150-409: Oseltamivir , sold under the brand name Tamiflu among others, is an antiviral medication used to treat and prevent influenza A and influenza B , viruses that cause the flu . Many medical organizations recommend it in people who have complications or are at high risk of complications within 48 hours of first symptoms of infection. They recommend it to prevent infection in those at high risk, but not
300-551: A broad-spectrum antiviral is effective against a wide range of viruses. Antiviral drugs are a class of antimicrobials , a larger group which also includes antibiotic (also termed antibacterial), antifungal and antiparasitic drugs, or antiviral drugs based on monoclonal antibodies . Most antivirals are considered relatively harmless to the host, and therefore can be used to treat infections . They should be distinguished from virucides , which are not medication but deactivate or destroy virus particles, either inside or outside
450-481: A collective noun (also describing First Nations, Inuit, and Métis) is a specific term of art used in some legal documents, including the Constitution Act, 1982 . Over time, as societal perceptions and government–indigenous relationships have shifted, many historical terms have changed definitions or been replaced as they have fallen out of favor. The use of the term "Indian" is frowned upon because it represents
600-808: A genome and sometimes a few enzymes stored in a capsule made of protein (called a capsid ), and sometimes covered with a lipid layer (sometimes called an 'envelope'). Viruses cannot reproduce on their own and instead propagate by subjugating a host cell to produce copies of themselves, thus producing the next generation. Researchers working on such " rational drug design " strategies for developing antivirals have tried to attack viruses at every stage of their life cycles. Some species of mushrooms have been found to contain multiple antiviral chemicals with similar synergistic effects. Compounds isolated from fruiting bodies and filtrates of various mushrooms have broad-spectrum antiviral activities, but successful production and availability of such compounds as frontline antiviral
750-616: A 2014 Cochrane Review. The Cochrane Review further recommended: "On the basis of the findings of this review, clinicians and healthcare policy-makers should urgently revise current recommendations for use of the neuraminidase inhibitors (NIs) for individuals with influenza." That is not utilizing NIs for prevention or treatment "Based on these findings there appears to be no evidence for patients, clinicians or policy-makers to use these drugs to prevent serious outcomes, both in annual influenza and pandemic influenza outbreaks." The CDC, ECDC, Public Health England, Infectious Disease Society of America,
900-639: A colonial state. The peopling of the Americas began when Paleolithic hunter-gatherers ( Paleo-Indians ) entered North America from the North Asian Mammoth steppe via the Beringia land bridge , which had formed between northeastern Siberia and western Alaska due to the lowering of sea level during the Last Glacial Maximum (26,000 to 19,000 years ago). These populations expanded south of
1050-640: A connection to residential schools. Additionally, Indigenous respondents with higher HLS and HLASS scores had one or more negative health outcomes. While there are many studies that found an association between IHT and adverse health outcomes, scholars continue to suggest that it remains difficult to understand the impact of IHT. IHT needs to be systematically measured. Indigenous people also need to be understood in separate categories based on similar experiences, location, and background as opposed to being categorized as one monolithic group. For thousands of years, Indigenous peoples domesticated, bred, and cultivated
1200-835: A few still considered uncontacted peoples . The Americas also host millions of individuals of mixed Indigenous, European, and sometimes African or Asian descent, historically referred to as mestizos in Spanish-speaking countries. In many Latin American nations, people of partial Indigenous descent constitute a majority or significant portion of the population, particularly in Central America , Mexico , Peru, Bolivia, Ecuador , Colombia , Venezuela , Chile , and Paraguay. Mestizos outnumber Indigenous peoples in most Spanish-speaking countries, according to estimates of ethnic cultural identification. However, since Indigenous communities in
1350-532: A high frequency of mutations. DNA viruses, such as HPV and herpesvirus, hijack host cell replication machinery, which gives them proofreading capabilities during replication. DNA viruses are therefore less error prone, are generally less diverse, and are more slowly evolving than RNA viruses. In both cases, the likelihood of mutations is exacerbated by the speed with which viruses reproduce, which provides more opportunities for mutations to occur in successive replications. Billions of viruses are produced every day during
1500-470: A large array of plant species. These species now constitute between 50% and 60% of all crops in cultivation worldwide. In certain cases, the Indigenous peoples developed entirely new species and strains through artificial selection , as with the domestication and breeding of maize from wild teosinte grasses in the valleys of southern Mexico. Numerous such agricultural products retain their native names in
1650-424: A large citizenry. Indigenous civilizations also displayed impressive accomplishments in astronomy and mathematics, including the most accurate calendar in the world. The domestication of maize or corn required thousands of years of selective breeding, and continued cultivation of multiple varieties was done with planning and selection, generally by women. Inuit, Yupik, Aleut, and Indigenous creation myths tell of
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#17328633723271800-544: A multitude of ways because the Indigenous community and their history are diverse. Many studies (such as Whitbeck et al., 2014; Brockie, 2012; Anastasio et al., 2016; Clark & Winterowd, 2012; Tucker et al., 2016) have evaluated the impact of IHT on health outcomes of Indigenous communities from the United States and Canada. IHT is a difficult term to standardize and measure because of the vast and variable diversity of Indigenous people and their communities. Therefore, it
1950-639: A new influenza A(H1N1)2009 variant with mildly reduced oseltamivir (and zanamivir) sensitivity was detected in more than 10% of community specimens in Singapore and more than 30% of samples from northern Australia. While there is concern that antiviral resistance may develop in people with haematologic malignancies due to their inability to reduce viral loads and several surveillance studies found oseltamivir-resistant pH1N1 after administration of oseltamivir in those people, as of November 2013, widespread transmission of oseltamivir-resistant pH1N1 has not occurred. During
2100-416: A pre-Columbian high of an estimated three million to some 300,000 in 1997. The Spanish Empire and other Europeans re-introduced horses to the Americas. Some of these animals escaped and began to breed and increase their numbers in the wild. The reintroduction of the horse , extinct in the Americas for over 7500 years, had a profound impact on Indigenous cultures in several regions, such as those of
2250-572: A second, more recent wave of migration several thousand years later and have much more recent genetic and cultural commonalities with the Indigenous peoples of Siberia . However, these groups are nonetheless considered "Indigenous peoples of the Americas". The term Amerindian , a portmanteau of "American Indian", was coined in 1902 by the American Anthropological Association . It has been controversial ever since its creation. It
2400-579: A starting point for synthesis ; shikimic acid was originally available only as an extract of Chinese star anise ; but by 2006, 30% of the supply was manufactured recombinantly in E. coli. Gilead exclusively licensed their relevant patents to Roche in 1996. The drug has not been patent-protected in Thailand, the Philippines, Indonesia, and several other countries. In 1999, the FDA approved oseltamivir phosphate for
2550-601: A threat to livestock. Several bird species, such as turkeys , Muscovy ducks , Puna ibis , and neotropic cormorants were domesticated by various peoples in Mesoamerica and South America to be used for poultry. In the Andean region, indigenous peoples domesticated llamas and alpacas to produce fiber and meat. The llama was the only beast of burden in the Americas before European colonization. Guinea pigs were domesticated from wild cavies to be raised for meat consumption in
2700-545: A treatment for hepatitis B. Antiviral resistance can be defined by a decreased susceptibility to a drug caused by changes in viral genotypes. In cases of antiviral resistance, drugs have either diminished or no effectiveness against their target virus. The issue inevitably remains a major obstacle to antiviral therapy as it has developed to almost all specific and effective antimicrobials , including antiviral agents. The Centers for Disease Control and Prevention (CDC) inclusively recommends anyone six months and older to get
2850-493: A variety of origins of their respective peoples. Some were "always there" or were created by gods or animals, some migrated from a specified compass point , and others came from "across the ocean". The European colonization of the Americas fundamentally changed the lives and cultures of the resident Indigenous peoples. Although the exact pre-colonization population count of the Americas is unknown, scholars estimate that Indigenous populations diminished by between 80% and 90% during
3000-642: A violent poison. Eventually, a Taíno Cacique named Enriquillo managed to hold out in the Baoruco Mountain Range for thirteen years, causing serious damage to the Spanish, Carib-held plantations and their Indian auxiliaries . Hearing of the seriousness of the revolt, Emperor Charles V (also King of Spain) sent Captain Francisco Barrionuevo to negotiate a peace treaty with the ever-increasing number of rebels. Two months later, after consultation with
3150-449: A weakened immune response; the results suggest that higher and earlier dosing may be necessary in such populations. In 2007, Japanese investigators detected neuraminidase-resistant influenza B virus strains in individuals not treated with these drugs. The prevalence was 1.7%. According to the CDC, As of 2019, transmission of oseltamivir-resistant influenza B virus strains—from persons treated with
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#17328633723273300-437: A whole, in general, most Indigenous peoples prefer to be identified by the name of their specific nation, tribe, or band. Early settlers often adopted terms that some tribes used for each other, not realizing these were derogatory terms used by enemies. When discussing broader subsets of peoples, naming has often been based on shared language, region, or historical relationship. Many English exonyms have been used to refer to
3450-528: A whole. Since the 1970s, the word "Indigenous", which is capitalized when referring to people, has gradually emerged as a favored umbrella term. The capitalization is to acknowledge that Indigenous peoples have cultures and societies that are equal to Europeans, Africans, and Asians. This has recently been acknowledged in the AP Stylebook . Some consider it improper to refer to Indigenous people as "Indigenous Americans" or to append any colonial nationality to
3600-465: A yearly vaccination to protect them from influenza A viruses (H1N1) and (H3N2) and up to two influenza B viruses (depending on the vaccination). Comprehensive protection starts by ensuring vaccinations are current and complete. However, vaccines are preventative and are not generally used once a patient has been infected with a virus. Additionally, the availability of these vaccines can be limited based on financial or locational reasons which can prevent
3750-457: Is a neuraminidase inhibitor , a competitive inhibitor of influenza's neuraminidase enzyme. The enzyme cleaves the sialic acid which is found on glycoproteins on the surface of human cells that helps new virions to exit the cell, preventing new viral particles from being released. The vast majority of mutations conferring resistance are single amino acid residue substitutions (His274Tyr in N1) in
3900-524: Is a common term, though nativos or pueblos nativos ('native peoples') may also be heard; moreover, aborigen ('aborigine') is used in Argentina and pueblos originarios ('original peoples') is common in Chile . In Brazil, indígenas and povos originários ('Indigenous peoples') are common formal-sounding designations, while índio ('Indian') is still the more often heard term (the noun for
4050-409: Is a component of reverse transcriptase that splits the synthesized DNA from the original viral RNA. Another target is integrase , which integrate the synthesized DNA into the host cell genome. Examples of integrase inhibitors include raltegravir , elvitegravir , and dolutegravir . Once a virus genome becomes operational in a host cell, it then generates messenger RNA (mRNA) molecules that direct
4200-483: Is a group of experimental antiviral drugs initially developed at the Massachusetts Institute of Technology . In cell culture, DRACO was reported to have broad-spectrum efficacy against many infectious viruses, including dengue flavivirus , Amapari and Tacaribe arenavirus , Guama bunyavirus , H1N1 influenza and rhinovirus , and was additionally found effective against influenza in vivo in weanling mice. It
4350-403: Is a long way away. Viral life cycles vary in their precise details depending on the type of virus, but they all share a general pattern: One antiviral strategy is to interfere with the ability of a virus to infiltrate a target cell. The virus must go through a sequence of steps to do this, beginning with binding to a specific " receptor " molecule on the surface of the host cell and ending with
4500-663: Is a nucleoside analogue, and is effective against herpesvirus infections. The first antiviral drug to be approved for treating HIV, zidovudine (AZT), is also a nucleoside analogue. An improved knowledge of the action of reverse transcriptase has led to better nucleoside analogues to treat HIV infections. One of these drugs, lamivudine , has been approved to treat hepatitis B, which uses reverse transcriptase as part of its replication process. Researchers have gone further and developed inhibitors that do not look like nucleosides, but can still block reverse transcriptase. Another target being considered for HIV antivirals include RNase H —which
4650-469: Is a set of drugs based on ribozymes , which are enzymes that will cut apart viral RNA or DNA at selected sites. In their natural course, ribozymes are used as part of the viral manufacturing sequence, but these synthetic ribozymes are designed to cut RNA and DNA at sites that will disable them. A ribozyme antiviral to deal with hepatitis C has been suggested, and ribozyme antivirals are being developed to deal with HIV. An interesting variation of this idea
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4800-416: Is an arduous task to assign an operational definition and systematically collect data when studying IHT. Many of the studies that incorporate IHT measure it in different ways, making it hard to compile data and review it holistically. This is an important point that provides context for the following studies that attempt to understand the relationship between IHT and potential adverse health impacts. Some of
4950-419: Is currently widespread in seasonal H1N1 strains. The genetic makeup of viruses is constantly changing, which can cause a virus to become resistant to currently available treatments. Viruses can become resistant through spontaneous or intermittent mechanisms throughout the course of an antiviral treatment. Immunocompromised patients, more often than immunocompetent patients, hospitalized with pneumonia are at
5100-540: Is general agreement that the Americas were first settled from Asia, the pattern of migration and the place(s) of origin in Eurasia of the peoples who migrated to the Americas remain unclear. The traditional theory is that Ancient Beringians moved when sea levels were significantly lowered due to the Quaternary glaciation , following herds of now-extinct Pleistocene megafauna along ice-free corridors that stretched between
5250-399: Is no evidence of reduction in complications of influenza. Two meta-analyses have concluded that benefits in those who are otherwise healthy do not outweigh its risks. They also found little evidence regarding whether treatment changes the risk of hospitalization or death in high risk populations. However, another meta-analysis found that oseltamivir was effective for prevention of influenza at
5400-424: Is over 80% and is extensively metabolised to its active form upon first-pass through the liver. It has a volume of distribution of 23–26 litres. Its half-life is about 1–3 hours and its active carboxylate metabolite has a half-life of 6–10 hours. More than 90% of the oral dose is eliminated in the urine as the active metabolite. Oseltamivir was discovered by scientists at Gilead Sciences using shikimic acid as
5550-513: Is partly trial and error, it can be a relatively slow process until an adequate molecule is produced. A very early stage of viral infection is viral entry , when the virus attaches to and enters the host cell. A number of "entry-inhibiting" or "entry-blocking" drugs are being developed to fight HIV. HIV most heavily targets a specific type of lymphocyte known as "helper T cells", and identifies these target cells through T-cell surface receptors designated " CD4 " and " CCR5 ". Attempts to interfere with
5700-574: Is provided to support the use of oseltamivir in seasonal and pandemic outbreaks, the next Expert Committee might consider oseltamivir for deletion. The US Centers for Disease Control and Prevention (CDC), European Centre for Disease Prevention and Control (ECDC), Public Health England and the American Academy of Pediatrics (AAP) recommend the use of oseltamivir for people who have complications or are at high risk for complications. This includes those who are hospitalized, young children, those over
5850-550: Is similar in most strains of rhinoviruses and enteroviruses , which can cause diarrhea, meningitis , conjunctivitis , and encephalitis . Some scientists are making the case that a vaccine against rhinoviruses, the predominant cause of the common cold, is achievable. Vaccines that combine dozens of varieties of rhinovirus at once are effective in stimulating antiviral antibodies in mice and monkeys, researchers reported in Nature Communications in 2016. Rhinoviruses are
6000-412: Is that it potentially may not only prevent the spread of the virus within an infected individual but also the spread from an infected to an uninfected individual. One possible advantage of the therapeutic approach of blocking viral entry (as opposed to the currently dominant approach of viral enzyme inhibition) is that it may prove more difficult for the virus to develop resistance to this therapy than for
6150-406: Is the use of genetically modified cells that can produce custom-tailored ribozymes. This is part of a broader effort to create genetically modified cells that can be injected into a host to attack pathogens by generating specialized proteins that block viral replication at various phases of the viral life cycle. Interference with post translational modifications or with targeting of viral proteins in
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6300-453: Is to synthesize antibodies , protein molecules that can bind to a pathogen and mark it for attack by other elements of the immune system. Once researchers identify a particular target on the pathogen, they can synthesize quantities of identical "monoclonal" antibodies to link up that target. A monoclonal drug is now being sold to help fight respiratory syncytial virus in babies, and antibodies purified from infected individuals are also used as
6450-555: Is to target the processes that synthesize virus components after a virus invades a cell. One way of doing this is to develop nucleotide or nucleoside analogues that look like the building blocks of RNA or DNA , but deactivate the enzymes that synthesize the RNA or DNA once the analogue is incorporated. This approach is more commonly associated with the inhibition of reverse transcriptase (RNA to DNA) than with "normal" transcriptase (DNA to RNA). The first successful antiviral, aciclovir ,
6600-474: Is used for the prevention and treatment of influenza caused by influenza A and B viruses. It is on the World Health Organization's List of Essential Medicines . The WHO supports its use for severe illness due to confirmed or suspected influenza virus infection in critically ill people who have been hospitalized. Oseltamivir's risk-benefit ratio is controversial. In 2017, it was moved from the core to
6750-670: Is used preventatively it decreases the risk of exposed people developing symptomatic disease. A systematic review of systematic reviews found low to moderate evidence that it decreases the risk of getting symptomatic influenza by 1 to 12% (a relative decrease of 64 to 92%). It recommended against its use in healthy, low-risk persons due to cost, the risk of resistance development, and side effects and concluded it might be useful for prevention in unvaccinated high risk persons. Common adverse drug reactions (ADRs) associated with oseltamivir therapy (occurring in over 1 percent of people) include nausea and vomiting. In adults, oseltamivir increased
6900-557: The Archaic period of North American cultures. Technology had advanced to the point where pottery had started to become common and the small-scale felling of trees had become feasible. Concurrently, the Archaic Indigenous peoples began using fire in a controlled manner. They carried out the intentional burning of vegetation to mimic the effects of natural fires that tended to clear forest understories. It made travel easier and facilitated
7050-597: The Chiribaya to herd llamas . The vast majority of indigenous dog breeds in the Americas went extinct, due to being replaced by dogs of European origin. The Fuegian dog was a domesticated variation of the culpeo that was raised by several cultures in Tierra del Fuego , like the Selk'nam and the Yahgan . It was exterminated by Argentine and Chilean settlers, due to supposedly posing as
7200-733: The Great Plains , the Northwest Plateau , the Great Basin , Aridoamerica , the Gran Chaco and the Southern Cone . By domesticating horses, some tribes had great success: horses enabled them to expand their territories, exchange more goods with neighboring tribes, and more easily capture game , such as bison . According to Erin McKenna and Scott L. Pratt, the Indigenous population of the Americas
7350-496: The Inca Civil War of 1529–1532. Smallpox was only the first epidemic. Typhus (probably) in 1546, influenza and smallpox together in 1558, smallpox again in 1589, diphtheria in 1614, and measles in 1618—all ravaged the remains of Inca culture. Smallpox killed millions of native inhabitants of Mexico. Unintentionally introduced at Veracruz with the arrival of Pánfilo de Narváez on 23 April 1520, smallpox ravaged Mexico in
7500-562: The Laurentide and Cordilleran ice sheets. Another route proposed is that, either on foot or using boats , they migrated down the Pacific coast to South America as far as Chile . Any archaeological evidence of coastal occupation during the last Ice Age would now have been covered by the sea level rise , up to a hundred metres since then. While technically referring to the era before Christopher Columbus ' voyages of 1492 to 1504, in practice
7650-540: The Laurentide Ice Sheet and spread rapidly southward, occupying both North and South America by 12,000 to 14,000 years ago. The earliest populations in the Americas, before roughly 10,000 years ago, are known as Paleo-Indians . Indigenous peoples of the Americas have been linked to Siberian populations by proposed linguistic factors , the distribution of blood types , and in genetic composition as reflected by molecular data, such as DNA . While there
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#17328633723277800-790: The Menominee of Wisconsin—suggest that longstanding "sacred values" may represent a summary of sustainable millennial traditions. Numerous Native American dog breeds have been used by the people of the Americas, such as the Canadian Eskimo dog , the Carolina dog , and the Chihuahua . Some indigenous peoples in the Great Plains used dogs for pulling travois , while others like the Tahltan bear dog were bred to hunt larger game. Some Andean cultures also bred
7950-477: The history and prehistory of the Americas before the appearance of significant European and African influences on the American continents, spanning the time of the original arrival in the Upper Paleolithic to European colonization during the early modern period . The Norte Chico civilization (in present-day Peru) is one of the defining six original civilizations of the world, arising independently around
8100-635: The neuraminidase enzyme. A 2011 meta-analysis of 15 studies found a pooled incidence rate for oseltamivir resistance of 2.6%. Subgroup analyses detected higher rates among influenza A patients, especially the H1N1 subtype. It was found that a substantial number of patients might become oseltamivir-resistant as a result of oseltamivir use, and that oseltamivir resistance might be significantly associated with pneumonia. In severely immunocompromised patients there were reports of prolonged shedding of oseltamivir- (or zanamivir )-resistant virus, even after oseltamivir treatment
8250-448: The residential school ancestry studies ask respondents if their parents, grandparents, great-grandparents, or "elders from their community" went to a residential school to understand if family or community history in residential schools is associated with negative health outcomes. In a comprehensive review of the research literature, Joseph Gone and colleagues compiled and compared outcomes for studies using these IHT measures relative to
8400-431: The " West Indies " (or " Antilles "), a name that is still used to describe the islands. This led to the blanket term "Indies" and "Indians" ( Spanish : indios ; Portuguese : índios ; French : indiens ; Dutch : indianen ) for the Indigenous inhabitants, which implied some kind of ethnic or cultural unity among the Indigenous peoples of the Americas. This unifying concept, codified in law, religion, and politics,
8550-603: The 1520s, possibly killing over 150,000 in Tenochtitlán (the heartland of the Aztec Empire) alone, and aiding in the victory of Hernán Cortés over the Aztec Empire at Tenochtitlan (present-day Mexico City) in 1521. There are many factors as to why Indigenous peoples suffered such immense losses from Afro-Eurasian diseases. Many Old World diseases, like cow pox, are acquired from domesticated animals that are not indigenous to
8700-846: The 15th century, as well as the ethnic groups that identify with the pre-Columbian population of the Americas as such. These populations exhibit significant diversity; some Indigenous peoples were historically hunter-gatherers , while others practiced agriculture and aquaculture . Various Indigenous societies developed complex social structures , including pre-contact monumental architecture, organized cities , city-states , chiefdoms , states , kingdoms , republics , confederacies , and empires . These societies possessed varying levels of knowledge in fields such as engineering , architecture , mathematics , astronomy , writing , physics , medicine , agriculture , irrigation , geology , mining , metallurgy , art , sculpture , and goldsmithing . Indigenous peoples continue to inhabit many regions of
8850-577: The 16th century were Constantinople and Paris with 300,000 and 200,000 inhabitants respectively. The population in London, Madrid, and Rome hardly exceeded 50,000 people. In 1523, right around the time of the Spanish conquest, the entire population in the country of England was just under three million people. This fact speaks to the level of sophistication, agriculture, governmental procedure, and rule of law that existed in Tenochtitlan, needed to govern over such
9000-460: The 1980s, when the full genetic sequences of viruses began to be unraveled, did researchers begin to learn how viruses worked in detail, and exactly what chemicals were needed to thwart their reproductive cycle. The general idea behind modern antiviral drug design is to identify viral proteins, or parts of proteins, that can be disabled. These "targets" should generally be as unlike any proteins or parts of proteins in humans as possible, to reduce
9150-465: The 2007–08 flu season, the US CDC found 10.9% of H1N1 samples (n=1,020) to be resistant. In the 2008–09 season, the proportion of resistant H1N1 increased to 99.4%, while no other seasonal strains (H3N2, B) showed resistance. From 2009 to 2014, oseltamivir resistance was very low in seasonal flu. In the 2010–11 flu season, 99.1% of H1N1, 99.8% of H3N, and 100% of Influenza B remained oseltamivir susceptible in
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#17328633723279300-610: The 250,000 Taínos of Hispaniola , represented the dominant culture in the Greater Antilles and the Bahamas. Within thirty years about 70% of the Taínos had died. They had no immunity to European diseases, so outbreaks of measles and smallpox ravaged their population. One such outbreak occurred in a camp of enslaved Africans, where smallpox spread to the nearby Taíno population and reduced their numbers by 50%. Increasing punishment of
9450-522: The AAP, and Roche (the originator) reject the conclusions of the Cochrane Review, arguing in part that the analysis inappropriately forms conclusions about outcomes in people who are seriously ill based on results obtained primarily in healthy populations, and that the analysis inappropriately included results from people not infected with influenza. The EMA did not change its labeling of the drug in response to
9600-462: The Americas are defined by cultural identification and kinship rather than ancestry or race , mestizos are typically not counted among the Indigenous population unless they speak an Indigenous language or identify with a specific Indigenous culture. Additionally, many individuals of wholly Indigenous descent who do not follow Indigenous traditions or speak an Indigenous language have been classified or self-identify as mestizo due to assimilation into
9750-519: The Americas have been more vocal about how they want to be addressed, pushing to suppress the use of terms widely considered to be obsolete, inaccurate, or racist . During the latter half of the 20th century and the rise of the Indian rights movement , the United States federal government responded by proposing the use of the term " Native American ", to recognize the primacy of Indigenous peoples' tenure in
9900-993: The Americas, with significant populations in countries such as Bolivia , Canada , Chile , Colombia , Ecuador , Guatemala , Mexico , Peru , and the United States . There are at least 1,000 different indigenous languages spoken across the Americas, with 574 federally recognized tribes in the US alone. Some languages, including Quechua , Arawak , Aymara , Guaraní , Mayan , and Nahuatl , have millions of speakers and are recognized as official by governments in Bolivia , Peru , Paraguay , and Greenland . Indigenous peoples, whether residing in rural or urban areas, often maintain aspects of their cultural practices, including religion , social organization , and subsistence practices. Over time, these cultures have evolved, preserving traditional customs while adapting to modern needs. Some Indigenous groups remain relatively isolated from Western culture , with
10050-451: The Americas. European populations had adapted to these diseases, and built up resistance, over many generations. Many of the Old World diseases that were brought over to the Americas were diseases, like yellow fever , that were relatively manageable if infected as a child, but were deadly if infected as an adult. Children could often survive the disease, resulting in immunity to the disease for
10200-555: The Audencia of Santo Domingo, Enriquillo was offered any part of the island to live in peace. The Laws of Burgos, 1512–1513 , were the first codified set of laws governing the behavior of Spanish settlers in America, particularly concerning Indigenous peoples. The laws forbade the maltreatment of them and endorsed their conversion to Catholicism . The Spanish crown found it difficult to enforce these laws in distant colonies. Epidemic disease
10350-487: The CDC does not recommend to use oseltamivir generally for prevention due to concerns that widespread use will encourage resistance development. They recommend that it be considered in those at high risk, who have been exposed to influenza within 48 hours and have not received or only recently been vaccinated. They recommended it during outbreaks in long term care facilities and in those who are significantly immunosuppressed. As of 2011, reviews concluded that when oseltamivir
10500-468: The Cochrane study. A 2014 review recommended that all people admitted to intensive care units during influenza outbreaks with a diagnosis of community-acquired pneumonia receive oseltamivir until the absence of influenza infection is established by polymerase chain reaction (PCR) testing. A 2015 systematic review and meta-analysis found oseltamivir effective at treating the symptoms of influenza, reducing
10650-513: The Cochrane team published an interim review based on those reports. In 2013, Roche released 74 full clinical study reports of oseltamivir trials after GSK released the data on zanamivir studies. In 2014, Cochrane published an updated review based solely on full clinical study reports and regulatory documents. In 2016, Roche's oseltamivir patents began to expire. There have been reports of oseltamivir reducing disease severity and hospitalization time in canine parvovirus infection. The drug may limit
10800-570: The English and Spanish lexicons. The South American highlands became a center of early agriculture. Genetic testing of the wide variety of cultivars and wild species suggests that the potato has a single origin in the area of southern Peru , from a species in the Solanum brevicaule complex. Over 99% of all modern cultivated potatoes worldwide are descendants of a subspecies indigenous to south-central Chile , Solanum tuberosum ssp. tuberosum , where it
10950-528: The Europeans began the human trafficking of massive numbers of enslaved Western and Central African people to the Americas. Like Indigenous peoples, these African people, newly exposed to European diseases, lacked any inherited resistance to the diseases of Europe. In 1520, an African who had been infected with smallpox had arrived in Yucatán. By 1558, the disease had spread throughout South America and had arrived at
11100-728: The Indian drug company Cipla won a case in India's court system allowing it to manufacture a cheaper generic version of Tamiflu, called Antiflu. In May 2009, Cipla won approval from the World Health Organization (WHO) certifying that its drug Antiflu was as effective as Tamiflu, and Antiflu is included in the WHO list of prequalified medicinal products. In 2009, a new A/H1N1 influenza virus was discovered to be spreading in North America. In June 2009,
11250-401: The Indigenous peoples of the Americas. Some of these names were based on foreign language terms used by earlier explorers and colonists, while others resulted from the colonists' attempts to translate or transliterate endonyms from the native languages. Other terms arose during periods of conflict between the colonists and Indigenous peoples. Since the late 20th century, Indigenous peoples in
11400-597: The Indigenous population of North America in the first hundred years after the arrival of Europeans. Some 90 percent of the native population near Massachusetts Bay Colony died of smallpox in an epidemic in 1617–1619. In 1633, in Fort Orange (New Netherland) , the Native Americans there were exposed to smallpox because of contact with Europeans. As it had done elsewhere, the virus wiped out entire population groups of Native Americans. It reached Lake Ontario in 1636, and
11550-772: The Indigenous-European mixed-race mestizos (or caboclos in Brazil) of Hispanic America who, with their larger population (in most Latin American countries constituting either outright majorities, pluralities, or at the least large minorities), identify largely as a new ethnic group distinct from both Europeans and Indigenous, but still considering themselves a subset of the European-derived Hispanic or Brazilian peoplehood in culture and ethnicity ( cf. ladinos ). Among Spanish-speaking countries , indígenas or pueblos indígenas ('Indigenous peoples')
11700-646: The Plata basin. Colonist violence towards Indigenous peoples accelerated the loss of lives. European colonists perpetrated massacres on the Indigenous peoples and enslaved them. According to the U.S. Bureau of the Census (1894), the North American Indian Wars of the 19th century had a known death toll of about 19,000 Europeans and 30,000 Native Americans, and an estimated total death toll of 45,000 Native Americans. The first Indigenous group encountered by Columbus,
11850-729: The South-Asian nationality being indiano ), but for the past 10 years has been considered offensive and pejorative. Aborígene and nativo are rarely used in Brazil in Indigenous-specific contexts (e.g., aborígene is usually understood as the ethnonym for Indigenous Australians ). The Spanish and Portuguese equivalents to Indian , nevertheless, could be used to mean any hunter-gatherer or full-blooded Indigenous person, particularly to continents other than Europe or Africa—for example, indios filipinos . Indigenous peoples of
12000-421: The Taínos for revolting against forced labor, despite measures put in place by the encomienda , which included religious education and protection from warring tribes, eventually led to the last great Taíno rebellion (1511–1529). Following years of mistreatment, the Taínos began to adopt suicidal behaviors, with women aborting or killing their infants and men jumping from cliffs or ingesting untreated cassava ,
12150-505: The US. In January 2012, the US and European CDCs reported all seasonal flu samples tested since October 2011 to be oseltamivir susceptible. In the 2013–14 season only 1% of 2009 H1N1 viruses showed oseltamivir resistance. No other influenza viruses were resistant to oseltamivir. Three studies have found resistance in 0%, 3.3%, and 18% of subjects. In the study with the 18% resistance rate, the subjects were children, many of whom had not been previously exposed to influenza virus and therefore had
12300-561: The United States are commonly known as Native Americans , Indians, as well as Alaska Natives . The term "Indian" is still used in some communities and remains in use in the official names of many institutions and businesses in Indian Country . The various nations, tribes, and bands of Indigenous peoples of the Americas have differing preferences in terminology for themselves. While there are regional and generational variations in which umbrella terms are preferred for Indigenous peoples as
12450-638: The WHO declared the A/H1N1 influenza a pandemic. The National Institute for Health and Care Excellence (NICE), the CDC, the WHO, and the ECDC maintained their recommendation to use oseltamivir. From 2010 to 2012, Cochrane requested Roche's full clinical study reports of their trials, which they did not provide. In 2011, a freedom of information request to the European Medicines Agency (EMA) provided Cochrane with reports from 16 Roche oseltamivir trials. In 2012,
12600-520: The ability of the virus to invade the crypt cells of the small intestine and decrease gastrointestinal bacterial colonization and toxin production. Oseltamivir has been deemed ineffective at treating COVID-19 , consistent with the SARS-CoV-2 virus lacking influenza's neuraminidase enzyme. Antiviral medication Antiviral drugs are a class of medication used for treating viral infections . Most antivirals target specific viruses , while
12750-534: The age of 65, people with other significant health problems, those who are pregnant, and Indigenous peoples of the Americas among others. The Infectious Disease Society of America takes the same position as the CDC. A systematic review of systematic reviews in PLoS One did not find evidence for benefits in people who are at risk, noting that "the trials were not designed or powered to give results regarding serious complications, hospitalization and mortality", as did
12900-495: The binding of HIV with the CD4 receptor have failed to stop HIV from infecting helper T cells, but research continues on trying to interfere with the binding of HIV to the CCR5 receptor in hopes that it will be more effective. HIV infects a cell through fusion with the cell membrane, which requires two different cellular molecular participants, CD4 and a chemokine receptor (differing depending on
13050-603: The binding of these antisense segments to these target sections blocks the operation of those genomes. A phosphorothioate antisense drug named fomivirsen has been introduced, used to treat opportunistic eye infections in AIDS patients caused by cytomegalovirus , and other antisense antivirals are in development. An antisense structural type that has proven especially valuable in research is morpholino antisense. Morpholino oligos have been used to experimentally suppress many viral types: Yet another antiviral technique inspired by genomics
13200-403: The body. Natural virucides are produced by some plants such as eucalyptus and Australian tea trees . Most of the antiviral drugs now available are designed to help deal with HIV , herpes viruses , the hepatitis B and C viruses, and influenza A and B viruses. Viruses use the host's cells to replicate and this makes it difficult to find targets for the drug that would interfere with
13350-464: The candidate at the molecular level with a computer-aided design program. The target proteins can be manufactured in the lab for testing with candidate treatments by inserting the gene that synthesizes the target protein into bacteria or other kinds of cells. The cells are then cultured for mass production of the protein, which can then be exposed to various treatment candidates and evaluated with "rapid screening" technologies. Viruses consist of
13500-424: The cascade, and cleave a variety of cellular proteins, thereby killing the cell. Rifampicin acts at the assembly phase. The final stage in the life cycle of a virus is the release of completed viruses from the host cell, and this step has also been targeted by antiviral drug developers. Two drugs named zanamivir (Relenza) and oseltamivir (Tamiflu) that have been recently introduced to treat influenza prevent
13650-632: The cell is also possible. Some viruses include an enzyme known as a protease that cuts viral protein chains apart so they can be assembled into their final configuration. HIV includes a protease, and so considerable research has been performed to find " protease inhibitors " to attack HIV at that phase of its life cycle. Protease inhibitors became available in the 1990s and have proven effective, though they can have unusual side effects, for example causing fat to build up in unusual places. Improved protease inhibitors are now in development. Protease inhibitors have also been seen in nature. A protease inhibitor
13800-402: The cell type). Approaches to blocking this virus/cell fusion have shown some promise in preventing entry of the virus into a cell. At least one of these entry inhibitors—a biomimetic peptide called Enfuvirtide , or the brand name Fuzeon—has received FDA approval and has been in use for some time. Potentially, one of the benefits from the use of an effective entry-blocking or entry-inhibiting agent
13950-687: The complementary list based on its lower cost-effectiveness. The Expert Committee did not recommend the deletion of oseltamivir from the EML and EMLc, recognizing that it is the only medicine included on the Model Lists for critically ill patients with influenza and for influenza pandemic preparedness. However, the Committee noted that, since the inclusion of oseltamivir on the Model List in 2009, new evidence in seasonal and pandemic influenza has lowered earlier estimates of
14100-671: The contact and colonization period and were documented in historical accounts of the time. A few, such as the Mayan, Olmec, Mixtec, Aztec , and Nahua peoples , had their written languages and records. However, the European colonists of the time worked to eliminate non-Christian beliefs and burned many pre-Columbian written records. Only a few documents remained hidden and survived, leaving contemporary historians with glimpses of ancient culture and knowledge. According to both Indigenous and European accounts and documents, American civilizations before and at
14250-458: The course of an infection, with each replication giving another chance for mutations that encode for resistance to occur. Multiple strains of one virus can be present in the body at one time, and some of these strains may contain mutations that cause antiviral resistance. This effect, called the quasispecies model , results in immense variation in any given sample of virus, and gives the opportunity for natural selection to favor viral strains with
14400-437: The cultures chemicals which they thought might inhibit viral activity and observed whether the level of virus in the cultures rose or fell. Chemicals that seemed to have an effect were selected for closer study. This was a very time-consuming, hit-or-miss procedure, and in the absence of a good knowledge of how the target virus worked, it was not efficient in discovering effective antivirals which had few side effects . Only in
14550-498: The dominant Hispanic culture . In recent years, the self-identified Indigenous population in many countries has increased as individuals reclaim their heritage amid rising Indigenous-led movements for self-determination and social justice . Application of the term " Indian " originated with Christopher Columbus , who, in his search for India , thought that he had arrived in the East Indies . The islands came to be known as
14700-505: The drug—is rare. As of 2013, H274Y and N294S mutations that confer resistance to oseltamivir have been identified in a few H5N1 isolates from infected patients treated with oseltamivir, and have emerged spontaneously in Egypt. As of 2013, two of 14 adults infected with A(H7N9) and treated with oseltamivir developed oseltamivir-resistant virus with the Arg292Lys mutation. Its oral bioavailability
14850-458: The effectiveness of herd immunity, making effective antivirals a necessity. The three FDA-approved neuraminidase antiviral flu drugs available in the United States, recommended by the CDC, include: oseltamivir (Tamiflu), zanamivir (Relenza), and peramivir (Rapivab). Influenza antiviral resistance often results from changes occurring in neuraminidase and hemagglutinin proteins on the viral surface. Currently, neuraminidase inhibitors (NAIs) are
15000-658: The evidence of small benefit and increased risk of harms. The US Centers for Disease Control and Prevention (CDC), the European Centre for Disease Prevention and Control (ECDC), the Public Health England (PHE), the Infectious Disease Society of America (IDSA), the American Academy of Pediatrics (AAP), and Roche (the originator) rejected the recommendations of the 2014 Cochrane Review to urgently change treatment guidelines and drug labels. As of 2017,
15150-626: The first centuries of European colonization. Most scholars estimate a pre-colonization population of around 50 million, with other scholars arguing for an estimate of 100 million. Estimates reach as high as 145 million. Epidemics ravaged the Americas with diseases, such as smallpox , measles , and cholera , which the early colonists brought from Europe. The spread of infectious diseases was slow initially, as most Europeans were not actively or visibly infected, due to inherited immunity from generations of exposure to these diseases in Europe. This changed when
15300-466: The general population. The Centers for Disease Control and Prevention (CDC) recommends that clinicians use their discretion to treat those at lower risk who present within 48 hours of first symptoms of infection. It is taken by mouth, either as a pill or liquid. Recommendations regarding oseltamivir are controversial as are criticisms of the recommendations. A 2014 Cochrane Review concluded that oseltamivir does not reduce hospitalizations, and that there
15450-571: The growth of herbs and berry-producing plants, which were important both for food and for medicines. In the Mississippi River valley, Europeans noted that Native Americans managed groves of nut and fruit trees not far from villages and towns and their gardens and agricultural fields. They would have used prescribed burning farther away, in forest and prairie areas. Many crops first domesticated by Indigenous peoples are now produced and used globally, most notably maize (or "corn") arguably
15600-435: The health outcomes of Indigenous peoples. The study defined negative health outcomes to include such concepts as anxiety , suicidal ideation , suicide attempts , polysubstance abuse , PTSD , depression , binge eating , anger, and sexual abuse. The connection between IHT and health conditions is complicated because of the difficult nature of measuring IHT, the unknown directionality of IHT and health outcomes, and because
15750-474: The heart is unclear: it may reduce cardiac symptoms, but may also induce serious arrhythmias. Postmarketing reports include liver inflammation and elevated liver enzymes, rash, allergic reactions including anaphylaxis , toxic epidermal necrolysis , abnormal heart rhythms , seizure, confusion, aggravation of diabetes, and haemorrhagic colitis and Stevens–Johnson syndrome . Neuropsychiatric symptoms and body pain, followed by skin problems, were identified as
15900-553: The highest fitness every time the virus is spread to a new host. Recombination, the joining of two different viral variants, and reassortment , the swapping of viral gene segments among viruses in the same cell, also play a role in resistance, especially in influenza. Indigenous peoples of the Americas In the Americas , indigenous peoples comprise the two continents' pre-Columbian inhabitants prior to European settlement in
16050-577: The highest risk of developing oseltamivir resistance during treatment. Subsequent to exposure to someone else with the flu, those who received oseltamivir for "post-exposure prophylaxis" are also at higher risk of resistance. The mechanisms for antiviral resistance development depend on the type of virus in question. RNA viruses such as hepatitis C and influenza A have high error rates during genome replication because RNA polymerases lack proofreading activity. RNA viruses also have small genome sizes that are typically less than 30 kb, which allow them to sustain
16200-410: The immune system to attack a range of pathogens. One of the best-known of this class of drugs are interferons , which inhibit viral synthesis in infected cells. One form of human interferon named "interferon alpha" is well-established as part of the standard treatment for hepatitis B and C, and other interferons are also being investigated as treatments for various diseases. A more specific approach
16350-557: The imposition and restriction of Indigenous peoples and cultures by the Canadian Government. The terms "Native" and " Eskimo " are generally regarded as disrespectful (in Canada), and so are rarely used unless specifically required. While "Indigenous peoples" is the preferred term, many individuals or communities may choose to describe their identity using a different term. The Métis people of Canada can be contrasted, for instance, to
16500-429: The individual and household levels. Common side effects include vomiting , diarrhea , headache, and trouble sleeping. Other side effects may include psychiatric symptoms and seizures . In the United States it is recommended for influenza infection during pregnancy. It has been taken by a small number of pregnant women without signs of problems. Dose adjustment may be needed in those with kidney problems. Oseltamivir
16650-684: The lands of the Iroquois by 1679. During the 1770s smallpox killed at least 30% of the West Coast Native Americans. The 1775–82 North American smallpox epidemic and the 1837 Great Plains smallpox epidemic brought devastation and drastic population depletion among the Plains Indians . In 1832 the federal government of the United States established a smallpox vaccination program for Native Americans ( The Indian Vaccination Act of 1832 ). The Indigenous peoples in Brazil declined from
16800-457: The length of hospitalization, and reducing the risk of otitis media . The same review found that oseltamivir did not significantly increase the risk of adverse events. A 2016 systematic review found that oseltamivir slightly reduced the time it takes for the symptoms of influenza to be alleviated, and that it also increased the risk of "nausea, vomiting, [and] psychiatric events in adults and vomiting in children." The decrease in duration of sickness
16950-565: The likelihood of side effects and toxicity. The targets should also be common across many strains of a virus, or even among different species of virus in the same family, so a single drug will have broad effectiveness. For example, a researcher might target a critical enzyme synthesized by the virus, but not by the patient, that is common across strains, and see what can be done to interfere with its operation. Once targets are identified, candidate drugs can be selected, either from drugs already known to have appropriate effects or by actually designing
17100-569: The magnitude of effect of oseltamivir on relevant clinical outcomes. The Committee recommended that the listing of oseltamivir be amended, moving the medicine from the core to the Complementary List, and that its use be restricted to severe illness due to confirmed or suspected influenza virus infection in critically ill hospitalized patients. The Expert Committee noted that WHO guidelines for pharmacological management of pandemic and seasonal influenza would be updated in 2017: unless new information
17250-476: The methodologies to measure IHT include a "Historical Losses Scale" (HLS), "Historical Losses Associated Symptoms Scale" (HLASS), and residential school ancestry studies. HLS uses a survey format that includes "12 kinds of historical losses", such as loss of language and loss of land and asks participants how often they think about those losses. The HLASS includes 12 emotional reactions, and asks participants how they feel when they think about these losses. Lastly,
17400-465: The most common cause of the common cold; other viruses such as respiratory syncytial virus , parainfluenza virus and adenoviruses can cause them too. Rhinoviruses also exacerbate asthma attacks. Although rhinoviruses come in many varieties, they do not drift to the same degree that influenza viruses do. A mixture of 50 inactivated rhinovirus types should be able to stimulate neutralizing antibodies against all of them to some degree. A second approach
17550-461: The most frequently prescribed antivirals because they are effective against both influenza A and B. However, antiviral resistance is known to develop if mutations to the neuraminidase proteins prevent NAI binding. This was seen in the H257Y mutation, which was responsible for oseltamivir resistance to H1N1 strains in 2009. The inability of NA inhibitors to bind to the virus allowed this strain of virus with
17700-882: The most important crop in the world. Other significant crops include cassava ; chia ; squash (pumpkins, zucchini, marrow , acorn squash , butternut squash ); the pinto bean , Phaseolus beans including most common beans , tepary beans , and lima beans ; tomatoes ; potatoes ; sweet potatoes ; avocados ; peanuts ; cocoa beans (used to make chocolate ); vanilla ; strawberries ; pineapples ; peppers (species and varieties of Capsicum , including bell peppers , jalapeños , paprika , and chili peppers ); sunflower seeds ; rubber ; brazilwood ; chicle ; tobacco ; coca ; blueberries , cranberries , and some species of cotton . Studies of contemporary Indigenous environmental management—including agro-forestry practices among Itza Maya in Guatemala and hunting and fishing among
17850-410: The nation. As may be expected among people of over 400 different cultures in the US alone, not all of the people intended to be described by this term have agreed on its use or adopted it. No single group naming convention has been accepted by all Indigenous peoples in the Americas. Most prefer to be addressed as people of their tribe or nations when not speaking about Native Americans/American Indians as
18000-437: The need for hospitalizations, and that there is no proof of reduction of complications of influenza (such as pneumonia) because of a lack of diagnostic definitions, or reduction of the spread of the virus. There was also evidence that suggested that oseltamivir prevented some people from producing sufficient numbers of their own antibodies to fight infection. The authors recommended that guidance should be revised to take account of
18150-438: The pressure placed on the medical profession to deal with the human immunodeficiency virus (HIV), the cause of acquired immunodeficiency syndrome ( AIDS ). The first experimental antivirals were developed in the 1960s, mostly to deal with herpes viruses , and were found using traditional trial-and-error drug discovery methods. Researchers grew cultures of cells and infected them with the target virus. They then introduced into
18300-477: The production and stockpile of oseltamivir, after Congress had already approved $ 1.8 billion for military use of the drug. Defense Secretary Donald Rumsfeld, who was a past chairman of Gilead Sciences, recused himself from all government decisions regarding the drug. In 2006, a Cochrane Review (since withdrawn) raised controversy by concluding that oseltamivir should not be used during routine seasonal influenza because of its low effectiveness. In December 2008,
18450-426: The release of viral particles by blocking a molecule named neuraminidase that is found on the surface of flu viruses, and also seems to be constant across a wide range of flu strains. Rather than attacking viruses directly, a second category of tactics for fighting viruses involves encouraging the body's immune system to attack them. Some antivirals of this sort do not focus on a specific pathogen, instead stimulating
18600-502: The resistance mutation to spread due to natural selection. Furthermore, a study published in 2009 in Nature Biotechnology emphasized the urgent need for augmentation of oseltamivir stockpiles with additional antiviral drugs including zanamivir. This finding was based on a performance evaluation of these drugs supposing the 2009 H1N1 'Swine Flu' neuraminidase (NA) were to acquire the oseltamivir-resistance (His274Tyr) mutation, which
18750-757: The rest of their lives. But contact with adult populations without this childhood or inherited immunity would result in these diseases proving fatal. Colonization of the Caribbean led to the destruction of the Arawaks of the Lesser Antilles . Their culture was destroyed by 1650. Only 500 had survived by the year 1550, though the bloodlines continued through to the modern populace. In Amazonia, Indigenous societies weathered, and continue to suffer, centuries of colonization and genocide. Contact with European diseases such as smallpox and measles killed between 50 and 67 percent of
18900-415: The risk of complications such as pneumonia , while three other reviews found a decreased risk. Together, published studies suggest that oseltamivir reduces the duration of symptoms by 0.5–1.0 day. Any benefit of treatment must be balanced against side effects, which include psychiatric symptoms and increased rates of vomiting. The 2014 Cochrane Collaboration review concluded that oseltamivir did not affect
19050-422: The risk of nausea for which the number needed to harm was 28 and for vomiting was 22. So, for every 22 adult people on oseltamivir one experienced vomiting. In the treatment of children, oseltamivir also induced vomiting. The number needed to harm was 19. So, for every 19 children on oseltamivir one experienced vomiting. In prevention there were more headaches, kidney, and psychiatric events. Oseltamivir's effect on
19200-540: The same time as that of Egypt . Many later pre-Columbian civilizations achieved great complexity, with hallmarks that included permanent or urban settlements, agriculture, engineering, astronomy, trade, civic and monumental architecture, and complex societal hierarchies . Some of these civilizations had long faded by the time of the first significant European and African arrivals (ca. late 15th–early 16th centuries), and are known only through oral history and through archaeological investigations. Others were contemporary with
19350-448: The side effects most significantly reducing patient satisfaction on a drug review platform. The US and EU package inserts for oseltamivir contain a warning of psychiatric effects observed in post-marketing surveillance. The frequency of these appears to be low and a causative role for oseltamivir has not been established. The 2014 Cochrane Review found a dose-response effect on psychiatric events. In trials of prevention in adults one person
19500-488: The synthesis of viral proteins. Production of mRNA is initiated by proteins known as transcription factors . Several antivirals are now being designed to block attachment of transcription factors to viral DNA. Genomics has not only helped find targets for many antivirals, it has provided the basis for an entirely new type of drug, based on "antisense" molecules. These are segments of DNA or RNA that are designed as complementary molecule to critical sections of viral genomes, and
19650-474: The term Indigenous people used in the various samples comprises a huge population of individuals with drastically different experiences and histories. That being said some studies such as Bombay, Matheson, and Anisman (2014), Elias et al. (2012), and Pearce et al. (2008) found that Indigenous respondents with a connection to residential schools have more negative health outcomes (e.g., suicide ideation, suicide attempts, and depression) than those who did not have
19800-497: The term because Indigenous cultures existed before European colonization. Indigenous groups have territorial claims that are different from modern national and international borders, and when labeled as part of a country, their traditional lands are not acknowledged. Some who have written guidelines consider it more appropriate to describe an Indigenous person as "living in" or "of" the Americas, rather than calling them "American"; or simply calling them "Indigenous" without any addition of
19950-565: The term usually includes the history of Indigenous cultures until Europeans either conquered or significantly influenced them. "Pre-Columbian" is used especially often in the context of discussing the pre-contact Mesoamerican Indigenous societies : Olmec ; Toltec ; Teotihuacano ' Zapotec ; Mixtec ; Aztec and Maya civilizations ; and the complex cultures of the Andes : Inca Empire , Moche culture , Muisca Confederation , and Cañari . The Pre-Columbian era refers to all period subdivisions in
20100-454: The time of European encounter had achieved great complexity and many accomplishments. For instance, the Aztecs built one of the largest cities in the world, Tenochtitlan (the historical site of what would become Mexico City ), with an estimated population of 200,000 for the city proper and a population of close to five million for the extended empire. By comparison, the largest European cities in
20250-538: The treatment of influenza in adults based on two double-blind, randomized, placebo-controlled clinical trials. In June 2002, the European Medicines Agency (EMA) approved oseltamivir phosphate for prophylaxis and treatment of influenza. In 2003, a pooled analysis of ten randomised clinical trials concluded that oseltamivir reduced the risk of lower respiratory tract infections resulting in antibiotic use and hospital admissions in adults. Oseltamivir (as Tamiflu)
20400-413: The virus "uncoating" inside the cell and releasing its contents. Viruses that have a lipid envelope must also fuse their envelope with the target cell, or with a vesicle that transports them into the cell before they can uncoat. This stage of viral replication can be inhibited in two ways: This strategy of designing drugs can be very expensive, and since the process of generating anti-idiotypic antibodies
20550-408: The virus to mutate or evolve its enzymatic protocols. Inhibitors of uncoating have also been investigated. Amantadine and rimantadine have been introduced to combat influenza. These agents act on penetration and uncoating. Pleconaril works against rhinoviruses , which cause the common cold , by blocking a pocket on the surface of the virus that controls the uncoating process. This pocket
20700-433: The virus without also harming the host organism's cells. Moreover, the major difficulty in developing vaccines and antiviral drugs is due to viral variation. The emergence of antivirals is the product of a greatly expanded knowledge of the genetic and molecular function of organisms, allowing biomedical researchers to understand the structure and function of viruses, major advances in the techniques for finding new drugs, and
20850-456: Was 145 million in the late 15th and by the late 17th century, had been reduced to 15 million due to epidemics , wars, massacres, mass rapes , starvation, and enslavement. Indigenous historical trauma (IHT) is the trauma that can accumulate across generations and develop as a result of the historical ramifications of colonization and is linked to mental and physical health hardships and population decline. IHT affects many different people in
21000-462: Was about 18 hours. In those who are otherwise healthy the CDC states that antivirals may be considered within the first 48 hours. A German clinical practice guideline recommends against its use. Two 2013 meta-analyses have concluded that benefits in those who are otherwise healthy do not outweigh its risks. When the analysis was restricted to people with confirmed infection, the same 2014 Cochrane Review (see above) found unclear evidence of change in
21150-432: Was approved for medical use in the US in 1999. It was the first neuraminidase inhibitor available by mouth. It is on the World Health Organization's List of Essential Medicines but was downgraded to "complementary" status in 2017. A generic version was approved in the US in 2016. In 2022, it was the 205th most commonly prescribed medication in the United States, with more than 1 million prescriptions. Oseltamivir
21300-632: Was cultivated as long as 10,000 years ago. According to Linda Newson , "It is clear that in pre-Columbian times some groups struggled to survive and often suffered food shortages and famines , while others enjoyed a varied and substantial diet." Persistent drought around AD 850 coincided with the collapse of the Classic Maya civilization, and the famine of One Rabbit (AD 1454) was a major catastrophe in Mexico. Indigenous peoples of North America began practicing farming approximately 4,000 years ago, late in
21450-453: Was harmed for every 94 treated. Neither of the two most cited published treatment trials of oseltamivir reported any drug-attributable serious adverse events. It is pregnancy category B in Australia, meaning that it has been taken by a small number of women without signs of problems and in animal studies it looks safe. Dose adjustment may be needed in those with kidney problems. Oseltamivir
21600-635: Was immediately rejected by some leading members of the Association, and, while adopted by many, it was never universally accepted. While never popular in Indigenous communities themselves, it remains a preferred term among some anthropologists, notably in some parts of Canada and the English-speaking Caribbean . " Indigenous peoples in Canada " is used as the collective name for First Nations , Inuit , and Métis . The term Aboriginal peoples as
21750-484: Was isolated from the shiitake mushroom ( Lentinus edodes ). The presence of this may explain the Shiitake mushrooms' noted antiviral activity in vitro . Most viruses produce long dsRNA helices during transcription and replication. In contrast, uninfected mammalian cells generally produce dsRNA helices of fewer than 24 base pairs during transcription. DRACO ( double-stranded RNA activated caspase oligomerizer )
21900-497: Was not originally accepted by the myriad groups of Indigenous peoples themselves but has since been embraced or tolerated by many over the last two centuries. The term "Indian" generally does not include the culturally and linguistically distinct Indigenous peoples of the Arctic regions of the Americas, including the Aleuts , Inuit , or Yupik peoples . These peoples entered the continent as
22050-402: Was reported to induce rapid apoptosis selectively in virus-infected mammalian cells, while leaving uninfected cells unharmed. DRACO effects cell death via one of the last steps in the apoptosis pathway in which complexes containing intracellular apoptosis signalling molecules simultaneously bind multiple procaspases . The procaspases transactivate via cleavage, activate additional caspases in
22200-595: Was stopped. As of December 15, 2010, the World Health Organization (WHO) reported 314 samples of the prevalent 2009 pandemic H1N1 flu tested worldwide showed resistance to oseltamivir. The CDC found sporadic oseltamivir-resistant 2009 H1N1 virus infections had been identified, including with rare episodes of limited transmission, but the public health impact had been limited. Those sporadic cases of resistance were found in immunosuppressed patients during oseltamivir treatment and persons who developed illness while receiving oseltamivir chemoprophylaxis. During 2011,
22350-508: Was the overwhelming cause of the population decline of the Indigenous peoples. After initial contact with Europeans and Africans, Old World diseases caused the deaths of 90 to 95% of the native population of the New World in the following 150 years. Smallpox killed from one-third to half of the native population of Hispaniola in 1518. By killing the Incan ruler Huayna Capac , smallpox caused
22500-651: Was widely used during the H5N1 avian influenza epidemic in Southeast Asia in 2005. In response to the epidemic, various governments – including those of the United Kingdom, Canada, Israel, United States, and Australia – stockpiled quantities of oseltamivir in preparation for a possible pandemic and there were worldwide shortages of the drug, driven by the high demand for stockpiling. In November 2005, US President George W. Bush requested that Congress fund US$ 1 billion for
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