I. Background:

A. Information And Statistics About Diabetes

Diabetes mellitus is a disease of metabolism presenting as a complex group of syndromes that have in common elevated blood glucose levels. It occurs because the insulin produced by the beta cells of the pancreas is either absent, insufficient, or not used properly by target tissues. As a result, the body is unable to metabolize macronutrients in food in the normal way. Since the body cannot convert glucose into energy, high levels of glucose remain in the blood and spill into the urine, eventually resulting in micro-vascular complications (for example, kidney disease and eye disease) and macro-vascular complications (for example, stroke and ischemic heart disease).

There are two major types of diabetes that affect the Medicare population, Type 1 diabetes, previously called insulin dependent diabetes mellitus, and Type 2 diabetes, previously called non-insulin dependent diabetes mellitus.

The goals in the management of diabetes are to achieve normal metabolic control and reduce the risk of micro and macro-vascular complications. Numerous epidemiologic and interventional studies point to the necessity of maintaining good glycemic control to reduce the risk of the complications of diabetes.

Despite this knowledge, diabetes remains the leading cause of blindness, lower extremity amputations, and kidney disease requiring dialysis. Diabetes and its complications are primary or secondary factors in an estimated 9 percent of hospitalizations (Aubert, RE, et al., Diabetes-related hospitalizations and hospital utilization. In: Diabetes in America. 2nd ed. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Disease, NIH, Pub. No. 9514681995: 553570).

Overall, beneficiaries with diabetes are hospitalized 1.5 times more often than beneficiaries without diabetes. Ten percent of these hospitalizations are a direct result of uncontrolled diabetes, and more than half of these admissions occur in beneficiaries 65 and older (National Hospital Discharge Survey, U.S. National Center for Health Statistics, U.S. Department of Health and Human Services, 1990). In expanding the Medicare program to include outpatient diabetes self-management training services, the Congress intended to empower Medicare beneficiaries with diabetes to better manage and control their conditions. The Conference Report indicates that the conferees believed that this provision will provide significant Medicare savings over time due to reduced hospitalizations and complications arising from diabetes. (H.R. Conf. Rep. No. 105217, at 701 (1997)).

According to the National Health and Nutrition Examination Survey (NHANES):

(Diabetes Fact Sheet, The Centers for Disease Control & Prevention https://www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf)

According to the Department of Health and Human Services Centers for Disease Control and Prevention (CDC):

B. Statutory Authority for Diabetic Self-Management Training (DSMT)

Section 4105(a) of the Balanced Budget Act of 1997 (BBA) (pub. L. 105-33), enacted on August 5, 1997, provides for Medicare coverage for DSMT services provided by a certified provider. Section 4105 of the BBA amended section 1861 of the Social Security Act (The Act) by adding a new section (q)(q).

Section 1861(qq) of the Social Security Act (the Act) provides CMS with the statutory authority to regulate Medicare outpatient coverage of DSMT services.

Section 1861(q)(q)(2) provides that the Secretary may recognize a physician, individual, or entity that is recognized by an organization as meeting standards for furnishing these services as a certified DSMT provider. This statute also provides that a physician or other individual or entity shall be deemed to have met such standards if they meet applicable standards originally established by the National Diabetes Advisory Board.

Section 1861(q)(q)(2)(B) of the Act states that a physician, or such other individual or entity, meets the quality standards if the physician, or individual or entity, meets quality standards established by the Secretary, except that the physician or other individual or entity shall be deemed to have met such standards if the physician or other individual or entity meets applicable standards originally established by the National Diabetes Advisory Board and subsequently revised by organizations who participated in the establishment of standards by such Board, or is recognized by an organization that represents individuals (including individuals under this title) with diabetes as meeting standards for furnishing the services.''

Additionally, section 4105(c)(1) of the BBA requires the Secretary to establish outcome measurements for purposes of evaluating the improvement of the health status of Medicare beneficiaries with diabetes.

A final rule (65 FR 83130) was published in the Federal Register on December 29, 2000 which implemented the BBA provisions addressing the coverage, payment, quality standards, and accreditation requirements for DSMT. This final rule also implemented the DSMT regulations which are codified at Title 42 of the Code of Federal Regulation (CFR) sections 410.140 to 410.146.

The CMS regulations at 42 CFR 410.144 provide the authority for the CMS to require the DSMT AOs to use one of the following types of accreditation standards: (1) the accreditation standards set forth at 410.144(a); (2) the accreditation standards issued by the National Standards for Diabetes Self-Management Education Support (NSDSMES) (410.144(b)); or (3) other accreditation standards, so long as they have been submitted to CMS and approved as meeting or exceeding the CMS quality standards described at 410.144(a).

The American Diabetes Association (ADA) and the American Association of Diabetic Educators (AADE) are the two national DSMT AOs approved by CMS to accredit entities that furnish DSMT services. These DSMT AOs are approved by CMS for six-year terms. Section 410.143(a) sets forth the ongoing responsibilities of the DSMT AOs. The requirement at section 410.143(b) sets forth the oversight activities that CMS, or its agent, will perform to ensure that a CMS approved DSMT AO and the entities the organization accredits continue to meet a set of quality standards described at 410.144.

Section 410.145 of the regulations specifies requirements that DSMT entities must meet. Section 410.146 requires that approved entity must collect and record in an organized systematic manner, patient assessment information at least on a quarterly basis for a beneficiary who receives DSMT training.

II. Information about the Diabetic Self-Management Training Accrediting Organizations

A. General Information

B. Information About The ADA Education Recognition Program (ERP)

C. Information About the AADE

III. Contact Information for CMS-designated DSMT Accrediting Organizations

There are two accrediting organizations approved by CMS to accredit DSMT entities. The contact information for these DSMT AO is listed below.

American Diabetes Association (ADA)

2451 Crystal City Drive

Suite 800

Arlington, VA 22202

703-549-1500

Phone: 800-342-2383

Website: http://www.diabetes.org

American Association of Diabetic Educators (AADE)

200 W. Madison

Suite 800

Chicago, IL 60606

Phone: 800-338-3633

Website: https://www.diabeteseducator.org

IV. Oversight and Validation Process for DSMT Accrediting Organizations Accreditation Processes

V. Where to Submit Questions Related to the DSMT Accreditation Program

Questions about the DSMT Accreditation Program may be submitted to the DSMT Accreditation email box at DSMTAccreditation@cms.hhs.gov.

We monitor this email box on a frequent basis and will respond to your email as soon as possible.

Read more here:
Diabetic Self-Management Training (DSMT) Accreditation Program

Process of producing genetically identical individuals of an organism

Cloning is the process of producing individual organisms with identical or virtually identical DNA, either by natural or artificial means. In nature, some organisms produce clones through asexual reproduction. In the field of biotechnology, cloning is the process of creating cloned organisms (copies) of cells and of DNA fragments (molecular cloning).

Coined by Herbert J. Webber, the term clone derives from the Ancient Greek word (kln), twig, which is the process whereby a new plant is created from a twig. In botany, the term lusus was used.[1] In horticulture, the spelling clon was used until the early twentieth century; the final e came into use to indicate the vowel is a "long o" instead of a "short o".[2][3] Since the term entered the popular lexicon in a more general context, the spelling clone has been used exclusively.

Cloning is a natural form of reproduction that has allowed life forms to spread for hundreds of millions of years. It is a reproduction method used by plants, fungi, and bacteria, and is also the way that clonal colonies reproduce themselves.[4][5] Examples of these organisms include blueberry plants, Hazel trees, the Pando trees,[6][7] the Kentucky coffeetree, Myrica, and the American sweetgum.

Molecular cloning refers to the process of making multiple molecules. Cloning is commonly used to amplify DNA fragments containing whole genes, but it can also be used to amplify any DNA sequence such as promoters, non-coding sequences and randomly fragmented DNA. It is used in a wide array of biological experiments and practical applications ranging from genetic fingerprinting to large scale protein production. Occasionally, the term cloning is misleadingly used to refer to the identification of the chromosomal location of a gene associated with a particular phenotype of interest, such as in positional cloning. In practice, localization of the gene to a chromosome or genomic region does not necessarily enable one to isolate or amplify the relevant genomic sequence. To amplify any DNA sequence in a living organism, that sequence must be linked to an origin of replication, which is a sequence of DNA capable of directing the propagation of itself and any linked sequence. However, a number of other features are needed, and a variety of specialised cloning vectors (small piece of DNA into which a foreign DNA fragment can be inserted) exist that allow protein production, affinity tagging, single-stranded RNA or DNA production and a host of other molecular biology tools.

Cloning of any DNA fragment essentially involves four steps[8]

Although these steps are invariable among cloning procedures a number of alternative routes can be selected; these are summarized as a cloning strategy.

Initially, the DNA of interest needs to be isolated to provide a DNA segment of suitable size. Subsequently, a ligation procedure is used where the amplified fragment is inserted into a vector (piece of DNA). The vector (which is frequently circular) is linearised using restriction enzymes, and incubated with the fragment of interest under appropriate conditions with an enzyme called DNA ligase. Following ligation, the vector with the insert of interest is transfected into cells. A number of alternative techniques are available, such as chemical sensitisation of cells, electroporation, optical injection and biolistics. Finally, the transfected cells are cultured. As the aforementioned procedures are of particularly low efficiency, there is a need to identify the cells that have been successfully transfected with the vector construct containing the desired insertion sequence in the required orientation. Modern cloning vectors include selectable antibiotic resistance markers, which allow only cells in which the vector has been transfected, to grow. Additionally, the cloning vectors may contain colour selection markers, which provide blue/white screening (alpha-factor complementation) on X-gal medium. Nevertheless, these selection steps do not absolutely guarantee that the DNA insert is present in the cells obtained. Further investigation of the resulting colonies must be required to confirm that cloning was successful. This may be accomplished by means of PCR, restriction fragment analysis and/or DNA sequencing.

Cloning a cell means to derive a population of cells from a single cell. In the case of unicellular organisms such as bacteria and yeast, this process is remarkably simple and essentially only requires the inoculation of the appropriate medium. However, in the case of cell cultures from multi-cellular organisms, cell cloning is an arduous task as these cells will not readily grow in standard media.

A useful tissue culture technique used to clone distinct lineages of cell lines involves the use of cloning rings (cylinders).[9] In this technique a single-cell suspension of cells that have been exposed to a mutagenic agent or drug used to drive selection is plated at high dilution to create isolated colonies, each arising from a single and potentially clonal distinct cell. At an early growth stage when colonies consist of only a few cells, sterile polystyrene rings (cloning rings), which have been dipped in grease, are placed over an individual colony and a small amount of trypsin is added. Cloned cells are collected from inside the ring and transferred to a new vessel for further growth.

Somatic-cell nuclear transfer, popularly known as SCNT, can also be used to create embryos for research or therapeutic purposes. The most likely purpose for this is to produce embryos for use in stem cell research. This process is also called "research cloning" or "therapeutic cloning". The goal is not to create cloned human beings (called "reproductive cloning"), but rather to harvest stem cells that can be used to study human development and to potentially treat disease. While a clonal human blastocyst has been created, stem cell lines are yet to be isolated from a clonal source.[10]

Therapeutic cloning is achieved by creating embryonic stem cells in the hopes of treating diseases such as diabetes and Alzheimer's. The process begins by removing the nucleus (containing the DNA) from an egg cell and inserting a nucleus from the adult cell to be cloned.[11] In the case of someone with Alzheimer's disease, the nucleus from a skin cell of that patient is placed into an empty egg. The reprogrammed cell begins to develop into an embryo because the egg reacts with the transferred nucleus. The embryo will become genetically identical to the patient.[11] The embryo will then form a blastocyst which has the potential to form/become any cell in the body.[12]

The reason why SCNT is used for cloning is because somatic cells can be easily acquired and cultured in the lab. This process can either add or delete specific genomes of farm animals. A key point to remember is that cloning is achieved when the oocyte maintains its normal functions and instead of using sperm and egg genomes to replicate, the donor's somatic cell nucleus is inserted into the oocyte.[13] The oocyte will react to the somatic cell nucleus, the same way it would to a sperm cell's nucleus.[13]

The process of cloning a particular farm animal using SCNT is relatively the same for all animals. The first step is to collect the somatic cells from the animal that will be cloned. The somatic cells could be used immediately or stored in the laboratory for later use.[13] The hardest part of SCNT is removing maternal DNA from an oocyte at metaphase II. Once this has been done, the somatic nucleus can be inserted into an egg cytoplasm.[13] This creates a one-cell embryo. The grouped somatic cell and egg cytoplasm are then introduced to an electrical current.[13] This energy will hopefully allow the cloned embryo to begin development. The successfully developed embryos are then placed in surrogate recipients, such as a cow or sheep in the case of farm animals.[13]

SCNT is seen as a good method for producing agriculture animals for food consumption. It successfully cloned sheep, cattle, goats, and pigs. Another benefit is SCNT is seen as a solution to clone endangered species that are on the verge of going extinct.[13] However, stresses placed on both the egg cell and the introduced nucleus can be enormous, which led to a high loss in resulting cells in early research. For example, the cloned sheep Dolly was born after 277 eggs were used for SCNT, which created 29 viable embryos. Only three of these embryos survived until birth, and only one survived to adulthood.[14] As the procedure could not be automated, and had to be performed manually under a microscope, SCNT was very resource intensive. The biochemistry involved in reprogramming the differentiated somatic cell nucleus and activating the recipient egg was also far from being well understood. However, by 2014 researchers were reporting cloning success rates of seven to eight out of ten[15] and in 2016, a Korean Company Sooam Biotech was reported to be producing 500 cloned embryos per day.[16]

In SCNT, not all of the donor cell's genetic information is transferred, as the donor cell's mitochondria that contain their own mitochondrial DNA are left behind. The resulting hybrid cells retain those mitochondrial structures which originally belonged to the egg. As a consequence, clones such as Dolly that are born from SCNT are not perfect copies of the donor of the nucleus.

Organism cloning (also called reproductive cloning) refers to the procedure of creating a new multicellular organism, genetically identical to another. In essence this form of cloning is an asexual method of reproduction, where fertilization or inter-gamete contact does not take place. Asexual reproduction is a naturally occurring phenomenon in many species, including most plants and some insects. Scientists have made some major achievements with cloning, including the asexual reproduction of sheep and cows. There is a lot of ethical debate over whether or not cloning should be used. However, cloning, or asexual propagation,[17] has been common practice in the horticultural world for hundreds of years.

The term clone is used in horticulture to refer to descendants of a single plant which were produced by vegetative reproduction or apomixis. Many horticultural plant cultivars are clones, having been derived from a single individual, multiplied by some process other than sexual reproduction.[18] As an example, some European cultivars of grapes represent clones that have been propagated for over two millennia. Other examples are potato and banana.[19]

Grafting can be regarded as cloning, since all the shoots and branches coming from the graft are genetically a clone of a single individual, but this particular kind of cloning has not come under ethical scrutiny and is generally treated as an entirely different kind of operation.

Many trees, shrubs, vines, ferns and other herbaceous perennials form clonal colonies naturally. Parts of an individual plant may become detached by fragmentation and grow on to become separate clonal individuals. A common example is in the vegetative reproduction of moss and liverwort gametophyte clones by means of gemmae. Some vascular plants e.g. dandelion and certain viviparous grasses also form seeds asexually, termed apomixis, resulting in clonal populations of genetically identical individuals.

Clonal derivation exists in nature in some animal species and is referred to as parthenogenesis (reproduction of an organism by itself without a mate). This is an asexual form of reproduction that is only found in females of some insects, crustaceans, nematodes,[20] fish (for example the hammerhead shark[21]), and lizards including the Komodo dragon[21] and several whiptails. The growth and development occurs without fertilization by a male. In plants, parthenogenesis means the development of an embryo from an unfertilized egg cell, and is a component process of apomixis. In species that use the XY sex-determination system, the offspring will always be female. An example is the little fire ant (Wasmannia auropunctata), which is native to Central and South America but has spread throughout many tropical environments.

Artificial cloning of organisms may also be called reproductive cloning.

Hans Spemann, a German embryologist was awarded a Nobel Prize in Physiology or Medicine in 1935 for his discovery of the effect now known as embryonic induction, exercised by various parts of the embryo, that directs the development of groups of cells into particular tissues and organs. In 1924 he and his student, Hilde Mangold, were the first to perform somatic-cell nuclear transfer using amphibian embryos one of the first steps towards cloning.[22]

Reproductive cloning generally uses "somatic cell nuclear transfer" (SCNT) to create animals that are genetically identical. This process entails the transfer of a nucleus from a donor adult cell (somatic cell) to an egg from which the nucleus has been removed, or to a cell from a blastocyst from which the nucleus has been removed.[23] If the egg begins to divide normally it is transferred into the uterus of the surrogate mother. Such clones are not strictly identical since the somatic cells may contain mutations in their nuclear DNA. Additionally, the mitochondria in the cytoplasm also contains DNA and during SCNT this mitochondrial DNA is wholly from the cytoplasmic donor's egg, thus the mitochondrial genome is not the same as that of the nucleus donor cell from which it was produced. This may have important implications for cross-species nuclear transfer in which nuclear-mitochondrial incompatibilities may lead to death.

Artificial embryo splitting or embryo twinning, a technique that creates monozygotic twins from a single embryo, is not considered in the same fashion as other methods of cloning. During that procedure, a donor embryo is split in two distinct embryos, that can then be transferred via embryo transfer. It is optimally performed at the 6- to 8-cell stage, where it can be used as an expansion of IVF to increase the number of available embryos.[24] If both embryos are successful, it gives rise to monozygotic (identical) twins.

Dolly, a Finn-Dorset ewe, was the first mammal to have been successfully cloned from an adult somatic cell. Dolly was formed by taking a cell from the udder of her 6-year-old biological mother.[25] Dolly's embryo was created by taking the cell and inserting it into a sheep ovum. It took 435 attempts before an embryo was successful.[26] The embryo was then placed inside a female sheep that went through a normal pregnancy.[27] She was cloned at the Roslin Institute in Scotland by British scientists Sir Ian Wilmut and Keith Campbell and lived there from her birth in 1996 until her death in 2003 when she was six. She was born on 5 July 1996 but not announced to the world until 22 February 1997.[28] Her stuffed remains were placed at Edinburgh's Royal Museum, part of the National Museums of Scotland.[29]

Dolly was publicly significant because the effort showed that genetic material from a specific adult cell, designed to express only a distinct subset of its genes, can be redesigned to grow an entirely new organism. Before this demonstration, it had been shown by John Gurdon that nuclei from differentiated cells could give rise to an entire organism after transplantation into an enucleated egg.[30] However, this concept was not yet demonstrated in a mammalian system.

The first mammalian cloning (resulting in Dolly) had a success rate of 29 embryos per 277 fertilized eggs, which produced three lambs at birth, one of which lived. In a bovine experiment involving 70 cloned calves, one-third of the calves died quite young. The first successfully cloned horse, Prometea, took 814 attempts. Notably, although the first[clarification needed] clones were frogs, no adult cloned frog has yet been produced from a somatic adult nucleus donor cell.

There were early claims that Dolly had pathologies resembling accelerated aging. Scientists speculated that Dolly's death in 2003 was related to the shortening of telomeres, DNA-protein complexes that protect the end of linear chromosomes. However, other researchers, including Ian Wilmut who led the team that successfully cloned Dolly, argue that Dolly's early death due to respiratory infection was unrelated to problems with the cloning process. This idea that the nuclei have not irreversibly aged was shown in 2013 to be true for mice.[31]

Dolly was named after performer Dolly Parton because the cells cloned to make her were from a mammary gland cell, and Parton is known for her ample cleavage.[32]

The modern cloning techniques involving nuclear transfer have been successfully performed on several species. Notable experiments include:

Human cloning is the creation of a genetically identical copy of a human. The term is generally used to refer to artificial human cloning, which is the reproduction of human cells and tissues. It does not refer to the natural conception and delivery of identical twins. The possibility of human cloning has raised controversies. These ethical concerns have prompted several nations to pass legislation regarding human cloning and its legality. As of right now, scientists have no intention of trying to clone people and they believe their results should spark a wider discussion about the laws and regulations the world needs to regulate cloning.[68]

Two commonly discussed types of theoretical human cloning are therapeutic cloning and reproductive cloning. Therapeutic cloning would involve cloning cells from a human for use in medicine and transplants, and is an active area of research, but is not in medical practice anywhere in the world, as of 2021[update]. Two common methods of therapeutic cloning that are being researched are somatic-cell nuclear transfer and, more recently, pluripotent stem cell induction. Reproductive cloning would involve making an entire cloned human, instead of just specific cells or tissues.[69]

There are a variety of ethical positions regarding the possibilities of cloning, especially human cloning. While many of these views are religious in origin, the questions raised by cloning are faced by secular perspectives as well. Perspectives on human cloning are theoretical, as human therapeutic and reproductive cloning are not commercially used; animals are currently cloned in laboratories and in livestock production.

Advocates support development of therapeutic cloning to generate tissues and whole organs to treat patients who otherwise cannot obtain transplants,[70] to avoid the need for immunosuppressive drugs,[69] and to stave off the effects of aging.[71] Advocates for reproductive cloning believe that parents who cannot otherwise procreate should have access to the technology.[72]

Opponents of cloning have concerns that technology is not yet developed enough to be safe[73] and that it could be prone to abuse (leading to the generation of humans from whom organs and tissues would be harvested),[74][75] as well as concerns about how cloned individuals could integrate with families and with society at large.[76][77]

Religious groups are divided, with some opposing the technology as usurping "God's place" and, to the extent embryos are used, destroying a human life; others support therapeutic cloning's potential life-saving benefits.[78][79]

Cloning of animals is opposed by animal-groups due to the number of cloned animals that suffer from malformations before they die, and while food from cloned animals has been approved by the US FDA,[80][81] its use is opposed by groups concerned about food safety.[82][83]

Cloning, or more precisely, the reconstruction of functional DNA from extinct species has, for decades, been a dream. Possible implications of this were dramatized in the 1984 novel Carnosaur and the 1990 novel Jurassic Park.[84][85] The best current cloning techniques have an average success rate of 9.4 percent[86] (and as high as 25 percent[31]) when working with familiar species such as mice,[note 1] while cloning wild animals is usually less than 1 percent successful.[89]

Several tissue banks have come into existence, including the "Frozen zoo" at the San Diego Zoo, to store frozen tissue from the world's rarest and most endangered species.[84][90][91] This is also referred to as "Conservation cloning".[92][93]

In 2001, a cow named Bessie gave birth to a cloned Asian gaur, an endangered species, but the calf died after two days. In 2003, a banteng was successfully cloned, followed by three African wildcats from a thawed frozen embryo. These successes provided hope that similar techniques (using surrogate mothers of another species) might be used to clone extinct species. Anticipating this possibility, tissue samples from the last bucardo (Pyrenean ibex) were frozen in liquid nitrogen immediately after it died in 2000. Researchers are also considering cloning endangered species such as the Giant panda and Cheetah.[94][95][96][97]

In 2002, geneticists at the Australian Museum announced that they had replicated DNA of the thylacine (Tasmanian tiger), at the time extinct for about 65 years, using polymerase chain reaction.[98] However, on 15 February 2005 the museum announced that it was stopping the project after tests showed the specimens' DNA had been too badly degraded by the (ethanol) preservative. On 15 May 2005 it was announced that the thylacine project would be revived, with new participation from researchers in New South Wales and Victoria.[99]

In 2003, for the first time, an extinct animal, the Pyrenean ibex mentioned above was cloned, at the Centre of Food Technology and Research of Aragon, using the preserved frozen cell nucleus of the skin samples from 2001 and domestic goat egg-cells. The ibex died shortly after birth due to physical defects in its lungs.[100]

One of the most anticipated targets for cloning was once the woolly mammoth, but attempts to extract DNA from frozen mammoths have been unsuccessful, though a joint Russo-Japanese team is currently working toward this goal.[when?] In January 2011, it was reported by Yomiuri Shimbun that a team of scientists headed by Akira Iritani of Kyoto University had built upon research by Dr. Wakayama, saying that they will extract DNA from a mammoth carcass that had been preserved in a Russian laboratory and insert it into the egg cells of an Asian elephant in hopes of producing a mammoth embryo. The researchers said they hoped to produce a baby mammoth within six years.[101][102] It was noted, however that the result, if possible, would be an elephant-mammoth hybrid rather than a true mammoth.[103] Another problem is the survival of the reconstructed mammoth: ruminants rely on a symbiosis with specific microbiota in their stomachs for digestion.[103]

Scientists at the University of Newcastle and University of New South Wales announced in March 2013 that the very recently extinct gastric-brooding frog would be the subject of a cloning attempt to resurrect the species.[104]

Many such "De-extinction" projects are described in the Long Now Foundation's Revive and Restore Project.[105]

After an eight-year project involving the use of a pioneering cloning technique, Japanese researchers created 25 generations of healthy cloned mice with normal lifespans, demonstrating that clones are not intrinsically shorter-lived than naturally born animals.[31][106] Other sources have noted that the offspring of clones tend to be healthier than the original clones and indistinguishable from animals produced naturally.[107]

Some posited that Dolly the sheep may have aged more quickly than naturally born animals, as she died relatively early for a sheep at the age of six. Ultimately, her death was attributed to a respiratory illness, and the "advanced aging" theory is disputed.[108][dubious discuss]

A detailed study released in 2016 and less detailed studies by others suggest that once cloned animals get past the first month or two of life they are generally healthy. However, early pregnancy loss and neonatal losses are still greater with cloning than natural conception or assisted reproduction (IVF). Current research is attempting to overcome these problems.[32]

Discussion of cloning in the popular media often presents the subject negatively. In an article in the 8 November 1993 article of Time, cloning was portrayed in a negative way, modifying Michelangelo's Creation of Adam to depict Adam with five identical hands.[109] Newsweek's 10 March 1997 issue also critiqued the ethics of human cloning, and included a graphic depicting identical babies in beakers.[110]

The concept of cloning, particularly human cloning, has featured a wide variety of science fiction works. An early fictional depiction of cloning is Bokanovsky's Process which features in Aldous Huxley's 1931 dystopian novel Brave New World. The process is applied to fertilized human eggs in vitro, causing them to split into identical genetic copies of the original.[111][112] Following renewed interest in cloning in the 1950s, the subject was explored further in works such as Poul Anderson's 1953 story UN-Man, which describes a technology called "exogenesis", and Gordon Rattray Taylor's book The Biological Time Bomb, which popularised the term "cloning" in 1963.[113]

Cloning is a recurring theme in a number of contemporary science fiction films, ranging from action films such as Anna to the Infinite Power, The Boys from Brazil, Jurassic Park (1993), Alien Resurrection (1997), The 6th Day (2000), Resident Evil (2002), Star Wars: Episode II Attack of the Clones (2002), The Island (2005) and Moon (2009) to comedies such as Woody Allen's 1973 film Sleeper.[114]

The process of cloning is represented variously in fiction. Many works depict the artificial creation of humans by a method of growing cells from a tissue or DNA sample; the replication may be instantaneous, or take place through slow growth of human embryos in artificial wombs. In the long-running British television series Doctor Who, the Fourth Doctor and his companion Leela were cloned in a matter of seconds from DNA samples ("The Invisible Enemy", 1977) and then in an apparent homage to the 1966 film Fantastic Voyage shrunk to microscopic size to enter the Doctor's body to combat an alien virus. The clones in this story are short-lived, and can only survive a matter of minutes before they expire.[115] Science fiction films such as The Matrix and Star Wars: Episode II Attack of the Clones have featured scenes of human foetuses being cultured on an industrial scale in mechanical tanks.[116]

Cloning humans from body parts is also a common theme in science fiction. Cloning features strongly among the science fiction conventions parodied in Woody Allen's Sleeper, the plot of which centres around an attempt to clone an assassinated dictator from his disembodied nose.[117] In the 2008 Doctor Who story "Journey's End", a duplicate version of the Tenth Doctor spontaneously grows from his severed hand, which had been cut off in a sword fight during an earlier episode.[118]

The 2021 film, Girl Next in which a woman is adducted, drugged and brainwashed into becoming obedient, living sex doll. Later proving that she is a clone of a clone designed to assassin the traffickers.

After the death of her beloved 14-year-old Coton de Tulear named Samantha in late 2017, Barbra Streisand announced that she had cloned the dog, and was now "waiting for [the two cloned pups] to get older so [she] can see if they have [Samantha's] brown eyes and her seriousness".[119] The operation cost $50,000 through the pet cloning company ViaGen.[120]

Science fiction has used cloning, most commonly and specifically human cloning, to raise the controversial questions of identity.[121][122] A Number is a 2002 play by English playwright Caryl Churchill which addresses the subject of human cloning and identity, especially nature and nurture. The story, set in the near future, is structured around the conflict between a father (Salter) and his sons (Bernard 1, Bernard 2, and Michael Black) two of whom are clones of the first one. A Number was adapted by Caryl Churchill for television, in a co-production between the BBC and HBO Films.[123]

In 2012, a Japanese television series named "Bunshin" was created. The story's main character, Mariko, is a woman studying child welfare in Hokkaido. She grew up always doubtful about the love from her mother, who looked nothing like her and who died nine years before. One day, she finds some of her mother's belongings at a relative's house, and heads to Tokyo to seek out the truth behind her birth. She later discovered that she was a clone.[124]

In the 2013 television series Orphan Black, cloning is used as a scientific study on the behavioral adaptation of the clones.[125] In a similar vein, the book The Double by Nobel Prize winner Jos Saramago explores the emotional experience of a man who discovers that he is a clone.[126]

Cloning has been used in fiction as a way of recreating historical figures. In the 1976 Ira Levin novel The Boys from Brazil and its 1978 film adaptation, Josef Mengele uses cloning to create copies of Adolf Hitler.[127]

In Michael Crichton's 1990 novel Jurassic Park, which spawned a series of Jurassic Park feature films, the bioengineering company InGen develops a technique to resurrect extinct species of dinosaurs by creating cloned creatures using DNA extracted from fossils. The cloned dinosaurs are used to populate the Jurassic Park wildlife park for the entertainment of visitors. The scheme goes disastrously wrong when the dinosaurs escape their enclosures. Despite being selectively cloned as females to prevent them from breeding, the dinosaurs develop the ability to reproduce through parthenogenesis.[128]

The use of cloning for military purposes has also been explored in several fictional works. In Doctor Who, an alien race of armour-clad, warlike beings called Sontarans was introduced in the 1973 serial "The Time Warrior". Sontarans are depicted as squat, bald creatures who have been genetically engineered for combat. Their weak spot is a "probic vent", a small socket at the back of their neck which is associated with the cloning process.[129] The concept of cloned soldiers being bred for combat was revisited in "The Doctor's Daughter" (2008), when the Doctor's DNA is used to create a female warrior called Jenny.[130]

The 1977 film Star Wars was set against the backdrop of a historical conflict called the Clone Wars. The events of this war were not fully explored until the prequel films Attack of the Clones (2002) and Revenge of the Sith (2005), which depict a space war waged by a massive army of heavily armoured clone troopers that leads to the foundation of the Galactic Empire. Cloned soldiers are "manufactured" on an industrial scale, genetically conditioned for obedience and combat effectiveness. It is also revealed that the popular character Boba Fett originated as a clone of Jango Fett, a mercenary who served as the genetic template for the clone troopers.[131][132]

A recurring sub-theme of cloning fiction is the use of clones as a supply of organs for transplantation. The 2005 Kazuo Ishiguro novel Never Let Me Go and the 2010 film adaption[133] are set in an alternate history in which cloned humans are created for the sole purpose of providing organ donations to naturally born humans, despite the fact that they are fully sentient and self-aware. The 2005 film The Island[134] revolves around a similar plot, with the exception that the clones are unaware of the reason for their existence.

The exploitation of human clones for dangerous and undesirable work was examined in the 2009 British science fiction film Moon.[135] In the futuristic novel Cloud Atlas and subsequent film, one of the story lines focuses on a genetically-engineered fabricant clone named Sonmi~451, one of millions raised in an artificial "wombtank", destined to serve from birth. She is one of thousands created for manual and emotional labor; Sonmi herself works as a server in a restaurant. She later discovers that the sole source of food for clones, called 'Soap', is manufactured from the clones themselves.[136]

In the film Us, at some point prior to the 1980s, the US Government creates clones of every citizen of the United States with the intention of using them to control their original counterparts, akin to voodoo dolls. This fails, as they were able to copy bodies, but unable to copy the souls of those they cloned. The project is abandoned and the clones are trapped exactly mirroring their above-ground counterparts' actions for generations. In the present day, the clones launch a surprise attack and manage to complete a mass-genocide of their unaware counterparts.[137][138]

In the series of A Certain Magical Index and A Certain Scientific Railgun, one of the espers, Mikoto Misaka, had DNA was harvested unknowingly, creating 20,000 exact but not equally powerful clones for an experiment. They were used as target practice by Accelerator, just to level up, as killing the original multiple times is impossible. The experiment ended when Toma Kamijo saved and foiled the experiment. The remaining clones have been dispersed everywhere in the world to conduct further experiments to expand their lifespans, save for at least 10 who remained in Academy City, and the last clone, who was not fully developed when the experiment stopped.[citation needed]

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Cloning - Wikipedia

Malignant tumor characterized by uncontrolled cell growth in lung tissue

Medical condition

Lung cancer, also known as lung carcinoma[8] (since about 9899% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissues of the lung.[9] Lung carcinomas derive from transformed, malignant cells that originate as epithelial cells, or from tissues composed of epithelial cells. Other lung cancers, such as the rare sarcomas of the lung, are generated by the malignant transformation of connective tissues (i.e. nerve, fat, muscle, bone), which arise from mesenchymal cells. Lymphomas and melanomas (from lymphoid and melanocyte cell lineages) can also rarely result in lung cancer.

In time, this uncontrolled growth can metastasize (spreading beyond the lung) either by direct extension, by entering the lymphatic circulation, or via hematogenous, bloodborne spread into nearby tissue or other, more distant parts of the body.[10] Most cancers that start in the lung, known as primary lung cancers, are carcinomas. The two main types are small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC).[3] The most common symptoms are coughing (including coughing up blood), weight loss, shortness of breath, and chest pains.[1]

The vast majority (85%) of cases of lung cancer are due to long-term tobacco smoking.[4] About 1015% of cases occur in people who have never smoked.[11] These cases are often caused by a combination of genetic factors and exposure to radon gas, asbestos, second-hand smoke, or other forms of air pollution.[4][5][12][13] Lung cancer may be seen on chest radiographs and computed tomography (CT) scans.[14] The diagnosis is confirmed by biopsy, which is usually performed by bronchoscopy or CT-guidance.[3][15]

The major method of prevention is the avoidance of risk factors, including smoking and air pollution.[16] Treatment and long-term outcomes depend on the type of cancer, the stage (degree of spread), and the person's overall health.[14] Most cases are not curable.[3] Common treatments include surgery, chemotherapy, and radiotherapy.[14] NSCLC is sometimes treated with surgery, whereas SCLC usually responds better to chemotherapy and radiotherapy.[17]

Worldwide in 2020, lung cancer occurred in 2.2 million people and resulted in 1.8 million deaths.[6] It is the most common cause of cancer-related death in both men and women.[18][19] The most common age at diagnosis is 70 years.[2] In most countries the five-year survival rate is around 10 to 20%,[6] while in Japan it is 33%, in Israel 27%, and in the Republic of Korea 25%.[6] Outcomes typically are worse in the developing world.[20]

Signs and symptoms that may suggest lung cancer include:[1]

If the cancer grows in the airways, it may obstruct airflow causing breathing difficulties. The obstruction can also lead to accumulation of secretions behind the blockage, and increase the risk of pneumonia.[1]

Many of the symptoms of lung cancer (poor appetite, weight loss, fever, fatigue) are not specific.[3] In many people, the cancer has already spread beyond the original site by the time they have symptoms and seek medical attention.[21] Symptoms that suggest the presence of metastatic disease include weight loss, bone pain, and neurological symptoms (headaches, fainting, convulsions, or limb weakness).[1] Common sites of spread include the brain, bone, adrenal glands, opposite lung, liver, pericardium, and kidneys.[21] About 10% of people with lung cancer do not have symptoms at diagnosis; these cancers are incidentally found on routine chest radiography.[15]

Depending on the type of tumor, paraneoplastic phenomena symptoms not due to the local presence of cancer may initially attract attention to the disease.[22] In lung cancer, these phenomena may include hypercalcemia, syndrome of inappropriate antidiuretic hormone (abnormally concentrated urine and diluted blood), ectopic ACTH production, or LambertEaton myasthenic syndrome (muscle weakness due to autoantibodies). Tumors in the top of the lung, known as Pancoast tumors, may invade the local part of the sympathetic nervous system, resulting in Horner's syndrome (dropping of the eyelid and a small pupil on that side), as well as damage to the brachial plexus.[1]

Cancer develops after genetic damage to DNA and epigenetic changes. Those changes affect the cell's normal functions, including cell proliferation, programmed cell death (apoptosis), and DNA repair. As more damage accumulates, the risk for cancer increases.[23]

Tobacco smoking is by far the main contributor to lung cancer.[4] Cigarette smoke contains at least 73 known carcinogens,[24] including benzo[a]pyrene,[25] NNK, 1,3-butadiene, and a radioactive isotope of polonium polonium-210.[24] Across the developed world, 90% of lung cancer deaths in men and 70% of those in women during 2000 were attributed to smoking.[26] Smoking accounts for about 85% of lung cancer cases.[14] Vaping may be a risk factor for lung cancer, but less than that of cigarettes, and further research is necessary due to the length of time it can take for lung cancer to develop following an exposure to carcinogens.[27][28]

Passive smoking the inhalation of smoke from another's smoking is a cause of lung cancer in nonsmokers. A passive smoker can be defined as someone either living or working with a smoker. Studies from the US,[29][30][31] the UK[32] and other European countries[33] have consistently shown a significantly-increased risk among those exposed to passive smoking.[34] The risk of developing lung cancer increases by 2528%.[35] Investigations of sidestream smoke (the main component of second-hand smoke; around 85%) suggest that it is more dangerous than direct mainstream smoke.[36]

Cannabis smoke contains many of the same carcinogens as those found in tobacco smoke,[37] but the effect of smoking cannabis on lung cancer risk is not clear.[38][39] A 2013 review did not find an increased risk from light to moderate use.[40] A 2014 review found that smoking cannabis doubled the risk of lung cancer, though cannabis is in many countries commonly mixed with tobacco.[41]

Radon is a colorless and odorless gas generated by the breakdown of radioactive radium, which in turn is the decay product of uranium, found in the Earth's crust. The radiation decay products ionize genetic material, causing mutations that sometimes become cancerous. Radon is the second-most common cause of lung cancer in the US,[42] causing about 21,000 deaths each year.[43] The risk increases 816% for every 100 Bq/m increase in the radon concentration.[44] Radon gas levels vary by locality and the composition of the underlying soil and rocks. About one in 15 homes in the US has radon levels above the recommended guideline of 4 picocuries per liter (pCi/l) (148 Bq/m).[45]

Asbestos can cause a variety of lung diseases such as lung cancer. Tobacco smoking and exposure to asbestos together have synergistic effects on the development of lung cancer.[5] In smokers who work with asbestos, the risk of lung cancer is increased 45-fold compared to the general population.[46] Asbestos can also cause cancer of the pleura, called mesothelioma which actually is different from lung cancer.[47]

Outdoor air pollutants, especially chemicals released from the burning of fossil fuels, increase the risk of lung cancer.[4] Fine particulates (PM2.5) and sulfate aerosols, which may be released in traffic exhaust fumes, are associated with a slightly increased risk.[4][48] For nitrogen dioxide, an incremental increase of 10 parts per billion increases the risk of lung cancer by 14%.[49] Outdoor air pollution is estimated to cause 12% of lung cancers.[4]

Tentative evidence supports an increased risk of lung cancer from indoor air pollution in relation to the burning of wood, charcoal, dung, or crop residue for cooking and heating.[50] Women who are exposed to indoor coal smoke have roughly twice the risk, and many of the by-products of burning biomass are known or suspected carcinogens.[51] This risk affects about 2.4billion people worldwide,[50] and it is believed to result in 1.5% of lung cancer deaths.[51]

About 8% of lung cancer cases are caused by inherited (genetic) factors.[52] In relatives of people who are diagnosed with lung cancer, the risk is doubled, likely due to a combination of genes.[53] Polymorphisms on chromosomes 5, 6, and 15 have been identified and are associated with an increased risk of lung cancer.[54] Single-nucleotide polymorphisms of the genes encoding the nicotinic acetylcholine receptor (nAChR) CHRNA5, CHRNA3, and CHRNB4 are of those associated with an increased risk of lung cancer, as well as RGS17 a gene regulating G-protein signaling.[54] Newer genetic studies, have identified 18 susceptibility loci achieving genome-wide significance. These loci highlight a heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, again identifying the cholinergic nicotinic receptors, e.g. CHRNA2.[55]

Numerous other substances, occupations, and environmental exposures have been linked to lung cancer. The International Agency for Research on Cancer states that "sufficient evidence" exists to show that the following are carcinogenic in the lungs:[56]

Similar to many other cancers, lung cancer is initiated by either the activation of oncogenes or the inactivation of tumor suppressor genes.[57] Carcinogens cause mutations in these genes that induce the development of cancer.[58]

Mutations in the K-ras proto-oncogene contribute to roughly 1030% of lung adenocarcinomas.[59][60] Nearly 4% of non-small-cell lung carcinomas involve an EML4-ALK tyrosine kinase fusion gene.[61]

Epigenetic changes such as alteration of DNA methylation, histone tail modification, or microRNA regulation may result in the inactivation of tumor suppressor genes.[62] Importantly, cancer cells develop resistance to oxidative stress, which enables them to withstand and exacerbate inflammatory conditions that inhibit the activity of the immune system against the tumor.[63][64]

The epidermal growth factor receptor (EGFR) regulates cell proliferation, apoptosis, angiogenesis, and tumor invasion.[59] Mutations and amplification of EGFR are common in NSCLC, and they provide the basis for treatment with EGFR inhibitors. Her2/neu is affected less frequently.[59] Other genes that are often mutated or amplified include c-MET, NKX2-1, LKB1, PIK3CA, and BRAF.[59]

The cell lines of origin are not fully understood.[1] The mechanism may involve the abnormal activation of stem cells. In the proximal airways, stem cells that express keratin 5 are more likely to be affected, typically leading to squamous-cell lung carcinoma. In the middle airways, implicated stem cells include club cells and neuroepithelial cells that express club-cell secretory protein. SCLC may originate from these cell lines[65] or neuroendocrine cells,[1] and it may express CD44.[65]

Metastasis of lung cancer requires transition from epithelial to mesenchymal cell type. This may occur through the activation of signaling pathways such as Akt/GSK3Beta, MEK-ERK, Fas, and Par6.[66]

Performing a chest radiograph (x-ray) is one of the first investigative steps if a person reports symptoms that may be suggestive of lung cancer. The x-ray may reveal an obvious mass, the widening of the mediastinum (suggestive of spread to lymph nodes there), atelectasis (lung collapse), consolidation (pneumonia), or pleural effusion.[14] Computed tomography (CT) imaging of the chest is often used for diagnosis and may reveal a spiculated mass which is highly suggestive of lung cancer. CT imaging is also used to provide more information about the type and extent of disease. Bronchoscopic or CT-guided biopsy is often used to sample the tumor for histopathology.[15]

Lung cancer can often appear as a solitary pulmonary nodule on a chest radiograph. However, the differential diagnosis is wide and many other diseases can also give this appearance, including metastatic cancer, hamartomas, and infectious granulomas caused by tuberculosis, histoplasmosis, or coccidioidomycosis.[67] Lung cancer can also be an incidental finding, as a solitary pulmonary nodule on a chest radiograph or CT scan done for an unrelated reason.[68] The definitive diagnosis of lung cancer is based on the histological examination of the suspicious tissue in the context of the clinical and radiological features.[1][3]

Clinical practice guidelines recommend specific frequencies (suggested intervals of time between tests) for pulmonary nodule surveillance.[69] CT imaging is not suggested to be used for longer or more frequently than indicated in the clinical guidelines, as any additional surveillance exposes people to increased radiation and is costly.[69]

Lung cancers are classified according to histological type.[3] This classification is important for determining both the management and predicting outcomes of the disease. Lung cancers are carcinomas malignancies that arise from epithelial cells. Lung carcinomas are categorized by the size and appearance of the malignant cells seen by a histopathologist under a microscope. For therapeutic purposes, two broad classes are distinguished: non-small-cell lung carcinoma (NSCLC) and small-cell lung carcinoma (SCLC).[71]

The three main subtypes of NSCLC are adenocarcinoma, squamous-cell carcinoma, and large-cell carcinoma.[1] Rare subtypes include pulmonary enteric adenocarcinoma.[72]

Nearly 40% of lung cancers are adenocarcinomas, which usually come from peripheral lung tissue.[3] Although most cases of adenocarcinoma are associated with smoking, it is also the most common form of lung cancer among people who have smoked fewer than 100 cigarettes in their lifetimes ("never-smokers")[1][73] and ex-smokers with a modest smoking history.[1] A subtype of adenocarcinoma, the bronchioloalveolar carcinoma, is more common in female never-smokers, and may have a better long-term survival.[74]

Squamous-cell carcinoma causes about 30% of lung cancers. They typically occur close to large airways. A hollow cavity and associated cell death are commonly found at the center of the tumor.[3]

About 10 to 15% of lung cancers are large-cell carcinoma.[75] These are so named because the cancer cells are large, with excess cytoplasm, large nuclei, and conspicuous nucleoli.[3]

In SCLC, the cells contain dense neurosecretory granules (vesicles containing neuroendocrine hormones), which give this tumor an endocrine or paraneoplastic syndrome association.[76] Most cases arise in the larger airways (primary and secondary bronchi).[15] About 6070% have extensive disease (which cannot be targeted within a single radiation therapy field) at presentation.[1]

Four main histological subtypes are recognised, although some cancers may contain a combination of different subtypes,[71] such as adenosquamous carcinoma.[3] Rare subtypes include carcinoid tumors, bronchial gland carcinomas, and sarcomatoid carcinomas.[3]

The lungs are a common place for the spread of tumors from other parts of the body. These tumors are called metastases or secondary tumors. The most common appearance on chest x-ray is the presence of multiple nodules in the lower lobes.[77]

Primary lung cancers also most commonly metastasize to the brain, bones, liver, and adrenal glands.[3] Immunostaining of a biopsy usually helps determine the original source.[78] The presence of Napsin-A, TTF-1, CK7, and CK20 help confirm the subtype of lung carcinoma. SCLC that originates from neuroendocrine cells may express CD56, neural cell adhesion molecule, synaptophysin, or chromogranin.[1]

Lung cancer staging is an assessment of the degree of spread of the cancer from its original source.[3] It is one of the factors affecting both the prognosis and the potential treatment of lung cancer.[1][3]

The evaluation of NSCLC staging uses the TNM classification (tumor, node, metastasis). This is based on the size of the primary tumor, lymph node involvement, and distant metastasis.[1]

Using the TNM descriptors, a group is assigned, ranging from occult cancer, through stages 0, IA (one-A), IB, IIA, IIB, IIIA, IIIB, and IV (four). This stage group assists with the choice of treatment and estimation of prognosis.[81]

SCLC has traditionally been classified as "limited stage" (confined to one-half of the chest and within the scope of a single tolerable radiotherapy field) or "extensive stage" (more widespread disease).[1] However, the TNM classification and grouping are useful in estimating prognosis.[81]

For both NSCLC and SCLC, the two general types of staging evaluations are clinical staging and surgical staging. Clinical staging is performed before definitive surgery. It is based on the results of imaging studies (such as CT scans and PET scans) and biopsy results. Surgical staging is evaluated either during or after the operation. It is based on the combined results of surgical and clinical findings, including surgical sampling of thoracic lymph nodes.[3]

Stage IA and IB lung cancer

One option for stage IIB lung cancer, with T2b; but if tumor is within 2cm of the carina, this is stage 3

Stage IIIA lung cancer, if there is one feature from the list on each side

Smoking prevention and smoking cessation are effective ways of reducing the risk of lung cancer.[82]

While in most countries industrial and domestic carcinogens have been identified and banned, tobacco smoking is still widespread. Eliminating tobacco smoking is a primary goal in the prevention of lung cancer, and smoking cessation is an important preventive tool in this process.[82]

Policy interventions to decrease passive smoking in public areas such as restaurants and workplaces have become more common in many Western countries.[83] Bhutan has had a complete smoking ban since 2005[84] while India introduced a ban on smoking in public in October 2008.[85] The World Health Organization has called for governments to institute a total ban on tobacco advertising to prevent young people from taking up smoking.[86] They assess that such bans have reduced tobacco consumption by 16% where instituted.[86]

Cancer screening uses medical tests to detect disease in large groups of people who have no symptoms.[87] For individuals with high risk of developing lung cancer, computed tomography (CT) screening can detect cancer and give a person options to respond to it in a way that prolongs life.[69][88] This form of screening reduces the chance of death from lung cancer by an absolute amount of 0.3% (relative amount of 20%).[89][90] High-risk people are those age 5574 who have smoked equivalent amount of a pack of cigarettes daily for 30 years including time within the past 15 years.[69]

CT screening is associated with a high rate of falsely positive tests, which may result in unneeded treatment.[91] For each accurate positive scan there are about 19 false positive scans.[90] Other concerns include radiation exposure[91] and the cost of testing along with follow up.[69] Research has not found two other available tests sputum cytology or chest radiograph (CXR) screening tests to have any benefit.[88][92]

The United States Preventive Services Task Force recommends yearly screening using low-dose CT in those who have a total smoking history of 30 pack-years and are between 55 and 80 years old until a person has not been smoking for more than 15 years.[93] Their recommendation excludes those with other health problems that would make treatment of lung cancer if found not an option.[93] The English National Health Service was in 2014 re-examining the evidence for screening.[94]

The long-term use of supplemental vitamin A,[95] B vitamins,[95] vitamin D[95] or vitamin E[95] does not reduce the risk of lung cancer. Vitamin C supplementation might reduce the risk of lung cancer.[96][97] Some studies have found vitamins A, B, and E may increase the risk of lung cancer in those who have a history of smoking.[95]

Some studies suggest that people who eat food with a higher proportion of vegetables and fruit tend to have a lower risk,[31][98] but this may be due to confounding with the lower risk actually due to the association of a high fruit and vegetables diet with less smoking.[99] Several rigorous studies have not demonstrated a clear association between diet and lung cancer risk,[1][98] although meta-analysis that accounts for smoking status may show benefit from a healthy diet.[100]

Treatment for lung cancer depends on the cancer's specific cell type, how far it has spread, and the person's performance status. Common treatments include palliative care,[101] surgery, chemotherapy, and radiation therapy.[1] Targeted therapy of lung cancer is growing in importance for advanced lung cancer.[102] In addition, smoking cessation and exercise is sometimes suggested.[103][104]

If investigations confirm NSCLC, the stage is assessed to determine whether the disease is localized and amenable to surgery or if it has spread to the point where it cannot be cured surgically. CT scan and PET-CT, noninvasive tests, can be used to help rule out malignancy or mediastinal lymph node involvement.[1][105] If mediastinal lymph node involvement is suspected using PET-CT, the nodes can be sampled (using a biopsy) to assist staging, a PET-CT scan is not accurate enough to be used alone.[105] Techniques used for obtaining a sample include transthoracic needle aspiration, transbronchial needle aspiration (with or without endobronchial ultrasound), endoscopic ultrasound with needle aspiration, mediastinoscopy, and thoracoscopy.[106] Blood tests and pulmonary function testing are used to assess whether a person is well enough for surgery.[15] If pulmonary function tests reveal poor respiratory reserve, surgery may not be possible.[1]

In most cases of early-stage NSCLC, removal of a lobe of lung (lobectomy) is the surgical treatment of choice. In people who are unfit for a full lobectomy, a smaller sublobar excision (wedge resection) may be performed. However, wedge resection has a higher risk of recurrence than lobectomy. Radioactive iodine brachytherapy at the margins of wedge excision may reduce the risk of recurrence. Rarely, removal of a whole lung (pneumonectomy) is performed.[107] Video-assisted thoracoscopic surgery (VATS) and VATS lobectomy use a minimally invasive approach to lung cancer surgery.[108] VATS lobectomy is equally effective compared to conventional open lobectomy, with less postoperative illness.[109]

In SCLC, chemotherapy or radiotherapy is typically used, or sometimes both.[110] However, the role of surgery in SCLC is being reconsidered. Surgery might improve outcomes when added to chemotherapy and radiation in early-stage SCLC.[111]

The effectiveness of lung cancer surgery (resection) for people with stage I IIA NSCLC is not clear, but weak evidence suggests that a combined approach of lung cancer resection and removing the mediastinal lymph nodes (mediastinal lymph node dissection) may improve survival compared to lung resection and a sample of mediastinal nodes (not a complete node dissection).[needs update][112]

Radiotherapy is often given together with chemotherapy, and may be used with curative intent in people with NSCLC who are not eligible for surgery.[113] This form of high-intensity radiotherapy is called radical radiotherapy.[46] A refinement of this technique is continuous hyperfractionated accelerated radiotherapy (CHART), in which a high dose of radiotherapy is given in a short time period.[114] Radiosurgery refers to the radiotherapy technique of giving a precise high-dose of radiotherapy that is guided by a computer.[115] Postoperative (adjuvant) thoracic radiotherapy generally is not used after curative-intent surgery for NSCLC.[116] Some people with mediastinal N2 lymph node involvement might benefit from post-operative radiotherapy.[117]

For potentially curable SCLC cases treated with surgery, post-operative chest radiotherapy is recommended.[3] The ideal timing of these therapies (the optimal time to give radiotherapy and chemotherapy for improving survival) is not known.[118]

If cancer growth blocks a short section of bronchus, brachytherapy (localized radiotherapy) may be given directly inside the airway to open the passage. Compared to external beam radiotherapy, brachytherapy allows a reduction in treatment time and reduced radiation exposure to healthcare staff.[119] Evidence for brachytherapy, however, is less than that for external beam radiotherapy.[120]

Prophylactic cranial irradiation is a type of radiotherapy to the brain, used to reduce the risk of metastasis. PCI is used in SCLC.[46] In limited-stage disease, PCI increases three-year survival from 15% to 20%; in extensive disease, one-year survival increases from 13% to 27%.[121] For people who have NSCLC and a single brain metastasis, it is not clear if surgery is more effective than radiosurgery.[115]

Improvements in targeting and imaging have led to the development of stereotactic radiation in the treatment of early-stage lung cancer. In this form of radiotherapy, high doses are delivered over a number of sessions using stereotactic targeting techniques. Its use is primarily in patients who are not surgical candidates due to medical comorbidities.[122]

For both NSCLC and SCLC patients, smaller doses of radiation to the chest may be used for symptom control (palliative radiotherapy).[123][124] The use of higher doses of radiotherapy for palliative care are not shown to prolong survival.[124]

The chemotherapy regimen depends on the tumor type.[3] SCLC, even relatively early-stage disease, is treated primarily with chemotherapy and radiation.[125] In SCLC, cisplatin/carboplatin and etoposide are most commonly used.[126] Combinations with carboplatin, gemcitabine, paclitaxel, vinorelbine, topotecan, and irinotecan are also used.[127][128] In advanced NSCLC, chemotherapy improves survival and is used as first-line treatment, provided the person is well enough for the treatment.[129] Typically, two drugs are used, of which one is often platinum-based (either cisplatin or carboplatin). Other commonly used drugs are gemcitabine, paclitaxel, docetaxel,[130][131] pemetrexed,[132] etoposide or vinorelbine.[131] Platinum-based drugs and combinations that include platinum therapy do not appear to be more beneficial for prolonging survival compared to other nonplatinum medications, and may lead to a higher risk of serious adverse effects, such as nausea, vomiting, anaemia, and thrombocytopenia,[133] especially in people over the age of 70.[134] Evidence is insufficient to determine which chemotherapy approach is associated with the highest quality of life.[133] Also, evidence is lacking to determine if treating people with NSCLC a second time when the first round of chemotherapy was not successful (second-line chemotherapy) causes more benefit or harm.[135]

Adjuvant chemotherapy refers to the use of chemotherapy after apparently curative surgery to improve the outcome. In NSCLC, samples are taken of nearby lymph nodes during surgery to assist staging. If stage-II or -III disease is confirmed, adjuvant chemotherapy (including or not including postoperative radiotherapy) improves survival by 4% at five years.[136][137][138] The combination of vinorelbine and cisplatin is more effective than older regimens.[137] Adjuvant chemotherapy for people with stage IB cancer is controversial, as clinical trials have not clearly demonstrated a survival benefit.[139] Chemotherapy before surgery in NSCLC that can be removed surgically may improve outcomes.[140][141]

Chemotherapy may be combined with palliative care in the treatment of the NSCLC.[142] In advanced cases, appropriate chemotherapy improves average survival over supportive care alone, as well as improving quality of life.[142][143] With adequate physical fitness maintaining chemotherapy during lung cancer palliation offers 1.5 to 3 months of prolongation of survival, symptomatic relief, and an improvement in quality of life, with better results seen with modern agents.[144][145] The NSCLC Meta-Analyses Collaborative Group recommends if the recipient wants and can tolerate treatment, then chemotherapy can be considered in advanced NSCLC.[129][146]

Several drugs that target molecular pathways in lung cancer are available, especially for the treatment of advanced disease. Erlotinib, gefitinib, afatinib, dacomitinib, and osimertinib inhibit tyrosine kinase activity of the epidermal growth factor receptor (EGFR). These EGFR inhibitors may help delay the spread of cancer cells for people with EGFR M+ lung cancer and may improve a person's quality of life.[147] EGFR inhibitors have not been shown to help people survive longer.[147] For people with EGFR mutations, treatment with gefitinib may result in an improved quality of life compared to treatment with chemotherapy.[148]

Immunotherapy may be used for both SCLC and NSCLC.[149][150] NSCLC cells expressing programmed death-ligand 1 (PD-L1) could interact with programmed death receptor 1 (PD-1) expressed on the surface of T cells, and result in decreased tumor cell kill by the immune system.[151] Atezolizumab is an anti PD-L1 monoclonal antibody. Nivolumab and Pembrolizumab are anti PD-1 monoclonal antibodies. Ipilimumab is a monoclonal antibody that targets Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) on the surface of T cells. Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor in the circulation, and functions as an angiogenesis inhibitor.[151] Multiple phase 3 clinical trials utilizing immunotherapy in the first line for treatment of NSCLC were published, including Pembrolizumab in KEYNOTE-024, KEYNOTE-042, KEYNOTE-189 and KEYNOTE-407; Nivolumab and Ipilimumab in CHECKMATE-227 and CHECKMATE 9LA; and Atezolizumab in IMpower110, IMpower130 and IMpower150.[151]Denosumab, a monoclonal antibody directed against receptor activator of nuclear factor kappa-B ligand, and zoledronic acid may be useful in the treatment of bone metastases.[152]

Vaccine-based immunotherapy treatment after surgery or radiotherapy may not lead to improved survival for people with stages I-III NSCLC.[153]

Several treatments can be provided via bronchoscopy for the management of airway obstruction or bleeding. If an airway becomes obstructed by cancer growth, options include rigid bronchoscopy, balloon bronchoplasty, stenting, and microdebridement.[154] Laser photosection involves the delivery of laser light inside the airway via a bronchoscope to remove the obstructing tumor.[155]

Palliative care when added to usual cancer care benefits people even when they are still receiving chemotherapy.[156] These approaches allow additional discussion of treatment options and provide opportunities to arrive at well-considered decisions.[157][158] Palliative care may avoid unhelpful but expensive care not only at the end of life, but also throughout the course of the illness. For individuals who have more advanced disease, hospice care may also be appropriate.[15][158]

The most effective intervention for avoiding death from lung cancer is to stop smoking; even people who already have lung cancer are encouraged to stop smoking.[104] There is no clear evidence which smoking cessation program is most effective for people who have been diagnosed with lung cancer.[104]

Some weak evidence suggests that certain supportive care interventions (noninvasive) that focus on well-being for people with lung cancer may improve quality of life.[159] Interventions such as nurse follow-ups, psychotherapy, psychosocial therapy, and educational programs may be beneficial, however, the evidence is not strong (further research is needed).[159] Counseling may help people cope with emotional symptoms related to lung cancer.[159] Reflexology may be effective in the short-term, however more research is needed.[159] No evidence has been found to suggest that nutritional interventions or exercise programs for a person with lung cancer result in an improvement in the quality of life that are relevant or last very long.[159]

Exercise training may benefit people with NSCLC who are recovering from lung surgery.[160] In addition, exercise training may benefit people with NSCLC who have received radiotherapy, chemotherapy, chemoradiotherapy, or palliative care.[161] Exercise training before lung cancer surgery may also improve outcomes.[103] It is unclear if exercise training or exercise programs are beneficial for people who have advanced lung cancer.[162][159] A home-based component in a personalized physical rehabilitation program may be useful for recovery.[161] It is unclear if home-based prehabilitation (before surgery) leads to less adverse events or hospitalization time.[161] Physical rehabilitation with a home-based component may improve recovery after treatment and overall lung health.[161]

Of all people with lung cancer in the US, around 17% to 20% survive for at least five years after diagnosis.[163][2][164] In England and Wales, between 2013 and 2017, overall five-year survival for lung cancer was estimated at 13.8%.[165] Outcomes are generally worse in the developing world.[20] Due to late detection, the stage of lung cancer is often advanced at the time of diagnosis. At presentation, about one-third of cases of NSCLC have metastatic disease, and 6070% of SCLC have extensive-stage disease.[3] Survival for lung cancer falls as the stage at diagnosis becomes more advanced; the English data suggest that around 70% of patients survive at least a year when diagnosed at the earliest stage, but this falls to just 14% for those diagnosed with the most advanced disease (stage IV).[166]

Prognostic factors in NSCLC include presence of pulmonary symptoms, large tumor size (>3cm), nonsquamous cell type (histology), degree of spread (stage) and metastases to multiple lymph nodes, and vascular invasion. For people with inoperable disease, outcomes are worse in those with poor performance status and weight loss of more than 10%.[167] Prognostic factors in small cell lung cancer include performance status, biological sex, stage of disease, and involvement of the central nervous system or liver at the time of diagnosis.[168]

For NSCLC, the best prognosis is achieved with complete surgical resection of stage-IA disease, with up to 70% five-year survival.[169] People with extensive-stage SCLC have an average five-year survival rate less than 1%. The average survival time for limited-stage disease is 20 months, with a five-year survival rate of 20%.[14] The prognosis of patients with NSCLC improved significantly in the last years with the introduction of immunotherapy.[151]

According to data provided by the National Cancer Institute, the median age at diagnosis of lung cancer in the US is 70 years,[needs update][170] and the median age at death is 72 years.[needs update][171] In the US, people with medical insurance are more likely to have a better outcome.[172]

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Worldwide, lung cancer is the most common cancer among men for both incidence and mortality, and among women has the third-highest incidence (after breast and colorectal cancers) and second-highest mortality (after breast cancer). In 2020, 2.2million new cases were found worldwide, and 1.8million deaths were due to lung cancer, representing 18.0% of all deaths from cancer. The highest rates are in Micronesia, Polynesia, Europe, Asia, North America and Europe. Rates in Africa and Central America are much lower.[6]

People who have a long history of smoking have the highest risk of developing lung cancer, with the risk increasing with duration of smoking. The incidence in men rose until the mid-1980s, and has declined since then. In women, the incidence rose until the late 1990s, and has since been stable.[3]

For every 34million cigarettes smoked, one lung cancer death can occur.[173] The influence of "Big Tobacco" plays a significant role in smoking.[174] Young nonsmokers who see tobacco advertisements are more likely to smoke.[175] The role of passive smoking is increasingly being recognized as a risk factor for lung cancer,[34] resulting in policy interventions to decrease the undesired exposure of nonsmokers to others' tobacco smoke.[176]

From the 1960s, the rates of lung adenocarcinoma started to rise in relation to other kinds of lung cancer, partially due to the introduction of filter cigarettes. The use of filters removes larger particles from tobacco smoke, thus reducing deposition in larger airways. However, the smoker has to inhale more deeply to receive the same amount of nicotine, increasing particle deposition in small airways where adenocarcinoma tends to arise.[177] Rates of lung adenocarcinoma continues to rise.[178]

In the US, both black men and black women have a higher incidence.[179][180] The lifetime risk of developing lung cancer is 8% in men and 6% in women.[1]

Also in the US, military veterans have a 2550% higher rate of lung cancer primarily due to higher rates of smoking.[181] During World War II and the Korean War, asbestos also played a role, and Agent Orange may have caused some problems during the Vietnam War.[182]

Lung cancer is the third-most common cancer in the UK (47,968 people were diagnosed with the disease in 2017),[183] and it is the most common cause of cancer-related death (around 34,600 people died in 2018).[184]

Lung cancer rates are currently lower in developing countries.[185] With increased smoking in developing countries, the rates are expected to increase in the next few years, notably in both China[186] and India.[187]

Lung cancer was uncommon before the advent of cigarette smoking; it was not even recognized as a distinct disease until 1761.[188] Different aspects of lung cancer were described further in 1810.[189] Malignant lung tumors made up only 1% of all cancers seen at autopsy in 1878, but had risen to 1015% by the early 1900s.[190] Case reports in the medical literature numbered only 374 worldwide in 1912,[191] but a review of autopsies showed the incidence of lung cancer had increased from 0.3% in 1852 to 5.66% in 1952.[192] In Germany in 1929, physician Fritz Lickint recognized the link between smoking and lung cancer,[190] which led to an aggressive antismoking campaign.[193] The British Doctors' Study, published in the 1950s, was the first solid epidemiological evidence of the link between lung cancer and smoking.[194] As a result, in 1964, the Surgeon General of the United States recommended smokers should stop smoking.[195]

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Researchers at University Hospitals create a breakthrough in CAR-T cell therapy for cancer patients  News 5 Cleveland WEWS

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Researchers at University Hospitals create a breakthrough in CAR-T cell therapy for cancer patients - News 5 Cleveland WEWS

Problems soon after transplant

Many of the problems that can happen shortly after the transplant come from having the bone marrow wiped out by medicines or radiation just before the transplant. Others may be side effects of the conditioning treatments themselves.

Your transplant team can help you cope with side effects. Some can be prevented, and most can be treated to help you feel better. This is not a complete list and you should tell your doctor or transplant team about any problems you have or changes you notice. Some of these problems can be life-threatening, so its important to be able to reach your doctor or transplant team at night, on weekends, and during holidays. Ask for their after hours contact numbers to makesure you will be able to do this.

Mucositis (inflammation or sores in the mouth) is a short-term side effect that can happen with chemo and radiation. It usually gets better within a few weeks after treatment, but it can make it very painful to eat and drink.

Good nutrition is important for people with cancer. If mouth pain or sores make it hard to eat or swallow, your transplant team can help you develop a plan to manage your symptoms.

Because chemotherapy drugs can cause severe nausea and vomiting, doctors often give anti-nausea medicines at the same time as chemo to try to prevent it. As much as possible, the goal is to prevent nausea and vomiting, because its easier to prevent it than it is to stop it once it starts. Preventive treatment should start before chemo is given and should continue for as long as the chemo is likely to cause vomiting, which can be up to 7 to 10 days after the last dose.

No one drug can prevent or control chemo-related nausea and vomiting 100% of the time. In many cases, two or more medicines are used. Youll need to tell your transplant team how well the medicines are controlling your nausea and vomiting. If they arent working, they will need to be changed.

For at least the first 6 weeks after transplant, until the new stem cells start making white blood cells (engraftment), you can easily get serious infections. Bacterial infections are most common during this time, but viral infections that were controlled by your immune system can become active again. Fungal infections can also be an issue. And even infections that cause only mild symptoms in people with normal immune systems can be quite dangerous for you. This is because right after the transplant you don't have many white blood cells that are working well, and they are the primary immune cells that fight off infections.

You may be given antibiotics to try to prevent infections until your blood counts reach a certain level. For instance, pneumocystis pneumonia (often called PCP) is a common infection thats easy to catch. Even though the germ doesnt harm people with normal immune systems, for others it can cause fever, cough, and serious breathing problems. Antibiotics are often used to keep transplant patients from getting this.

Your doctor may check you before the transplant for signs of certain infections that may become active after transplant, and give you special medicines to keep those germs under control. For example, the virus called CMV (cytomegalovirus) is a common infection that many adults have or had in the past. Adults with healthy immune systems may not have any symptoms because their immune system can keep the virus under control. But, CMV can be a cause of serious pneumonia in people who have had transplants, because the transplant lowers the amount of white blood cells they have. Pneumonia from CMVmainly happens to people who were already infected with CMV, or whose donor had the virus. If neither you nor your donor had CMV, the transplant team might follow special precautions to prevent this infection while you are in the hospital.

After engraftment, the risk of infection is lower, but it still can happen. It can take 6 months to a year after transplant for the immune system to work as well as it should. It can take even longer for patients with graft-versus-host disease (GVHD, see below). It's important to talk to your cancer care team about your risk for infection during this time.

Because of the increased risk, you will be watched closely for signs of infection, such as fever, cough, shortness of breath, or diarrhea. Your doctor may check your blood often, and extra precautions will be needed to keep you from being exposed to germs. While in the hospital, everyone who enters your room must wash their hands well. They may also wear gowns, shoe coverings, gloves, and masks.

Since flowers and plants can carry bacteria and fungi, theyre not allowed in your room. For the same reason, you may be told not to eat certain fresh fruits and vegetables. All your food must be well cooked and handled very carefully by you and family members. You might need to avoid certain foods for a while.

You may also be told to avoid contact with soil, feces (stool, both human and animal), aquariums, reptiles, and exotic pets. Your team may tell you to avoid being near disturbed soil, bird droppings, or mold. You will need to wash your hands after touching pets. Your family may need to move the cats litter box away from places you eat or spend your time. Also, you should not clean pet cages or litter boxes during this time. Instead, give this task to a family member or friend.

Your transplant team will tell you and your family in detail about the precautions you need to follow. There are many viruses, bacteria, and fungi that can cause infection after your transplant. You may be at risk for some more than others.

Despite all these precautions, patients often develop fevers, one of the first signs of infection. In fact, sometimes fever is the only sign of infection, so it's very important to contact your cancer care team if you have one or if you have any other signs of infection. You'll probably be asked to take your temperature by mouth every day or twice a day for a while. And your cancer care team will let you know when you should call in your temperature to them. If you get a fever, tests will be done to look for possible causes of the infection (chest x-rays, urine tests, and blood cultures) and antibiotics will be started.

After transplant, youre at risk for bleeding because the conditioning treatment destroys your bodys ability to make platelets. Platelets are the blood cells that help blood to clot. While you wait for your transplanted stem cells to start working, your transplant team may have you follow special precautions to avoid injury and bleeding.

Platelet counts are low for at least several weeks after transplant. In the meantime, you might notice easy bruising and bleeding, such as nosebleeds and bleeding gums. If your platelet count drops below a certain level, a platelet transfusion may be needed. Youll need to follow precautions until your platelet counts stay at safe levels.

It also takes time for your bone marrow to start making red blood cells, and you might need red blood cell transfusions from time to time as you recover.

For more information on the transfusion process, see Blood Transfusion and Donation.

Pneumonitis is a type of inflammation (swelling) in lung tissue thats most common in the first 100 days after transplant. But some lung problems can happen much later even 2 or more years after transplant.

Pneumonia caused by infection happens more often, but pneumonitis may be caused by radiation, graft-versus-host disease, or chemo rather than germs. Its caused by damage to the areas between the cells of the lungs (called interstitial spaces).

Pneumonitis can be severe, especially if total body irradiation was given with chemo as part of the pre-transplant (conditioning) treatment. Chest x-rays will be taken in the hospital to watch for pneumonitis as well as pneumonia. Some doctors will do breathing tests every few months if you have graft-versus-host disease (see next section).

You should report any shortness of breath or changes in your breathing to your doctor or transplant team right away. There are many other types of lung and breathing problems that also need to be handled quickly.

Graft-versus-host disease (GVHD) can happen in allogeneic transplants when the immune cells from the donor see your body as foreign. (Remember: The recipients immune system has mostly been destroyed by conditioning treatment and cannot fight back, so the new stem cells make up most of the immune system after transplant.) The donor immune cells may attack certain organs, most often the skin, gastrointestinal (GI) tract, and liver. This can change the way the organs work and increase the chances of infection.

GVHD reactions are very common and can range from barely noticeable to life-threatening. Doctors think of GVHD as acute or chronic. Acute GVHD starts soon after transplant and lasts a short time. Chronic GVHD starts later and lasts a long time. A person could have one, both, or neither type of GVHD.

Acute GVHD can happen 10 to 90 days after a transplant, though the average time is around 25 days.

About one-third to one-half of allogeneic transplant recipients will develop acute GVHD. Its less common in younger patients and in those with closer HLA matches between donor and the patient.

The first signs are usually a rash, burning, and redness of the skin on the palms and soles. This can spread over the entire body. Other symptoms can include:

Doctors try to prevent acute GVHD by giving drugs that suppress the immune system, such as steroids (glucocorticoids), methotrexate, cyclosporine, tacrolimus, or certain monoclonal antibodies. These drugs are given before acute GVHD starts and can help prevent serious GVHD. Still, mild GVHD will almost always happen in allogeneic transplant patients. Other drugs are being tested in different combinations for GVHD prevention.

The risk of acute GVHD can also be lowered by removing immune cells called T-cells from the donor stem cells before the transplant. But this can also increase the risk of viral infection, leukemia relapse, and graft failure (which is discussed later). Researchers are looking at new ways to remove only certain cells, called alloactivated T-cells, from donor grafts. This would reduce the severity of GVHD and still let the donor T-cells destroy any cancer cells left.

If acute GVHD does occur, it is most often mild, mainly affecting the skin. But sometimes it can be more serious, or even life-threatening.

Mild cases can often be treated with a steroid drug applied to the skin (topically) as an ointment, cream, or lotion, or with other skin treatments. More serious cases of GVHD might need to be treated with a steroid drug taken as a pill or injected into a vein. If steroids arent effective, other drugs that affect the immune system can be used.

Chronic GVHD

Chronic GVHD can start anywhere from about 90 to 600 days after the stem cell transplant. A rash on the palms of the hands or the soles of the feet is often the earliest sign. The rash can spread and is usually itchy and dry. In severe cases, the skin may blister and peel, like a bad sunburn. A fever may also develop. Other symptoms of chronic GVHD can include:

Chronic GVHD is treated with medicines that suppress the immune system, much like those used for acute GVHD. These drugs can increase your risk of infection for as long as you are treated for GVHD. Most patients with chronic GVHD can stop the immunosuppressive drugs after their symptoms improve.

Hepatic veno-occlusive disease (VOD) is a serious problem in which tiny veins and other blood vessels inside the liver become blocked. Its not common, and it only happens in people with allogeneic transplants, and mainly in those who got the drugs busulfan or melphalan as part of conditioning, or treatment that was given before the transplant.

VOD usually happens within about 3 weeks after transplant. Its more common in older people who had liver problems before the transplant, and in those with acute GVHD. It starts with yellowing skin and eyes, dark urine, tenderness below the right ribs (this is where the liver is), and quick weight gain (mostly from fluid that bloats the belly). It is life-threatening, so early diagnosis of VOD is very important. Researchers continue to find ways to try to measure a person's chances of getting VOD so that treatment can start as soon as possible.

Grafts fail when the body does not accept the new stem cells (the graft). The stem cells that were given do not go into the bone marrow and multiply like they should. Graft failure is more common when the patient and donor are not well matched and when patients get stem cells that have had the T-cells removed. It can also happen in patients who get a low number of stem cells, such as a single umbilical cord unit. Still, its not very common.

Graft failure can lead to serious bleeding and/or infection. Graft failure is suspected in patients whose counts do not start going up within 3 to 4 weeks of a bone marrow or peripheral blood transplant, or within 7 weeks of a cord blood transplant.

Although it can be very upsetting to have this happen, these people can get treated with a second dose of stem cells, if they are available. Grafts rarely fail, but if they do it can result in death.

The type of problems that can happen after a transplant depend on many factors, such as the type of transplant done, the pre-transplant chemo or radiation treatment used, the patients overall health, the patients age when the transplant was done, the length and degree of immune system suppression, and whether chronic graft-versus-host-disease (GVHD) is present and how bad it is. The problems can be caused by the conditioning treatment (the pre-transplant chemotherapy and radiation therapy), especially total body irradiation, or by other drugs used during transplant (such as the drugs that may be needed to suppress the immune system after transplant). Possible long-term risks of transplant include:

The medicines used in transplants can harm the bodys organs, such as the heart, lungs, kidneys, liver, bones/joints, and nervous system. You may need careful follow-up with close monitoring and treatment of the long-term organ problems that the transplant can cause. Some of these, like infertility, should be discussed before the transplant, so you can prepare for them.

Its important to find and quickly treat any long-term problems. Tell your doctor right away if you notice any changes or problems. Physical exams by your doctor, blood work, imaging tests, lung/breathing studies, and other tests will help look for and keep tabs on organ problems.

As transplant methods have improved, more people are living longer and doctors are learning more about the long-term results of stem cell transplant. Researchers continue to look for better ways to care for these survivors to give them the best possible quality of life.

The goal of a stem cell transplant in cancer is to prolong life and, in many cases, even cure the cancer. But in some cases, the cancer comes back (sometimes called relapse or recurrence depending on when it might occur after a transplant). Relapse or recurrence can happen a few months to a few years after transplant. It happens much more rarely 5 or more years after transplant.

If cancer comes back, treatment options are often quite limited. A lot depends on your overall health at that point, and whether the type of cancer you have responds well to drug treatment. Treatment for those who are otherwise healthy and strong may include chemotherapy or targeted therapy. Some patients who have had allogeneic transplants may be helped by getting white blood cells from the same donor (this is called donor lymphocyte infusion) to boost the graft-versus-cancer effect. Sometimes a second transplant is possible. But most of these treatments pose serious risks even to healthier patients, so those who are frail, older, or have chronic health problems are often unable to have them.

Other options may include palliative (comfort) care, or a clinical trial of an investigational treatment. Its important to know what the expected outcome of any further treatment might be, so talk with your doctor about the purpose of the treatment. Be sure you understand the benefits and risks before you decide.

Along with the possibility of the original cancer coming back (relapse) after it was treated with a stem cell transplant, there is also a chance of having a second cancer after transplant. Studies have shown that people who have had allogeneic transplants have a higher risk of second cancer than people who got a different type of stem cell transplant.

A cancer called post-transplant lymphoproliferative disease (PTLD), if it occurs, usually develops within the first year after the transplant. Other conditions and cancers that can happen are solid tumor cancers in different organs, leukemia, and myelodysplastic syndromes. These other conditions, if they occur, tend to develop a few years or longer after the transplant.

Risk factors for developing a second cancer are being studied and may include:

Successfully treating a first cancer gives a second cancer time (and the chance) to develop. No matter what type of cancer is treated, and even without the high doses used for transplant, treatments like radiation and chemo can lead to a second cancer in the future.

Post-transplant lymphoproliferative disorder (PTLD) is an out-of-control growth of lymph cells, actually a type of lymphoma, that can develop after an allogeneic stem cell transplant. Its linked to T-cells (a type of white blood cell that is part of the immune system) and the presence of Epstein-Barr virus (EBV). T-cells normally help rid the body of cells that contain viruses. When the T-cells arent working well, EBV-infected B-lymphocytes (a type of white blood cell) can grow and multiply. Most people are infected with EBV at some time during their lives, but the infection is controlled by a healthy immune system. The pre-transplant treatment given weakens the immune system, allowing the EBV infection to get out of control, which can lead to a PTLD.

Still, PTLD after allogeneic stem cell transplant is fairly rare. It most often develops within 1 to 6 months after allogeneic stem cell transplant, when the immune system is still very weak.

PTLD is life-threatening. It may show up as lymph node swelling, fever, and chills. Theres no one standard treatment, but its often treated by cutting back on immunosuppressant drugs to let the patients immune system fight back. Other treatments include white blood cell (lymphocyte) transfusions to boost the immune response, using drugs like rituximab to kill the B cells, and giving anti-viral drugs to treat the EBV.

Even though PTLD doesnt often happen after transplant, its more likely to occur with less well-matched donors and when strong suppression of the immune system is needed. Studies are being done to identify risk factors for PTLD and look for ways to prevent it in transplant patients who are at risk.

Most people who have stem cell transplants become infertile (unable to have children). This is not caused by the cells that are transplanted, but rather by the high doses of chemo and/or radiation therapy used. These treatments affect both normal and abnormal cells, and often damage reproductive organs.

If having children is important to you, or if you think it might be important in the future, talk to your doctor about ways to protect your fertility before treatment. Your doctor may be able to tell you if a particular treatment will be likely to cause infertility.

After chemo or radiation, some women may find their menstrual periods become irregular or stop completely. This doesnt always mean they cannot get pregnant, so birth control should be used before and after a transplant. The drugs used in transplants can harm a growing fetus.

The drugs used during transplant can also damage sperm, so men should use birth control to avoid starting a pregnancy during and for some time after the transplant process. Transplants may cause temporary or permanent infertility for men as well. Fertility returns in some men, but the timing is unpredictable. Men might consider storing their sperm before having a transplant.

For more information on having children after being treated for canceror sexual problems related to cancer treatment, see Fertility and Sexual Side Effects.

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Stem Cell or Bone Marrow Transplant Side Effects - American Cancer Society

June CH, Sadelain M. Chimeric antigen receptor therapy. N Engl J Med. 2018;379(1):6473.

CAS PubMed PubMed Central Article Google Scholar

Dunbar CE, High KA, Joung JK, Kohn DB, Ozawa K, Sadelain M. Gene therapy comes of age. Science. 2018;359(6372):eaan4672.

PubMed Article CAS Google Scholar

Sordo-Bahamonde C, Vitale M. Mechanisms of resistance to NK cell immunotherapy. Cancers (Basel). 2020;12(4):893.

CAS Article Google Scholar

Weber EW, Maus MV, Mackall CL. The emerging landscape of immune cell therapies. Cell. 2020;181(1):4662.

CAS PubMed Article PubMed Central Google Scholar

Melaiu O, Lucarini V, Cifaldi L, Fruci D. Influence of the tumor microenvironment on NK cell function in solid tumors. Front Immunol. 2020;10:3038.

PubMed PubMed Central Article CAS Google Scholar

Stoiber S, Cadilha BL, Benmebarek M-R, Lesch S, Endres S, Kobold S. Limitations in the design of chimeric antigen receptors for cancer therapy. Cells. 2019;8(5):472.

CAS PubMed Central Article Google Scholar

Dotti G, Gottschalk S, Savoldo B, Brenner MK. Design and development of therapies using chimeric antigen receptor-expressing T cells. Immunol Rev. 2014;257(1):10726.

CAS PubMed Article Google Scholar

Wei J, Han X, Bo J, Han W. Target selection for CAR-T therapy. J Hematol Oncol. 2019;12(1):62.

PubMed PubMed Central Article Google Scholar

Fleischer LC, Spencer HT, Raikar SS. Targeting T cell malignancies using CAR-based immunotherapy: challenges and potential solutions. J Hematol Oncol. 2019;12(1):141.

PubMed PubMed Central Article Google Scholar

Walsh Z, Yang Y, Kohler ME. Immunobiology of chimeric antigen receptor T cells and novel designs. Immunol Rev. 2019;290(1):10013.

CAS PubMed Article Google Scholar

Wang W, Jiang J, Wu C. CAR-NK for tumor immunotherapy: clinical transformation and future prospects. Cancer Lett. 2020;472:17580.

CAS PubMed Article Google Scholar

Pfefferle A, Huntington ND. You have got a fast CAR: chimeric antigen receptor NK cells in cancer therapy. Cancers (Basel). 2020;12(3):706.

CAS Article Google Scholar

Burger MC, Zhang C, Harter PN, Romanski A, Strassheimer F, Senft C, Tonn T, Steinbach JP, Wels WS. CAR-engineered NK cells for the treatment of glioblastoma: turning innate effectors into precision tools for cancer immunotherapy. Front Immunol. 2019;10:2683.

CAS PubMed PubMed Central Article Google Scholar

Hu Y, Tian Z, Zhang C. Chimeric antigen receptor (CAR)-transduced natural killer cells in tumor immunotherapy. Acta Pharmacol Sin. 2018;39(2):16776.

CAS PubMed Article Google Scholar

Shimasaki N, Jain A, Campana D. NK cells for cancer immunotherapy. Nat Rev Drug Discov. 2020;19(3):20018.

CAS PubMed Article Google Scholar

Klichinsky M, Ruella M, Shestova O, Lu XM, Best A, Zeeman M, Schmierer M, Gabrusiewicz K, Anderson NR, Petty NE, et al. Human chimeric antigen receptor macrophages for cancer immunotherapy. Nat Biotechnol. 2020;38(8):94753.

CAS PubMed Article PubMed Central Google Scholar

June CH, OConnor RS, Kawalekar OU, Ghassemi S, Milone MC. CAR T cell immunotherapy for human cancer. Science. 2018;359(6382):13615.

CAS Article PubMed Google Scholar

Fang F, Xiao W, Tian Z. Challenges of NK cell-based immunotherapy in the new era. J Front Med. 2018;12(4):44050.

Article Google Scholar

Hu Y, Tian Z, Zhang C. Natural killer cell-based immunotherapy for cancer: advances and prospects. Engineering. 2019;5(1):10614.

CAS Article Google Scholar

Carotta S, Targeting NK. Cells for anticancer immunotherapy: clinical and preclinical approaches. Front Immunol. 2016;7:152.

PubMed PubMed Central Article Google Scholar

He Y, Tian Z. NK cell education via nonclassical MHC and non-MHC ligands. Cell Mol Immunol. 2017;14(4):32130.

CAS PubMed Article Google Scholar

Orr MT, Lanier LL. Natural killer cell education and tolerance. Cell. 2010;142(6):84756.

CAS PubMed PubMed Central Article Google Scholar

Miller JS, Soignier Y, Panoskaltsis-Mortari A, McNearney SA, Yun GH, Fautsch SK, McKenna D, Le C, Defor TE, Burns LJ, et al. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood. 2005;105(8):30517.

CAS PubMed Article Google Scholar

Ruggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD, Tosti A, Posati S, Rogaia D, Frassoni F, Aversa F, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science. 2002;295(5562):2097100.

CAS PubMed Article Google Scholar

Simonetta F, Alvarez M, Negrin RS. Natural killer cells in graft-versus-host-disease after allogeneic hematopoietic cell transplantation. Front Immunol. 2017;8:465.

PubMed PubMed Central Article CAS Google Scholar

Huang R-S, Lai M-C, Shih H-A, Lin S. A robust platform for expansion and genome editing of primary human natural killer cells. J Exp Med. 2021;218(3):e20201529.

CAS PubMed Article PubMed Central Google Scholar

Suen WC-W, Lee WY-W, Leung K-T, Pan X-H, Li G. Natural skiller cell-based cancer immunotherapy: a review on 10 years completed clinical trials. Cancer Investig. 2018;36(8):43157.

CAS Article Google Scholar

Li Y, Hermanson DL, Moriarity BS, Kaufman DS. Human iPSC-derived natural killer cells engineered with chimeric antigen receptors enhance anti-tumor activity. Cell Stem Cell. 2018;23(2):18192.

CAS PubMed PubMed Central Article Google Scholar

Quintarelli C, Sivori S, Caruso S, Carlomagno S, Falco M, Boffa I, Orlando D, Guercio M, Abbaszadeh Z, Sinibaldi M, et al. Efficacy of third-party chimeric antigen receptor modified peripheral blood natural killer cells for adoptive cell therapy of B-cell precursor acute lymphoblastic leukemia. Leukemia. 2020;34(4):110215.

CAS PubMed Article Google Scholar

Liu E, Marin D, Banerjee P, Macapinlac HA, Thompson P, Basar R, Nassif Kerbauy L, Overman B, Thall P, Kaplan M, et al. Use of CAR-transduced natural killer cells in CD19-positive lymphoid tumors. N Engl J Med. 2020;382(6):54553.

CAS PubMed PubMed Central Article Google Scholar

Ying Z, Huang XF, Xiang X, Liu Y, Kang X, Song Y, Guo X, Liu H, Ding N, Zhang T, et al. A safe and potent anti-CD19 CAR T cell therapy. Nat Med. 2019;25(6):94753.

CAS PubMed PubMed Central Article Google Scholar

Allan DSJ, Chakraborty M, Waller GC, Hochman MJ, Poolcharoen A, Reger RN, Childs RW. Systematic improvements in lentiviral transduction of primary human natural killer cells undergoing ex vivo expansion. Mol Ther Methods Clin Dev. 2021;20:55971.

CAS PubMed PubMed Central Article Google Scholar

Kulemzin SV, Matvienko DA, Sabirov AH, Sokratyan AM, Chernikova DS, Belovezhets TN, Chikaev AN, Taranin AV, Gorchakov AA. Design and analysis of stably integrated reporters for inducible transgene expression in human T cells and CAR NK-cell lines. BMC Med Genomics. 2019;12(2):44.

PubMed PubMed Central Article CAS Google Scholar

Milone MC, Fish JD, Carpenito C, Carroll RG, Binder GK, Teachey D, Samanta M, Lakhal M, Gloss B, Danet-Desnoyers G, et al. Chimeric receptors containing CD137 signal transduction domains mediate enhanced survival of T cells and increased antileukemic efficacy in vivo. Mol Ther. 2009;17(8):145364.

CAS PubMed PubMed Central Article Google Scholar

Jones S, Peng PD, Yang S, Hsu C, Cohen CJ, Zhao Y, Abad J, Zheng Z, Rosenberg SA, Morgan RA. Lentiviral vector design for optimal T cell receptor gene expression in the transduction of peripheral blood lymphocytes and tumor-infiltrating lymphocytes. Hum Gene Ther. 2009;20(6):63040.

CAS PubMed PubMed Central Article Google Scholar

Fujiwara K, Masutani M, Tachibana M, Okada N. Impact of scFv structure in chimeric antigen receptor on receptor expression efficiency and antigen recognition properties. Biochem Biophys Res Commun. 2020;527(2):3507.

CAS PubMed Article Google Scholar

Rad SMAH, Poudel A, Tan GMY, McLellan AD. Promoter choice: Who should drive the CAR in T cells? PLoS ONE. 2020;15(7):e0232915e0232915.

Article CAS Google Scholar

Zimmermann K, Kuehle J, Dragon AC, Galla M, Kloth C, Rudek LS, Sandalcioglu IE, Neyazi B, Moritz T, Meyer J, et al. Design and characterization of an All-in-One lentiviral vector system combining constitutive anti-GD2 CAR expression and inducible cytokines. Cancers (Basel). 2020;12(2):375.

CAS Article Google Scholar

Li W, Qiu S, Chen J, Jiang S, Chen W, Jiang J, Wang F, Si W, Shu Y, Wei P, et al. Chimeric antigen receptor designed to prevent ubiquitination and downregulation showed durable antitumor efficacy. Immunity. 2020;53(2):45670.

CAS PubMed Article Google Scholar

Eyquem J, Mansilla-Soto J, Giavridis T, van der Stegen SJ, Hamieh M, Cunanan KM, Odak A, Gonen M, Sadelain M. Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection. Nature. 2017;543(7643):1137.

CAS PubMed PubMed Central Article Google Scholar

Torikai H, Reik A, Liu PQ, Zhou Y, Zhang L, Maiti S, Huls H, Miller JC, Kebriaei P, Rabinovich B, et al. A foundation for universal T-cell based immunotherapy: T cells engineered to express a CD19-specific chimeric-antigen-receptor and eliminate expression of endogenous TCR. Blood. 2012;119(24):5697705.

CAS PubMed PubMed Central Article Google Scholar

Nguyen DN, Roth TL, Li PJ, Chen PA, Apathy R, Mamedov MR, Vo LT, Tobin VR, Goodman D, Shifrut E, et al. Polymer-stabilized Cas9 nanoparticles and modified repair templates increase genome editing efficiency. Nat Biotechnol. 2020;38(1):449.

CAS PubMed Article Google Scholar

Pomeroy EJ, Hunzeker JT, Kluesner MG, Lahr WS, Smeester BA, Crosby MR, Lonetree C, Yamamoto K, Bendzick L, Miller JS, et al. A genetically engineered primary human natural killer cell platform for cancer immunotherapy. Mol Ther. 2020;28(1):5263.

CAS PubMed Article Google Scholar

Owji H, Nezafat N, Negahdaripour M, Hajiebrahimi A, Ghasemi Y. A comprehensive review of signal peptides: structure, roles, and applications. Eur J Cell Biol. 2018;97(6):42241.

CAS PubMed Article Google Scholar

Nyathi Y, Wilkinson BM, Pool MR. Co-translational targeting and translocation of proteins to the endoplasmic reticulum. Biochim Biophys Acta. 2013;1833(11):2392402.

CAS PubMed Article Google Scholar

Voss M, Schrder B, Fluhrer R. Mechanism, specificity, and physiology of signal peptide peptidase (SPP) and SPP-like proteases. Biochimica et Biophysica Acta BBA Biomembranes. 2013;1828(12):282839.

CAS PubMed Article Google Scholar

Haso W, Lee DW, Shah NN, Stetler-Stevenson M, Yuan CM, Pastan IH, Dimitrov DS, Morgan RA, FitzGerald DJ, Barrett DM, et al. Anti-CD22-chimeric antigen receptors targeting B-cell precursor acute lymphoblastic leukemia. Blood. 2013;121(7):116574.

CAS PubMed PubMed Central Article Google Scholar

Wilkie S, Picco G, Foster J, Davies DM, Julien S, Cooper L, Arif S, Mather SJ, Taylor-Papadimitriou J, Burchell JM, et al. Retargeting of human T cells to tumor-associated MUC1: the evolution of a chimeric antigen receptor. J Immunol. 2008;180(7):49019.

CAS PubMed Article Google Scholar

Posey AD, Schwab RD, Boesteanu AC, Steentoft C, Mandel U, Engels B, Stone JD, Madsen TD, Schreiber K, Haines KM. Engineered CAR T cells targeting the cancer-associated Tn-glycoform of the membrane mucin MUC1 control adenocarcinoma. Immunity. 2016;44(6):144454.

CAS PubMed PubMed Central Article Google Scholar

Morgan RA, Yang JC, Kitano M, Dudley ME, Laurencot CM, Rosenberg SA. Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol Ther. 2010;18(4):84351.

CAS PubMed PubMed Central Article Google Scholar

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Chimeric antigen receptor natural killer (CAR-NK) cell design and ...

As fun as gift-giving is, it can also bring upon some anxiety when you start thinking about how much you may have to spend. But, thanks to Amazon, those worries are a thing of the past. You no longer have to go out searching for an expensive present thatll impress your loved ones. All you have to do is scroll through this list to get a ton of ideas and have your final picks delivered straight to your door for under $30 or even $10 (like this travel cosmetics bag).

All these products are things that can be incorporated into someones everyday life, so you know that youre giving them something thatll actually be used. Plus, many of them, like this Apple watch charging stand and these wireless earbuds, have over 30,000 reviews from happy customers, so you can feel confident giving these out. So get to shopping and wrapping now before it all sells out.

01

These Shatterproof Wine Glasses That Are Made Of Stainless Steel

To keep drinks cold for longer and avoid any dangerous breaks at their next dinner party, gift the host with the most this set of stainless steel wine glasses. The stemless shape is comfortable to hold but you can rest assured knowing that if there is an accident, the cup wont shatter or even dent. The set comes in a bunch of different styles (including a rustic wood option), making it easy to match to your friends decor.

02

A Candle Wick Trimmer Set To Prevent Black Smoke

Add this wick trimmer set to the candle fiend in your life so that they have everything they need to make their home smell and feel like a spa. This wick dipper, wick trimmer, and candle snuffer lets them properly care for their candle. By making sure the wick is clean every time and put out instantly, theyll have smooth wax without any fallen ashes melted in and less black smoke each time. The trio comes in gold and rose gold finishes and will make any countertop look a little more fancy when displayed.

03

This Chic Glass Teapot With A Built-In Steeper

Any tea lover would appreciate this glass teapot not just because of its stylish look but its built-in steeper too. The stainless steel mesh infuser is rust-free and fit to steep any kind of loose tea leaves without them escaping into your cup. Plus, the small vent in the lid allows steam to be released during the process. Grab the matching set of glass cups to complete the gift.

04

This Zippered Passport Holder That Protects Against Data Theft

This passport holder zips shut to assure that nothing slips out or gets damaged inside its water-resistant nylon. In addition to the twill lining and soft foam that make up the case, a layer of RFID-blocking material is built in as well to keep your ID and credit cards safe from data theft. The holder has pockets for up to four passports in addition to multiple card slots and zippered pockets so one person can keep everything in track for the whole family, all in one place.

05

A Makeup Brush Cleaner That Washes & Dries

Whether your friend is a pro makeup artist or just loves to do their own glam, this electric makeup brush cleaner can save them a ton of time. The kit includes a handheld electric cleaner and eight collars to fit any size brush to the device. As the collars hold the brush within the included bowl, use the handheld piece to spin the tool. This method can be used to both wash and dry each brush so that theyre all germ-free within minutes.

06

These Reusable Baking Mats That Cookies Wont Get Stuck To

Make things easier for the bakers in your life with these silicone baking mats that can be used time and time again. They wont have to use any kind of cooking oil or single-use parchment paper to get their delicious creations to slide right off the non-stick surface. The mat can handle temperatures from -40 to 480 degrees Fahrenheit, so it is safe to keep in the freezer for overnight recipes.

07

The Wine Aerator That Fits Right Onto The Mouth Of Any Bottle

Instead of just bringing a bottle of wine to the next dinner party, gift the hosts this set of two wine aerators. The small gadget can be popped into the mouth of any bottle and infuses oxygen inside to bring out all the underlying flavors of the blend. The stainless steel plate regulator spreads the wine through the holes while pouring to maximize air exposure, making even cheap wine taste expensive.

08

These Clear Containers That Are Shaped Like Sweet Sheep

These acrylic storage containers can act as a gift for both a parent and their little one. The duo comes in either a sheep or elephant shape so that even cotton balls and Q-tips can have a fun home in the bathroom. Each clear holder stands firm on the four legs and comes with a lid to keep everything clean and in order. Theyre a great way to store things in plain sight without it being an eyesore.

09

This Scalp Massager With 2 Removable Heads

This scalp massager is a must for anyone whos obsessed with hair care. The gentle silicone bristles can remove dry skin, dandruff, and product buildup to give hair follicles a healthy base to grow from while acting as a soothing massage at the same time. Both heads can be used on wet or dry hair.

10

A Measuring Spoon That You Can Adjust To 6 Different Increments

Made of food-grade zinc alloy and plastic, this measuring spoon isnt just an average tablespoon. It actually adjusts to six different measurements from 1/2 teaspoon all the way to 1 tablespoon. It can be used for wet or dry ingredients, which means that this one tool will help you seriously declutter your kitchen drawers.

11

The Packing Cube Set That Keeps Luggage Organized

Even the most seasoned traveler will benefit from these packing cubes. This five-pack comes with various sizes all made of water-resistant nylon and breathable mesh thats shut tight with a snag-free zipper that wont damage clothes. Separate your bras and underwear from your tops and pants so that everything is easy to find once its time to unpack. You can also separate your dirty clothes using the included laundry bag.

12

This Body Glitter Gel Made With Aloe For A Healthy Glow

Whether its for a costume party or to spruce up a concert outfit, this glitter gel is a great way to add a bit of sparkle without damaging your skin. With ingredients like aloe vera and peppermint essential oil, the gel soothes and brightens so that your glow comes from much more than just the shimmer. The formula dries quickly and washes away with soap and water. Grab a few of fun colors so they can mix and match.

13

A UV Flashlight That Helps Find Hidden Scents & Stains

For the clean freak in your life, its hard to beat this UV flashlight. Bright enough to even be used with the lights on, this flashlight has 68 LED bulbs that help you to find hidden scents and stains that may be lingering. This flashlight is easy to operate too, thanks to an anti-slip grip and single-button on/off feature.

14

This Set Of Shower Steamers That Are So Soothing

Turn any shower into a five-star spa with this six-pack of shower steamers. Made in relaxing scents like grapefruit, peony & pear, and lemongrass & coconut, these steamers are made with essential oils that are strong but not overwhelming. Any residue left over will rinse right out post-shower, so theres no need to worry about clean up.

15

This Clip-On Strainer That Saves Drawer Space

This clip-on colander is a great present for those who love to cook but dont exactly have all the space to store the tools they need. Though its half the size of a typical strainer, this piece works even better. Your pasta, fruit, or veggies can be strained and kept in the same pot or bowl by just clipping the silicone piece to any pot or pan. The grip of the BPA-free silicone keeps the food from falling out as the water is released through the built-in spout that prevents splashing.

16

A Foot Peel Mask That Removes Calluses

Who doesnt want baby-soft feet? This foot peel mask slides on like a sock to exfoliate and moisturize even the roughest, driest skin. After wearing for one hour, soak your feet, and watsh as your skin slowly peels off over the course of two weeks to reveal smooth heels without any cracks or calluses. With over 12,000 five-star reviews, you know this is one you have to immediately add to cart.

17

This Salt & Pepper Grinder Set That Looks So Expensive

These salt and pepper grinders are seriously chic, but theres more to this duo than just looks. Theyre made with durable glass and stainless steel that is meant to last, and the grinder element is on the top, which means you wont get weird residue on your counters. The entire set comes in a convenient caddy, so you can carry these from the counter to the table with ease.

18

This Rip-Resistant Towel That Offers Serious Exfoliation

For the skincare guru, its hard to beat this exfoliating towel. Made in the textile capital of Japan, this towel is soft yet super textured to scrub away dry, old skin. This towel also has an oversized design that means you can scrub at hard-to-reach spots including the middle of your back.

19

A Pour-Over Coffee Maker With A Steel Mesh Filter

At just 6 inches tall, this pour-over coffee maker is perfect for anyone who lives alone and doesnt want too much precious counter space taken up. All they have to do is place their favorite ground blend into the stainless steel mesh filter, pour over boiling water, and within minutes theyll have a flavorful pick-me-up thats as good as any cafes brew. And the insulated collar makes it easy to enjoy right away without burning your hands.

20

A Marshmallow Whip Maker That Turns Any Cleanser Into Foam

For that friend whos always looking for the next beauty tool on the market, surprise them with this marshmallow whip maker. The magical product can turn any gel, liquid, or even powder cleanser into a foam for a gentle product to use every day. Placing in just a pearl-sized amount of product and filling the tub with water will give you a ton more product to work with after giving it a few pumps.

21

A Pack Of Silicone Straws That Come With A Cleaning Brush

To reduce waste and cut everyday costs, this pack of silicone straws is great to have around. The flexible pieces can be used in any tumbler and even be cut to the perfect length for shorter cups. This pack comes with five different fun colors, none of which fade after use in both cold and hot drinks. Use the long cleaning brush to make sure theyre spotless after sipping.

22

These Shiny Silk Scrunchies That Dont Tug On Hair

Let your friends in on the secret that these silk scrunchies are much gentler than typical hair ties. The super soft band reduces tugging and pulling to prevent breakage and even stops that weird crease from forming after wearing a ponytail. Plus, the pretty sheen is a fabulous touch to any outfit.

23

This Mushroom-Shaped Funnel Thats Extremely Handy

This funnel isnt just mushroom shaped to be adorable though it certainly is that. This shape actually comes seriously in handy for funneling into slim bottles. Flip up the dotted mushroom top to create a funnel, and the stem can fit into your bottle for a seamless pour. The flexible silicone means this mushroom is suitable for vessels of various sizes.

24

A Makeup Remover Oil With A Non-Greasy Formula

This makeup remover oil is full of natural ingredients like baobab seed oil and essential oils. The formula works to dissolve buildup from pores, remove dead skin cells, and restore moisture so that your skin is left clean and glowing. The non-greasy blend wont leave residual oil, so you dont have to think twice about using it when you want a deep clean or a smooth base to give yourself a face massage.

25

These Clip-On Book Lights That Have 3 Lighting Modes

These clip-on book lights have three different lighting modes: white, amber, and daylight, so you can adjust the hue to best suit your comfort level and needs. Unlike a lot of book lights, these are rechargeable via USB, and one power-up lasts for 30 hours of late-night reading. These lights also feature a flexible gooseneck and lightweight design, so you wont get tired when holding up your book.

26

A Pair Of Silicone Oven Mitts with A Comfy Quilted Lining

Being heat-resistant up to 450 degrees Fahrenheit, these silicone oven mitts are sure to last a lot longer than typical cotton ones. The durable exterior is both steam-resistant and waterproof so your hands are protected from any boiling pasta. Plus, the textured surface gives you a sturdy grip on baking sheets and pot handles so you can avoid any dangerous messes. The interior, meanwhile, is lined in a quilted cotton, making them comfy to wear throughout the entire cooking process. Use the attached loops to hang them right on the wall so theyre always close by.

27

This 6-Pack Of Car Air Fresheners That Clip Onto Any Vent

These car air fresheners are so cute that people will think theyre just a decoration. These flower clips snap onto any car vent and release a refreshing scent thatll mask any odors so it may be perfect for anyone with a pet who likes to go on joy rides. The durable tear-resistant material is meant to last and can even handle a paw or two coming its way.

28

This Cuticle Cream Made With Shea Butter & Vitamin E

This cuticle cream is made with a ton of nourishing ingredients like Japanese seaweed, aloe vera, and and shea butter, and the serum replenishes lost minerals that help nails grow. After massaging into your nail beds, youll be left with an instant shine and silky smooth feel. The formula is paraben-free and fragrance-free, making it perfect for anyone who loves beauty but is conscious about what they use.

29

A Cold Brew Maker Thats Super Easy To Use

The body of this cold brew maker is a glass pitcher that can brew up to 4 cups overnight and has measurement indicators so you know just how much youre making. The stainless-steel precision-cut filter in addition to the silicone rings that line the tight cap keep the blend as fresh as can be so it can be kept in the fridge and enjoyed for days without letting grinds into your coffee. The silicone base keeps it in place even on smooth countertops and wide handle gives you a comfortable grip when pouring.

30

This Non-Slip Yoga Mat With 70 Pose Illustrations Drawn On

For anyone who has wanted to get into zen practices, this instructional yoga mat is the perfect way to start. The 70 illustrations right on the mat demonstrate different poses so that they always have inspiration and a guide to follow. The mat itself is 5 millimeters thick and has a great grip to keep you sturdy. Plus, its made of earth-friendly materials that are easy to wipe clean after a sweat session.

31

This Bread Banneton That Creates A Spiral Ring Pattern

Upgrade the baker in your lifes creations with this bread banneton. The 9-inch proofing bowl is made of natural cane wood that is durable enough too hold 1.5 pounds of dough. The material wicks away moisture to leave the crust perfectly crispy, and the round shape creates a spiral ring in the dough. Itll make any batch look like it was baked by a pro.

32

This Calming Mist That You Can Spritz On Your Linens

Made from plant-based essential oils, this calming pillow mist smells like one of the most relaxing things out there: lavender. This mist is free of dyes, synthetic fragrances, parabens, phosphates, and other undesirable things. But it is jam-packed with a soothing scent that you can spritz onto your pillow, linens, clothes, bathroom, and anywhere else you want a good fragrance.

33

A Desktop Organizer With 4 Separate Compartments

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75 Clever Gifts That Are Really, Really Cheap On Amazon - Elite Daily

halioua began 2020 with $5.1 million in funding. By way of thanks she sent all of her investors, including Rosen, fluffy toy puppies wearing company bandanas. She secured an office on the edge of downtown San Francisco, but the lease began in March, the same month the Bay Area became the first part of the US to enter pandemic lockdown. Her companys formative months, and first hires, took place via Zoom, Slack, and eventually socially distanced meetups. Halioua raised another $6 million and hired scientists, veterinarians, and an expert in getting new animal drugs past the FDA.

She embraced the role of dog company CEOpainting a mural of a giant German shepherd in Loyals office and ordering shirts with the slogan Save the dogs, save the world. She adopted a fluffy white husky named Wolfie, whom she has described as her cofounder and Loyals chief evangelist. Her management style, she says, was informed by her bad experiences at Oxford. When she talks to her team about her goals or beliefs, she tries to pair her statements with evidence to convince her workers that the boss is being straight with them. Even if you dont trust me, you still know this is true, she says.

Haliouas new science team, including a scientist who previously led aging research at pharma giant Regeneron, helped refine her original idea. They identified a compound they believed could be given to young dogs of the largest breeds, such as French mastiffs, to delay their accelerated aging process. They found a second compound they thought could target processes that cause cognitive decline and kidney problems in older dogs of all sizes.

As her company gained traction, Halioua noticed certain patterns in her business interactions. She tried to recruit women investors but found it difficult because there werent many to ask. When she met with investors who were men, some would try to flip a business meeting into a date, and others would confidently explain science to her that she knew inside out. Mostly she brushed off such momentsher time at Oxford had lowered her expectations of those with more power and prestige than her.

She often felt different. Describing herself as an Oxford dropout helped convince people to take her seriouslynever mind that she had left her PhD in part due to dissatisfaction with a harassment investigation, a circumstance missing from the dropout tales of archetypal boy geniuses like Mark Zuckerberg. She listened to hundreds of Silicon Valley podcasts to try to learn the industrys patois. She trained herself to smile less and wrote in a blog post aimed at women entrepreneurs: I come off as more of a grump now, but I am a grump who has the money she needs to build her company.

In the spring of 2021, Halioua published a blog post about her Oxford PhD supervisor titled The Gifts of My Harasser, leaving him nameless. She described the paradox of one of her worst experiences laying a foundation stone for her later successes by teaching her to be skeptical of social hierarchies and institutional power. Its been two years since I left. I am not broken anymore, but I still feel the cracks, she wrote. His abuse shattered my preconceived notions of how the world worked and cleared a path I otherwise never would have found.

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The Search for a Pill That Can Help Dogsand HumansLive Longer - WIRED

There isnt a cure for diabetes right now. But our scientists across the UK are pushing boundaries and taking steps to build a future where diabetes can do no harm.

Our scientists are busy with exciting developments. Here, we take a look at the life-changing research taking place both for type 1 and type2 diabetes.

Theres no cure yet, but our scientists are working on a ground-breaking weight management study, to help people put their type 2 diabetes into remission.

Remission is when blood glucose (or blood sugar) levels are in a normal range again. This doesnt mean diabetes has gone for good. Its still really important for people in remission to get regular healthcare checks. But being in remission can be life changing.

Our ground-breaking study is called DiRECT, short for Diabetes Remission Clinical Trial, and it could completely change the way type 2 diabetes is treated in the future.

Latest on our low-calorie DiRECT study

In type 1 diabetes, insulin-producing beta cells in the pancreas are destroyed by the immune system. This means you cant make the insulin you need to live.

To stop type 1 diabetes we need to disrupt the immune systems attack on beta cells. And our scientists are working on it. Theyre aiming to develop and test treatments called immunotherapies that target the immune system to stop it destroying beta cells.

But our scientists across the UK aren't finished. And its only with your help that we can push ahead with ground-breaking research to find a cure. Will you donate today and help us lead the fight against diabetes?

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Is there a cure for diabetes? | Research | Diabetes UK

Halloween is so much fun for us..but honestly, it's probably pretty horrifying for our pets who don't understand a thing about our scary celebrations. I spoke with Dr. Nancy at Companions Animal Hospital and Vicki Davis from the Tri-County Humane Society, and they gave me some great tips I've kept in mind over the years. I hope these are helpful to you as well.

If you are going to have pumpkins with candles inside, or other lit decorations that cats could knock off a countertop, be watchful. We want you and your pets to have a safe and happy Halloween.

BE CAREFUL WITH COSTUMES

Don't put your dog or cat in a costume if they really hate it. Make sure it's not pinching them, and that they can see, walk and move comfortably. Your pet may look super cute in it, but if they are dancing around and trying to get out of it, don't torcher them.

Photo by Meyer Zinn on Unsplash

You know pets. If there is something they aren't supposed to get into, they'll find a way to get into it. Those treats for example. Unfortunately, many Halloween treats are toxic for your pets. Chocolate can be very dangerous for your cats and dogs, and sugar-free candies and fake sugar sweeteners are also very dangerous.

Does your dog bark, jump, and run every time the doorbell rings? Just think about the number of times it might happen on Halloween. If your pet gets stressed or is super protective, it might be a good night to give them a great chew toy, their favorite blanket, and a room with the tv or radio on, and the door shut.

Photo by Justin Jason on Unsplash

Glow sticks are important when your kids are trick or treating in the dark. Just make sure that if kids come to your home drop them in your yard, and that you pick them up before your pets find them. If your kids are using glow sticks, make sure to collect them once they get home.

To prepare yourself for a potential incident, always keep your vet's phone number handy, along with an after-hours clinic you can call in an emergency. The ASPCA Animal Poison Control Center also has a hotline you can call at (888) 426-4435 for advice.

Even with all of these resources, however, the best cure for food poisoning is preventing it in the first place. To give you an idea of what human foods can be dangerous, Stacker has put together a slideshow of 30 common foods to avoid. Take a look to see if there are any that surprise you.

KEEP READING: Here are 6 foods from your cookout that could harm your dog

Why do they meow? Why do they nap so much? Why do they have whiskers? Cats, and their undeniably adorable babies known as kittens, are mysterious creatures. Their larger relatives, after all, are some of the most mystical and lethal animals on the planet. Many questions related to domestic felines, however, have perfectly logical answers. Heres a look at some of the most common questions related to kittens and cats, and the answers cat lovers are looking for.

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Five Simple Tips To Keep Your Pets Safe This Halloween - Minnesota's New Country