be via private medical practices or by state-owned hospitals and clinics, or by charities, most commonly by a combination of all three.

Most tribal societies provide no guarantee of healthcare for the population as a whole. In such societies, healthcare is available to those that can afford to pay for it or have self-insured it (either directly or as part of an employment contract) or who may be covered by care financed by the government or tribe directly.

Transparency of information is another factor defining a delivery system. Access to information on conditions, treatments, quality, and pricing greatly affects the choice by patients/consumers and, therefore, the incentives of medical professionals. While the US healthcare system has come under fire for lack of openness,[18] new legislation may encourage greater openness. There is a perceived tension between the need for transparency on the one hand and such issues as patient confidentiality and the possible exploitation of information for commercial gain on the other.

Provision of medical care is classified into primary, secondary, and tertiary care categories.

Primary care medical services are provided by physicians, physician assistants, nurse practitioners, or other health professionals who have first contact with a patient seeking medical treatment or care. These occur in physician offices, clinics, nursing homes, schools, home visits, and other places close to patients. About 90% of medical visits can be treated by the primary care provider. These include treatment of acute and chronic illnesses, preventive care and health education for all ages and both sexes.

Secondary care medical services are provided by medical specialists in their offices or clinics or at local community hospitals for a patient referred by a primary care provider who first diagnosed or treated the patient. Referrals are made for those patients who required the expertise or procedures performed by specialists. These include both ambulatory care and inpatient services, emergency rooms, intensive care medicine, surgery services, physical therapy, labor and delivery, endoscopy units, diagnostic laboratory and medical imaging services, hospice centers, etc. Some primary care providers may also take care of hospitalized patients and deliver babies in a secondary care setting.

Tertiary care medical services are provided by specialist hospitals or regional centers equipped with diagnostic and treatment facilities not generally available at local hospitals. These include trauma centers, burn treatment centers, advanced neonatology unit services, organ transplants, high-risk pregnancy, radiation oncology, etc.

Modern medical care also depends on information still delivered in many health care settings on paper records, but increasingly nowadays by electronic means.

In low-income countries, modern healthcare is often too expensive for the average person. International healthcare policy researchers have advocated that "user fees" be removed in these areas to ensure access, although even after removal, significant costs and barriers remain.[19]

Working together as an interdisciplinary team, many highly trained health professionals besides medical practitioners are involved in the delivery of modern health care. Examples include: nurses, emergency medical technicians and paramedics, laboratory scientists, pharmacists, podiatrists, physiotherapists, respiratory therapists, speech therapists, occupational therapists, radiographers, dietitians, and bioengineers, surgeons, surgeon's assistant, surgical technologist.

The scope and sciences underpinning human medicine overlap many other fields. Dentistry, while considered by some a separate discipline from medicine, is a medical field.

A patient admitted to the hospital is usually under the care of a specific team based on their main presenting problem, e.g., the Cardiology team, who then may interact with other specialties, e.g., surgical, radiology, to help diagnose or treat the main problem or any subsequent complications/developments.

Physicians have many specializations and subspecializations into certain branches of medicine, which are listed below. There are variations from country to country regarding which specialties certain subspecialties are in.

The main branches of medicine are:

In the broadest meaning of "medicine", there are many different specialties. In the UK, most specialities have their own body or college, which have its own entrance examination. These are collectively known as the Royal Colleges, although not all currently use the term "Royal". The development of a speciality is often driven by new technology (such as the development of effective anaesthetics) or ways of working (such as emergency departments); the new specialty leads to the formation of a unifying body of doctors and the prestige of administering their own examination.

Within medical circles, specialities usually fit into one of two broad categories: "Medicine" and "Surgery." "Medicine" refers to the practice of non-operative medicine, and most of its subspecialties require preliminary training in Internal Medicine. In the UK, this was traditionally evidenced by passing the examination for the Membership of the Royal College of Physicians (MRCP) or the equivalent college in Scotland or Ireland. "Surgery" refers to the practice of operative medicine, and most subspecialties in this area require preliminary training in General Surgery, which in the UK leads to membership of the Royal College of Surgeons of England (MRCS). At present, some specialties of medicine do not fit easily into either of these categories, such as radiology, pathology, or anesthesia. Most of these have branched from one or other of the two camps above; for example anaesthesia developed first as a faculty of the Royal College of Surgeons (for which MRCS/FRCS would have been required) before becoming the Royal College of Anaesthetists and membership of the college is attained by sitting for the examination of the Fellowship of the Royal College of Anesthetists (FRCA).

Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, to help improve bodily function or appearance or to repair unwanted ruptured areas (for example, a perforated ear drum). Surgeons must also manage pre-operative, post-operative, and potential surgical candidates on the hospital wards. Surgery has many sub-specialties, including general surgery, ophthalmic surgery, cardiovascular surgery, colorectal surgery, neurosurgery, oral and maxillofacial surgery, oncologic surgery, orthopedic surgery, otolaryngology, plastic surgery, podiatric surgery, transplant surgery, trauma surgery, urology, vascular surgery, and pediatric surgery. In some centers, anesthesiology is part of the division of surgery (for historical and logistical reasons), although it is not a surgical discipline. Other medical specialties may employ surgical procedures, such as ophthalmology and dermatology, but are not considered surgical sub-specialties per se.

Surgical training in the U.S. requires a minimum of five years of residency after medical school. Sub-specialties of surgery often require seven or more years. In addition, fellowships can last an additional one to three years. Because post-residency fellowships can be competitive, many trainees devote two additional years to research. Thus in some cases surgical training will not finish until more than a decade after medical school. Furthermore, surgical training can be very difficult and time-consuming.

Internal medicine is the medical specialty dealing with the prevention, diagnosis, and treatment of adult diseases. According to some sources, an emphasis on internal structures is implied.[20] In North America, specialists in internal medicine are commonly called "internists." Elsewhere, especially in Commonwealth nations, such specialists are often called physicians.[21] These terms, internist or physician (in the narrow sense, common outside North America), generally exclude practitioners of gynecology and obstetrics, pathology, psychiatry, and especially surgery and its subspecialities.

Because their patients are often seriously ill or require complex investigations, internists do much of their work in hospitals. Formerly, many internists were not subspecialized; such general physicians would see any complex nonsurgical problem; this style of practice has become much less common. In modern urban practice, most internists are subspecialists: that is, they generally limit their medical practice to problems of one organ system or to one particular area of medical knowledge. For example, gastroenterologists and nephrologists specialize respectively in diseases of the gut and the kidneys.[22]

In the Commonwealth of Nations and some other countries, specialist pediatricians and geriatricians are also described as specialist physicians (or internists) who have subspecialized by age of patient rather than by organ system. Elsewhere, especially in North America, general pediatrics is often a form of Primary care.

There are many subspecialities (or subdisciplines) of internal medicine:

Training in internal medicine (as opposed to surgical training), varies considerably across the world: see the articles on Medical education and Physician for more details. In North America, it requires at least three years of residency training after medical school, which can then be followed by a one- to three-year fellowship in the subspecialties listed above. In general, resident work hours in medicine are less than those in surgery, averaging about 60 hours per week in the USA. This difference does not apply in the UK where all doctors are now required by law to work less than 48 hours per week on average.

The followings are some major medical specialties that do not directly fit into any of the above-mentioned groups.

Some interdisciplinary sub-specialties of medicine include:

Medical education and training varies around the world. It typically involves entry level education at a university medical school, followed by a period of supervised practice or internship, and/or residency. This can be followed by postgraduate vocational training. A variety of teaching methods have been employed in medical education, still itself a focus of active research. In Canada and the United States of America, a Doctor of Medicine degree, often abbreviated M.D., or a Doctor of Osteopathic Medicine degree, often abbreviated as D.O. and unique to the United States, must be completed in and delivered from a recognized university.

Since knowledge, techniques, and medical technology continue to evolve at a rapid rate, many regulatory authorities require continuing medical education. Medical practitioners upgrade their knowledge in various ways, including medical journals, seminars, conferences, and online programs.

In most countries, it is a legal requirement for a medical doctor to be licensed or registered. In general, this entails a medical degree from a university and accreditation by a medical board or an equivalent national organization, which may ask the applicant to pass exams. This restricts the considerable legal authority of the medical profession to physicians that are trained and qualified by national standards. It is also intended as an assurance to patients and as a safeguard against charlatans that practice inadequate medicine for personal gain. While the laws generally require medical doctors to be trained in "evidence based", Western, or Hippocratic Medicine, they are not intended to discourage different paradigms of health.

In the European Union, the profession of doctor of medicine is regulated. A profession is said to be regulated when access and exercise is subject to the possession of a specific professional qualification. The regulated professions database contains a list of regulated professions for doctor of medicine in the EU member states, EEA countries and Switzerland. This list is covered by the Directive 2005/36/EC.

Doctors who are negligent or intentionally harmful in their care of patients can face charges of medical malpractice and be subject to civil, criminal, or professional sanctions.

Medical ethics is a system of moral principles that apply values and judgments to the practice of medicine. As a scholarly discipline, medical ethics encompasses its practical application in clinical settings as well as work on its history, philosophy, theology, and sociology. Six of the values that commonly apply to medical ethics discussions are:

Values such as these do not give answers as to how to handle a particular situation, but provide a useful framework for understanding conflicts. When moral values are in conflict, the result may be an ethical dilemma or crisis. Sometimes, no good solution to a dilemma in medical ethics exists, and occasionally, the values of the medical community (i.e., the hospital and its staff) conflict with the values of the individual patient, family, or larger non-medical community. Conflicts can also arise between health care providers, or among family members. For example, some argue that the principles of autonomy and beneficence clash when patients refuse blood transfusions, considering them life-saving; and truth-telling was not emphasized to a large extent before the HIV era.

Prehistoric medicine incorporated plants (herbalism), animal parts, and minerals. In many cases these materials were used ritually as magical substances by priests, shamans, or medicine men. Well-known spiritual systems include animism (the notion of inanimate objects having spirits), spiritualism (an appeal to gods or communion with ancestor spirits); shamanism (the vesting of an individual with mystic powers); and divination (magically obtaining the truth). The field of medical anthropology examines the ways in which culture and society are organized around or impacted by issues of health, health care and related issues.

Early records on medicine have been discovered from ancient Egyptian medicine, Babylonian Medicine, Ayurvedic medicine (in the Indian subcontinent), classical Chinese medicine (predecessor to the modern traditional Chinese Medicine), and ancient Greek medicine and Roman medicine.

In Egypt, Imhotep (3rd millennium BC) is the first physician in history known by name. The oldest Egyptian medical text is the Kahun Gynaecological Papyrus from around 2000 BCE, which describes gynaecological diseases. The Edwin Smith Papyrus dating back to 1600 BCE is an early work on surgery, while the Ebers Papyrus dating back to 1500 BCE is akin to a textbook on medicine.[24]

In China, archaeological evidence of medicine in Chinese dates back to the Bronze Age Shang Dynasty, based on seeds for herbalism and tools presumed to have been used for surgery.[25] The Huangdi Neijing, the progenitor of Chinese medicine, is a medical text written beginning in the 2nd century BCE and compiled in the 3rd century.[26]

In India, the surgeon Sushruta described numerous surgical operations, including the earliest forms of plastic surgery.[27][dubious discuss][28][29] Earliest records of dedicated hospitals come from Mihintale in Sri Lanka where evidence of dedicated medicinal treatment facilities for patients are found.[30][31]

In Greece, the Greek physician Hippocrates, the "father of western medicine",[32][33] laid the foundation for a rational approach to medicine. Hippocrates introduced the Hippocratic Oath for physicians, which is still relevant and in use today, and was the first to categorize illnesses as acute, chronic, endemic and epidemic, and use terms such as, "exacerbation, relapse, resolution, crisis, paroxysm, peak, and convalescence".[34][35] The Greek physician Galen was also one of the greatest surgeons of the ancient world and performed many audacious operations, including brain and eye surgeries. After the fall of the Western Roman Empire and the onset of the Early Middle Ages, the Greek tradition of medicine went into decline in Western Europe, although it continued uninterrupted in the Eastern Roman (Byzantine) Empire.

Most of our knowledge of ancient Hebrew medicine during the 1stmillenniumBC comes from the Torah, i.e.the Five Books of Moses, which contain various health related laws and rituals. The Hebrew contribution to the development of modern medicine started in the Byzantine Era, with the physician Asaph the Jew.[36]

After 750 CE, the Muslim world had the works of Hippocrates, Galen and Sushruta translated into Arabic, and Islamic physicians engaged in some significant medical research. Notable Islamic medical pioneers include the Persian polymath, Avicenna, who, along with Imhotep and Hippocrates, has also been called the "father of medicine".[37] He wrote The Canon of Medicine, considered one of the most famous books in the history of medicine.[38] Others include Abulcasis,[39]Avenzoar,[40]Ibn al-Nafis,[41] and Averroes.[42]Rhazes[43] was one of the first to question the Greek theory of humorism, which nevertheless remained influential in both medieval Western and medieval Islamic medicine.[44]Al-Risalah al-Dhahabiah by Ali al-Ridha, the eighth Imam of Shia Muslims, is revered as the most precious Islamic literature in the Science of Medicine.[45] The Islamic Bimaristan hospitals were an early example of public hospitals.[46][47]

In Europe, Charlemagne decreed that a hospital should be attached to each cathedral and monastery and the historian Geoffrey Blainey likened the activities of the Catholic Church in health care during the Middle Ages to an early version of a welfare state: "It conducted hospitals for the old and orphanages for the young; hospices for the sick of all ages; places for the lepers; and hostels or inns where pilgrims could buy a cheap bed and meal". It supplied food to the population during famine and distributed food to the poor. This welfare system the church funded through collecting taxes on a large scale and possessing large farmlands and estates. The Benedictine order was noted for setting up hospitals and infirmaries in their monasteries, growing medical herbs and becoming the chief medical care givers of their districts, as at the great Abbey of Cluny. The Church also established a network of cathedral schools and universities where medicine was studied. The Schola Medica Salernitana in Salerno, looking to the learning of Greek and Arab physicians, grew to be the finest medical school in Medieval Europe.[48]

However, the fourteenth and fifteenth century Black Death devastated both the Middle East and Europe, and it has even been argued that Western Europe was generally more effective in recovering from the pandemic than the Middle East.[49] In the early modern period, important early figures in medicine and anatomy emerged in Europe, including Gabriele Falloppio and William Harvey.

The major shift in medical thinking was the gradual rejection, especially during the Black Death in the 14th and 15th centuries, of what may be called the 'traditional authority' approach to science and medicine. This was the notion that because some prominent person in the past said something must be so, then that was the way it was, and anything one observed to the contrary was an anomaly (which was paralleled by a similar shift in European society in general see Copernicus's rejection of Ptolemy's theories on astronomy). Physicians like Vesalius improved upon or disproved some of the theories from the past. The main tomes used both by medicine students and expert physicians were Materia Medica and Pharmacopoeia.

Andreas Vesalius was the author of De humani corporis fabrica, an important book on human anatomy.[50] Bacteria and microorganisms were first observed with a microscope by Antonie van Leeuwenhoek in 1676, initiating the scientific field microbiology.[51] Independently from Ibn al-Nafis, Michael Servetus rediscovered the pulmonary circulation, but this discovery did not reach the public because it was written down for the first time in the "Manuscript of Paris"[52] in 1546, and later published in the theological work for which he paid with his life in 1553. Later this was described by Renaldus Columbus and Andrea Cesalpino. Herman Boerhaave is sometimes referred to as a "father of physiology" due to his exemplary teaching in Leiden and textbook 'Institutiones medicae' (1708). Pierre Fauchard has been called "the father of modern dentistry".[53]

Veterinary medicine was, for the first time, truly separated from human medicine in 1761, when the French veterinarian Claude Bourgelat founded the world's first veterinary school in Lyon, France. Before this, medical doctors treated both humans and other animals.

Modern scientific biomedical research (where results are testable and reproducible) began to replace early Western traditions based on herbalism, the Greek "four humours" and other such pre-modern notions. The modern era really began with Edward Jenner's discovery of the smallpox vaccine at the end of the 18th century (inspired by the method of inoculation earlier practiced in Asia), Robert Koch's discoveries around 1880 of the transmission of disease by bacteria, and then the discovery of antibiotics around 1900.

The post-18th century modernity period brought more groundbreaking researchers from Europe. From Germany and Austria, doctors Rudolf Virchow, Wilhelm Conrad Rntgen, Karl Landsteiner and Otto Loewi made notable contributions. In the United Kingdom, Alexander Fleming, Joseph Lister, Francis Crick and Florence Nightingale are considered important. Spanish doctor Santiago Ramn y Cajal is considered the father of modern neuroscience.

From New Zealand and Australia came Maurice Wilkins, Howard Florey, and Frank Macfarlane Burnet.

In the United States, William Williams Keen, William Coley, James D. Watson, Italy (Salvador Luria), Switzerland (Alexandre Yersin), Japan (Kitasato Shibasabur), and France (Jean-Martin Charcot, Claude Bernard, Paul Broca) and others did significant work. Russian Nikolai Korotkov also did significant work, as did Sir William Osler and Harvey Cushing.

As science and technology developed, medicine became more reliant upon medications. Throughout history and in Europe right until the late 18th century, not only animal and plant products were used as medicine, but also human body parts and fluids.[54]Pharmacology developed in part from herbalism and some drugs are still derived from plants (atropine, ephedrine, warfarin, aspirin, digoxin, vinca alkaloids, taxol, hyoscine, etc.).[55]Vaccines were discovered by Edward Jenner and Louis Pasteur.

The first antibiotic was arsphenamine (Salvarsan) discovered by Paul Ehrlich in 1908 after he observed that bacteria took up toxic dyes that human cells did not. The first major class of antibiotics was the sulfa drugs, derived by German chemists originally from azo dyes.

Pharmacology has become increasingly sophisticated; modern biotechnology allows drugs targeted towards specific physiological processes to be developed, sometimes designed for compatibility with the body to reduce side-effects. Genomics and knowledge of human genetics is having some influence on medicine, as the causative genes of most monogenic genetic disorders have now been identified, and the development of techniques in molecular biology and genetics are influencing medical technology, practice and decision-making.

Evidence-based medicine is a contemporary movement to establish the most effective algorithms of practice (ways of doing things) through the use of systematic reviews and meta-analysis. The movement is facilitated by modern global information science, which allows as much of the available evidence as possible to be collected and analyzed according to standard protocols that are then disseminated to healthcare providers. The Cochrane Collaboration leads this movement. A 2001 review of 160 Cochrane systematic reviews revealed that, according to two readers, 21.3% of the reviews concluded insufficient evidence, 20% concluded evidence of no effect, and 22.5% concluded positive effect.[56]

Traditional medicine (also known as indigenous or folk medicine) comprises knowledge systems that developed over generations within various societies before the era of modern medicine. The World Health Organization (WHO) defines traditional medicine as "the sum total of the knowledge, skills, and practices based on the theories, beliefs, and experiences indigenous to different cultures, whether explicable or not, used in the maintenance of health as well as in the prevention, diagnosis, improvement or treatment of physical and mental illness."[57]

In some Asian and African countries, up to 80% of the population relies on traditional medicine for their primary health care needs. When adopted outside of its traditional culture, traditional medicine is often called alternative medicine.[57] Practices known as traditional medicines include Ayurveda, Siddha medicine, Unani, ancient Iranian medicine, Irani, Islamic medicine, traditional Chinese medicine, traditional Korean medicine, acupuncture, Muti, If, and traditional African medicine.

The WHO notes however that "inappropriate use of traditional medicines or practices can have negative or dangerous effects" and that "further research is needed to ascertain the efficacy and safety" of several of the practices and medicinal plants used by traditional medicine systems.[57] The line between alternative medicine and quackery is a contentious subject.

Traditional medicine may include formalized aspects of folk medicine, that is to say longstanding remedies passed on and practised by lay people. Folk medicine consists of the healing practices and ideas of body physiology and health preservation known to some in a culture, transmitted informally as general knowledge, and practiced or applied by anyone in the culture having prior experience.[58] Folk medicine may also be referred to as traditional medicine, alternative medicine, indigenous medicine, or natural medicine. These terms are often considered interchangeable, even though some authors may prefer one or the other because of certain overtones they may be willing to highlight. In fact, out of these terms perhaps only indigenous medicine and traditional medicine have the same meaning folk medicine, while the others should be understood rather in a modern or modernized context.[59]

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Medicine - Wikipedia, the free encyclopedia

Whether your father, mother or siblings have had heart disease may seem like the most important predictor of your own chances of a heart attack. Not so says a large Swedish study published in the Journal of the American College of Cardiology in 2014. In fact, it showed that 5 specific lifestyle factors like eating right, regular exercise and quitting smoking can combine to prevent 80% of first heart attacks.

The researchers, from the Karolinska Institute in Stockholm, set out to determine to what degree healthy habits individually - or in concert - help adults avoid a future heart attack, or myocardial infarction.

Rates of coronary heart disease have dropped in many parts of the world, write the authors, thanks to advances in medications that work to fight high blood pressure and lower cholesterol. Since huge populations are at risk of cardiovascular disease, however, the use of prescription drugs - with their own risks of side effects and significant cost if taken over the long term - are not an effective wide-scale preventative strategy, argue the researchers. They write that their own past research on women and that of other scientists on both genders shows lifestyle changes can dramatically cut heart attack risk.

What the study examined: Men between the ages of 45 and 79 were recruited in 1997, and surveyed about their eating and activity habits, along with data including their weight, family history of heart disease, and level of education.

A total of 20,721 men without any history of cardiovascular disease, cancer, or diabetes were then tracked over an 11-year period.

Five diet and lifestyle factors were examined: diet, smoking habits, alcohol consumption, belly fat and daily activity level.

What the researchers discovered: Each of the five lifestyle habits or conditions was found to offer its own individual benefit in preventing a future heart attack.

The best odds were found among men adhering to all five - reaping an 80% reduction in heart attack risk - although only 1% of the study population was in this category.

Here's how the habits ranked according to heart attack protection:

1. Quitting smoking (36% lower risk): Consistent with extensive previous research, quitting smoking is one of the top longevity-threatening habits you should abandon. In this Swedish trial, men who had either never smoked, or quit at least 20 years prior to the beginning of the study enjoyed a 36% lower chance of a first heart attack.

This jives with findings of many previous investigations including the Million Women Study in the UK, in which almost 1.2 million women were tracked over a 12-year period. That longitudinal research found that quitting by the age of 30 or 40 reaped an extra 11 years of life on average, thanks not only to fewer heart attacks, but less cancer and respiratory disease as well.

2. Eating a nutritious diet (20% lower risk): Again, no surprise that a healthy plant-based diet can help ward off a heart attack (and other age-related diseases like diabetes and cancer). The Swedish study characterized a healthy diet using the Recommended Food Score from the National Health and Nutrition Examination Survey (NHANES) in the US, which is "strongly predictive of mortality" and includes the following:

Those subjects who followed these guidelines most closely had a 20% lower risk of a first heart attack, even if they also ate foods from the "non-recommended" list such as red and processed meat, refined cereals and sweets.

3. Getting rid of belly fat (12% lower risk): Increasingly, epidemiologists are finding waist circumference and waist-to-hip ratio to be a better predictor of ill health than sheer body weight, especially when it comes to abdominal fat that surrounds your internal organs (visceral fat) and not just the pudge that sits under the skin of your belly making your waistband too tight.

Indeed, subjects in this Swedish study whose waistlines measured less than 95 cm (about 38") over the course of the trial, had a 12% lower risk of a first heart attack compared with men with more belly fat.

4. Drinking only in moderation (11% lower risk): In this study, drinking in moderation cut the risk of a first heart attack by about 11%. This is in line with very consistent evidence that consuming alcohol in moderation reduces the risk of cardiovascular disease, including heart attacks and stroke.

Still, the researchers offer certain reservations about alcohol's benefits, since as soon as consumption goes beyond light-to-moderate intakes of 1-2 drinks per day, there are far more hazards than benefits to health in the form of heart disease, cancer and accidents.

To recap: people who drink in moderation may be healthier than teetotalers, but only if they drink in moderation.

5. Being physically active (3% reduction in risk): Men who walked or cycled 40 minutes per day, and exercised at least one hour per week were found to have a 3% lower risk of a first heart attack in this study. That number is surprisingly low, considering other evidence that exercise is very beneficial for heart health. Still, exercise has such strong benefits not only for your cardiovascular system, but towards strengthening your bones, your respiratory system, helping ward off dementia and also stress relief (not to mention avoiding the hazards of sitting still), it should not be considered a fringe health strategy. The more you move, the better.

Wait - didn't this study just look at healthy men? These male subjects were all free of disease when the study launched in the late 1990s. A separate analysis was conducted among more than 7,000 men with hypertension and high cholesterol in 1997, which found that the risk reduction of each healthy behavior was similar to that of men without either condition.

Bottom line: Unlike your genetic makeup, diet, exercise and whether or not you smoke are all within your control; in science jargon, "modifiable lifestyle factors". Such changes may not always be easy to implement, but it can be inspiring to discover that what you do each day can play a greater role in determining your chances of a first heart attack than what you inherit.

In this large study, 86% of first heart attacks were avoided by the small proportion of men who adhered to all 5 healthy habits, regardless of family history of cardiovascular disease. Generalized to the greater population, that means 4 out of 5 first heart attacks might be prevented with straightforward and manageable lifestyle changes.

Get motivated to build healthy habits:

Sources:

Agneta kesson, Susanna C. Larsson, Andrea Discacciati, Alicja Wolk. "Low-Risk Diet and Lifestyle Habits in the Primary Prevention of Myocardial Infarction in Men: A Population-Based Prospective Cohort Study." Journal of the American College of Cardiology Volume 64, Issue 13, Pages A1-A24, 1299-1306 (30 September 2014)

Mozaffarian, Dariush. "The Promise of Lifestyle for Cardiovascular Health." Journal of the American College of Cardiology Volume 64, Issue 13, 1307-1309 (30 September 2014)

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Excerpt from:
5 Ways to Prevent a First Heart Attack - Verywell

Curriculum Vitae

J. W. Thomas Byrd, MD

Society Memberships

Publications

Publications in Medical Journals

International Publications

Medical Textbook Publications

Multimedia Education publications

Sport Team Affiliations

Appointments

Arthroscopy Association of North America

Arthroscopy Journal

Orthopaedic Learning Center

International Society for Hip Arthroscopy

American Orthopaedic Society for Sports Medicine

Herodicus Society

Nashville Sports Council

Titleist Performance Institute

Department of Orthopaedics and Rehabilitation, Vanderbilt University School of Medicine

United States Olympic Committee Volunteer Physicians Program

First Presbyterian Church Nashville, Tennessee

Lectures

AOSSM/NHLTPS: Keep Your Edge: Hockey Sports Medicine in 2012, Toronto Canada

AOSSM 39th Annual Meeting, Baltimore, Maryland

Herodicus Society, White Sulphur Springs, West Virginia

Community Health Systems, Orthopedic Excellence Advisory Group Meeting, Franklin, Tennessee

Atlanta Orthopaedic Society, Atlanta, Georgia

Grand Rounds: Dept of Orthopaedics Emory University School of Medicine, Atlanta, Georgia

Visiting Surgeon Day for Hip Arthroscopy, Nashville, Tennessee

Orthopaedic Grand Rounds, Medical University of South Carolina, South Carolina

Charleston Orthopaedic Society, Charleston, South Carolina

Wider Scope of Arthroscopy Smith & Nephew Fellowship Program: Spring Session, Cordova, Tennessee

AANA 31st Annual Meeting, Orlando, Florida

AANA/SLARD Pre-Course, Orlando, Florida

AAOS/ORS Femoroacetabular Impingement Research Symposium, Chicago, Illinois

AOAO Hip Arthroscopy Course, White Sulphur Springs, West Virginia

2012 Children's Healthcare of Atlanta, Atlanta, Georgia

Visiting Surgeon Day for Hip Arthroscopy, Nashville, TN

Visiting Surgeon Day for Hip Arthroscopy, Nashville, TN

AANA Masters Experience, Hip Arthroscopy, Rosemont, Illinois

Current Topics in Sports Medicine, The Cactis Foundation, Scottsdale, Arizona

Smith & Nephew Hip Arthroscopy Symposium, Vail, Colorado

University of Pennsylvania Grand Rounds, Philadelphia, Pennsylvania

AOSSM Specialty Day, AAOS 2012 Annual Meeting, San Francisco, California

AANA Specialty Day, AAOS 2012 Annual Meeting, San Francisco, California

Smith & Nephew Presentation Theatre, AAOS 2012 Annual Meeting, San Francisco California

AAOS 2012 Annual Meeting, San Francisco, California

12th International Sports Medicine Fellows Conference, Carlsbad, California

Duke Sports Medicine Conference, Durham, North Carolina

Emerging Techniques in Orthopaedics, Las Vegas, Nevada

AANA 2011 Fall Course, Palm Desert, California

Boston Shoulder & Sports Symposium, Waltham, Massachusetts

41st Annual Advances in Arthroplasty Course, Boston, Massachusetts

ISHA 2011 Annual Meeting, Paris, France

Orthopaedic Surgery Controversies: Shoulder & Hip Arthroscopy, Napa, California

Hip Arthroscopy 2011, San Diego, California

2011 Wavering Lecture Series, NorthShore University Health System, Evanston, Illinois

2011 Summer Meeting of The Hip Society, New Albany, Ohio

Treatment & Surgical Management of Hip & Knee Conditions, Methodist Sports Medicine, Indianapolis, Indiana

Brazilian Hip Society XIV Congress, Iguassu Falls, Brazil

AANA Masters Experience, Hip Arthroscopy, Rosemont, Illinois

AOSSM 38th Annual Meeting, San Diego, California

Smith & Nephew Workshop, AOSSM 38th Annual Meeting, San Diego, California

2011 Herodicus Society Annual Meeting, Sun Valley, Idaho

Ninth Symposium on Joint Preserving and Minimally Invasive Surgery of the Hip, New York, NY

American Sports Medicine Fellowship Society, Hughston Society, Pine Mountain, Georgia

ACSM 58th Annual Meeting, Denver, Colorado

Visiting Surgeon Day for Hip Arthroscopy, Nashville, Tennessee

ISAKOS 8th Biennial Congress, Rio de Janeiro, Brazil

Pre-course: ISAKOS 8th Biennial Congress, Rio de Janeiro, Brazil

Smith & Nephew/DJO Fellowship Program, The Wider Scope of Arthroscopy, Andover, Massachusetts

10th Annual Update: An International Perspective, SIA-AAOS with SIOT, SIGASCOT & SICSeG, Rosemont, Illinois

Visiting Surgeons Workshop, Nashville, Tennessee

AANA 30th Annual Meeting, San Francisco, California

Visiting Surgeons Workshop, Nashville, Tennessee

Arthroscopic Surgery 2011, Robert W. Metcalf, MD & AANA Meeting, Snowbird, Utah

VI Curso de Ciruga Reconstructiva Articular, Buenos Aires Argentina

Smith & Nephew Hip Arthroscopy Symposium, Vail, Colorado

Current Topics in Sports Medicine: A Spring Training Symposium , Scottsdale, Arizona

AANA Masters Experience, Hip Arthroscopy, Rosemont, Illinois

Hip Society Specialty Day, AAOS 2011 Annual Meeting, San Diego, California

AANA Specialty Day, AAOS 2011 Annual Meeting, San Diego, California

Subgluteal Space: Disorders & Treatment, February 19, 2011

Smith & Nephew Lecture Series, San Diego, California

AAOS 2011 Annual Meeting, San Diego, California

Michigan/Ohio Hip Arthroscopy Course, Toledo, Ohio

Visiting Surgeons Workshop, Nashville, Tennessee

Grand Rounds, University of Alabama School of Medicine, Division of Orthopaedic Surgery, Birmingham, Alabama

11th International Sports Medicine Fellows Conference, Carlsbad, California

Mississippi Sports Medicine & Orthopaedic Center, Jackson, Mississippi

1 Curso Internacional Interinstitucional de Artroscopia do Quadril, Sao Paulo, Brasil

Arthroscopy Association of North America, Fall Course, Phoenix, Arizona

Visiting Surgeons Workshop, Nashville, Tennessee

San Diego, California

20th Century Orthopaedic Association, Hilton Head, South Carolina

SIGASCOT 2010 3rd National Congress, Verona, Italy

OrthoGeorgia, Macon, Georgia

40th Annual Advances in Arthroplasty Course, Cambridge, Massachusetts

Hip Society 2010 Summer Meeting, New York, New York

Visiting Surgeons Workshop, Nashville, Tennessee

Continued here:
Dr Thomas Byrd Nashville Sports Medicine & Orthopaedic ...

Overview

Dr. Harold Miller is an endocrinologist in Hammond, Louisiana and is affiliated with multiple hospitals in the area, including East Jefferson General Hospital and Lakeview Regional Medical Center. He received his medical degree from Louisiana State University School of Medicine in New Orleans and has been in practice for more than 20 years. Dr. Miller accepts several types of health insurance, listed below. He is one of 6 doctors at East Jefferson General Hospital and one of 4 at Lakeview Regional Medical Center who specialize in Endocrinology, Diabetes & Metabolism.

Board Certifications: Internal Medicine, Endocrinology, Diabetes and Metabolism

15770 Paul Vega Md Dr 202 Hammond, LA 70403 [MAP]

Dr. Miller is affiliated with the following hospitals. Affiliation usually means doctors can admit patients to a hospital.

North Oaks Medical Center in Hammond, LA is not nationally ranked in any specialty. more

East Jefferson General Hospital in Metairie, LA is not nationally ranked in any specialty. more

West Jefferson Medical Center in Marrero, LA is not nationally ranked in any specialty. more

Endocrinologists treat disorders of the hormone-secreting glands that regulate countless body functions. These ailments include diabetes, thyroid ailments, metabolic and nutritional disorders, pituitary diseases, menstrual and sexual problems.

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Dr. Harold Miller, Endocrinologist in Hammond, LA | US ...

Over the years the compassionate, board certified surgeons and physical therapists at Torrance Orthopaedic & Sports Medicine Group have helped thousands of our patients recover from orthopedic injuries of the shoulder, arm, elbow, hand, spine, hip, leg, knee, ankle, and foot. Their journey from treatment to surgery and through physical therapy inspires us to keep doing what we love: putting our skilled hands and sharp minds to good use in the best community anywhere. More about what we do...

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Last week, I wrote about a man named Jim Gass, a former chief legal counsel for Sylvania, who had suffered a debilitating stroke in 2009 that left him without the use of his left arm, and weak left leg. He could still walk with a cane, but was understandably desperate to try anything to be able to walk unaided and function more normally in life. Unfortunately (at least given what ultimately happened), Mr. Gass was both driven enough, credulous enough, and wealthy enough to spend $300,000 pursuing stem cell tourism in China, Mexico, and Argentina over the course of four years. The result is that he now has a tumor growing in his spinal column, as reported in The New England Journal of Medicine (NEJM) and The New York Times (NYT). Genetic analysis has demonstrated that the cells in this tumor mass did not come from Jim Gass, and the mass has left him paralyzed from the neck down, except for his right arm, incontinent, and with severe chronic back pain. Worse, although radiation temporarily stopped the tumor from growing, apparently its growing again, and no one seems to know how to stop it. Given that the traits that make stem cells so desirable as a regenerative treatment, their plasticity and immortality (ability to divide indefinitely), are shared with cancer, scientists doing legitimate stem cell research have always feared such a complication and have therefore tried to take precautions to stop just this sort of thing from happening in clinical trials. Clearly, stem cell tourist clinics, which intentionally operate in countries where the regulatory environment isshall we say?less than rigorous are nowhere near as cautious.

At the time I wrote that article, I emphasized primarily clinics outside of the US, where shady operators locate in order to be able to operate largely unhindered by local governments. Youd think that such a thing couldnt possibly be going on in the US. Youd be wrong. About a week and a half ago, Paul Knoepfler, a stem cell scientist who maintains a blog about stem cells, teamed up with Leigh Turner to publish a paper in Cell Stem Cell estimating the number of stem cell clinics in the US. The number they came up with astonished me.

In their article, Selling Stem Cells in the USA: Assessing the Direct-to-Consumer Industry, Turner and Knoepfler explain:

Businesses marketing putative stem cell interventions have proliferated across the U.S. This commercial activity generates a host of serious ethical, scientific, legal, regulatory, and policy concerns. Perhaps the most obvious regulatory question is whether businesses advertising nonhomologous autologous, allogeneic, induced pluripotent, or xenogeneic stem cell therapies are exposing their clients to noncompliant cell-based interventions. Such practices also prompt ethical concerns about the safety and efficacy of marketed interventions, accuracy in advertising, the quality of informed consent, and the exposure of vulnerable individuals to unjustifiable risks.

Prior analyses of companies engaged in direct-to-consumer marketing of stem cell interventions have not explicitly focused on attempting to comprehensively locate and examine U.S. businesses (Lau et al., 2008, Ogbogu et al., 2013, Regenberg et al., 2009), although recent scholarship has identified some U.S. businesses engaged in such activity (Connolly et al., 2014). While such companies have attracted some scrutiny from researchers and journalists, these businesses have not yet been examined in a comprehensive manner (Perrone, 2015, Turner, 2015a). This gap in scholarship has contributed to misunderstandings that need to be corrected.

For example, health researchers, policy-makers, patient advocacy groups, and reporters often use the phrase stem cell tourism when addressing the subject of unapproved cell-based interventions and even in 2016 assume that U.S. citizens must travel to such destinations as China, India, Mexico, and the Caribbean if they wish to access businesses promoting stem cell procedures for a wide range of clinical indications. While travel from the U.S. to international stem cell clinics continues, the rhetoric of stem cell tourism often fails to acknowledge the hundreds of U.S. businesses engaged in direct-to-consumer advertising of stem cell interventions.

Of course, I did exactly this in my previous post, not really acknowledging this industry in the US. True, I did mention the San Diego-based company Stemedica, but I mentioned that company mainly because its business model appears to involve doing actual FDA-monitored clinical trials of its stem cell products in the US but referring any patients contacting the company who are ineligible for its US clinical trials to one of its foreign partners, particularly its affiliate right across border in Tijuana, Novastem. It was, for example, Novastem through which Gordie Howe was treated for his stroke a year and a half ago. Patients referred to Stemedicas partners, of course, pay full price for the stem cell injections, usually around $30,000 a pop.

But what about US-based businesses? Turner and Knoepfler used key words and phrases such as stem cell treatment and stem cell therapy to preliminarily identify putative stem cell businesses and then evaluated the text on the websites of these businesses to refine their analysis. As a result, they identified 351 businesses offering stem cell therapies at 570 clinics, which they listed on this map:

Stem cell clinics in the US.

They also helpfully include a link to an Excel spreadsheet listing all 570 sites, noting:

Many stem cell companies employ multiple physicians and advertise interventions available at numerous clinics. Although such businesses are widely distributed all over the county, we found that clinics tend to cluster in particular states. For example, we found 113 clinics in California, 104 in Florida, 71 in Texas, 37 in Colorado, 36 in Arizona, and 21 in New York. Hotspot cities including Beverly Hills (18), New York (14), San Antonio (13), Los Angeles (12), Austin (11), Scottsdale (11), and Phoenix (10) are designated with stars on the map. Some metropolitan areas, including Southern California around Los Angeles and San Diego, the South Florida region surrounding Miami, the greater Denver area, and the Dallas-Fort Worth metro region, have a relatively high number of clinics even if not all such facilities are technically in one city (Figure S1). While our analyses here do not explain why these businesses cluster in particular areas, we plan to investigate this question further. Possible factors include a relationship between number of clinics and population density, regional variations in use of alternative medical interventions, aging population demographics, and regulatory orientation of state medical boards and consumer protection agencies.

Im sure population density has something to do with so many clinics in California, although one would expect more in New York and Texas if it were just population density. I also suspect that the prevalence and popularity of alternative medicine practitioners has something to do with it, since, oddly enough, I frequently see ads for stem cell clinics and articles praising stem cell therapies on websites oriented towards alternative medicine. Given how often stem cells are advertised as anti-aging treatments (something mentioned by Turner and Knoepfler) and the popularity of plastic surgery in California, it wouldnt surprise me if there is a correlation there as well. These are definitely things that I hope Turner and Knoepfler will look at in future investigations.

So what are these clinics selling stem cells to treat? What are the claims they make? Unfortunately, the claims of US clinics are not much, if at all, different from the claims made by many stem cell tourist clinics in other countries. Claims are made that specific diseases can be treated that are just specific enough to attract customers but vague enough not to promise too much.

It has to be noted that there is not just one kind of stem cell. As I described last time, they range from embryonic stem cells that require human embryos to isolate, to adult stem cells, to cells induced to be stem cells by the introduction of genes responsible for maintaining the stem cell state. As Ill discuss later, this matters when it comes to asking just what the heck the FDA is or isnt doing about this proliferation of stem cell businesses.

Turner and Knoepfler note that most of the businesses that they identified market autologous stem cell-based interventions; i.e., stem cells isolated from the patient and then reinfused. Most isolated these stem cells (or claimed to isolate them, given that its not always clear how such clinics verify that what they have isolated are indeed autologous stem cells) from adipose tissue (fat) or from the bone marrow. Be that as it may, 61% of the clinics examined market autologous adipose-derived stem cell-based interventions; 48% what they describe as autologous stem cells obtained from bone marrow; and 4% stem cells reportedly isolated from peripheral blood. Not surprisingly, lots of clinics offer stem cells isolated from more than one source. Some offer mixed stem cells from both bone marrow and adipose tissue as combination stem cell therapy.

About one in five clinics advertised allogeneic stem cell treatments; i.e., stem cells from another person or source. The usual sources of these stem cells are advertised as amniotic material/fluid (17%), placenta (3.4%), and umbilical cords (0.6%). Its noted in the report the precise source for these products was not clear in all cases, in particular for amniotic stem cells. Indeed, one wonders (at least I do) what the source of amniotic fluid is from which these clinics claim to isolate stem cells. Do they have a deal with a local obstetrical clinic or hospital to provide amniotic fluid or membranes? Do they buy placentas and amniotic membranes from a hospital? Where do these clinics get the raw material (i.e., the human tissue and fluids) to generate these stem cells from? Inquiring minds want to know!

Turner and Knoepfler also noted one business that offers what it claims to be induced pluripotent stem cells. (Remember, these are cells genetically manipulated to revert to being stem cells.) I went back to the spreadsheet and found which company offered this, Regenerative Medical Group. RMG claims to provide induced pluri-potent stem cells from your own cells via an affiliated laboratory, but what I found more interesting were the diseases and conditions it claims to treat with stem cells. Not surprisingly, as was the case for most of the clinics listed, many of the indications were orthopedic, to regenerate cartilage and repair injury. However, RMG also claims to be able to treat kidney diseases, macular degeneration, Parkinsons disease, and, yes, autism. Under a tagline of An autism therapy that WORKS, theres even a video on the website that makes claims that can only be described as grandiose and not supported by science featuring Bryn J. Henderson, DO, JD, FACPE, CIME, the executive director of RMG:

In the video, Dr. Henderson claims that RMG has helped dozens of children with autism using stem cells. He claims that the stem cells circulate through the body, cross the blood-brain barrier and make new cells that change the course and prognosis of the patient with autism. He even claims that most of the time, the change is major. How does he know? He brags about the thank you cards hes gotten from parents. I mean, seriously. This is utterly pathetic. Even antivaccine quacks like Mark and David Geier or Andrew Wakefield can do better at providing evidence. Note that that is not a compliment, given how poor their attempts at studies invariably are. Dr. Henderson, however, presents no science, no clinical trials, no preclinical trials, no nothing other than testimonials, although he does use a lot of science-y-sounding terms. Hell, Ive seen homeopaths who provide more evidence and a more convincing presentation. At least they will cite actual patients rather than thank you notes from patients families. (Oh, and Dr. Henderson, dont bother taking your video down; Ive downloaded it.)

RMGs fact sheet on autism is no better. Citing no evidence, not even case reports, the sheet claims that stem cell infusions for autism can improve:

What evidence is presented? Again, none. This might as well be a chelation therapy clinic. The treatment, however, takes three days, and the patient doesnt have to come back to an RMG clinic at all, although, the fact sheet hastens to add, they can undergo repeat treatments if necessary. In other words, stem cells appear to have been added to the armamentarium of autism biomed quackery.

I could go on, but to me stem cells for autism is so obviously dubious at best and bogus at worst that, given my interest in vaccines and the antivaccine movements mistaken belief that vaccines cause autism, I hope youll forgive me if I zeroed right in on autism. Indeed, nine of the clinics listed in the spreadsheet claim to be able to use stem cells of one kind or another to treat autism.

But, wait, theres more. In addition to RMG:

Another business markets access to what it describes as embryonic stem cell interventions. In addition, we identified two clinics that marketed bovine amniotic cells, a xenogeneic product, for use in humans. Approximately 3% of businesses marketed stem cell interventions without mentioning a particular type of stem cells.

Perusing the list of clinics, I found it hard not to come to the conclusion that there isnt a single disease or condition that someone, somewhere, isnt claiming can be helped with stem cells of one kind or another. Diabetes, heart disease, degenerative diseases, Parkinsons disease, Alzheimers disease, spinal cord injuries, stroke, aging, and even cancer show up on the list of conditions that these 570 clinics claim to be able to treat with stem cells, as Turner and Knoepfler note:

U.S. businesses promoting stem cell interventions claim to treat a wide range of diseases and injuries, as well as advertising stem cells for cosmetic applications, anti-aging, and other purposes (Figure 2B). Some clinics occupy relatively specialized marketplace niches. For example, many cosmetic surgery clinics advertise such procedures as stem cell facelifts and stem cell breast augmentation as well as sexual enhancement procedures. Orthopedic and sports medicine clinics often promote stem cell interventions for joints and soft tissue injuries. Other clinics take a much broader approach and list stem cell interventions for 30 or more diseases and injuries. Such businesses commonly market treatments for neurological disorders and other degenerative conditions, spinal cord injuries, immunological conditions, cardiac diseases, pulmonary disorders, ophthalmological diseases and injuries, and urological diseases as well as cosmetic indications. Many of these marketing claims raise significant ethical issues given the lack of peer-reviewed evidence that advertised stem cell interventions are safe and efficacious for the treatment of particular diseases. Such promotional claims also generate regulatory concerns due to apparent noncompliance with federal regulations.

Unfortunately, these US businesses are less unlike the stem cell tourist clinics that Ive written about before than I would like.

I thought about perusing the list of clinics in more detail and picking out the most egregious examples other than RMG, but that can wait for a potential future post. (It is, after all, a holiday weekend, and well be having visitors.) So instead Ill move on to conclude with the question that many of you are probably wondering after seeing an example such as treating autism with stem cells: What the heck is the FDA doing?

This isnt as simple as it sounds. For one thing, as noted in Turner and Knoepflers supplemental methods section:

However, it should be noted that according to 21 CFR 1271.3 (d) (4), minimally manipulated bone marrow for homologous use does not require pre-marketing approval by the FDA. 21 CFR 1271.15 (b) states that facilities removing cells or tissues from an individual and implanting those cells or tissues in the same individual during the same surgical procedure likewise do not require premarketing approval. In addition, federal regulations contain detailed criteria specifying when autologous or allogeneic cells can be used without first obtaining FDA premarketing approval. These criteria are identified in 21 CFR 1271.10. We mention these important sections of 21 CFR 1271 for a reason. Our goal was to identify businesses that engage in direct-to-consumer marketing of stem cell interventions and fit within our inclusion criteria. Judgments about regulatory compliance or noncompliance had no bearing on whether specific businesses were included in our database. Federal regulations governing marketing, manufacture, administration, and registration of cell-based interventions are complex, products are classified into different risk- based regulatory tiers, and we in no way wish to claim or imply that inclusion of particular businesses in Supplemental Table 1 means that they are noncompliant with federal regulations. Such determinations, as well as other assessments of regulatory compliance, must be made by legally authorized regulatory agencies after rigorous evaluation processes.

This is, of course, the reason why so many of these businesses offeror claim to offerbone marrow or adipose stem cells. If they dont manipulate the cells too much, they can skirt FDA regulations, although the FDA is moving to crack down on unproven stem cell treatments and have started to issue warning letters. Its a complex issue, but its hard not to look at the number of clinics and the breadth of health claims documented by Turner and Knoepfler and not come to the conclusion that there is a serious problem here. Its also clear that big money and political interests are hindering the FDA. For example:

Some proponents of deregulation argue that current federal regulations governing the advertising, processing, and administration of autologous stem cells are too onerous and have resulted in few approved stem cell therapies reaching the American marketplace (Chirba and Garfield, 2011, McAllister et al., 2012). The REGROW Act is an example of the current push from some political quarters and even from some individual stem cell researchers for lowering safety and efficacy standards for adult stem cell-based interventions. However, we found that hundreds of U.S. businesses are already promoting stem cell interventions for an extraordinary range of clinical indications. Advocates of deregulation will perhaps be pleased by our findings that many putative stem cell interventions are currently available for sale in the U.S. In contrast, proponents of a marketplace in which cell-based therapies have traditionally been tested for safety and efficacy and subject to pre-marketing review by the FDA will likely be concerned by how many U.S. businesses are currently marketing stem cell interventions. We are particularly concerned that we found many advertising claims related to ALS, Alzheimers disease, Parkinsons disease, and many other conditions for which there is no established scientific consensus that proven safe and efficacious stem cell treatments now exist.

The REGROW Act sounds a lot like the 21st Century Cures Act, ideologically-driven solutions that mistakenly argue that the way to let loose a torrent of cures for every disease imaginable is to unleash the power of the market through deregulation. In the case of the 21st Century Cures Act, its proponents propose to give the NIH a bit more money in return for weakening the FDA. Its basically a solution to a nonexistent problem. The REGROW Act is cut from the same cloth, as it would allow provisional approval of stem cell therapies without phase III trials and establishing a conditional approval paradigm. Together with right to try laws, the REGROW Act and the 21st Century Cures Act are of a piece with a libertarian, free market-driven agenda to hamper government regulatory agencies. Fortunately, the the REGROW Act v.2.0 appears to be going nowhere fast. Meanwhile these stem cell clinics are scrambling to deny that they are doing anything unethical, illegal, or dangerous.

Perusing some of the websites, I couldnt help but notice how dubious stem cell therapies seem to have found a comfortable home in alternative medicine clinics. Perhaps the most blatant example I found was the Purety Family Medical Clinic, which advertises itself as holistic medicine specialists for women, men, and pediatrics as well as prolotherapy, IV, ozone, chelation, HRT and FMT. Right alongside stem cell injections for badly injured or degenerated tissue, Purety also offers chelation therapy for heavy metal detoxification, high dose vitamin C drips, ozone therapy for cancer, naturopathy, fecal transplants for a variety of illnesses, and, yes, homeopathy, The One Quackery to Rule Them All.

Unfortunately, given how potentially promising stem cell therapies are, right now they are tainted by association with quackery like that described above. Basically, stem cells are being sold as being every bit as magical as alternative medicine like homeopathy. However, as PZ Myers points out:

Stem cells are not magic. They are plastic cells that are pluripotent they can differentiate into a variety of different tissues. But they need instructions and signals in order to develop in a constructive way, and the hard part is reconstructing environmental cues to shape their actions. Theyre like Lego building blocks you can build model spaceships or submarines or houses with them, and they have a lot of creative potential, but its not enough to just throw the Lego blocks into a bag and shake them really hard.

Thats what these stem cell clinics are doing, injecting stem cells and hoping they do their thing without knowing how the body induces them to do their thing, all while charging patients large sums of money for the privilege of being in what is in essence a poorly designed, poorly regulated clinical trial.

I dont know about you, but if I were a legitimate advocate of stem cell therapies, Id be very disturbed at how easily stem cell therapies are currently integrated with pure quackery like chelation therapy and homeopathy. Being so easily associated with clinics like Purety is not a good way to make stem cell treatments respectable, but it is a good way to make a lot of money if you arent that concerned with medical evidence or ethicsat least until the next Jim Gass hits the news.

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Stem cell tourism: A problem right here in the good ol ...

The New Standard of Care

State-of-the-art health care has been redefined by combining the latest medical advances with complementary therapies. Called integrative health, this approach to healthcare is rapidly becoming the new standard because it introduces broader possibilities for healing and nurturing the body, mind and spirit.

Integrative health treats the whole person, not just the disease and gives patients more opportunities to participate in their care and enrich their health and well-being.

Many complementary therapies have been around for centuries, and there are numerous benefits associated with integrative health, such as:

Free Inpatient Services

Inpatients may call to schedule a free 15- to 20-minute in-room hand or foot massage, Reiki or Qigong healing session or Guided Imagery. Music and meditation CDs and CD players with disposable earphones are available by request.

Service Descriptions

Services are administered by qualified, credentialed practitioners and specialists. To schedule an appointment, or for more information, call Ext. 5257.

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Integrative Health - Raritan Bay Medical Center

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New Jerseyans are increasingly feeling the effects of diabetes as thousands of people suffer from the disease, and many others may have diabetes and not know it! It is estimated that one out of every three children born after 2000 in the United States will be directly affected by diabetes.

That is why the American Diabetes Association's New Jersey office is so committed to educating the public about how to stop diabetes and support those living with the disease.

We are here to help.

Additional Events

The American Diabetes Association's New Jersey office provides great local programs for people living with diabetes, their friends and family. Learn about our available programs.

The following New Jersey businesses and organizations have been designated Health Champions from the American Diabetes Association. This designation recognizes organizations that inspire and encourage organizational well-being and is part of the Association's Wellness Lives Here initiative. Learn more.

BD Horizon Blue Cross Blue Shield of New Jersey JBL Electric Nestle Nutrition Quest Diagnostics Verizon

Sign upfor our monthly newsletter to learn about news and events in the New Jersey area.

If you would like a representative from the American Diabetes Association to speak at your event or if you would like materials to distribute at a health fair or expo, please call 732-469-7979. You can also email your request tobmarsicano@diabetes.org.

We welcome your help.

Your involvement as an American Diabetes Association volunteer whether on a local or national level will help us expand our community outreach and impact, inspire healthy living, intensify our advocacy efforts, raise critical dollars to fund our mission, and uphold our reputation as the moving force and trusted leader in the diabetes community.

Find volunteer opportunities in our area through the Volunteer Center.

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The Molecular Genetics and GenomicsProgram in the Wake Forest School of Medicine is an interdisciplinary research and PhD training program composed of a diverse group of investigators employing molecular and genetic approaches to biomedical research.

The Program includes molecular biologists from each of the basic science departments of the School of Medicine as well as clinical faculty involved in laboratory research. Participating investigators include faculty from the departments of Biochemistry, Cancer Biology, Neurobiology and Anatomy, Medicine, Microbiology and Immunology, Pathology, Pediatrics, Physiology and Pharmacology, and Surgery. Many program faculty are also members of the Comprehensive Cancer Center of Wake Forest University.

Part of the first-year Molecular & Cellular Biosciences (MCB) track, the objective of the PhD training program is to provide an interdisciplinary curriculum that emphasizes the detailed analysis of fundamental biological processes using the tools of molecular biology and genetics. Individualized programs of study are designed to train students for independent careers in research and teaching. The first year MCB curriculum provides broad exposure to the fundamentals of molecular and cellular biology, biochemistry, and microbiology.

After the completion of the first year in the MCB track, students that select a Molecular Genetics & Genomics research advisor begin specialization in the research area of that laboratory. Areas of active investigation include the genetics of complex diseases, genetic epidemiology, epigenetics, and bioinformatics.

Click here to obtain information on the APPLICATION PROCESS for the Molecular Genetics and GenomicsProgram.

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Molecular Genetics and Genomics Program - Wake Forest ...

New England Centenarian Study

To Discover the Secrets of A Long Healthy and Happy Life

Our two major studies are the New England Centenarian Study (founded 1995) and the multi-center Long Life Family Study (Boston Medical Center is one of 5 study sites),established in 2006.

We are actively seekingparticipants to be in the New England Centenarian Study. The criteria are simply subjects age 103+ years oldor 100+ years with siblings.

If you would like to contact the study, please call us at 888-333-6327 (toll free) where you will hear a menu tobe connected toa member of the research staff (please choose this option). You can alsoemail the study manager, Stacy Andersen PhD at stacy@bu.edu or the Principal Investigator, Thomas Perls MD, MPH at thperls@bu.edu.

The New England Centenarian Study is funded by:

The Martin A. Samowitz Foundation

Since 2006, the Long Life Family Studyhas beenconducting a prospective study of 5,000 subjects belonging to about 550 families that demonstrateparticularly unusualclustering for exceptional longevity. The Long Life Family Study is funded by and collaborates closely with The National Institute on Aging.

Pleasecall Dr. Thomas Perls toll-free at 888-333-6327 or email him at thperls@bu.edu if you or a family member wish to discuss our studies, find out more information regarding enrollment or to discuss supporting our studies.

MEDIA INQUIRES: Please contact

Jenny Eriksen Leary Manager of Media Relations Boston Medical Center 617-638-6841 jenny.eriksen@bmc.org

Genes play a critical and complex role in facilitating exceptional longevity. The genetic influence becomes greater and greater with older and older ages, especially beyond 103 years of age.

Citation: Genetic Signatures of Exceptional Longevity in Humans. Paola Sebastiani, Nadia Solovieff, Andrew T. DeWan, Kyle M. Walsh, Annibale Puca, Stephen W. Hartley, Efthymia Melista, Stacy Andersen, Daniel A. Dworkis, Jemma B. Wilk, Richard H. Myers, Martin H. Steinberg, Monty Montano, Clinton T. Baldwin, Josephine Hoh, Thomas T. Perls. PloS ONE 2012. DOI: 10.1371/journal.pone.0029848.

Many of the above genetic findings were replicated in a combination of 5 collaborating centenarian studies.

Citation: Meta-analysis of genetic variants associated with human exceptional longevity. Paola Sebastiani, Harold Bae1, Fangui X. Sun, Stacy L. Andersen, E. Warwick Daw, Alberto Malovini, Toshio Kojima, Nobuyoshi Hirose, Nicole Schupf, Annibale Puca, Thomas T Perls. Aging (Albany NY) 2013 September; 5(9): 653661. Published online 2013 August 24. PMCID: PMC3808698

In another paper published January, 2012, we have produced perhaps some of our most exciting findings to date. Early oninThe New England Centenarian Study, we thought that centenarians had to markedly delay or even escape age-related diseases like heart attacks, stroke, diabetes and Alzheimers, or else they would never be able to get to their very old ages. In fact, in 1980, a Stanford researcher named James Fries proposed the Compression of Morbidity hypothesis which states that as one approaches the limit of human life span, they must compress the time that they develop diseases towards the very end of their life and he proposed that people around the age of 100 do this. However, in 2003 we found that many of our centenarian subjects had age related diseases even before the age of 80 (about 43%, and whom we called survivors), after the age of 80 (about 42% and whom we called delayers) and lastly, those who had no mortality-associated diseases at age 100 (about 15% and whom we called escapers). The key though was that 90% of all of the centenarians were still independently functioning at the average age of 93 years. Somehow, despite the presence of diseases, people who become centenarians dont die from those diseases, but rather they are able to deal with them much better than other people and remain independently functioning more than 30 years beyond the age of 60. Therefore it seemed to us that for these study participants, it was not so much the compression of morbidity that was important to their survival, but rather a compression of disability.

In this current paper though, titled Health span approximates life span among many supercentenarians: Compression of morbidity at the approximate limit of life span, we have found that we just werent looking at old enough subjects when investigating Jim Fries hypothesis. As some of you know, over the past few years we have been working hard on recruiting and enrolling the most extreme old, supercentenarians who are people that live to 110 years and older. Once we enrolled our hundredth super-centenarian (by far the largest collection of supers in the world), we were able to investigate whether or not people who truly approach the limit of human lifespan actually compress their morbidity towards the end of their lives. Inour study of a reference group, nonagenarians (subjects in their nineties), centenarians (ages 100-104), semi-supercentenarians (ages 105-109) and supercentenarians(ages 110+), the subjects had progressively shorter periods of their lives spent with age-related diseases, from 17.9% of their lives in the referent group, to 9.4% in the nonagenarians and down to 5.2% in the supercentenarians. These findings support the compression of morbidity hypothesis and the idea that there truly is a limit to human life span 125 years. Also the supercentenarians were much more alike in terms of the markedly delayed age of onset of age-related diseases compared to the subjects age 100-104 who were quite heterogeneous. That homogeneity indicates they must have some factors (presumably genetic) in common that allow them to be so similar. We believe that our oldest subjects, ages 105+ years, give us the best chance and discovering these genes.

Citations: Health span approximates life span among many supercentenarians: Compression of morbidity at the approximate limit of life span Andersen SL, Sebastiani P, Dworkis DA, Feldman L, Perls T. J Gerontol A Biol Sci Med Sci 2012;67A:395-405.

Families Enriched for Exceptional Longevity also have Increased Health-Span: Findings from the Long Life Family Study. Paola Sebastiani, Fangui X. Sun, Stacy L. Andersen, Joseph H. Lee, Mary K. Wojczynski, Jason L. Sanders, Anatoli Yashin, Anne B. Newman, Thomas T. Perls. Front Public Health. 2013; 1: 38. Prepublished online 2013 August 16. Published online 2013 September 30. doi:10.3389/fpubh.2013.00038. PMCID: PMC3859985.

The New England Centenarian Study, along with collaborators at the Scripps Institute and the University of Florida, Gainesville, performed and published the first-ever whole genome sequence of a supercentenarian and actually not one super, but two, both over the age of 114 years and one was a man and the other a woman. As with our paper on the genetic signatures of exceptional longevity, we found here as well that centenarians have just as many genetic variants associated with diseases as the general population. However, they likely also have longevity-associated variants that counteract such disease genes, thus allowing for slower aging and increased resistance to age-related diseases.

In this paper we also found several genes that occurred in our published genetic prediction model which had coding regions that led to differences in gene function. These findings support the validity of the genetic prediction model. The New England Centenarian Study has posted the whole genome sequences of these two subjects on a data repository (called dbGaP) based at the National Institutes of Health. This will allow researchers from around the world to access all of the data and use them for their own research. Our hope is that these data will lead to important discoveries about genes that help delay or allow the escape from age related diseases like Alzheimers disease.

Citation: Whole genome sequences of male and female supercentenairnas, Both ages >114 years. Sebastiani P, Riva A, Montano M, Pham P, Torkamani A, Scherba E, Benson G, Milton JN, Baldwin CT, Andersen S, Schork NJ, Steinberg MH, Perls T. Frontiers in Genetics of Aging 2012;2.

There is a growing body of evidence for a substantial genetic influence upon survival to the most extreme ages. An important question is what would be the selection pressure(s) for the evolution of longevity associated genetic variants. The pressure to have a longer period of time during which women can bear children and therefore have more of them and therefore have greater success in passing ones genes down to subsequent generations could be one such pressure. This hypothesis is consistent with the disposable soma theory where the tradeoff in energy allocation between reproductive fitness and repair/maintenance functions can be delayed when longevity associated variants facilitate slower aging and the delay or prevention of age-related diseases that also adversely affect fertility. Several studies have noted an association between older maternal age and an increased odds of exceptional survival. The New England Centenarian Study assessed maternal age history in its sample of female centenarians and a birth-cohort-matched referent sample of women who survived to the cohorts average life expectancy. Women who gave birth to a child after the age of 40 (fertility assistance was not technologically available to this cohort) had a four times greater odds of being a centenarian. Numerous investigators are now searching for and investigating genes that influence reproductive fitness in terms of their ability to also influence rate of aging and susceptibility to age-related diseases.

Citations: Middle-aged mothers live longer.Perls TT, Alpert L, Fretts RC. Nature. 1997 Sep 11;389(6647):133.PMID: 9296486 [PubMed indexed for MEDLINE]

Extended maternal age at birth of last child and womens longevity in the Long Life Family Study.Sun F, Sebastiani P, Schupf N, Bae H, Andersen SL, McIntosh A, Abel H, Elo IT, Perls TT. Menopause. 2015 Jan;22(1):26-31. doi: 10.1097/GME.0000000000000276. PMID: 24977462. [PubMed in process]

The reappearance of procaine hydrochloride (Gerovital H3) for antiaging.Perls T. J Am Geriatr Soc. 2013 Jun;61(6):1024-5. doi: 10.1111/jgs.12278. No abstract available. PMID: 23772727. [PubMed indexed for MEDLINE]

Growth hormone and anabolic steroids: athletes are the tip of the iceberg.Perls TT. Drug Test Anal. 2009 Sep;1(9-10):419-25. doi: 10.1002/dta.87. PMID: 20355224 [PubMed indexed for MEDLINE]. Abstract: Professional Athletes misuse of anabolic steroids, growth hormone and other drugs are the tip of a very large, mostly ignored iceberg, made up of people who receive these drugs for such non-medical uses as body-building, school sports and anti-aging. Although these drugs are often used in combination, this article focuses on growth hormone. Fuelling the demand for these drugs are drug manufacturers, pharmacies, websites, clinics and their doctors.

New developments in the illegal provision of growth hormone for anti-aging and bodybuilding.Olshansky SJ, Perls TT. JAMA. 2008 Jun 18;299(23):2792-4. doi: 10.1001/jama.299.23.2792. No abstract available. PMID: 18560007 [PubMed indexed for MEDLINE]

DHEA and testosterone in the elderly.Perls TT. N Engl J Med. 2007 Feb 8;356(6):636; author reply 637. No abstract available. PMID: 17288051 [PubMed indexed for MEDLINE]

Hope drives antiaging hype.Perls TT. Cleve Clin J Med. 2006 Dec;73(12):1039-40, 1044. Review. No abstract available. PMID: 17190307 [PubMed indexed for MEDLINE]

Provision or distribution of growth hormone for antiaging: clinical and legal issues.Perls TT, Reisman NR, Olshansky SJ. JAMA. 2005 Oct 26;294(16):2086-90. No abstract available. PMID: 16249424 [PubMed indexed for MEDLINE]

Anti-aging quackery: human growth hormone and tricks of the trademore dangerous than ever.Perls TT. J Gerontol A Biol Sci Med Sci. 2004 Jul;59(7):682-91. PMID: 15304532 [PubMed indexed for MEDLINE]

The hype and the realitypart I.Olshansky SJ, Hayflick L, Perls TT. J Gerontol A Biol Sci Med Sci. 2004 Jun;59(6):B513-4. No abstract available. PMID: 15215255 [PubMed indexed for MEDLINE]

Antiaging medicine: what should we tell our patients? Perls T. Aging HealthApril 2010, Vol. 6, No. 2, Pages 149-154 , DOI 10.2217/ahe.10.11 (doi:10.2217/ahe.10.11)

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The Current Landscape for Direct-to-Consumer Genetic ...

Integrative Medicine is healing-oriented medicine that encompasses the whole child, including all aspects of lifestyle. It emphasizes the therapeutic relationship and makes use of both conventional and alternative therapies.

First-time patients are asked to complete a patient history form in advance and bring all their medical records with them. A comprehensive evaluation takes place based on the medical history and physical findings. Then, a specific treatment plan is suggested and discussed.

During the first session, children may receive their first treatment, along with techniques to try at home. An initial consultation will usually last 45-60 minutes. Please note that it may take 6-8 clinic visits to see if a particular therapy is working for your child or to make adjustments to a therapy plan.

Discounts are available for patients who have no have no insurance or know acupuncture is a non-covered benefit by their insurance. There is an immediate 25% discount on the payment of estimated charges at the time of service. If the estimate is low, families have the opportunity with their first statement to receive an additional 5% discount by paying the balance in full. This brings the total discount to 30% on the entire bill. Call the number indicated on the statement to make these arrangements.

Families may elect to pay actual charges in full on the day of service in order to receive a 40% discount. This is the 25% discount for payment at the time of service plus an additional 15% discount for no balance billing needed.

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Integrative Medicine | Primary Children's Hospital

For 26 years, doctors could not piece together the medical puzzle of Stewart Altman's symptoms -- as a child growing up on Long Island, he was uncoordinated and slurred his speech. Later, as a volunteer fireman, he kept falling down and had trouble climbing the ladders.

It seemed unrelated at the time, but his older sister, who had a history of psychological symptoms, was hospitalized in a mental institution. Her psychiatrist suspected a physical disorder and consulted a geneticist who eventually connected the dots.

In 1978, Altman and his sister Roslyn Vaccaro were given a stunning diagnosis: Tay-Sachs -- an inherited neurological disease that typically affects babies, killing them between the ages of 3 and 5. Only several hundred cases exist in the United States.

Altman, now 58, has a non-fatal, adult form of the disease, late onset Tay-Sachs (LOTS), and depends on his wife and a service dog to perform most daily tasks.

"I am devastated," Altman said of the disease that has robbed him of much of his speech and muscle strength, confining him to a wheelchair. "But the alternative is much worse."

His sister died in 2000 after battling LOTS-related bipolar disorder and schizophrenia -- which occurs in 50 to 60 percent of all adult cases -- and Altman and his wife raised her two sons.

Now scientists are hopeful that gene therapy may help late-onset patients like Altman and look forward to human trials.

Tay-Sachs is caused by gene mutation results in the absence or insufficient levels of the enzyme, hexosamindase A or Hex A. Without it, a fatty substance or lipids accumulates in the cells, mostly in the brain. It comes in three forms: infantile, juvenile or adult onset.

Doctors say there can be great variations in the presentation of Tay-Sachs, even in the same family with the same mutations. Babies born with Tay-Sachs appear normal at first, but by 3 or 4 years old, their nerve cells deteriorate and they eventually die. Those with LOTS can live a long life, but, like Altman, are progressively disabled.

The story of Tay-Sachs is a miraculous one. It was first identified in the late 1800s by British ophthalmologist Warren Tay and New York neurologist Bernard Sachs, who noticed the disease was prevalent in Jews of Eastern European origin.

In the 1970s and 1980s, when genetic testing became available, synagogues launched public education campaigns encouraging prospective parents to be tested, and the disease was virtually eliminated in those of Jewish ancestry.

Now, mostly non-Jews, though their risk is not as great, are among the 100 American children who have the disease, according to the National Tay-Sachs and Allied Diseases Association (NTSAD), which leads the fight for a cure.

Altman's speech is difficult to understand, so his wife Lorrie said her husband of 37 years wanted the public to know, "it's not just an infant's disease."

"Tay-Sachs is also in the general population and people don't know," she said. "He thinks we need to get the word out. One in 250 Americans carries the gene."

French Canadians, Louisiana Cajuns and even those of English-Irish ancestry have a greater chance of carrying the recessive gene that causes the disease.

Tay-Sachs is an autosomal recessive disorder, which means each parent must carry the gene. Their children have a 25 percent chance of developing Tay-Sachs, 50 percent chance of being a carrier and a 25 percent chance of being free of that recessive gene.

Altman was born in 1952, before genetic testing was available. Both his parents were carriers of the recessive gene that causes Tay-Sachs and both he and sister were stricken with the mildest form of the disease. Two of their brothers were unaffected, although one is a carrier.

The Massapequa, N.Y., couple have two healthy sons, who are carriers, but whose wives are not, and four healthy grandchildren.

For years, Altman was able to get around with a walker until he had to drop out of a clinical trial for a new drug because of debilitating side effects. After that, he said he lost 40 pounds and so much muscle that he could no longer stand on his own.

"Between the two of us we handle it and we lead kind of a normal life," said Lorrie. "But we have no idea what the future will bring."

Altman works at Nassau University Medical Center in the security monitoring department. He raises funds for about 11 different non-profit organizations, including NTSAD, and has given presentations to the Boy Scouts and senior citizens.

Much of the public work has now ended, as his speech has become more incomprehensible because the degeneration of the nerves that control his respiratory muscles.

"Stewart has a good way of just living in the moment," said his wife, who met Altman in college. "But the worst part for him is his speech. He is such a social, outgoing person."

He has faced discrimination along the way, especially after leaving a Manhattan engineering job because he couldn't climb the subway stairs.

"He has such a hard time getting a job -- it was devastating," said Lorrie Altman. "On paper, he looked so good, but his speech was terrible. He has a college degree and isn't stupid, but all people see is the wheelchair."

Doctors say that many with the milder adult form of Tay-Sachs can lead full lives, despite their disability. And science is getting closer to finding treatments for this devastating disease.

Dr. Edwin Kolodny, former department chair and now professor of neurology at New York University School of Medicine, has been a leader in the field for 30 years. He first helped identify the role of the enzyme Hex-A and later tested more than 30,000 young adults in the 1970s and 1980s.

Today, he and others are involved in the promising gene therapy studies involving first mice, then cats and now sheep. Injecting genes into the brains of Jacob lambs has doubled their life span.

Clinical trials on humans are set to begin as soon as researchers can raise another $700,000 -- in addition to a grant from the National Institutes of Health -- to manufacture the vectors required to insert the genes into the body.

"It seems like every parent in the world would like to be part of the trial," said Kolodny. "And there are reasons to think there will be success here, especially for children who have a slightly later onset and not the classic form Tay-Sachs."

In the past, infantile Tay-Sachs has seen most of the medical attention. "These children have zero quality of life," he said.

Those with mild mutations, like Altman, who have 5 to 10 percent of Hex A enzyme activity, "sometimes lead full lives," according to Kolodny. "Intellectually, most of their cognitive function is retained. We have patients who are lawyers and accountants."

Pre-conception testing is still the gold standard for fighting the disease. "If your parents don't have the same recessive genes, you are home free," he said.

Those identified as at risk for having a child with Tay-Sachs can decide to adopt or conceive through in vitro fertilization, where geneticists can test the embryos before implantation to ensure the child will be disease-free.

Doctors can also do prenatal genetic testing and if the fetus is affected, the decision is up to the parents whether or not they want to terminate the pregnancy. "Three out of four times, they are reassured they have a normal child," said Kolodny.

Doctors say such testing -- at a cost of around $100 -- should be done routinely for 18 autosomal recessive disorders, including the gene for cystic fibrosis, which occurs in one in 20 caucasians, said Kolodny. Even with advances in Tay-Sachs testing in the Jewish community, public education must continue.

"The problem is each generation forgets what happened in the prior generation -- the grandmothers die out, " said Kolodny. "We need to educate health care professionals. Each new group of students graduating from medical school isn't prepared to ask the right questions."

Susan Kahn, NTSAD's executive director, who is involved in fundraising for research, agrees that along with a fight for a cure, genetic testing is critical.

"When there is a genetic disease, it's not just about that person, there is a whole implication for the rest of the family and how they deal with it," she said.

Stewart Altman sits on the association's board of directors and is a tireless crusader for a cure.

"He's got some disabilities that make it difficult for him to do certain things, but of all the board members asking for money to support, he is probably the boldest in our group," said Kahn. "He does have a lot of limitations, but he is still very energetic and wants to do something important. Not everyone responds with the same attitude."

His wife Lorrie backed that up with a laugh. "He is persistent," she said. "He carries these little envelopes around and will ask anyone he meets for a donation. It's almost embarrassing. He's not afraid to ask."

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Gene Therapy in Sheep May Bring Hope to Adults With Tay ...

July 7, 2016 11:30 AM

Dental checkup. (Photo by Philippe Huguen/AFP/Getty Images)

CAMBRIDGE (CBS) Could root canals one day become a thing of the past?

That might just happen if a new treatment developed by scientists at Harvard University and the University of Nottingham catches on.

The freshapproach by researchers that was just awarded a Royal Society of Chemistry prize works to stimulate native stem cells inside teeth, triggering repair and regeneration of pulp tissue.

Dental fillings in their current state dont do anything to help heal teeth and are actually toxic to cells, Dr. Adam Celiz of the University of Nottingham says.

In cases of dental pulp disease and injury a root canal is typically performed to remove the infected tissues, Celiz said in a statement. The new treatment can be used similarly to dental fillings but can be placed in direct contact with pulp tissue to stimulate the native stem cell population for repair and regeneration of pulp tissue and the surrounding dentin.

The breakthrough could potentially impact millions of dental patients every year, the scientists say.

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Goodbye Root Canals? New Treatment Uses Dental Stem Cells ...

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Showing all 4 plot summaries

A city is ravaged by an epidemic of instant "white blindness". Those first afflicted are quarantined by the authorities in an abandoned mental hospital where the newly created "society of the blind" quickly breaks down. Criminals and the physically powerful prey upon the weak, hoarding the meager food rations and committing horrific acts. There is, however, one eyewitness to the nightmare. A woman whose sight is unaffected by the plague follows her afflicted husband to quarantine. There, keeping her sight a secret, she guides seven strangers who have become, in essence, a family. She leads them out of quarantine and onto the ravaged streets of the city, which has seen all vestiges of civilization crumble.

A doctor's wife becomes the only person with the ability to see in a town where everyone is struck with a mysterious case of sudden blindness. She feigns illness in order to take care of her husband as her surrounding community breaks down into chaos and disorder.

When a big city has a mysterious outbreak of blindness, the victims are quarantined by the government in a hospital without any medical care, treatment or hygiene. Among the first people affected by the so called "white blindness" are an ophthalmologist and his reluctant healthy wife who has not lost her sight but stays with him to help him in the difficult moment. The place immediately crowds and a group of criminals takes the power, demanding jewels and electronics first and sex later for the limited ratio of food they control.

A city is ravaged by an epidemic of instant white blindness.

The story of Blindness begins on a morning in an unnamed city during rush-hour traffic. As the traffic lights change...

Continue reading here:
Blindness (2008) - Plot Summary - IMDb

Gene therapy is a way of inserting genes into a patient's cells and replacing the preexisting alleles, or gene variants, to perform some therapeutic function. It has been used thus far primarily to replace mutant defective genes, or alleles, with normal alleles, but could in theory be used to edit the human genome arbitrarily. If gene therapy were applied to reproductive cells in the gonads (the germline), these genetic changes would be heritable. This process has never been performed, but it has a name: germline genetic engineering.

Since the early 1980s, gene therapy has been used to produce medicines. Say that a human being needs a certain protein as a medicine. This therapy uses a viral vector, that is, a virus modified to contain the DNA to be introduced. Large quantities of the virus are injected to the target area, or, sometimes tissue is removed, infected with the virus, and then implanted again. The viruses are modified such that the vast majority are not capable of independent self-replication - providing little chance for pathogenic infection. The virus introduced the new DNA into the genome of human cells, much in the same way normal viruses introduce their own genetic material into human cells, hijacking the cellular machinery.

After the new DNA is integrated into the target cell, the cell begins to manufacture proteins specified by the new genetic material, which in some instances, can be lifesaving. For example, patients with severe diabetes may be given the cellular machinery to produce insulin, obviating the need for regular injections. The benefits of the therapy can last for weeks, months, or even years or a lifetime.

Gene therapy has been used successfully to treat inherited retinal disease, thalassaemia, cystic fibrosis, severe combined immunodeficiency, and some cancers. Medical miracles not possible with any other approach have been demonstrated by gene therapy, such as reprogramming the body's natural sentinels, T-cells, to attack cancer cells. Gene therapy shows promise for treating afflictions such as Huntington's disease and sickle cell anemia. As the therapy continues to mature, it could save millions of lives.

Read more here:
What is Gene Therapy? (with pictures) - wiseGEEK

This article is about the heritable unit for transmission of biological traits. For other uses, see Gene (disambiguation).

A gene is a locus (or region) of DNA which is made up of nucleotides and is the molecular unit of heredity.[1][2]:Glossary The transmission of genes to an organism's offspring is the basis of the inheritance of phenotypic traits. Most biological traits are under the influence of polygenes (many different genes) as well as the geneenvironment interactions. Some genetic traits are instantly visible, such as eye colour or number of limbs, and some are not, such as blood type, risk for specific diseases, or the thousands of basic biochemical processes that comprise life.

Genes can acquire mutations in their sequence, leading to different variants, known as alleles, in the population. These alleles encode slightly different versions of a protein, which cause different phenotype traits. Colloquial usage of the term "having a gene" (e.g., "good genes," "hair colour gene") typically refers to having a different allele of the gene. Genes evolve due to natural selection or survival of the fittest of the alleles.

The concept of a gene continues to be refined as new phenomena are discovered.[3] For example, regulatory regions of a gene can be far removed from its coding regions, and coding regions can be split into several exons. Some viruses store their genome in RNA instead of DNA and some gene products are functional non-coding RNAs. Therefore, a broad, modern working definition of a gene is any discrete locus of heritable, genomic sequence which affect an organism's traits by being expressed as a functional product or by regulation of gene expression.[4][5]

The existence of discrete inheritable units was first suggested by Gregor Mendel (18221884).[6] From 1857 to 1864, he studied inheritance patterns in 8000 common edible pea plants, tracking distinct traits from parent to offspring. He described these mathematically as 2ncombinations where n is the number of differing characteristics in the original peas. Although he did not use the term gene, he explained his results in terms of discrete inherited units that give rise to observable physical characteristics. This description prefigured the distinction between genotype (the genetic material of an organism) and phenotype (the visible traits of that organism). Mendel was also the first to demonstrate independent assortment, the distinction between dominant and recessive traits, the distinction between a heterozygote and homozygote, and the phenomenon of discontinuous inheritance.

Prior to Mendel's work, the dominant theory of heredity was one of blending inheritance, which suggested that each parent contributed fluids to the fertilisation process and that the traits of the parents blended and mixed to produce the offspring. Charles Darwin developed a theory of inheritance he termed pangenesis, from Greek pan ("all, whole") and genesis ("birth") / genos ("origin").[7][8] Darwin used the term gemmule to describe hypothetical particles that would mix during reproduction.

Mendel's work went largely unnoticed after its first publication in 1866, but was rediscovered in the late 19th-century by Hugo de Vries, Carl Correns, and Erich von Tschermak, who (claimed to have) reached similar conclusions in their own research.[9] Specifically, in 1889, Hugo de Vries published his book Intracellular Pangenesis,[10] in which he postulated that different characters have individual hereditary carriers and that inheritance of specific traits in organisms comes in particles. De Vries called these units "pangenes" (Pangens in German), after Darwin's 1868 pangenesis theory.

Sixteen years later, in 1905, the word genetics was first used by William Bateson,[11] while Eduard Strasburger, amongst others, still used the term pangene for the fundamental physical and functional unit of heredity.[12] In 1909 the Danish botanist Wilhelm Johannsen shortened the name to "gene".[13]

Advances in understanding genes and inheritance continued throughout the 20th century. Deoxyribonucleic acid (DNA) was shown to be the molecular repository of genetic information by experiments in the 1940s to 1950s.[14][15] The structure of DNA was studied by Rosalind Franklin using X-ray crystallography, which led James D. Watson and Francis Crick to publish a model of the double-stranded DNA molecule whose paired nucleotide bases indicated a compelling hypothesis for the mechanism of genetic replication.[16][17] Collectively, this body of research established the central dogma of molecular biology, which states that proteins are translated from RNA, which is transcribed from DNA. This dogma has since been shown to have exceptions, such as reverse transcription in retroviruses. The modern study of genetics at the level of DNA is known as molecular genetics.

In 1972, Walter Fiers and his team at the University of Ghent were the first to determine the sequence of a gene: the gene for Bacteriophage MS2 coat protein.[18] The subsequent development of chain-termination DNA sequencing in 1977 by Frederick Sanger improved the efficiency of sequencing and turned it into a routine laboratory tool.[19] An automated version of the Sanger method was used in early phases of the Human Genome Project.[20]

The theories developed in the 1930s and 1940s to integrate molecular genetics with Darwinian evolution are called the modern evolutionary synthesis, a term introduced by Julian Huxley.[21] Evolutionary biologists subsequently refined this concept, such as George C. Williams' gene-centric view of evolution. He proposed an evolutionary concept of the gene as a unit of natural selection with the definition: "that which segregates and recombines with appreciable frequency."[22]:24 In this view, the molecular gene transcribes as a unit, and the evolutionary gene inherits as a unit. Related ideas emphasizing the centrality of genes in evolution were popularized by Richard Dawkins.[23][24]

The vast majority of living organisms encode their genes in long strands of DNA (deoxyribonucleic acid). DNA consists of a chain made from four types of nucleotide subunits, each composed of: a five-carbon sugar (2'-deoxyribose), a phosphate group, and one of the four bases adenine, cytosine, guanine, and thymine.[2]:2.1

Two chains of DNA twist around each other to form a DNA double helix with the phosphate-sugar backbone spiralling around the outside, and the bases pointing inwards with adenine base pairing to thymine and guanine to cytosine. The specificity of base pairing occurs because adenine and thymine align to form two hydrogen bonds, whereas cytosine and guanine form three hydrogen bonds. The two strands in a double helix must therefore be complementary, with their sequence of bases matching such that the adenines of one strand are paired with the thymines of the other strand, and so on.[2]:4.1

Due to the chemical composition of the pentose residues of the bases, DNA strands have directionality. One end of a DNA polymer contains an exposed hydroxyl group on the deoxyribose; this is known as the 3'end of the molecule. The other end contains an exposed phosphate group; this is the 5'end. The two strands of a double-helix run in opposite directions. Nucleic acid synthesis, including DNA replication and transcription occurs in the 5'3'direction, because new nucleotides are added via a dehydration reaction that uses the exposed 3'hydroxyl as a nucleophile.[25]:27.2

The expression of genes encoded in DNA begins by transcribing the gene into RNA, a second type of nucleic acid that is very similar to DNA, but whose monomers contain the sugar ribose rather than deoxyribose. RNA also contains the base uracil in place of thymine. RNA molecules are less stable than DNA and are typically single-stranded. Genes that encode proteins are composed of a series of three-nucleotide sequences called codons, which serve as the "words" in the genetic "language". The genetic code specifies the correspondence during protein translation between codons and amino acids. The genetic code is nearly the same for all known organisms.[2]:4.1

The total complement of genes in an organism or cell is known as its genome, which may be stored on one or more chromosomes. A chromosome consists of a single, very long DNA helix on which thousands of genes are encoded.[2]:4.2 The region of the chromosome at which a particular gene is located is called its locus. Each locus contains one allele of a gene; however, members of a population may have different alleles at the locus, each with a slightly different gene sequence.

The majority of eukaryotic genes are stored on a set of large, linear chromosomes. The chromosomes are packed within the nucleus in complex with storage proteins called histones to form a unit called a nucleosome. DNA packaged and condensed in this way is called chromatin.[2]:4.2 The manner in which DNA is stored on the histones, as well as chemical modifications of the histone itself, regulate whether a particular region of DNA is accessible for gene expression. In addition to genes, eukaryotic chromosomes contain sequences involved in ensuring that the DNA is copied without degradation of end regions and sorted into daughter cells during cell division: replication origins, telomeres and the centromere.[2]:4.2 Replication origins are the sequence regions where DNA replication is initiated to make two copies of the chromosome. Telomeres are long stretches of repetitive sequence that cap the ends of the linear chromosomes and prevent degradation of coding and regulatory regions during DNA replication. The length of the telomeres decreases each time the genome is replicated and has been implicated in the aging process.[27] The centromere is required for binding spindle fibres to separate sister chromatids into daughter cells during cell division.[2]:18.2

Prokaryotes (bacteria and archaea) typically store their genomes on a single large, circular chromosome. Similarly, some eukaryotic organelles contain a remnant circular chromosome with a small number of genes.[2]:14.4 Prokaryotes sometimes supplement their chromosome with additional small circles of DNA called plasmids, which usually encode only a few genes and are transferable between individuals. For example, the genes for antibiotic resistance are usually encoded on bacterial plasmids and can be passed between individual cells, even those of different species, via horizontal gene transfer.[28]

Whereas the chromosomes of prokaryotes are relatively gene-dense, those of eukaryotes often contain regions of DNA that serve no obvious function. Simple single-celled eukaryotes have relatively small amounts of such DNA, whereas the genomes of complex multicellular organisms, including humans, contain an absolute majority of DNA without an identified function.[29] This DNA has often been referred to as "junk DNA". However, more recent analyses suggest that, although protein-coding DNA makes up barely 2% of the human genome, about 80% of the bases in the genome may be expressed, so the term "junk DNA" may be a misnomer.[5]

The structure of a gene consists of many elements of which the actual protein coding sequence is often only a small part. These include DNA regions that are not transcribed as well as untranslated regions of the RNA.

Firstly, flanking the open reading frame, all genes contain a regulatory sequence that is required for their expression. In order to be expressed, genes require a promoter sequence. The promoter is recognized and bound by transcription factors and RNA polymerase to initiate transcription.[2]:7.1 A gene can have more than one promoter, resulting in messenger RNAs (mRNA) that differ in how far they extend in the 5'end.[30] Promoter regions have a consensus sequence, however highly transcribed genes have "strong" promoter sequences that bind the transcription machinery well, whereas others have "weak" promoters that bind poorly and initiate transcription less frequently.[2]:7.2Eukaryotic promoter regions are much more complex and difficult to identify than prokaryotic promoters.[2]:7.3

Additionally, genes can have regulatory regions many kilobases upstream or downstream of the open reading frame. These act by binding to transcription factors which then cause the DNA to loop so that the regulatory sequence (and bound transcription factor) become close to the RNA polymerase binding site.[31] For example, enhancers increase transcription by binding an activator protein which then helps to recruit the RNA polymerase to the promoter; conversely silencers bind repressor proteins and make the DNA less available for RNA polymerase.[32]

The transcribed pre-mRNA contains untranslated regions at both ends which contain a ribosome binding site, terminator and start and stop codons.[33] In addition, most eukaryotic open reading frames contain untranslated introns which are removed before the exons are translated. The sequences at the ends of the introns, dictate the splice sites to generate the final mature mRNA which encodes the protein or RNA product.[34]

Many prokaryotic genes are organized into operons, with multiple protein-coding sequences that are transcribed as a unit.[35][36] The products of operon genes typically have related functions and are involved in the same regulatory network.[2]:7.3

Defining exactly what section of a DNA sequence comprises a gene is difficult.[3]Regulatory regions of a gene such as enhancers do not necessarily have to be close to the coding sequence on the linear molecule because the intervening DNA can be looped out to bring the gene and its regulatory region into proximity. Similarly, a gene's introns can be much larger than its exons. Regulatory regions can even be on entirely different chromosomes and operate in trans to allow regulatory regions on one chromosome to come in contact with target genes on another chromosome.[37][38]

Early work in molecular genetics suggested the model that one gene makes one protein. This model has been refined since the discovery of genes that can encode multiple proteins by alternative splicing and coding sequences split in short section across the genome whose mRNAs are concatenated by trans-splicing.[5][39][40]

A broad operational definition is sometimes used to encompass the complexity of these diverse phenomena, where a gene is defined as a union of genomic sequences encoding a coherent set of potentially overlapping functional products.[11] This definition categorizes genes by their functional products (proteins or RNA) rather than their specific DNA loci, with regulatory elements classified as gene-associated regions.[11]

In all organisms, two steps are required to read the information encoded in a gene's DNA and produce the protein it specifies. First, the gene's DNA is transcribed to messenger RNA (mRNA).[2]:6.1 Second, that mRNA is translated to protein.[2]:6.2 RNA-coding genes must still go through the first step, but are not translated into protein.[41] The process of producing a biologically functional molecule of either RNA or protein is called gene expression, and the resulting molecule is called a gene product.

The nucleotide sequence of a gene's DNA specifies the amino acid sequence of a protein through the genetic code. Sets of three nucleotides, known as codons, each correspond to a specific amino acid.[2]:6 Additionally, a "start codon", and three "stop codons" indicate the beginning and end of the protein coding region. There are 64possible codons (four possible nucleotides at each of three positions, hence 43possible codons) and only 20standard amino acids; hence the code is redundant and multiple codons can specify the same amino acid. The correspondence between codons and amino acids is nearly universal among all known living organisms.[42]

Transcription produces a single-stranded RNA molecule known as messenger RNA, whose nucleotide sequence is complementary to the DNA from which it was transcribed.[2]:6.1 The mRNA acts as an intermediate between the DNA gene and its final protein product. The gene's DNA is used as a template to generate a complementary mRNA. The mRNA matches the sequence of the gene's DNA coding strand because it is synthesised as the complement of the template strand. Transcription is performed by an enzyme called an RNA polymerase, which reads the template strand in the 3' to 5'direction and synthesizes the RNA from 5' to 3'. To initiate transcription, the polymerase first recognizes and binds a promoter region of the gene. Thus, a major mechanism of gene regulation is the blocking or sequestering the promoter region, either by tight binding by repressor molecules that physically block the polymerase, or by organizing the DNA so that the promoter region is not accessible.[2]:7

In prokaryotes, transcription occurs in the cytoplasm; for very long transcripts, translation may begin at the 5'end of the RNA while the 3'end is still being transcribed. In eukaryotes, transcription occurs in the nucleus, where the cell's DNA is stored. The RNA molecule produced by the polymerase is known as the primary transcript and undergoes post-transcriptional modifications before being exported to the cytoplasm for translation. One of the modifications performed is the splicing of introns which are sequences in the transcribed region that do not encode protein. Alternative splicing mechanisms can result in mature transcripts from the same gene having different sequences and thus coding for different proteins. This is a major form of regulation in eukaryotic cells and also occurs in some prokaryotes.[2]:7.5[43]

Translation is the process by which a mature mRNA molecule is used as a template for synthesizing a new protein.[2]:6.2 Translation is carried out by ribosomes, large complexes of RNA and protein responsible for carrying out the chemical reactions to add new amino acids to a growing polypeptide chain by the formation of peptide bonds. The genetic code is read three nucleotides at a time, in units called codons, via interactions with specialized RNA molecules called transfer RNA (tRNA). Each tRNA has three unpaired bases known as the anticodon that are complementary to the codon it reads on the mRNA. The tRNA is also covalently attached to the amino acid specified by the complementary codon. When the tRNA binds to its complementary codon in an mRNA strand, the ribosome attaches its amino acid cargo to the new polypeptide chain, which is synthesized from amino terminus to carboxyl terminus. During and after synthesis, most new proteins must folds to their active three-dimensional structure before they can carry out their cellular functions.[2]:3

Genes are regulated so that they are expressed only when the product is needed, since expression draws on limited resources.[2]:7 A cell regulates its gene expression depending on its external environment (e.g. available nutrients, temperature and other stresses), its internal environment (e.g. cell division cycle, metabolism, infection status), and its specific role if in a multicellular organism. Gene expression can be regulated at any step: from transcriptional initiation, to RNA processing, to post-translational modification of the protein. The regulation of lactose metabolism genes in E. coli (lac operon) was the first such mechanism to be described in 1961.[44]

A typical protein-coding gene is first copied into RNA as an intermediate in the manufacture of the final protein product.[2]:6.1 In other cases, the RNA molecules are the actual functional products, as in the synthesis of ribosomal RNA and transfer RNA. Some RNAs known as ribozymes are capable of enzymatic function, and microRNA has a regulatory role. The DNA sequences from which such RNAs are transcribed are known as non-coding RNA genes.[41]

Some viruses store their entire genomes in the form of RNA, and contain no DNA at all.[45][46] Because they use RNA to store genes, their cellular hosts may synthesize their proteins as soon as they are infected and without the delay in waiting for transcription.[47] On the other hand, RNA retroviruses, such as HIV, require the reverse transcription of their genome from RNA into DNA before their proteins can be synthesized. RNA-mediated epigenetic inheritance has also been observed in plants and very rarely in animals.[48]

Organisms inherit their genes from their parents. Asexual organisms simply inherit a complete copy of their parent's genome. Sexual organisms have two copies of each chromosome because they inherit one complete set from each parent.[2]:1

According to Mendelian inheritance, variations in an organism's phenotype (observable physical and behavioral characteristics) are due in part to variations in its genotype (particular set of genes). Each gene specifies a particular trait with different sequence of a gene (alleles) giving rise to different phenotypes. Most eukaryotic organisms (such as the pea plants Mendel worked on) have two alleles for each trait, one inherited from each parent.[2]:20

Alleles at a locus may be dominant or recessive; dominant alleles give rise to their corresponding phenotypes when paired with any other allele for the same trait, whereas recessive alleles give rise to their corresponding phenotype only when paired with another copy of the same allele. For example, if the allele specifying tall stems in pea plants is dominant over the allele specifying short stems, then pea plants that inherit one tall allele from one parent and one short allele from the other parent will also have tall stems. Mendel's work demonstrated that alleles assort independently in the production of gametes, or germ cells, ensuring variation in the next generation. Although Mendelian inheritance remains a good model for many traits determined by single genes (including a number of well-known genetic disorders) it does not include the physical processes of DNA replication and cell division.[49][50]

The growth, development, and reproduction of organisms relies on cell division, or the process by which a single cell divides into two usually identical daughter cells. This requires first making a duplicate copy of every gene in the genome in a process called DNA replication.[2]:5.2 The copies are made by specialized enzymes known as DNA polymerases, which "read" one strand of the double-helical DNA, known as the template strand, and synthesize a new complementary strand. Because the DNA double helix is held together by base pairing, the sequence of one strand completely specifies the sequence of its complement; hence only one strand needs to be read by the enzyme to produce a faithful copy. The process of DNA replication is semiconservative; that is, the copy of the genome inherited by each daughter cell contains one original and one newly synthesized strand of DNA.[2]:5.2

After DNA replication is complete, the cell must physically separate the two copies of the genome and divide into two distinct membrane-bound cells.[2]:18.2 In prokaryotes(bacteria and archaea) this usually occurs via a relatively simple process called binary fission, in which each circular genome attaches to the cell membrane and is separated into the daughter cells as the membrane invaginates to split the cytoplasm into two membrane-bound portions. Binary fission is extremely fast compared to the rates of cell division in eukaryotes. Eukaryotic cell division is a more complex process known as the cell cycle; DNA replication occurs during a phase of this cycle known as S phase, whereas the process of segregating chromosomes and splitting the cytoplasm occurs during M phase.[2]:18.1

The duplication and transmission of genetic material from one generation of cells to the next is the basis for molecular inheritance, and the link between the classical and molecular pictures of genes. Organisms inherit the characteristics of their parents because the cells of the offspring contain copies of the genes in their parents' cells. In asexually reproducing organisms, the offspring will be a genetic copy or clone of the parent organism. In sexually reproducing organisms, a specialized form of cell division called meiosis produces cells called gametes or germ cells that are haploid, or contain only one copy of each gene.[2]:20.2 The gametes produced by females are called eggs or ova, and those produced by males are called sperm. Two gametes fuse to form a diploid fertilized egg, a single cell that has two sets of genes, with one copy of each gene from the mother and one from the father.[2]:20

During the process of meiotic cell division, an event called genetic recombination or crossing-over can sometimes occur, in which a length of DNA on one chromatid is swapped with a length of DNA on the corresponding sister chromatid. This has no effect if the alleles on the chromatids are the same, but results in reassortment of otherwise linked alleles if they are different.[2]:5.5 The Mendelian principle of independent assortment asserts that each of a parent's two genes for each trait will sort independently into gametes; which allele an organism inherits for one trait is unrelated to which allele it inherits for another trait. This is in fact only true for genes that do not reside on the same chromosome, or are located very far from one another on the same chromosome. The closer two genes lie on the same chromosome, the more closely they will be associated in gametes and the more often they will appear together; genes that are very close are essentially never separated because it is extremely unlikely that a crossover point will occur between them. This is known as genetic linkage.[51]

DNA replication is for the most part extremely accurate, however errors (mutations) do occur.[2]:7.6 The error rate in eukaryotic cells can be as low as 108 per nucleotide per replication,[52][53] whereas for some RNA viruses it can be as high as 103.[54] This means that each generation, each human genome accumulates 12 new mutations.[54] Small mutations can be caused by DNA replication and the aftermath of DNA damage and include point mutations in which a single base is altered and frameshift mutations in which a single base is inserted or deleted. Either of these mutations can change the gene by missense (change a codon to encode a different amino acid) or nonsense (a premature stop codon).[55] Larger mutations can be caused by errors in recombination to cause chromosomal abnormalities including the duplication, deletion, rearrangement or inversion of large sections of a chromosome. Additionally, the DNA repair mechanisms that normally revert mutations can introduce errors when repairing the physical damage to the molecule is more important than restoring an exact copy, for example when repairing double-strand breaks.[2]:5.4

When multiple different alleles for a gene are present in a species's population it is called polymorphic. Most different alleles are functionally equivalent, however some alleles can give rise to different phenotypic traits. A gene's most common allele is called the wild type, and rare alleles are called mutants. The genetic variation in relative frequencies of different alleles in a population is due to both natural selection and genetic drift.[56] The wild-type allele is not necessarily the ancestor of less common alleles, nor is it necessarily fitter.

Most mutations within genes are neutral, having no effect on the organism's phenotype (silent mutations). Some mutations do not change the amino acid sequence because multiple codons encode the same amino acid (synonymous mutations). Other mutations can be neutral if they lead to amino acid sequence changes, but the protein still functions similarly with the new amino acid (e.g. conservative mutations). Many mutations, however, are deleterious or even lethal, and are removed from populations by natural selection. Genetic disorders are the result of deleterious mutations and can be due to spontaneous mutation in the affected individual, or can be inherited. Finally, a small fraction of mutations are beneficial, improving the organism's fitness and are extremely important for evolution, since their directional selection leads to adaptive evolution.[2]:7.6

Genes with a most recent common ancestor, and thus a shared evolutionary ancestry, are known as homologs.[57] These genes appear either from gene duplication within an organism's genome, where they are known as paralogous genes, or are the result of divergence of the genes after a speciation event, where they are known as orthologous genes,[2]:7.6 and often perform the same or similar functions in related organisms. It is often assumed that the functions of orthologous genes are more similar than those of paralogous genes, although the difference is minimal.[58][59]

The relationship between genes can be measured by comparing the sequence alignment of their DNA.[2]:7.6 The degree of sequence similarity between homologous genes is called conserved sequence. Most changes to a gene's sequence do not affect its function and so genes accumulate mutations over time by neutral molecular evolution. Additionally, any selection on a gene will cause its sequence to diverge at a different rate. Genes under stabilizing selection are constrained and so change more slowly whereas genes under directional selection change sequence more rapidly.[60] The sequence differences between genes can be used for phylogenetic analyses to study how those genes have evolved and how the organisms they come from are related.[61][62]

The most common source of new genes in eukaryotic lineages is gene duplication, which creates copy number variation of an existing gene in the genome.[63][64] The resulting genes (paralogs) may then diverge in sequence and in function. Sets of genes formed in this way comprise a gene family. Gene duplications and losses within a family are common and represent a major source of evolutionary biodiversity.[65] Sometimes, gene duplication may result in a nonfunctional copy of a gene, or a functional copy may be subject to mutations that result in loss of function; such nonfunctional genes are called pseudogenes.[2]:7.6

De novo or "orphan" genes, whose sequence shows no similarity to existing genes, are extremely rare. Estimates of the number of de novo genes in the human genome range from 18[66] to 60.[67] Such genes are typically shorter and simpler in structure than most eukaryotic genes, with few if any introns.[63] Two primary sources of orphan protein-coding genes are gene duplication followed by extremely rapid sequence change, such that the original relationship is undetectable by sequence comparisons, and formation through mutation of "cryptic" transcription start sites that introduce a new open reading frame in a region of the genome that did not previously code for a protein.[68][69]

Horizontal gene transfer refers to the transfer of genetic material through a mechanism other than reproduction. This mechanism is a common source of new genes in prokaryotes, sometimes thought to contribute more to genetic variation than gene duplication.[70] It is a common means of spreading antibiotic resistance, virulence, and adaptive metabolic functions.[28][71] Although horizontal gene transfer is rare in eukaryotes, likely examples have been identified of protist and alga genomes containing genes of bacterial origin.[72][73]

The genome is the total genetic material of an organism and includes both the genes and non-coding sequences.[74]

The genome size, and the number of genes it encodes varies widely between organisms. The smallest genomes occur in viruses (which can have as few as 2 protein-coding genes),[83] and viroids (which act as a single non-coding RNA gene).[84] Conversely, plants can have extremely large genomes,[85] with rice containing >46,000 protein-coding genes.[86] The total number of protein-coding genes (the Earth's proteome) is estimated to be 5million sequences.[87]

Although the number of base-pairs of DNA in the human genome has been known since the 1960s, the estimated number of genes has changed over time as definitions of genes, and methods of detecting them have been refined. Initial theoretical predictions of the number of human genes were as high as 2,000,000.[88] Early experimental measures indicated there to be 50,000100,000 transcribed genes (expressed sequence tags).[89] Subsequently, the sequencing in the Human Genome Project indicated that many of these transcripts were alternative variants of the same genes, and the total number of protein-coding genes was revised down to ~20,000[82] with 13 genes encoded on the mitochondrial genome.[80] Of the human genome, only 12% consists of protein-coding genes,[90] with the remainder being 'noncoding' DNA such as introns, retrotransposons, and noncoding RNAs.[90][91]Every organism has all his genes in all cells of his body but it is not important that every gene must function in every cell .

Essential genes are the set of genes thought to be critical for an organism's survival.[93] This definition assumes the abundant availability of all relevant nutrients and the absence of environmental stress. Only a small portion of an organism's genes are essential. In bacteria, an estimated 250400 genes are essential for Escherichia coli and Bacillus subtilis, which is less than 10% of their genes.[94][95][96] Half of these genes are orthologs in both organisms and are largely involved in protein synthesis.[96] In the budding yeast Saccharomyces cerevisiae the number of essential genes is slightly higher, at 1000 genes (~20% of their genes).[97] Although the number is more difficult to measure in higher eukaryotes, mice and humans are estimated to have around 2000 essential genes (~10% of their genes).[98] The synthetic organism, Syn 3, has a minimal genome of 473 essential genes and quasi-essential genes (necessary for fast growth), although 149 have unknown function.[92]

Essential genes include Housekeeping genes (critical for basic cell functions)[99] as well as genes that are expressed at different times in the organisms development or life cycle.[100] Housekeeping genes are used as experimental controls when analysing gene expression, since they are constitutively expressed at a relatively constant level.

Gene nomenclature has been established by the HUGO Gene Nomenclature Committee (HGNC) for each known human gene in the form of an approved gene name and symbol (short-form abbreviation), which can be accessed through a database maintained by HGNC. Symbols are chosen to be unique, and each gene has only one symbol (although approved symbols sometimes change). Symbols are preferably kept consistent with other members of a gene family and with homologs in other species, particularly the mouse due to its role as a common model organism.[101]

Genetic engineering is the modification of an organism's genome through biotechnology. Since the 1970s, a variety of techniques have been developed to specifically add, remove and edit genes in an organism.[102] Recently developed genome engineering techniques use engineered nuclease enzymes to create targeted DNA repair in a chromosome to either disrupt or edit a gene when the break is repaired.[103][104][105][106] The related term synthetic biology is sometimes used to refer to extensive genetic engineering of an organism.[107]

Genetic engineering is now a routine research tool with model organisms. For example, genes are easily added to bacteria[108] and lineages of knockout mice with a specific gene's function disrupted are used to investigate that gene's function.[109][110] Many organisms have been genetically modified for applications in agriculture, industrial biotechnology, and medicine.

For multicellular organisms, typically the embryo is engineered which grows into the adult genetically modified organism.[111] However, the genomes of cells in an adult organism can be edited using gene therapy techniques to treat genetic diseases.

Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2002). Molecular Biology of the Cell (Fourth ed.). New York: Garland Science. ISBN978-0-8153-3218-3. A molecular biology textbook available free online through NCBI Bookshelf.

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Jan Dommerholt, PT, DPT, MPS, DAAPM, is a Dutch-trained physical therapist who holds a Master of Professional Studies degree with a concentration in biomechanical trauma and health care administration, and a Doctorate in Physical Therapy from the University of St. Augustine for Health Sciences. Dr. Dommerholt has taught many courses and lectured at conferences throughout the United States, Europe, South America, and the Middle East while maintaining an active clinical practice. He is on the editorial board of the Journal of Musculoskeletal Pain (editor Dr. I. Jon Russell), the Journal of Bodywork and Movement Therapies (editor Dr. Leon Chaitow), the Journal of Manual and Manipulative Therapy (editor Chad Cook, PT, PhD), and Cuestiones de Fisioterapia.

He has authored many chapters and articles on myofascial pain, fibromyalgia, complex regional pain syndrome, and performing arts physical therapy, and prepares a quarterly literature review column on myofascial pain for the Journal of Musculoskeletal Pain. Read "Treating the Trigger" (PDF), a 2008 interview with Dr. Dommerholt published in Advance magazine. Dr. Dommerholt is the president of Bethesda Physiocare and editor of several books on myofascial trigger points.

Robert Gerwin, MD, FAAN, is Co-Founder, Vice President, and Co-Director of Myopain Seminars. He is a Board Certified Neurologist and a Fellow of the American Academy of Neurology. He is also a Diplomate of the American Board of Pain Medicine and a member of the American Academy of Pain Medicine. Dr. Gerwin graduated from the University of Chicago School of Medicine. He had two years of Internal Medicine post-graduate training at New York University--Bellevue Hospital and did his Neurology Residency at Case-Western Reserve University/Cleveland Metropolitan General Hospital, Cleveland, Ohio. He had a two year special fellowship at NIH in neurology and immunology. He has been in private practice in the Washington DC area for many years. Dr. Gerwin has been working in the area of Myofascial Pain and Fibromyalgia for many years. Dr. Janet G. Travell was his mentor while she lived in Washington DC. Dr. Gerwin is former President of the International Myopain Society. He was the Scientific Program Chairman for the 2007 International Congress of the Myopain Society.

He is the author of over 30 peer reviewed articles, reviews, book chapters and consensus statements. He reviews articles for over a dozen medical journals. He is on the editorial board of the Journal of Musculoskeletal Pain. He is co-editor of the books Tension-Type and Cervicogenic Headache: Pathophysiology, Diagnosis, and Management and Clinical Mastery in the Treatment of Myofascial Pain (see Books). He has been teaching courses and seminars worldwide in the field of neuromuscular and myofascial pain for many years. He founded the Focus on Pain series of neuromuscular and myofascial pain conferences in 1990. His interests lie in the area of Myofascial Pain and Fibromyalgia, and in the related issues of chronic headache, low back pain, and pelvic region pain, in addition to practicing neurological medicine. He is particularly concerned with the problem of persistent or chronic pain, and why some persons do not recover as expected. Dr. Gerwin is the Medical Director of Pain and Rehabilitation Medicine in Bethesda, MD and is an associate professor in the Department of Neurology at Johns Hopkins University School of Medicine.

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