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103-460: While a beautiful area, the Mangochi area has been decimated by Africa's nemesis - AIDS . Couple that with poverty, climate change and a severe lack of infrastructure and the scenario is desperate. It is a very beautiful place, full of natural minerals, loads of fish, for example chambo, and of course Nkopola Lodge , Sun and Sand Palm Beach and many more. In fact there are numerous lovely lodges along

206-617: A 10- to 20-fold reduction in transmission risk. Pre-exposure prophylaxis for HIV (" PrEP ") with a daily dose of the medications tenofovir , with or without emtricitabine , is effective in people at high risk including men who have sex with men, couples where one is HIV-positive, and young heterosexuals in Africa. It may also be effective in intravenous drug users, with a study finding a decrease in risk of 0.7 to 0.4 per 100 person years. The USPSTF , in 2019, recommended PrEP in those who are at high risk. Universal precautions within

309-529: A brief period of influenza-like illness . During this period the person may not know that they are HIV-positive, yet they will be able to pass on the virus . Typically, this period is followed by a prolonged incubation period with no symptoms. Eventually the HIV infection increases the risk of developing other infections such as tuberculosis , as well as other opportunistic infections , and tumors which are rare in people who have normal immune function. The late stage

412-477: A cancer is formed, it usually has genome instability . This instability is likely due to reduced DNA repair or excessive DNA damage. Because of such instability, the cancer continues to evolve and to produce sub clones. For example, a renal cancer, sampled in 9 areas, had 40 ubiquitous mutations, demonstrating tumor heterogeneity (i.e. present in all areas of the cancer), 59 mutations shared by some (but not all areas), and 29 "private" mutations only present in one of

515-406: A couple in which one person is infected, the rate of HIV infection is less than 1% per year. There is some evidence to suggest that female condoms may provide an equivalent level of protection. Application of a vaginal gel containing tenofovir (a reverse transcriptase inhibitor ) immediately before sex seems to reduce infection rates by approximately 40% among African women. By contrast, use of

618-448: A factor. During the chronic phase, the consequences of generalized immune activation coupled with the gradual loss of the ability of the immune system to generate new T cells appear to account for the slow decline in CD4 T cell numbers. Although the symptoms of immune deficiency characteristic of AIDS do not appear for years after a person is infected, the bulk of CD4 T cell loss occurs during

721-460: A high viral load and the cut was deep. In the United States, intravenous drug users made up 12% of all new cases of HIV in 2009, and in some areas more than 80% of people who inject drugs are HIV-positive. HIV is transmitted in about 90% of blood transfusions using infected blood. In developed countries the risk of acquiring HIV from a blood transfusion is extremely low (less than one in half

824-402: A long incubation period . Lentiviruses are transmitted as single-stranded, positive- sense , enveloped RNA viruses . Upon entry into the target cell, the viral RNA genome is converted (reverse transcribed) into double-stranded DNA by a virally encoded reverse transcriptase that is transported along with the viral genome in the virus particle. The resulting viral DNA is then imported into

927-538: A million) where improved donor selection and HIV screening is performed; for example, in the UK the risk is reported at one in five million and in the United States it was one in 1.5 million in 2008. In low-income countries, only half of transfusions may be appropriately screened (as of 2008), and it is estimated that up to 15% of HIV infections in these areas come from transfusion of infected blood and blood products, representing between 5% and 10% of global infections. It

1030-488: A minority of sporadic cancers have a deficiency in DNA repair due to mutation in a DNA repair gene. However, a majority of sporadic cancers have deficiency in DNA repair due to epigenetic alterations that reduce or silence DNA repair gene expression. For example, of 113 sequential colorectal cancers, only four had a missense mutation in the DNA repair gene MGMT , while the majority had reduced MGMT expression due to methylation of

1133-410: A mutator phenotype. The protein-coding DNA within the nucleus is about 1.5% of the total genomic DNA. Within this protein-coding DNA (called the exome ), an average cancer of the breast or colon can have about 60 to 70 protein altering mutations, of which about 3 or 4 may be "driver" mutations, and the remaining ones may be "passenger" mutations. However, the average number of DNA sequence mutations in

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1236-401: A needle during drug injection is between 0.63% and 2.4% per act, with an average of 0.8%. The risk of acquiring HIV from a needle stick from an HIV-infected person is estimated as 0.3% (about 1 in 333) per act and the risk following mucous membrane exposure to infected blood as 0.09% (about 1 in 1000) per act. This risk may, however, be up to 5% if the introduced blood was from a person with

1339-433: A patch of abnormal tissue may arise. The figure in this section includes a photo of a freshly resected and lengthwise-opened segment of the colon showing a colon cancer and four polyps. Below the photo, there is a schematic diagram of how a large patch of mutant or epigenetically altered cells may have formed, shown by the large area in yellow in the diagram. Within this first large patch in the diagram (a large clone of cells),

1442-616: A process of cell-to-cell spread. The hybrid spreading mechanisms of HIV contribute to the virus' ongoing replication against antiretroviral therapies. Two types of HIV have been characterized: HIV-1 and HIV-2. HIV-1 is the virus that was originally discovered (and initially referred to also as LAV or HTLV-III). It is more virulent , more infective , and is the cause of the majority of HIV infections globally. The lower infectivity of HIV-2 as compared with HIV-1 implies that fewer people exposed to HIV-2 will be infected per exposure. Because of its relatively poor capacity for transmission, HIV-2

1545-430: A proliferative advantage, generating a field defect. Although the mutations/epimutations in DNA repair genes do not, themselves, confer a selective advantage, they may be carried along as passengers in cells when the cells acquire additional mutations/epimutations that do provide a proliferative advantage. The term neoplasm is a synonym of tumor . Neoplasia denotes the process of the formation of neoplasms/tumors, and

1648-430: A result of long-term treatment has effectively no risk of transmitting HIV sexually. Campaigns by UNAIDS and organizations around the world have communicated this as Undetectable = Untransmittable . Without treatment the infection can interfere with the immune system , and eventually progress to AIDS , sometimes taking many years. Following initial infection an individual may not notice any symptoms, or may experience

1751-422: A second such mutation or epigenetic alteration may occur so that a given stem cell acquires an advantage compared to other stem cells within the patch, and this altered stem cell may expand clonally forming a secondary patch, or sub-clone, within the original patch. This is indicated in the diagram by four smaller patches of different colors within the large yellow original area. Within these new patches (sub-clones),

1854-406: A sexually transmitted illness. In many areas of the world, a third of HIV carriers only discover they are infected at an advanced stage of the disease when AIDS or severe immunodeficiency has become apparent. Most people infected with HIV develop seroconverted (antigen-specific) antibodies within three to twelve weeks after the initial infection. Diagnosis of primary HIV before seroconversion

1957-472: A single population of neoplastic cells. These cells are presumed to be monoclonal – that is, they are derived from the same cell, and all carry the same genetic or epigenetic anomaly – evident of clonality. For lymphoid neoplasms, e.g. lymphoma and leukemia , clonality is proven by the amplification of a single rearrangement of their immunoglobulin gene (for B cell lesions) or T cell receptor gene (for T cell lesions). The demonstration of clonality

2060-410: A solid skeleton formed by sticky cells and an organic liquid filling the spaces in which cells can grow. Under this type of model, mechanical stresses and strains can be dealt with and their influence on the growth of the tumor and the surrounding tissue and vasculature elucidated. Recent findings from experiments that use this model show that active growth of the tumor is restricted to the outer edges of

2163-665: A tumor. Examples are arteriovenous fistulae or aneurysms (with or without thrombosis), biliary fistulae or aneurysms, sclerosing cholangitis, cysticercosis or hydatid cysts, intestinal duplications, and pulmonary inclusions as seen with cystic fibrosis. It can be dangerous to biopsy a number of types of tumor in which the leakage of their contents would potentially be catastrophic. When such types of tumors are encountered, diagnostic modalities such as ultrasound, CT scans, MRI, angiograms, and nuclear medicine scans are employed prior to (or during) biopsy or surgical exploration/excision in an attempt to avoid such severe complications. DNA damage

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2266-402: A tumor; these include leukemia and most forms of carcinoma in situ . Tumor is also not synonymous with cancer . While cancer is by definition malignant, a tumor can be benign , precancerous , or malignant . The terms mass and nodule are often used synonymously with tumor . Generally speaking, however, the term tumor is used generically, without reference to the physical size of

2369-618: Is a type of abnormal and excessive growth of tissue . The process that occurs to form or produce a neoplasm is called neoplasia . The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists in growing abnormally, even if the original trigger is removed. This abnormal growth usually forms a mass, which may be called a tumour or tumor . ICD-10 classifies neoplasms into four main groups: benign neoplasms , in situ neoplasms , malignant neoplasms , and neoplasms of uncertain or unknown behavior. Malignant neoplasms are also simply known as cancers and are

2472-433: Is almost invariably associated with activation of CD8 T cells , which kill HIV-infected cells, and subsequently with antibody production, or seroconversion . The CD8 T cell response is thought to be important in controlling virus levels, which peak and then decline, as the CD4 T cell counts recover. A good CD8 T cell response has been linked to slower disease progression and a better prognosis, though it does not eliminate

2575-538: Is also believed to carry an increased risk of HIV transmission as condoms are rarely worn, physical trauma to the vagina or rectum is likely, and there may be a greater risk of concurrent sexually transmitted infections. The second-most frequent mode of HIV transmission is via blood and blood products. Blood-borne transmission can be through needle-sharing during intravenous drug use, needle-stick injury, transfusion of contaminated blood or blood product, or medical injections with unsterilized equipment. The risk from sharing

2678-478: Is called acute HIV, primary HIV or acute retroviral syndrome. Many individuals develop an illness like influenza , mononucleosis or glandular fever 2–4 weeks after exposure while others have no significant symptoms. Symptoms occur in 40–90% of cases and most commonly include fever , large tender lymph nodes , throat inflammation , a rash , headache, tiredness, and/or sores of the mouth and genitals. The rash, which occurs in 20–50% of cases, presents itself on

2781-436: Is considered to be the primary underlying cause of malignant neoplasms known as cancers. Its central role in progression to cancer is illustrated in the figure in this section, in the box near the top. (The central features of DNA damage, epigenetic alterations and deficient DNA repair in progression to cancer are shown in red.) DNA damage is very common. Naturally occurring DNA damages (mostly due to cellular metabolism and

2884-653: Is defined as an HIV infection with either a CD4 T cell count below 200 cells per μL or the occurrence of specific diseases associated with HIV infection. In the absence of specific treatment, around half of people infected with HIV develop AIDS within ten years. The most common initial conditions that alert to the presence of AIDS are pneumocystis pneumonia (40%), cachexia in the form of HIV wasting syndrome (20%), and esophageal candidiasis . Other common signs include recurrent respiratory tract infections . Opportunistic infections may be caused by bacteria , viruses , fungi , and parasites that are normally controlled by

2987-760: Is disputed, and whether it is of benefit in developed countries and among men who have sex with men is undetermined. Programs encouraging sexual abstinence do not appear to affect subsequent HIV risk. Evidence of any benefit from peer education is equally poor. Comprehensive sexual education provided at school may decrease high-risk behavior. A substantial minority of young people continues to engage in high-risk practices despite knowing about HIV/AIDS, underestimating their own risk of becoming infected with HIV. Voluntary counseling and testing people for HIV does not affect risky behavior in those who test negative but does increase condom use in those who test positive. Enhanced family planning services appear to increase

3090-422: Is done by measuring HIV- RNA or p24 antigen . Positive results obtained by antibody or PCR testing are confirmed either by a different antibody or by PCR. Antibody tests in children younger than 18 months are typically inaccurate, due to the continued presence of maternal antibodies . Thus HIV infection can only be diagnosed by PCR testing for HIV RNA or DNA, or via testing for the p24 antigen. Much of

3193-595: Is especially high, estimated as 1.4–1.7% per act in both heterosexual and homosexual contacts. While the risk of transmission from oral sex is relatively low, it is still present. The risk from receiving oral sex has been described as "nearly nil"; however, a few cases have been reported. The per-act risk is estimated at 0–0.04% for receptive oral intercourse. In settings involving prostitution in low-income countries, risk of female-to-male transmission has been estimated as 2.4% per act, and of male-to-female transmission as 0.05% per act. Risk of transmission increases in

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3296-704: Is evidence that more than 80% of the somatic mutations found in mutator phenotype human colorectal tumors occur before the onset of terminal clonal expansion. Similarly, Vogelstein et al. point out that more than half of somatic mutations identified in tumors occurred in a pre-neoplastic phase (in a field defect), during growth of apparently normal cells. Likewise, epigenetic alterations present in tumors may have occurred in pre-neoplastic field defects. An expanded view of field effect has been termed "etiologic field effect", which encompasses not only molecular and pathologic changes in pre-neoplastic cells but also influences of exogenous environmental factors and molecular changes in

3399-400: Is largely confined to West Africa . After the virus enters the body, there is a period of rapid viral replication , leading to an abundance of virus in the peripheral blood. During primary infection, the level of HIV may reach several million virus particles per milliliter of blood. This response is accompanied by a marked drop in the number of circulating CD4 T cells . The acute viremia

3502-603: Is now considered to be necessary to identify a lymphoid cell proliferation as neoplastic. The word tumor or tumour comes from the Latin word for swelling , which is one of the cardinal signs of inflammation. The word originally referred to any form of swelling , neoplastic or not. In modern English, tumor (non-US spelling: tumour) is used as a synonym for a neoplasm (a solid or fluid-filled cystic lesion that may or may not be formed by an abnormal growth of neoplastic cells) that appears enlarged in size. Some neoplasms do not form

3605-531: Is often also associated with unintended weight loss . Without treatment a person living with HIV can expect to live for 11 years. Early testing can show if treatment is needed to stop this progression and to prevent infecting others. HIV is spread primarily by unprotected sex (including anal and vaginal sex ), contaminated hypodermic needles or blood transfusions , and from mother to child during pregnancy , delivery, or breastfeeding. Some bodily fluids, such as saliva, sweat, and tears, do not transmit

3708-403: Is often used as a synonym for a cystic (liquid-filled) growth or solid neoplasm (cancerous or non-cancerous), with other forms of swelling often referred to as "swellings" . Related terms occur commonly in the medical literature, where the nouns tumefaction and tumescence (derived from the adjective tumescent ) are current medical terms for non-neoplastic swelling. This type of swelling

3811-562: Is possible to acquire HIV from organ and tissue transplantation , although this is rare because of screening . Unsafe medical injections play a role in HIV spread in sub-Saharan Africa . In 2007, between 12% and 17% of infections in this region were attributed to medical syringe use. The World Health Organization estimates the risk of transmission as a result of a medical injection in Africa at 1.2%. Risks are also associated with invasive procedures, assisted delivery, and dental care in this area of

3914-420: Is referred to as post-exposure prophylaxis (PEP). The use of the single agent zidovudine reduces the risk of an HIV infection five-fold following a needle-stick injury. As of 2013 , the prevention regimen recommended in the United States consists of three medications— tenofovir , emtricitabine and raltegravir —as this may reduce the risk further. PEP treatment is recommended after a sexual assault when

4017-542: Is spread by three main routes: sexual contact , significant exposure to infected body fluids or tissues, and from mother to child during pregnancy, delivery, or breastfeeding (known as vertical transmission ). There is no risk of acquiring HIV if exposed to feces , nasal secretions, saliva, sputum , sweat, tears, urine, or vomit unless these are contaminated with blood. It is also possible to be co-infected by more than one strain of HIV—a condition known as HIV superinfection . The most frequent mode of transmission of HIV

4120-467: Is through sexual contact with an infected person. However, an HIV-positive person who has an undetectable viral load as a result of long-term treatment has effectively no risk of transmitting HIV sexually, known as Undetectable = Untransmittable . The existence of functionally noncontagious HIV-positive people on antiretroviral therapy was controversially publicized in the 2008 Swiss Statement , and has since become accepted as medically sound. Globally,

4223-561: The 2009 general election most of these constituencies (except Mangochi Monkey Bay, which has been held by members of the Democratic Progressive Party ) have been represented by politicians from the United Democratic Front . 14°30′S 35°15′E  /  14.500°S 35.250°E  / -14.500; 35.250 AIDS The human immunodeficiency virus ( HIV ) is a retrovirus that attacks

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4326-581: The WHO disease staging system for HIV infection and disease , and the CDC classification system for HIV infection . The CDC's classification system is more frequently adopted in developed countries. Since the WHO's staging system does not require laboratory tests, it is suited to the resource-restricted conditions encountered in developing countries, where it can also be used to help guide clinical management. Despite their differences,

4429-603: The World Health Organization (WHO) African Region. HIV/AIDS is considered a pandemic —a disease outbreak which is present over a large area and is actively spreading. The United States' National Institutes of Health (NIH) and the Gates Foundation have pledged $ 200 million focused on developing a global cure for AIDS. There are three main stages of HIV infection: acute infection, clinical latency, and AIDS. The initial period following infection with HIV

4532-423: The immune system . It is a preventable disease . There is no vaccine or cure for HIV. It can be managed with treatment and become a manageable chronic health condition. While there is no cure or vaccine, antiretroviral treatment can slow the course of the disease and enable people living with HIV to lead long and healthy lives. An HIV-positive person on treatment can expect to live a normal life, and die with

4635-598: The spermicide nonoxynol-9 may increase the risk of transmission due to its tendency to cause vaginal and rectal irritation. Circumcision in sub-Saharan Africa "reduces the acquisition of HIV by heterosexual men by between 38% and 66% over 24 months". Owing to these studies, both the World Health Organization and UNAIDS recommended male circumcision in 2007 as a method of preventing female-to-male HIV transmission in areas with high rates of HIV. However, whether it protects against male-to-female transmission

4738-489: The CCR5 protein when present in both chromosomes very effectively prevents HIV-1 infection. HIV seeks out and destroys CCR5 expressing CD4 T cells during acute infection. A vigorous immune response eventually controls the infection and initiates the clinically latent phase. CD4 T cells in mucosal tissues remain particularly affected. Continuous HIV replication causes a state of generalized immune activation persisting throughout

4841-523: The MGMT promoter region (an epigenetic alteration). Five reports present evidence that between 40% and 90% of colorectal cancers have reduced MGMT expression due to methylation of the MGMT promoter region. Similarly, out of 119 cases of mismatch repair-deficient colorectal cancers that lacked DNA repair gene PMS2 expression, PMS2 was deficient in 6 due to mutations in the PMS2 gene, while in 103 cases PMS2 expression

4944-507: The Mangochi Road other than Nkopola Lodge. One of the finest is Club Makokola (Club Mac). There are beautiful tropical fish, mostly cichlids , to be seen while swimming. There are also many fabulous bird rookeries along the lake with fish eagles , the national bird of Malawi, a member of the same genus as the American bald eagle . Mangochi is well known with its lake that generates income in

5047-565: The absence of treatment will eventually progress to AIDS, a small proportion (about 5%) retain high levels of CD4 T cells ( T helper cells ) without antiretroviral therapy for more than five years. These individuals are classified as "HIV controllers" or long-term nonprogressors (LTNP). Another group consists of those who maintain a low or undetectable viral load without anti-retroviral treatment, known as "elite controllers" or "elite suppressors". They represent approximately 1 in 300 infected persons. Acquired immunodeficiency syndrome (AIDS)

5150-499: The absence of treatment, the risk of transmission before or during birth is around 20%, and in those who also breastfeed 35%. Treatment decreases this risk to less than 5%. Antiretrovirals when taken by either the mother or the baby decrease the risk of transmission in those who do breastfeed. If blood contaminates food during pre-chewing it may pose a risk of transmission. If a woman is untreated, two years of breastfeeding results in an HIV/AIDS risk in her baby of about 17%. Due to

5253-498: The acute phase of disease. HIV/AIDS is diagnosed via laboratory testing and then staged based on the presence of certain signs or symptoms . HIV screening is recommended by the United States Preventive Services Task Force for all people 15 years to 65 years of age, including all pregnant women. Additionally, testing is recommended for those at high risk, which includes anyone diagnosed with

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5356-411: The areas of the cancer. Various other terms have been used to describe this phenomenon , including "field effect", "field cancerization", and "field carcinogenesis ". The term "field cancerization" was first used in 1953 to describe an area or "field" of epithelium that has been preconditioned by (at that time) largely unknown processes so as to predispose it towards development of cancer. Since then,

5459-406: The cell nucleus and integrated into the cellular DNA by a virally encoded integrase and host co-factors. Once integrated, the virus may become latent , allowing the virus and its host cell to avoid detection by the immune system. Alternatively, the virus may be transcribed , producing new RNA genomes and viral proteins that are packaged and released from the cell as new virus particles that begin

5562-632: The cell to divide and expand uncontrollably. A neoplasm can be caused by an abnormal proliferation of tissues, which can be caused by genetic mutations . Not all types of neoplasms cause a tumorous overgrowth of tissue (such as leukemia or carcinoma in situ ), however similarities between neoplasmic growths and regenerative processes, e.g., dedifferentiation and rapid cell proliferation, have been pointed out. Tumor growth has been studied using mathematics and continuum mechanics . Vascular tumors such as hemangiomas and lymphangiomas (formed from blood or lymph vessels) are thus looked at as being amalgams of

5665-425: The chronic phase. Immune activation, which is reflected by the increased activation state of immune cells and release of pro-inflammatory cytokines , results from the activity of several HIV gene products and the immune response to ongoing HIV replication. It is also linked to the breakdown of the immune surveillance system of the gastrointestinal mucosal barrier caused by the depletion of mucosal CD4 T cells during

5768-406: The colons of humans eating a high fat diet, also cause DNA damage and contribute to colon cancer . Katsurano et al. indicated that macrophages and neutrophils in an inflamed colonic epithelium are the source of reactive oxygen species causing the DNA damages that initiate colonic tumorigenesis (creation of tumors in the colon). Some sources of DNA damage are indicated in the boxes at the top of

5871-613: The early 1980s, HIV/AIDS has had a large impact on society, both as an illness and as a source of discrimination . The disease also has large economic impacts . There are many misconceptions about HIV/AIDS , such as the belief that it can be transmitted by casual non-sexual contact. The disease has become subject to many controversies involving religion , including the Catholic Church's position not to support condom use as prevention. It has attracted international medical and political attention as well as large-scale funding since it

5974-424: The end of this stage many people experience fever, weight loss, gastrointestinal problems and muscle pains. Between 50% and 70% of people also develop persistent generalized lymphadenopathy , characterized by unexplained, non-painful enlargement of more than one group of lymph nodes (other than in the groin) for over three to six months. Although most HIV-1 infected individuals have a detectable viral load and in

6077-405: The entire area of the field defect. Deficiencies in DNA repair cause increased mutation rates. A deficiency in DNA repair, itself, can allow DNA damages to accumulate, and error-prone translesion synthesis past some of those damages may give rise to mutations. In addition, faulty repair of these accumulated DNA damages may give rise to epimutations. These new mutations or epimutations may provide

6180-457: The entire genome (including non-protein-coding regions ) within a breast cancer tissue sample is about 20,000. In an average melanoma tissue sample (where melanomas have a higher exome mutation frequency ) the total number of DNA sequence mutations is about 80,000. This compares to the very low mutation frequency of about 70 new mutations in the entire genome between generations (parent to child) in humans. The high frequencies of mutations in

6283-700: The field defects surrounding those cancers. The Table, below, gives examples for which the DNA repair deficiency in a cancer was shown to be caused by an epigenetic alteration, and the somewhat lower frequencies with which the same epigenetically caused DNA repair deficiency was found in the surrounding field defect. Some of the small polyps in the field defect shown in the photo of the opened colon segment may be relatively benign neoplasms. Of polyps less than 10mm in size, found during colonoscopy and followed with repeat colonoscopies for 3 years, 25% were unchanged in size, 35% regressed or shrank in size while 40% grew in size. Cancers are known to exhibit genome instability or

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6386-578: The figure in this section. Individuals with a germline mutation causing deficiency in any of 34 DNA repair genes (see article DNA repair-deficiency disorder ) are at increased risk of cancer . Some germline mutations in DNA repair genes cause up to 100% lifetime chance of cancer (e.g., p53 mutations). These germline mutations are indicated in a box at the left of the figure with an arrow indicating their contribution to DNA repair deficiency. About 70% of malignant (cancerous) neoplasms have no hereditary component and are called "sporadic cancers". Only

6489-510: The figure) cause increased DNA damages (level 5 in the figure) which result in increased somatic mutations and epigenetic alterations (level 6 in the figure). Field defects, normal-appearing tissue with multiple alterations (and discussed in the section below), are common precursors to development of the disordered and improperly proliferating clone of tissue in a malignant neoplasm. Such field defects (second level from bottom of figure) may have multiple mutations and epigenetic alterations. Once

6592-465: The first 2.5 months of an HIV infection, a person's infectiousness is twelve times higher due to the high viral load associated with acute HIV. If the person is in the late stages of infection, rates of transmission are approximately eightfold greater. Commercial sex workers (including those in pornography ) have an increased likelihood of contracting HIV. Rough sex can be a factor associated with an increased risk of transmission. Sexual assault

6695-487: The first weeks of infection, especially in the intestinal mucosa, which harbors the majority of the lymphocytes found in the body. The reason for the preferential loss of mucosal CD4 T cells is that the majority of mucosal CD4 T cells express the CCR5 protein which HIV uses as a co-receptor to gain access to the cells, whereas only a small fraction of CD4 T cells in the bloodstream do so. A specific genetic change that alters

6798-414: The flesh. The Roman medical encyclopedist Celsus ( c. 30 BC–38 AD) described the four cardinal signs of acute inflammation as tumor , dolor , calor , and rubor (swelling, pain, increased heat, and redness). (His treatise, De Medicina , was the first medical book printed in 1478 following the invention of the movable-type printing press.) In contemporary English, the word tumor

6901-638: The focus of oncology . Prior to the abnormal growth of tissue, such as neoplasia, cells often undergo an abnormal pattern of growth, such as metaplasia or dysplasia . However, metaplasia or dysplasia does not always progress to neoplasia and can occur in other conditions as well. The word neoplasm is from Ancient Greek νέος- neo 'new' and πλάσμα plasma 'formation, creation'. A neoplasm can be benign , potentially malignant, or malignant ( cancer ). Neoplastic tumors are often heterogeneous and contain more than one type of cell, but their initiation and continued growth are usually dependent on

7004-414: The health care environment are believed to be effective in decreasing the risk of HIV. Intravenous drug use is an important risk factor, and harm reduction strategies such as needle-exchange programs and opioid substitution therapy appear effective in decreasing this risk. A course of antiretrovirals administered within 48 to 72 hours after exposure to HIV-positive blood or genital secretions

7107-425: The human immune system such as CD4 T cells, macrophages and dendritic cells . It directly and indirectly destroys CD4 T cells. HIV is a member of the genus Lentivirus , part of the family Retroviridae . Lentiviruses share many morphological and biological characteristics. Many species of mammals are infected by lentiviruses, which are characteristically responsible for long-duration illnesses with

7210-400: The immune system. Which infections occur depends partly on what organisms are common in the person's environment. These infections may affect nearly every organ system . People with AIDS have an increased risk of developing various viral-induced cancers, including Kaposi's sarcoma , Burkitt's lymphoma , primary central nervous system lymphoma , and cervical cancer . Kaposi's sarcoma is

7313-407: The increased risk of death without breastfeeding in many areas in the developing world, the World Health Organization recommends either exclusive breastfeeding or the provision of safe formula. All women known to be HIV-positive should be taking lifelong antiretroviral therapy. HIV is the cause of the spectrum of disease known as HIV/AIDS. HIV is a retrovirus that primarily infects components of

7416-456: The infection in five groups. In those greater than six years of age it is: For surveillance purposes, the AIDS diagnosis still stands even if, after treatment, the CD4 T cell count rises to above 200 per μL of blood or other AIDS-defining illnesses are cured. Consistent condom use reduces the risk of HIV transmission by approximately 80% over the long term. When condoms are used consistently by

7519-519: The initial clone, and sub-sub-clones inside those, then colon cancers generally should be associated with, and be preceded by, fields of increasing abnormality reflecting the succession of premalignant events. The most extensive region of abnormality (the outermost yellow irregular area in the diagram) would reflect the earliest event in formation of a malignant neoplasm. In experimental evaluation of specific DNA repair deficiencies in cancers, many specific DNA repair deficiencies were also shown to occur in

7622-528: The layer that lines the inner part of eyelids and the white part of the eye) is also more common in those with HIV. Additionally, people with AIDS frequently have systemic symptoms such as prolonged fevers, sweats (particularly at night), swollen lymph nodes, chills, weakness, and unintended weight loss . Diarrhea is another common symptom, present in about 90% of people with AIDS. They can also be affected by diverse psychiatric and neurological symptoms independent of opportunistic infections and cancers. HIV

7725-430: The lesion. More specifically, the term mass is often used when the lesion has a maximal diameter of at least 20 millimeters (mm) in the greatest direction, while the term nodule is usually used when the size of the lesion is less than 20 mm in its greatest dimension (25.4 mm = 1 inch). Tumors in humans occur as a result of accumulated genetic and epigenetic alterations within single cells, which cause

7828-413: The likelihood of women with HIV using contraception, compared to basic services. It is not known whether treating other sexually transmitted infections is effective in preventing HIV. Antiretroviral treatment among people with HIV whose CD4 count ≤ 550 cells/μL is a very effective way to prevent HIV infection of their partner (a strategy known as treatment as prevention, or TASP). TASP is associated with

7931-420: The local microenvironment on neoplastic evolution from tumor initiation to patient death. In the colon, a field defect probably arises by natural selection of a mutant or epigenetically altered cell among the stem cells at the base of one of the intestinal crypts on the inside surface of the colon. A mutant or epigenetically altered stem cell may replace the other nearby stem cells by natural selection. Thus,

8034-860: The majority of the 49 colon cancers evaluated by Facista et al. Epigenetic alterations causing reduced expression of DNA repair genes is shown in a central box at the third level from the top of the figure in this section, and the consequent DNA repair deficiency is shown at the fourth level. When expression of DNA repair genes is reduced, DNA damages accumulate in cells at a higher than normal level, and these excess damages cause increased frequencies of mutation or epimutation. Mutation rates strongly increase in cells defective in DNA mismatch repair or in homologous recombinational repair (HRR). During repair of DNA double strand breaks , or repair of other DNA damages, incompletely cleared sites of repair can cause epigenetic gene silencing . DNA repair deficiencies (level 4 in

8137-539: The many common infectious diseases with similar symptoms. Someone with an unexplained fever who may have been recently exposed to HIV should consider testing to find out if they have been infected. The initial symptoms are followed by a stage called clinical latency, asymptomatic HIV, or chronic HIV. Without treatment, this second stage of the natural history of HIV infection can last from about three years to over 20 years (on average, about eight years). While typically there are few or no symptoms at first, near

8240-437: The most common cancer, occurring in 10% to 20% of people with HIV. The second-most common cancer is lymphoma, which is the cause of death of nearly 16% of people with AIDS and is the initial sign of AIDS in 3% to 4%. Both these cancers are associated with human herpesvirus 8 (HHV-8). Cervical cancer occurs more frequently in those with AIDS because of its association with human papillomavirus (HPV). Conjunctival cancer (of

8343-653: The most common mode of HIV transmission is via sexual contacts between people of the opposite sex ; however, the pattern of transmission varies among countries. As of 2017 , most HIV transmission in the United States occurred among men who had sex with men (82% of new HIV diagnoses among males aged 13 and older and 70% of total new diagnoses). In the US, gay and bisexual men aged 13 to 24 accounted for an estimated 92% of new HIV diagnoses among all men in their age group and 27% of new diagnoses among all gay and bisexual men. With regard to unprotected heterosexual contacts, estimates of

8446-441: The perpetrator is known to be HIV-positive, but is controversial when their HIV status is unknown. The duration of treatment is usually four weeks and is frequently associated with adverse effects—where zidovudine is used, about 70% of cases result in adverse effects such as nausea (24%), fatigue (22%), emotional distress (13%) and headaches (9%). Tumors A neoplasm ( / ˈ n iː oʊ p l æ z əm , ˈ n iː ə -/ )

8549-455: The photo is external to the outer wall of the colon. In the segment of colon shown here, the colon was cut open lengthwise to expose the inner surface of the colon and to display the cancer and polyps occurring within the inner epithelial lining of the colon. If the general process by which sporadic colon cancers arise is the formation of a pre-neoplastic clone that spreads by natural selection, followed by formation of internal sub-clones within

8652-401: The polyps, 6mm, 5mm, and two of 3mm, and a cancer about 3 cm across in its longest dimension). These neoplasms are also indicated, in the diagram below the photo, by 4 small tan circles (polyps) and a larger red area (cancer). The cancer in the photo occurred in the cecal area of the colon, where the colon joins the small intestine (labeled) and where the appendix occurs (labeled). The fat in

8755-453: The presence of many sexually transmitted infections and genital ulcers . Genital ulcers increase the risk approximately fivefold. Other sexually transmitted infections, such as gonorrhea , chlamydia , trichomoniasis , and bacterial vaginosis , are associated with somewhat smaller increases in risk of transmission. The viral load of an infected person is an important risk factor in both sexual and mother-to-child transmission. During

8858-590: The process is referred to as a neoplastic process. The word neoplastic itself comes from Greek neo 'new' and plastic 'formed, molded'. The term tumor derives from the Latin noun tumor 'a swelling', ultimately from the verb tumēre 'to swell'. In the British Commonwealth, the spelling tumour is commonly used, whereas in the U.S. the word is usually spelled tumor . In its medical sense, tumor has traditionally meant an abnormal swelling of

8961-401: The process may be repeated multiple times, indicated by the still smaller patches within the four secondary patches (with still different colors in the diagram) which clonally expand, until stem cells arise that generate either small polyps or else a malignant neoplasm (cancer). In the photo, an apparent field defect in this segment of a colon has generated four polyps (labeled with the size of

9064-593: The properties of DNA in water at body temperatures) occur at a rate of more than 10,000 new damages, on average, per human cell, per day. Additional DNA damages can arise from exposure to exogenous agents. Tobacco smoke causes increased exogenous DNA damage, and these DNA damages are the likely cause of lung cancer due to smoking. UV light from solar radiation causes DNA damage that is important in melanoma . Helicobacter pylori infection produces high levels of reactive oxygen species that damage DNA and contributes to gastric cancer. Bile acids , at high levels in

9167-434: The replication cycle anew. HIV is now known to spread between CD4 T cells by two parallel routes: cell-free spread and cell-to-cell spread, i.e. it employs hybrid spreading mechanisms. In the cell-free spread, virus particles bud from an infected T cell, enter the blood/extracellular fluid and then infect another T cell following a chance encounter. HIV can also disseminate by direct transmission from one cell to another by

9270-487: The risk of HIV transmission per sexual act appear to be four to ten times higher in low-income countries than in high-income countries. In low-income countries, the risk of female-to-male transmission is estimated as 0.38% per act, and of male-to-female transmission as 0.30% per act; the equivalent estimates for high-income countries are 0.04% per act for female-to-male transmission, and 0.08% per act for male-to-female transmission. The risk of transmission from anal intercourse

9373-404: The terms "field cancerization" and "field defect" have been used to describe pre-malignant tissue in which new cancers are likely to arise. Field defects are important in progression to cancer. However, in most cancer research, as pointed out by Rubin "The vast majority of studies in cancer research has been done on well-defined tumors in vivo, or on discrete neoplastic foci in vitro. Yet there

9476-446: The total nucleotide sequences within cancers suggest that often an early alteration in the field defects giving rise to a cancer (e.g. yellow area in the diagram in this section) is a deficiency in DNA repair. The large field defects surrounding colon cancers (extending to at about 10 cm on each side of a cancer) were shown by Facista et al. to frequently have epigenetic defects in 2 or 3 DNA repair proteins ( ERCC1 , XPF or PMS2 ) in

9579-524: The tourism industry. Most of the indigenous people of Mangochi are the Yao people , and there are a few from other tribes. Lingamasa is known with its fresh rice that is sold in most parts of the country. At the time of the 2018 Census of Malawi , the distribution of the population of Mangochi District by ethnic group was as follows: There are thirteen National Assembly constituencies in Mangochi: Since

9682-480: The trunk and is maculopapular , classically. Some people also develop opportunistic infections at this stage. Gastrointestinal symptoms, such as vomiting or diarrhea may occur. Neurological symptoms of peripheral neuropathy or Guillain–Barré syndrome also occur. The duration of the symptoms varies, but is usually one or two weeks. These symptoms are not often recognized as signs of HIV infection. Family doctors or hospitals can misdiagnose cases as one of

9785-937: The tumor and that stiffening of the underlying normal tissue inhibits tumor growth as well. Benign conditions that are not associated with an abnormal proliferation of tissue (such as sebaceous cysts ) can also present as tumors, however, but have no malignant potential. Breast cysts (as occur commonly during pregnancy and at other times) are another example, as are other encapsulated glandular swellings (thyroid, adrenal gland, pancreas). Encapsulated hematomas, encapsulated necrotic tissue (from an insect bite, foreign body, or other noxious mechanism), keloids (discrete overgrowths of scar tissue) and granulomas may also present as tumors. Discrete localized enlargements of normal structures (ureters, blood vessels, intrahepatic or extrahepatic biliary ducts, pulmonary inclusions, or gastrointestinal duplications ) due to outflow obstructions or narrowings, or abnormal connections, may also present as

9888-552: The two systems allow a comparison for statistical purposes. The World Health Organization first proposed a definition for AIDS in 1986. Since then, the WHO classification has been updated and expanded several times, with the most recent version being published in 2007. The WHO system uses the following categories: The U.S. Centers for Disease Control and Prevention also created a classification system for HIV, and updated it in 2008 and 2014. This system classifies HIV infections based on CD4 count and clinical symptoms, and describes

9991-440: The virus, not of it. Effective treatment for HIV-positive people (people living with HIV ) involves a life-long regimen of medicine to suppress the virus, making the viral load undetectable. Without treatment it can lead to a spectrum of conditions including acquired immunodeficiency syndrome ( AIDS ). Treatment is recommended as soon as the diagnosis is made. An HIV-positive person who has an undetectable viral load as

10094-502: The virus. Ultimately, HIV causes AIDS by depleting CD4 T cells. This weakens the immune system and allows opportunistic infections . T cells are essential to the immune response and without them, the body cannot fight infections or kill cancerous cells. The mechanism of CD4 T cell depletion differs in the acute and chronic phases. During the acute phase, HIV-induced cell lysis and killing of infected cells by CD8 T cells accounts for CD4 T cell depletion, although apoptosis may also be

10197-463: The virus. Oral sex has little risk of transmitting the virus. Ways to avoid catching HIV and preventing the spread include safe sex , treatment to prevent infection (" PrEP "), treatment to stop infection in someone who has been recently exposed (" PEP "), treating those who are infected , and needle exchange programs . Disease in a baby can often be prevented by giving both the mother and child antiretroviral medication . Recognized worldwide in

10300-559: The world lacks access to reliable PCR testing, and people in many places simply wait until either symptoms develop or the child is old enough for accurate antibody testing. In sub-Saharan Africa between 2007 and 2009, between 30% and 70% of the population were aware of their HIV status. In 2009, between 3.6% and 42% of men and women in sub-Saharan countries were tested; this represented a significant increase compared to previous years. Two main clinical staging systems are used to classify HIV and HIV-related disease for surveillance purposes:

10403-482: The world. People giving or receiving tattoos , piercings , and scarification are theoretically at risk of infection but no confirmed cases have been documented. It is not possible for mosquitoes or other insects to transmit HIV. HIV can be transmitted from mother to child during pregnancy, during delivery, or through breast milk, resulting in the baby also contracting HIV. As of 2008, vertical transmission accounted for about 90% of cases of HIV in children. In

10506-705: Was deficient because its pairing partner MLH1 was repressed due to promoter methylation (PMS2 protein is unstable in the absence of MLH1). In the other 10 cases, loss of PMS2 expression was likely due to epigenetic overexpression of the microRNA, miR-155 , which down-regulates MLH1. In further examples, epigenetic defects were found at frequencies of between 13%-100% for the DNA repair genes BRCA1 , WRN , FANCB , FANCF , MGMT, MLH1 , MSH2 , MSH4 , ERCC1 , XPF , NEIL1 and ATM . These epigenetic defects occurred in various cancers, including breast, ovarian, colorectal, and head and neck cancers. Two or three deficiencies in expression of ERCC1, XPF or PMS2 occur simultaneously in

10609-634: Was identified in the 1980s. HIV made the jump from other primates to humans in west-central Africa in the early-to-mid-20th century. AIDS was first recognized by the U.S. Centers for Disease Control and Prevention (CDC) in 1981 and its cause—HIV infection—was identified in the early part of the decade. Between the first time AIDS was readily identified through 2024, the disease is estimated to have caused at least 42.3 million deaths worldwide. In 2023, 630,000 people died from HIV-related causes, an estimated 1.3 million people acquired HIV and about 39.9 million people worldwide living with HIV, 65% of whom are in

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