text:
Talk:Encephalopathy

Source
Part of this article is adapted from the public domain U.S. NINDS document "NINDS Encephalopathy Information Page" located at

Types
[mailto:brewhaha@freenet.edmonton.ab.ca]: I added the part about Alzheimer's and CJD. The former may not be transmissible, and it's certainly a neurodegenerative disease. 216.234.170.74 15:12, 31 July 2006 (UTC)

This article on inflammation in Alzheimer's and prion diseases shows that the distinction between Alz and human prion disease may be arbitrary. It seems to be a review, because it talks of a great many things that I find hard to put into one experiment. 216.234.170.74 15:51, 31 July 2006 (UTC)

PRES posterior reversible encephalopathy syndrome - I didn't stabilise for 3 days, 12 cases in medical history before me, nothing online on any browser, even the brain charities I emailed never heard of it. Why did I almost die from the most Excruciating brain-ripping pain and blindness, swelling until they flew someone 3 days later to diagnose, 12 cases in medical history he told my family, yet can't even find research? Also I am constantly reminded that stress could trigger it to happen again which would be fatal. There's no support except for hie and encephalitis who won't support an adult PRES sufferer. Unbelievable really in this day and age, it was only 2 yrs ago Morrigan81 (talk) 08:13, 3 October 2022 (UTC)

Introduction
Now that I look at the lead section, "non-specific" leaps out at me. Encephalopathy literally means "Disease of the pENIS". 216.234.170.74 15:20, 31 July 2006 (UTC)

Anthropocentrism
This article deals only with encephalopathy in humans. Since bovine spongiform encephalopathy is much more familiar to lay people than any of the other forms of encephalopathy listed, this amounts to a grave imbalance. And why, for that matter, isn't CJD listed, since it is the human form of this encephalopathy of cattle?

Also There are severe causes of encephalopathy Should this be "several causes"? Ireneshusband 18:01, 17 November 2006 (UTC)

severe causes?
In the section listing what appear to be 4 types of encephalopathy, there's a sentence at the top reading, 'There are severe causes of encephalopathy.' The section does not appear to list causes, but types, and I don't understand why 'severe' is in the sentence. Shouldn't it be something like 'There are several types of encephalopathy'? Mathtinder 02:29, 25 November 2006 (UTC)

Hypertension BP 190/130 Morrigan81 (talk) 08:09, 3 October 2022 (UTC)

Intro
I fixed the poor writing of the second paragraph of the introduction, but I have realized that it elucidates nothing, defeating the purpose of a hypothetical example. Therefore, I am removing it, since it is extremely long-winded, and the point of an introduction is to concisely introduce a topic. If anyone cares to prune it and reintroduce what is left, here is the text: A descriptive example may clarify the distinctions between these entities. An elderly man with Alzheimer's disease, manifested by mild dementia (forgetfulness and impaired judgment) develops pneumonia, a severe infection. He manifests depressed consciousness, myclonic jerks, jactitation (restless tossing in bed, picking at things), and Cheyne-Stokes respirations (rhythmic increase and decrease in respiratory frequency and depth). These are symptoms (not exclusively) of toxic-metabolic encephalopathy. Because of the severity of the patient's illness he is admitted to the intensive care unit, intubated with an endotracheal tube, mechanically ventilated, and sedated with medications. After a week his infection is cured and he is extubated and breathes independently. At this point he sleeps during the day and is awake and agitated at night, has hallucinations and alternating periods of lucidity and confusion, and manifests paranoia. This is delirium, arising from multiple previous insults (reduced baseline mental faculties, infection, psychoactive medications, altered environment, etc.). With cessation of psychoactive medications, enforcement of normal day/night dark/light cycles, and frequent, gentle re-orientation to his surroundings, his confusion clears, leaving him mentally with his previous baseline dementia.

--♦♦♦Vlmastra♦♦♦ 04:28, 4 November 2007 (UTC)

Hypoxic ischemic encephalopathy
should HIE be inclueded in this page, it is a term that is commonly used in medicine yet it is not on this page. should it be inclued?--Mygodshesfat (talk) 19:51, 22 April 2008 (UTC)

Copied
Some info on this site is copied from the NINDS site on Encephalopathy! Is this considered plagiarism. --Edward130603 (talk) 02:23, 24 February 2009 (UTC)

MRI
The MRI is pretty, but has nothing to do with encephalopathy. It should probably go away. —Preceding unsigned comment added by 75.15.115.174 (talk) 06:28, 17 May 2009 (UTC)

Agreed. I have removed the infobox containing the image. Perhaps it should be restored with a different image, or perhaps someone can explain why that MRI image had particular relevance to an article on encephalopathy. Rfontana (talk) 07:59, 25 June 2009 (UTC)

Prion diseases
I deleted the statement that prion diseases are invariably infectious - this is simply not true. The unique feature of prion diseases is that they can be infectious, spontaneous or hereditary. I would suggest deletion of mention of prion diseases in that section for a more conventional encephalopathy - while prion diseases may be very exciting and cutting edge, they don't make for good comparisons. 82.46.212.111 (talk) 23:38, 17 July 2010 (UTC)

Hepatic encephalopathy?
Hepatic encephalopathy (HE) was not listed, and is typically discussed in the context of specific toxic molecules like ammonium, resulting from TIPSS procedure. Should HE not be listed as a distinct form? — Preceding unsigned comment added by 130.238.224.23 (talk) 17:04, 18 January 2018 (UTC)

Toxicity from psychotropic medications
This section has no sources indicated.

> All therapeutic interventions are double-edged swords with benefits and adverse effects, and pharmacotherapy is not an exception.[...]

This is not the way one writes encyclopedic material. "double-edged swords" It's not just using unencyclopedic wording, but it's also unsourced. Gamma1138 (talk) 19:20, 23 July 2023 (UTC)

title: Talk:Encephalopathy


text:
Isosporiasis

Isosporiasis, also known as cystoisosporiasis, is a human intestinal disease caused by the parasite Cystoisospora belli (previously known as Isospora belli). It is found worldwide, especially in tropical and subtropical areas. Infection often occurs in immuno-compromised individuals, notably AIDS patients, and outbreaks have been reported in institutionalized groups in the United States. The first documented case was in 1915. It is usually spread indirectly, normally through contaminated food or water (CDC.gov).

Signs and symptoms
Infection causes acute, non-bloody diarrhea with crampy abdominal pain, which can last for weeks and result in malabsorption and weight loss. In immunodepressed patients, and in infants and children, the diarrhea can be severe. Eosinophilia may be present (differently from other protozoan infections).

Cause
The coccidian parasite Cystoisospora belli infects the epithelial cells of the small intestine, and is the least common of the three intestinal coccidia that infect humans (Toxoplasma, Cryptosporidium, and Cystoisospora).

Transmission
People become infected by swallowing the mature parasite; this normally occurs through the ingestion of contaminated food or water. The infected host then produces an immature form of the parasite in their feces, and when the parasite matures, it is capable of infecting its next host, via food or water containing the parasite.

Life cycle
At time of excretion, the immature oocyst usually contains one sporoblast (more rarely two). In further maturation after excretion, the sporoblast divides in two, so the oocyst now contains two sporoblasts. The sporoblasts secrete a cyst wall, thus becoming sporocysts; and the sporocysts divide twice to produce four sporozoites each. Infection occurs by ingestion of sporocyst-containing oocysts: the sporocysts excyst in the small intestine and release their sporozoites, which invade the epithelial cells and initiate schizogony. Upon rupture of the schizonts, the merozoites are released, invade new epithelial cells, and continue the cycle of asexual multiplication. Trophozoites develop into schizonts which contain multiple merozoites. After a minimum of one week, the sexual stage begins with the development of male and female gametocytes. Fertilization results in the development of oocysts that are excreted in the stool. Cystoisospora belli infects both humans and animals.

Diagnosis
Microscopic demonstration of the large typically shaped oocysts is the basis for diagnosis. Because the oocysts may be passed in small amounts and intermittently, repeated stool examinations and concentration procedures are recommended. If stool examinations are negative, examination of duodenal specimens by biopsy or string test (Enterotest) may be needed. The oocysts can be visualized on wet mounts by microscopy with bright-field, differential interference contrast (DIC), and epifluorescence. They can also be stained by modified acid-fast stain.

Typical laboratory analyses include:
 * Microscopy
 * Morphologic comparison with other intestinal parasites
 * Bench aids for Cystoisospora

Prevention
Avoiding food or water that may be contaminated with stools can help prevent the infection of Cystoisospora (Isosporiasis). Good hand-washing, and personal-hygiene practices should be used as well. One should wash their hands with soap and warm water after using the toilet, changing diapers, and before handling food (CDC.gov). It is also important to teach children the importance of washing their hands, and how to properly wash their hands.

Treatment
The treatment of choice is trimethoprim-sulfamethoxazole (Bactrim).

Epidemiology
While isosporiasis occurs throughout the world, it is more common in tropical and subtropical areas. Cystoisospora infections are more common in individuals with compromised immune systems, such as HIV or leukemia.

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

title: Isosporiasis


text:
Talk:Histoplasmosis

Plagiarism
This article is pretty much a word-for-word copy and paste of the WebMD article: Jasont82 17:14, 27 July 2007 (UTC)

There is a nice textbook style reference at the end of the article that made me suspect plagirism. --Kerwin15 (talk) 23:02, 15 January 2013 (UTC)

 * Thanks for the heads-up. The only part of this article I could find that matched any part of the WebMD version was the Symptom section. Am I missing something or was that what you were referring to? I've revised the relevant section (and added a ref). -- MarcoTolo 17:37, 27 July 2007 (UTC)

 * The Incidence and Transmission sections are also copied from the WebMD article with minor changes. —Preceding unsigned comment added by Jasont82 21:50, 28 July 2007 (UTC) (talk • contribs) 11:45, 28 July 2007 (UTC)

 * Okay, I've pulled both sections for now as potential copyvios (not that I don't believe you, 206.246.142.100, just that WebMD is giving me timeouts and I can't check it myself to fix the problems). -- MarcoTolo 14:41, 28 July 2007 (UTC)

WikiProject class rating
This article was automatically assessed because at least one WikiProject had rated the article as start, and the rating on other projects was brought up to start class. BetacommandBot 16:27, 10 November 2007 (UTC)

Popular Culture
You know, you don't have to do everything the Comics Curmudgeon says. =) Powers T 14:16, 22 January 2011 (UTC)

 * Hah. After reading that I came here to revert the inevitable addition to the article. And did so three times before I decided to give up for a day or two. The other pop culture references are weak, but the Spiderman one is extraordinarily weak. It's a brief, nonsensical, mention in a daily comic script. There's been about a hundred daily newspaper comics strips produced every day for about a hundred years, if everything they mentioned was automatically a notable pop-culture reference, every article would have a dozen comic strip links at the bottom.
 * WP:IPC proposes three "tests" for whether a pop culture reference is valid, The Spiderman comic clearly fails. In fact, going by references alone, the only one that passes the tests is the Bob Dylan one! It's the only one that asserts any real-world significance and/or third party references!  (I wouldn't be surprised if a third-party mention could be found for the Johnny Cash one, but I wouldn't know where to look. The song's lyrics are clearly not 'third-party'.) APL (talk) 21:21, 22 January 2011 (UTC)

granulomas?
If anyone has any info knowledge re histo and granulomas, it would be appreciated in the article!--Xris0 (talk) 17:38, 3 February 2012 (UTC)

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title: Talk:Histoplasmosis


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Talk:Alistair MacLeod

Untitled
Recommend changing the first line.... perhaps to a noted Canadian writer or the like - Hemanshu 15:41, 7 Dec 2003 (UTC)

An explanation of the title of MacLeod's novel:

General James Wolfe, the English commander at the battle of Québec, had previously helped put down the Jacobite rebellions in Scotland.

The following is from http://www.clanfraser.ca/78th1.htm, on the website of the Clan Fraser Society of Canada, written by Marie Fraser, Genealogy/Newsletter Editor, Clan Fraser Society of Canada and shown as updated on Nov. 30, 2004:

James Wolfe (1727-59), while serving with the 20th Regiment in Scotland, in a letter to Captain William Rickson, dated June 9, 1751, revealed his reasons for considering the formation of new Highland regiments, which are not wholly flattering to the Highlanders. "I should imagine,” wrote Wolfe, referring to Rickson’s duties in Nova Scotia, “that two or three independent Highland companies might be of use; they are hardy, intrepid, accustomed to a rough country, and no great mischief if they fall. How can you better employ a secret enemy than by making his end conducive to the common good? If this sentiment should take wind," he justly concludes, “what an execrable and bloody being should I be considered here in the midst of Popery and Jacobitism!" [James Wolfe: Man and Soldier by W.T. Waugh, M.A., Kingsford Professor of History, McGill University (Montreal, New York: Louis Carrier & Co., 1928) p. 101]

(emphasis added for clarity)

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Cynthia McKinney

Cynthia Ann McKinney (born March 17, 1955) is a former American politician. As a member of the Democratic Party, she served six terms in the United States House of Representatives. She was the first African American woman elected to represent Georgia in the House. She left the Democratic Party and ran in 2008 as the presidential nominee of the Green Party. She ran for vice president in 2020 after the Green Party of Alaska formally nominated her and draft-nominated Jesse Ventura for president.

McKinney served in the Georgia House of Representatives from 1988 to 1992. In the 1992 election, McKinney was elected in Georgia's newly re-created 11th district, and was re-elected in 1994. When her district was redrawn and renumbered due to the Supreme Court of the United States ruling in Miller v. Johnson, McKinney was elected from the new 4th district in the 1996 election. She was re-elected twice more without substantive opposition, but was defeated by Denise Majette in the 2002 Democratic primary.

After her 2002 loss, McKinney became a vocal supporter of conspiracy theories about the September 11 terrorist attacks, blaming her loss and the 9/11 attacks on "Zionists." McKinney was re-elected to the House in November 2004, following her successor's run for Senate. In Congress, she unsuccessfully tried to unseal FBI records on the assassination of Martin Luther King Jr. and the murder of Tupac Shakur. She continued to criticize the Bush administration over the 9/11 attacks. She supported anti-war legislation and introduced articles of impeachment against President Bush, Vice President Dick Cheney, and Secretary of State Condoleezza Rice.

McKinney sought re-election in 2006, but was defeated by Hank Johnson in the Democratic primary. In a March 29, 2006, Capitol Hill police incident, she struck a Capitol Hill Police officer for stopping her to ask for identification. McKinney left the Democratic Party in September 2007. She eventually sought and won the Green Party nomination in the 2008 presidential election, receiving 161,797 votes (0.12%) nationwide in the general election.

Early life and education
Cynthia McKinney was born and raised in the affluent middle-class historic Collier Heights area in Atlanta, Georgia, the daughter of Leola McKinney, a retired nurse, and Billy McKinney, a law enforcement officer and former Georgia State Representative.

McKinney was exposed to the Civil Rights movement through her father, an activist who regularly participated in demonstrations across the south. As a police officer, he challenged the discriminatory policies of the Atlanta Police Department, publicly protesting in front of the station, often carrying young McKinney on his shoulders. He was elected as a state representative. McKinney attributes her father's election victory, after several failed attempts, to the passage of the Voting Rights Act, which provided for federal oversight and enforcement of voting. Most blacks in the South had been disenfranchised by state legislative barriers since the turn of the 20th century.

McKinney earned a B.A. in international relations from the University of Southern California in 1978 and an M.A. in Law and Diplomacy from the Fletcher School of Law and Diplomacy at Tufts University in 1979. In 2015, McKinney completed her dissertation on Hugo Chavez and was awarded a Ph.D. in Leadership and Change by Antioch University.

Prior to entering politics, McKinney worked as a high school teacher and university professor. In 1984, she served as a diplomatic fellow at Spelman College in Atlanta, Georgia. She then taught political science at Agnes Scott College in Decatur and at Clark Atlanta University.

Georgia House of Representatives (1988–1992)
McKinney's political career began when her father, a representative in the Georgia House of Representatives, submitted her name as a write-in candidate for the Georgia state house in 1986. Despite the fact that she lived in Jamaica at the time, she received approximately 40% of the popular vote. In 1988, McKinney ran for the same seat and won, making the McKinneys the first father and daughter to simultaneously serve in the Georgia House of Representatives. In 1991, she decried the Gulf War in a speech on the House floor; many legislators left the chamber in protest of her remarks.

U.S. House of Representatives (1993-2003)
In the 1992 election, McKinney was elected to the U.S. House of Representatives as the member of Congress from the newly created 11th District, a 64% African American majority district reaching from Atlanta to Savannah. She was the first African American woman to represent Georgia in the House. She was re-elected in 1994.

In 1995, the U.S. Supreme Court ruled in Miller v. Johnson that the 11th District was an unconstitutional gerrymander because the boundaries were drawn based on the racial composition of the constituents. McKinney's district was subsequently renumbered as the 4th and redrawn to take in almost all of DeKalb County, prompting outrage from McKinney. She asserted that it was a racially discriminatory ruling, given the fact that the Supreme Court had previously ruled that Texas's 6th District, which is 91% white, was unconstitutional. The new 4th, however, was no less Democratic than the 11th. McKinney was easily elected from this district in 1996. She was re-elected two more times with no substantive opposition.

In her first period in Congress, she served on several committees, including the House Committees on Foreign Affairs, Banking and Finance, and Armed Services. She eventually ascended to the top Democratic spot on the International Relations Subcommittee on International Operations and Human Rights, serving as ranking member. In that role, she became a frequent critic of American foreign policy. Examples include her vocal opposition to President Bill Clinton’s interventionist policies in Kosovo, U.S. sanctions against Iraq, and other policies related to the Middle East.

On October 17, 2001, McKinney introduced a bill calling for "the suspension of the use, sale, development, production, testing, and export of depleted uranium munitions pending the outcome of certain studies of the health effects of such munitions." The bill was cosponsored by Reps. Aníbal Acevedo Vilá, Puerto Rico; Tammy Baldwin, D-Wis.; Dennis Kucinich, D-Ohio; Barbara Lee, D-Ca.; and Jim McDermott, D-Wash.

Criticism of Al Gore
During the 2000 presidential campaign, McKinney wrote that "Al Gore's Negro tolerance level has never been too high. I've never known him to have more than one black person around him at any given time." Gore's campaign pointed out that its manager, Donna Brazile, was black.

McKinney chastised Gore for failing to support the U'wa people of Colombia trying to oppose petroleum drilling near them. In a press release issued on February 22, 2000, entitled "No More Blood For Oil," McKinney wrote that "Oil drilling on Uwa land will result in considerable environmental damage and social conflict which will lead to greater militarization of the region as well as an increase in violence." Addressing herself to Gore, she wrote, "I am contacting you because you have remained silent on this issue despite your strong financial interests and family ties with Occidental."

Objection to the 2000 presidential election
McKinney and other members of the House of Representatives objected to the 25 electoral votes from Florida which George W. Bush narrowly won after a contentious recount. Because no senator joined her objection, the objection was dismissed by Vice President Al Gore, who was Bush's opponent in the 2000 presidential election. Without Florida's electoral votes, the election would have been decided by the U.S. House of Representatives, with each state having one vote in accordance with the Twelfth Amendment to the United States Constitution.

September 11 attacks
McKinney gained national attention for her remarks following the September 11 attacks in 2001. She asserted that the United States had "numerous warnings of the events to come" and called for an investigation. She enquired in a radio interview: "What did this administration know and when did it know it?" She said that US President George W. Bush may have been aware and allowed them to happen. She made allegations about the earlier president, George H. W. Bush: "It is known that President Bush's father, through The Carlyle Group, had—at the time of the attacks—joint business interests with the bin Laden construction company and many defense industry holdings, the stocks of which have soared since September 11." A spokesman for the Carlyle Group rejected her hypothesis. In a statement in April 2002, McKinney told The Washington Post: "I am not aware of any evidence showing that President Bush or members of his administration have personally profited from the attacks of 9–11. A complete investigation might reveal that to be the case."

In the month that followed the attacks, McKinney published an open letter to the Saudi Prince Alwaleed bin Talal. The New York City mayor Rudy Giuliani had refused to cash a $10 million check written by Saudi Prince because of the Prince's suggestion that the attacks were an indication that the United States "should re-examine its policies in the Middle East and adopt a more balanced stand toward the Palestinian cause." In the open letter, she expressed her disappointment at Giuliani's action: "Let me say that there are a growing number of people in the United States who recognize, like you, that U.S. policy in the Middle East needs serious examination...Your Royal Highness, many of us here in the United States have long been concerned about reports by Amnesty International and Human Rights Watch that reveal a pattern of excessive, and often indiscriminate, use of lethal force by Israeli security forces in situations where Palestinian demonstrators were unarmed and posed no threat of death or serious injury to the security forces or to others."

2002 primary defeat
In 2002, McKinney was defeated in the Democratic primary by DeKalb County judge Denise Majette. Majette defeated McKinney with 58% of the vote to McKinney's 42%.

McKinney protested the result in court, claiming that thousands of Republicans had voted in the Democratic primary, the real contest in the district, in revenge for her anti-Bush administration views and her allegations of voter fraud in Florida in the 2000 presidential election. Like 20 other states, Georgia operates an open primary: voters do not align with a political party when they register to vote and may participate in whichever party's primary election they choose. Thus, relying on the Supreme Court's decision in California Democratic Party v. Jones, which had held that California's blanket primary violated the First Amendment (despite the fact that the Court explicitly differentiated—albeit in dicta—the blanket primary from the open primary in Jones), on McKinney's behalf, five voters claimed that the open primary system was unconstitutional, operating in violation of the Equal Protection Clause of the Fourteenth Amendment, the associational right protected by the First Amendment, and various statutory rights protected by § 2 of the Voting Rights Act.

The district court dismissed the case, in the judgement stating the plaintiffs had presented no evidence in support of the 14th Amendment and Voting Rights Act claims, and lacked standing to bring the First Amendment claim. It interpreted the Supreme Court's Jones ruling to hold that the right to association involved in a dispute over a primary—and thus, standing to sue—belongs to a political party, not an individual voter. On appeal in May 2004, the Eleventh Circuit Court of Appeals upheld this result in Osburn v. Cox, assessing that not only were the plaintiffs' claims meritless, but the remedy they requested would likely be unconstitutional under the Supreme Court's decision in Tashjian v. Republican Party of Connecticut. On October 18, 2004, the Supreme Court brought an end to the litigation, denying certiorari without comment.

Other factors in McKinney's defeat included her allegations of Bush's involvement in 9/11, her opposition to aid to Israel, a perceived support of Palestinian and Arab causes, and open antisemitism in her comments. On the night before the primary election, McKinney's father stated on Atlanta television that "Jews have bought everybody. Jews. J-E-W-S." Cynthia McKinney had been through a long contentious relationship with the American Israel Public Affairs Committee (AIPAC). Georgia political analyst Bill Shipp addressed McKinney's defeat saying: "voters sent a message: 'We're tired of these over-the-top congressmen dealing in great international and national interests. How about somebody looking out for our interests?'"

2003–2005
During 2003 and 2004, McKinney toured the US and much of Europe publicly speaking about her defeat, her opposition to the Iraq War, and the Bush administration.

In 2004, McKinney served on the advisory committee for the group 2004 Racism Watch.

Having made no secret that she wanted to return to Congress, McKinney turned down the Green Party's nomination for president in the 2004 presidential election.

Return to the U.S. House of Representatives (2005–2007)
Majette declined to run for re-election to the House, opting instead to become a candidate to replace retiring Senator Zell Miller, a conservative Democrat. According to a report in The New York Times, John Lewis believed it was "going to be a real battle" for McKinney to return to Congress. It was feared McKinney's previous comments would have a negative effect on her chances. Since it was taken for granted that victory in the Democratic primary was tantamount to election in November, McKinney's opponents focused on clearing the field for a single candidate who could force her into a runoff election.

McKinney hosted the first delegation of Afro-Latinos from Central and South America and worked with the World Bank and the U.S. State Department to recognize Afro-Latinos. She stood with Aboriginals against Australian mining companies. She was one of the 31 in the House who objected to the official allotment of the electoral votes from Ohio in the 2004 United States presidential election to incumbent George W. Bush.

Objection to the 2004 presidential election
McKinney was one of the 31 House Democrats who voted not to count the 20 electoral votes from Ohio in the 2004 presidential election, despite Republican President George W. Bush winning the state by 118,457 votes. Without Ohio's electoral votes, the election would have been decided by the U.S. House of Representatives, with each state having one vote in accordance with the Twelfth Amendment to the United States Constitution.

9/11 Commission
On July 22, 2005, the first anniversary of the release of the 9/11 Commission Report, McKinney held a briefing on Capitol Hill about the attacks. The day-long briefing featured family members of victims, scholars, former intelligence officers and others who critiqued the 9/11 Commission account of 9/11 and its recommendations. The four morning panels addressed flaws, omissions, and a lack of historical and political analysis in the commission's report. Three afternoon panels critiqued the commission's recommendations in the areas of foreign and domestic policy and intelligence reform. An Atlanta Journal-Constitution editorial said that the purpose of the event was to discuss whether or not the Bush administration was involved in the 9/11 attacks, expressing surprise that McKinney was once again taking on the issue that was believed to have cost her House seat. The Journal-Constitution declined to publish McKinney's reply. The 9/11 Commission has sealed all the notes and transcripts of some 2,000 interviews, all the forensic evidence, and both classified and non-classified documents used in compiling its final report until January 2, 2009. McKinney's interest in 9/11 relates specifically to what she expresses as her opposition to excessive government secrecy, which she has challenged with numerous pieces of legislation.

McKinney has said that she "remain[s] hopeful that we will learn the truth" about 9/11 "because more and more people around the world are demanding it."

Hurricane Katrina activism
McKinney was an advocate for victims of 2005's Hurricane Katrina and a critic of the government's response to it. Over 100,000 evacuees from New Orleans and Mississippi relocated to the Atlanta area, and many have now settled there.

During the Katrina crisis, evacuees were turned away by Arthur Lawson's Gretna police when they attempted to cross the Crescent City Connection Bridge between New Orleans and Gretna, Louisiana. McKinney was the only member of Congress to participate in a march across the Crescent City Connection Bridge on November 7, 2005, to protest what had happened on that bridge in the aftermath of Hurricane Katrina.

In response, McKinney introduced a bill on November 2, 2005, that would temporarily deny federal assistance to the City of Gretna Police Department, Harry Lee's Jefferson Parish Sheriff's Office, and the Crescent City Connection Police Department, in the state of Louisiana. The bill was referred to the House Judiciary Subcommittee on Crime, Terrorism, and Homeland Security, but was not acted on. However, in August 2006, a grand jury began an investigation of the incident. On October 31, 2007, the Grand Jury ruled not to charge anyone. The Grand Jury accepted Gretna Police Chief Arthur Lawson's explanation, "Some of the people in the crowd acted aggressively and threatened to throw one of the officers off the bridge, the chief said. The shot was fired over the officer's shoulder and over the side of the bridge.

McKinney chose to be an active participant in the Select Bipartisan Committee to Investigate the Preparation for and Response to Hurricane Katrina, although the Democratic Party leadership called for Democratic members to boycott the committee. She submitted her own 72-page report. She sat as a guest along with only a few other Democrats. In questioning Department of Homeland Security Secretary Michael Chertoff, McKinney referred to a news story in which the owners of a nursing home had been charged with negligent homicide for abandoning 34 clients who died in the flood waters. McKinney asked Chertoff: "Mr. Secretary, if the nursing home owners are arrested for negligent homicide, why shouldn't you also be arrested for negligent homicide?"

The Congressional Black Caucus' Omnibus Bill (HR 4197) was introduced on November 2, 2005, to provide a comprehensive response to the Gulf Coast residents affected by Hurricane Katrina. The second title of the bill was submitted by McKinney, seeking a Comprehensive Environmental Sampling and Toxicity Assessment Plan, or CESTAP, to minimize harm to Gulf Coast residents from the toxic releases into the environment caused by the hurricane.

At the request of McKinney, the Select Bipartisan Committee to Investigate the Preparation for and Response to Hurricane Katrina, chaired by Thomas M. Davis, held a previously unscheduled hearing titled "Voices Inside the Storm" on December 6, 2005.

McKinney, in collaboration with Rep. Barbara Lee (CA), produced a "Katrina Legislative Summary," a chart summarizing House and Senate bills on Hurricane Katrina. On June 13, 2006, McKinney said on the House floor that only a dozen of the 176 Katrina bills identified on the chart had passed into law, leaving 163 bills stalled in committee.

On August 2, 2007, McKinney participated in a press conference in New Orleans to launch an International Tribunal on Hurricanes Katrina and Rita, which she described as an effort to seek justice for the victims of those hurricanes and their aftermath.

Anti-war and human rights legislation
Until 2000, McKinney served on the House International Relations Committee, where she was the highest-ranking Democrat on the Human Rights Subcommittee. McKinney worked on legislation to stop conventional weapons transfers to governments that are undemocratic or fail to respect human rights.

On November 18, 2005, McKinney was one of only three House members to vote for H.R. 571, introduced by Duncan Hunter, chairman of the House Armed Services Committee, on which McKinney sat. Hunter, a Republican, offered this resolution calling for an immediate withdrawal of U.S. forces in Iraq in place of John Murtha's H.J.Res. 73, which called for redeployment "at the earliest possible date." In her prepared statement, McKinney accused the Republicans of "trying to set a trap for the Democrats. A 'no' vote for this Resolution will obscure the fact that there is strong support for withdrawal of US forces from Iraq ... In voting for this bill, let me be perfectly clear that I am not saying the United States should exit Iraq without a plan. I agree with Mr. Murtha that security and stability in Iraq should be pursued through diplomacy. I simply want to vote 'yes' to an orderly withdrawal from Iraq."

Articles of impeachment introduced
At the end of the 2006 legislative session, McKinney introduced articles of impeachment against President George W. Bush as (H Res 1106), which made three charges against Bush:
 * Failure to uphold the constitution, specifically that "George Walker Bush ... in preparing the invasion of Iraq, did withhold intelligence from the Congress, by refusing to provide Congress with the full intelligence picture that he was being given, by redacting information ... and actively manipulating the intelligence on Iraq’s alleged weapons programs by pressuring the Central Intelligence Agency and other intelligence agencies.
 * Abuse of office and executive privilege, "obstructing and hindering the work of Congressional investigative bodies and by seeking to expand the scope of the powers of his office."
 * Failure to ensure that laws are faithfully executed, specifically by a program of illegal domestic spying and circumvention of the FISA Act.

The second article also made charges against Vice President Dick Cheney alleging he manipulated intelligence in order to justify the Iraq War, and against Secretary of State Condoleezza Rice alleging that she knowingly made false statements concerning Iraq's weapons of mass destruction program.

McKinney's bill was abandoned when it failed to clear the House Committee on the Judiciary.

Capitol Police incident
On the morning of March 29, 2006, McKinney entered the Longworth House Office Building's southeast entrance and proceeded past the security checkpoint, walking around the metal detector. Members of Congress have identifying lapel pins and were not required to pass through metal detectors at the time. The officers present failed to recognize McKinney as a member of Congress because she was not wearing the appropriate lapel pin and had recently changed her hairstyle. She proceeded westward down the ground floor hallway and about halfway down the hallway was stopped by United States Capitol Police officer Paul McKenna, who states that he had been calling after her: "Ma'am, Ma'am!"; at that time it is reported that McKinney struck the officer. Two days later, Officer McKenna filed a police report claiming that McKinney had struck "his chest with a closed fist".

In the midst of a media frenzy, McKinney made an apology on the floor of the House of Representatives on April 6, 2006, neither admitting to nor denying the charge, stating only that: "There should not have been any physical contact in this incident."

Though McKinney was not indicted for criminal charges or subjected to disciplinary action by the House, the president of the Fraternal Order of Police said of Officer McKenna, "We're going to make sure the officer won't be harassed. We want the officer to be able talk to experts, who can look at his legal recourses, if he needed to."

Unintentional on-air criticism
In the wake of the March 2006 incident with the Capitol Police officer, McKinney was in the news, and her office invited the media to attend one of her monthly "District Days," where she spends one full day meeting with constituents to discuss issues of concern. At her April 23, 2006, "District Days" event, McKinney was being interviewed by WGCL's Renee Starzyk, who repeatedly questioned her about the March 29 scuffle with a Capitol police officer. Frustrated, McKinney stood up and apparently forgot she was still wearing the microphone. Her offscreen comments were captured on tape. She was heard saying, "Oh, crap, now you know what ... they lied to [McKinney's senior aide Coz Carson], and Coz is a fool." McKinney returned on screen with the microphone, this time with instructions on what parts of the interview the station was allowed to use: "anything that is captured by your audio ... that is captured while I'm not seated in this chair is off the record and is not permissible to be used ... is that understood?"

MLK Records Act
McKinney submitted to Congress two different versions of the same bill, the "MLK Records Act" (one in 2003, the other in 2005), which, if signed into law, would release all currently sealed files concerning the 1968 assassination of Martin Luther King Jr. These records were sealed in 1978 and are not due to be declassified until the year 2028. The 2005 version of the MLK Records Act, HR 2554 had 67 cosponsors by the time McKinney left office at the end of 2006. A Senate version of the bill (S2499) was introduced by Senator John Kerry and was co-signed by Sen. Hillary Clinton. The bill has also received numerous endorsements from former members of the House Select Committee on Assassinations.

Tupac Shakur Records Act
Documents relating to the death of rapper Tupac Shakur, in which McKinney took an active interest, would be released under another bill she would introduce. In a statement, McKinney explained her reason for the bill: "The public has the right to know because he was a well-known figure. There is intense public interest in the life and death of Tupac Shakur." Legislation demanding release of records is a more direct route than requesting their release through the Freedom of Information Act (FOIA).

2006 primary and primary runoff
McKinney finished first in the July 18, 2006 Democratic primary, edging DeKalb County Commissioner Hank Johnson 47.1% to 44.4%, with a third candidate receiving 8.5%. However, as McKinney failed to get at least 50% of the vote, she and Johnson were forced into a runoff.

In the runoff of August 8, 2006, McKinney received about the same number of votes as in the July primary, even though there were about 8,000 more votes cast in the runoff than in the primary. Johnson won with 41,178 votes (59%) to McKinney's 28,832 (41%). McKinney's loss was attributed to a mid-decade redistricting, in which the 4th had absorbed portions of Gwinnett and Rockdale Counties, as well as her run-in with a police officer in the March 29, 2006, Capitol Hill police incident.

CNN reported that during her concession speech, McKinney hardly mentioned her opponent but praised the leftist political leaders elected in South America. She also questioned the efficacy of voting machines and criticized the media.

2008 Green Party presidential candidacy
McKinney was a Green Party candidate in the 2008 presidential election.

McKinney appeared at the July 15, 2007, Green Party National Meeting in Reading, Pennsylvania, where she suggested that the Green Party could become a progressive political force. "[T]he disgust of the American people with what they see before them—all they need is the blueprint and a road map. Why not have the Green Party provide the blueprint and the road map?"

At an August 27, 2007, peace rally in Kennebunkport, Maine, McKinney confirmed the depth of her disenchantment with the Democratic Party, urging San Francisco voters to replace Nancy Pelosi with antiwar activist Cindy Sheehan. On September 10, in a letter to the steering committee of the Green Party of the United States, McKinney stated she would not seek the Green Party nomination for president. However, in early October it appeared that McKinney was making moves toward declaring herself an official Green Party candidate.

On July 9, 2008, she named as her running mate journalist and community activist Rosa Clemente and clinched the party's nomination three days later at the 2008 Green Party National Convention.

On September 10, 2008, McKinney joined a press conference held by third-party and independent candidates, along with Ralph Nader, Chuck Baldwin, and initiator Ron Paul. The participants agreed on four basic principles:
 * An early end to the Iraq War, and an end to threats of war against other countries including Iran and Russia.
 * The safeguarding of privacy and civil liberties, including a call for the repeal of the Patriot Act, the Military Commissions Act, and FISA legislation
 * No increase in the National Debt
 * A "thorough investigation, evaluation and audit of the Federal Reserve System."

On November 4, 2008, McKinney received 161,797 votes, 0.12% of the total votes cast, placing her behind Obama, McCain, Nader, Barr, and Baldwin.

2008–2011
In March 2009, McKinney was present at a gathering of Holocaust deniers in London. In postings on the Green Party website, she said former Malaysian prime minister Mahathir Mohamad was "one of my heroes". She described David Pidcock as "my London friend". Pidcock is an individual whom the Southern Poverty Law Center and the Anti-Defamation League have described as an "anti-Semitic writer". In one post she related the conspiracy theory that individuals such as George Soros and Alan Greenspan (both Jewish) have plotted to create a "one-world government". In discussing this notion, she was drawing on a book entitled, The Shadow Money-Lenders by Matthias Chang, an advisor to Mahathir. McKinney praised the work.

Free Gaza Movement
On December 30, 2008, McKinney was aboard the ship Dignity when it attempted to enter the Gaza Strip, which had its coastal area declared a "closed military zone" by Israel, while on a humanitarian mission by the Free Gaza Movement from Cyprus. Aboard were physicians, medical supplies, and activists, including Caoimhe Butterly. The Israeli Navy confronted the ship at night in international waters. Members of the crew claimed that the ship was rammed, gunfire was directed at the water, and the ship was forced to dock in Lebanon after taking on water. Israeli officials claimed that the collision was accidental and occurred after the ship was informed they would not be allowed to enter Gaza and tried to outmaneuver the patrol boat; they decried McKinney's actions as being irresponsible and provocative for the sake of propaganda.

On June 30, 2009, McKinney was aboard the Greek-flagged Free Gaza Movement's ship Spirit of Humanity carrying 21 activists including Irish peace activist Mairead McGuire, medical supplies, a symbolic bag of cement, olive trees and toys, when it was seized by the Israeli Navy 18 mi off the Gaza coast. It was unclear whether they were in international waters or in Gazan waters, which is subject to the Israeli blockade of Gaza. Although both the Cypriot and Israeli authorities were officially informed the destination was Gaza before the vessel's departure, according to the Cypriot government the ship "was given permission by the competent Authorities of the Republic of Cyprus to sail off the port of Larnaca in Cyprus on the basis of its declaration that its intended destination was the port of Port Said in Egypt."

McKinney was held at the Givon immigration detention center in Ramle, until her release on July 5. McKinney initially refused to sign the deportation papers because they were written in Hebrew and that the papers would require them to admit that they were in violation of Israel's blockade, which they denied. According to The Atlanta Journal-Constitution, Israeli officials stated that the "Palestinian Authority and the rest of the international community had agreed to the off-shore blockade to prevent arms smuggling into Gaza." The Palestinian Chronicle reports that such an agreement to the off-shore blockade never happened. "No Palestinians have agreed nor did the international community agree to a blockade of Gaza by land or Sea." On June 17, 2009, a group of United Nations agencies and non-governmental organizations (NGOs) called for an end to Israel's blockade of the Gaza Strip.

On July 7, 2009, McKinney was deported to the United States. The Israeli government indicated it would deliver the supplies via land.

Libya, Iran and Hugo Chávez
On May 21, 2011, McKinney appeared on state-run television in Libya and stated that United States participation in military intervention in the 2011 Libyan civil war was "not what the people of the United States stand for and it's not what African-Americans stand for". In the same interview, McKinney stated: "On a previous visit to Libya, I was able to learn about The Green Book, and the form of direct democracy that is advocated in The Green Book."

Around the same time, during her first visit to Iran, McKinney was interviewed by Iran's state-run channel, Press TV: "it is clear that the people of Iran have one thing in mind, and that is that they are a revolutionary state. And as a revolutionary state, they understand colonialism, neo-colonialism, and imperialism. They understand being under the foot of oppression and occupation—even if it is mental occupation—from an outside force or outside power, and that is what centers the resistance".

U.S. House of Representatives election, 2012
McKinney announced in April 2012 that she would run for the 4th congressional district against Hank Johnson on the Green Party ticket. However, in August she failed to qualify for the ballot. Nevertheless, she received 58 write-in votes in the general election.

Later career and activities (2013–present)
In 2016, McKinney released a statement via Twitter accusing Israelis of conducting the 2016 Nice truck attack in France and the Würzburg train attack in Germany, she did not provide any evidence for either claim. In May 2020, The Algemeiner Journal and other medial outlets reported that McKinney released a series of statements via Twitter questioning the true number of Jewish people murdered during The Holocaust. In the tweets (in which she misrepresented an article from Haaretz) she stated: "So, the figure wasn't six million after all?? What about those punished and even imprisoned for saying so?? Is this a "You can't say, but I can" kind of thing??".

The Jerusalem Post reported that on June 28, 2021, McKinney posted a meme to Twitter that depicted the September 11 attacks on the World Trade Center as a puzzle with the "final piece of the puzzle" having the word "Zionists" on it. When adding that piece to the puzzle, the image read: "Zionists did it." New York Congressman Jamaal Bowman condemned McKinney's post as anti-semitic. The ADL in a tweet objected to McKinney continuing "to repeat an offensive #antisemitic trope falsely blaming Jews/Zionists for the terrorist attacks on 9/11." The Washington Post noted that, amid a sitewide increase in hate speech following Elon Musk's purchase of Twitter, McKinney had prominently amplified and made tweets in 2022 containing an antisemitic hashtag mainly used by neo-Nazis to imply a conspiracy of Jewish people in positions of power.

On February 19, 2023, McKinney participated in the Rage Against the War Machine rally. She gave remarks at the rally by video, where she claimed that there are "criminal elements" within the federal government of the United States, that the Democratic Party had become a "war party," that the Federal Election Commission can "control U.S. election outcomes," and more.

On September 11, 2023, McKinney promoted a livestream called "Can Black People and White People Work Together to Defeat Our Common Enemy" with the Star of David, indicating that the "common enemy" is the Jewish people. The livestream was to be hosted by Ayo Kimathi, the author of Jews Are the Problem and described by the ADL as "antisemitic and anti-LGBTQ+ Black nationalist extremist" and David Duke, a former Ku Klux Klan grand wizard and anti-semite. In the livestream, Kimathi explicitly advocated for ties with White nationalists to actively eradicate "the Jew."

McKinney is an assistant professor at North South University.

Awards and honors
On June 14, 2000, a part of Memorial Drive, a major thoroughfare running through her district, was renamed "Cynthia McKinney Parkway," but the naming has come under scrutiny since her primary defeat in 2006 as well as previous controversial statements that she had made.

Personal life
In 2007, McKinney moved from her longtime residence in the Atlanta suburb of Stone Mountain to California.

title: Cynthia McKinney


text:
Mycobacterium tuberculosis

Mycobacterium tuberculosis (M. tb), also known as Koch's bacillus, is a species of pathogenic bacteria in the family Mycobacteriaceae and the causative agent of tuberculosis. First discovered in 1882 by Robert Koch, M. tuberculosis has an unusual, waxy coating on its cell surface primarily due to the presence of mycolic acid. This coating makes the cells impervious to Gram staining, and as a result, M. tuberculosis can appear weakly Gram-positive. Acid-fast stains such as Ziehl–Neelsen, or fluorescent stains such as auramine are used instead to identify M. tuberculosis with a microscope. The physiology of M. tuberculosis is highly aerobic and requires high levels of oxygen. Primarily a pathogen of the mammalian respiratory system, it infects the lungs. The most frequently used diagnostic methods for tuberculosis are the tuberculin skin test, acid-fast stain, culture, and polymerase chain reaction.

The M. tuberculosis genome was sequenced in 1998.

Microbiology
M. tuberculosis requires oxygen to grow, and is nonmotile. It divides every 18–24 hours. This is extremely slow compared with other bacteria, which tend to have division times measured in minutes (Escherichia coli can divide roughly every 20 minutes). It is a small bacillus that can withstand weak disinfectants and can survive in a dry state for weeks. Its unusual cell wall, rich in lipids such as mycolic acid and cord factor glycolipid, is likely responsible for its resistance to desiccation and is a key virulence factor.

Microscopy
Other bacteria are commonly identified with a microscope by staining them with Gram stain. However, the mycolic acid in the cell wall of M. tuberculosis does not absorb the stain. Instead, acid-fast stains such as Ziehl–Neelsen stain, or fluorescent stains such as auramine are used. Cells are curved rod-shaped and are often seen wrapped together, due to the presence of fatty acids in the cell wall that stick together. This appearance is referred to as cording, like strands of cord that make up a rope. M. tuberculosis is characterized in tissue by caseating granulomas containing Langhans giant cells, which have a "horseshoe" pattern of nuclei.

Culture
M. tuberculosis can be grown in the laboratory. Compared to other commonly studied bacteria, M. tuberculosis has a remarkably slow growth rate, doubling roughly once per day. Commonly used media include liquids such as Middlebrook 7H9 or 7H12, egg-based solid media such as Lowenstein-Jensen, and solid agar-based such as Middlebrook 7H11 or 7H10. Visible colonies require several weeks to grow on agar plates. Mycobacteria growth indicator tubes can contain a gel that emits fluorescent light if mycobacteria are grown. It is distinguished from other mycobacteria by its production of catalase and niacin. Other tests to confirm its identity include gene probes and MALDI-TOF.

Morphology
Analysis of Mycobacterium tuberculosis via scanning electron microscope shows the bacteria are $2.71 um$ in length with an average diameter of $0.035 um$. The outer membrane and plasma membrane surface areas were measured to be $3.04 um2$ and $2.67 um2$, respectively. The cell, outer membrane, periplasm, plasma membrane, and cytoplasm volumes were $0.293 fl$ (= μm3), $0.006 fl$, $0.06 fl$, $0.019 fl$, and $0.21 fl$, respectively. The average total ribosome number was $1,672$ with ribosome density about $716.5$.

Related Mycobacterium species
M. tuberculosis is part of a genetically related group of Mycobacterium species that has at least 9 members:
 * M. tuberculosis sensu stricto
 * M. africanum
 * M. canettii
 * M. bovis
 * M. caprae
 * M. microti
 * M. pinnipedii
 * M. mungi
 * M. orygis

Pathophysiology
Humans are the only known reservoirs of M. tuberculosis. A misconception is that M. tuberculosis can be spread by shaking hands, making contact with toilet seats, sharing food or drink, or sharing toothbrushes. However, major spread is through air droplets originating from a person who has the disease either coughing, sneezing, speaking, or singing.

When in the lungs, M. tuberculosis is phagocytosed by alveolar macrophages, but they are unable to kill and digest the bacterium. Its cell wall is made of cord factor glycolipids that inhibit the fusion of the phagosome with the lysosome, which contains a host of antibacterial factors.

Specifically, M. tuberculosis blocks the bridging molecule, early endosomal autoantigen 1 (EEA1); however, this blockade does not prevent fusion of vesicles filled with nutrients. In addition, production of the diterpene isotuberculosinol prevents maturation of the phagosome. The bacteria also evades macrophage-killing by neutralizing reactive nitrogen intermediates. More recently, M. tuberculosis  has been shown to secrete and cover itself in 1-tuberculosinyladenosine (1-TbAd), a special nucleoside that acts as an antacid, allowing it to neutralize pH and induce swelling in lysosomes.

In M. tuberculosis infections, PPM1A levels were found to be upregulated, and this, in turn, would impact the normal apoptotic response of macrophages to clear pathogens, as PPM1A is involved in the intrinsic and extrinsic apoptotic pathways. Hence, when PPM1A levels were increased, the expression of it inhibits the two apoptotic pathways. With kinome analysis, the JNK/AP-1 signalling pathway was found to be a downstream effector that PPM1A has a part to play in, and the apoptotic pathway in macrophages are controlled in this manner. As a result of having apoptosis being suppressed, it provides M. tuberculosis with a safe replicative niche, and so the bacteria are able to maintain a latent state for a prolonged time.

Granulomas, organized aggregates of immune cells, are a hallmark feature of tuberculosis infection. Granulomas play dual roles during infection: they regulate the immune response and minimize tissue damage, but also can aid in the expansion of infection.

The ability to construct M. tuberculosis mutants and test individual gene products for specific functions has significantly advanced the understanding of its pathogenesis and virulence factors. Many secreted and exported proteins are known to be important in pathogenesis. For example, one such virulence factor is cord factor (trehalose dimycolate), which serves to increase survival within its host. Resistant strains of M. tuberculosis have developed resistance to more than one TB drug, due to mutations in their genes. In addition, pre-existing first-line TB drugs such as rifampicin and streptomycin have decreased efficiency in clearing intracellular M. tuberculosis due to their inability to effectively penetrate the macrophage niche.

JNK plays a key role in the control of apoptotic pathways—intrinsic and extrinsic. In addition, it is also found to be a substrate of PPM1A activity, hence the phosphorylation of JNK would cause apoptosis to occur. Since PPM1A levels are elevated during M. tuberculosis infections, by inhibiting the PPM1A signalling pathways, it could potentially be a therapeutic method to kill M. tuberculosis-infected macrophages by restoring its normal apoptotic function in defence of pathogens. By targeting the PPM1A-JNK signalling axis pathway, then, it could eliminate M. tuberculosis-infected macrophages.

The ability to restore macrophage apoptosis to M. tuberculosis-infected ones could improve the current tuberculosis chemotherapy treatment, as TB drugs can gain better access to the bacteria in the niche. thus decreasing the treatment times for M. tuberculosis infections.

Symptoms of M. tuberculosis include coughing that lasts for more than three weeks, hemoptysis, chest pain when breathing or coughing, weight loss, fatigue, fever, night sweats, chills, and loss of appetite. M. tuberculosis also has the potential of spreading to other parts of the body. This can cause blood in urine if the kidneys are affected, and back pain if the spine is affected.

Strain variation
Typing of strains is useful in the investigation of tuberculosis outbreaks, because it gives the investigator evidence for or against transmission from person to person. Consider the situation where person A has tuberculosis and believes he acquired it from person B. If the bacteria isolated from each person belong to different types, then transmission from B to A is definitively disproven; however, if the bacteria are the same strain, then this supports (but does not definitively prove) the hypothesis that B infected A.

Until the early 2000s, M. tuberculosis strains were typed by pulsed field gel electrophoresis. This has now been superseded by variable numbers of tandem repeats (VNTR), which is technically easier to perform and allows better discrimination between strains. This method makes use of the presence of repeated DNA sequences within the M. tuberculosis genome.

Three generations of VNTR typing for M. tuberculosis are noted. The first scheme, called exact tandem repeat, used only five loci, but the resolution afforded by these five loci was not as good as PFGE. The second scheme, called mycobacterial interspersed repetitive unit, had discrimination as good as PFGE. The third generation (mycobacterial interspersed repetitive unit – 2) added a further nine loci to bring the total to 24. This provides a degree of resolution greater than PFGE and is currently the standard for typing M. tuberculosis. However, with regard to archaeological remains, additional evidence may be required because of possible contamination from related soil bacteria.

Antibiotic resistance in M. tuberculosis typically occurs due to either the accumulation of mutations in the genes targeted by the antibiotic or a change in titration of the drug. M. tuberculosis is considered to be multidrug-resistant (MDR TB) if it has developed drug resistance to both rifampicin and isoniazid, which are the most important antibiotics used in treatment. Additionally, extensively drug-resistant M. tuberculosis (XDR TB) is characterized by resistance to both isoniazid and rifampin, plus any fluoroquinolone and at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin).

Genome
The genome of the H37Rv strain was published in 1998. Its size is 4 million base pairs, with 3,959 genes; 40% of these genes have had their function characterized, with possible function postulated for another 44%. Within the genome are also six pseudogenes.

Fatty acid metabolism. The genome contains 250 genes involved in fatty acid metabolism, with 39 of these involved in the polyketide metabolism generating the waxy coat. Such large numbers of conserved genes show the evolutionary importance of the waxy coat to pathogen survival. Furthermore, experimental studies have since validated the importance of a lipid metabolism for M. tuberculosis, consisting entirely of host-derived lipids such as fats and cholesterol. Bacteria isolated from the lungs of infected mice were shown to preferentially use fatty acids over carbohydrate substrates. M. tuberculosis can also grow on the lipid cholesterol as a sole source of carbon, and genes involved in the cholesterol use pathway(s) have been validated as important during various stages of the infection lifecycle of M. tuberculosis, especially during the chronic phase of infection when other nutrients are likely not available.

PE/PPE gene families. About 10% of the coding capacity is taken up by the PE/PPE gene families that encode acidic, glycine-rich proteins. These proteins have a conserved N-terminal motif, deletion of which impairs growth in macrophages and granulomas.

Noncoding RNAs. Nine noncoding sRNAs have been characterised in M. tuberculosis, with a further 56 predicted in a bioinformatics screen.

Antibiotic resistance genes. In 2013, a study on the genome of several sensitive, ultraresistant, and multiresistant M. tuberculosis strains was made to study antibiotic resistance mechanisms. Results reveal new relationships and drug resistance genes not previously associated and suggest some genes and intergenic regions associated with drug resistance may be involved in the resistance to more than one drug. Noteworthy is the role of the intergenic regions in the development of this resistance, and most of the genes proposed in this study to be responsible for drug resistance have an essential role in the development of M. tuberculosis.

Epigenome. Single-molecule real-time sequencing and subsequent bioinformatic analysis has identified three DNA methyltransferases in M. tuberculosis, M ycobacterial  A denine  M ethyltransferases A (MamA), B (MamB), and C (MamC''). All three are adenine methyltransferases, and each are functional in some clinical strains of M. tuberculosisand not in others. Unlike DNA methyltransferases in most bacteria, which invariably methylate the adenines at their targeted sequence, some strains of M. tuberculosis'' carry mutations in MamA that cause partial methylation of targeted adenine bases. This occurs as intracellular stochastic methylation, where a some targeted adenine bases on a given DNA molecule are methylated while others remain unmethylated. MamA mutations causing intercellular mosaic methylation are most common in the globally successful Beijing sublineage of ''M. tuberculosis. '' Due to the influence of methylation on gene expression at some locations in the genome, it has been hypothesized that IMM may give rise to phenotypic diversity, and partially responsible for the global success of Beijing sublineage.

Evolution
The M. tuberculosis complex evolved in Africa and most probably in the Horn of Africa. In addition to M. tuberculosis, the M. tuberculosis complex (MTBC) has a number of members infecting various animal species, these include M. africanum, M. bovis (Dassie's bacillus), M. caprae, M. microti, M. mungi, M. orygis, and M. pinnipedii. This group may also include the M. canettii clade. These animal strains of MTBC do not strictly deserve species status, as they are all closely related and embedded in the M. tuberculosis phylogeny, but for historic reasons, they currently hold species status.

The M. canettii clade – which includes M. prototuberculosis – is a group of smooth-colony Mycobacterium species. Unlike the established members of the M. tuberculosis group, they undergo recombination with other species. The majority of the known strains of this group have been isolated from the Horn of Africa. The ancestor of M. tuberculosis appears to be M. canettii, first described in 1969.

The established members of the M. tuberculosis complex are all clonal in their spread. The main human-infecting species have been classified into seven lineages. Translating these lineages into the terminology used for spoligotyping, a very crude genotyping methodology, lineage 1 contains the East African-Indian (EAI), the Manila family of strains and some Manu (Indian) strains; lineage 2 is the Beijing group; lineage 3 includes the Central Asian (CAS) strains; lineage 4 includes the Ghana and Haarlem (H/T), Latin America-Mediterranean (LAM) and X strains; types 5 and 6 correspond to M. africanum and are observed predominantly and at high frequencies in West Africa. A seventh type has been isolated from the Horn of Africa. The other species of this complex belong to a number of spoligotypes and do not normally infect humans.

Lineages 2, 3 and 4 all share a unique deletion event (tbD1) and thus form a monophyletic group. Types 5 and 6 are closely related to the animal strains of MTBC, which do not normally infect humans. Lineage 3 has been divided into two clades: CAS-Kili (found in Tanzania) and CAS-Delhi (found in India and Saudi Arabia).

Lineage 4 is also known as the Euro-American lineage. Subtypes within this type include Latin American Mediterranean, Uganda I, Uganda II, Haarlem, X, and Congo.

A much cited study reported that M. tuberculosis has co-evolved with human populations, and that the most recent common ancestor of the M. tuberculosis complex evolved between 40,000 and 70,000 years ago. However, a later study that included genome sequences from M. tuberculosis complex members extracted from three 1,000-year-old Peruvian mummies, came to quite different conclusions. If the most recent common ancestor of the M. tuberculosis complex were 40,000 to 70,000 years old, this would necessitate an evolutionary rate much lower than any estimates produced by genomic analyses of heterochronous samples, suggesting a far more recent common ancestor of the M. tuberculosis complex as little as 6000 years ago.

An analysis of over 3000 strains of M. bovis from 35 countries suggested an Africa origin for this species.

Co-evolution with modern humans
There are currently two narratives existing in parallel regarding the age of MTBC and how it has spread and co-evolved with humans through time. One study compared the M. tuberculosis phylogeny to a human mitochondrial genome phylogeny and interpreted these as being highly similar. Based on this, the study suggested that M. tuberculosis, like humans, evolved in Africa and subsequently spread with anatomically modern humans out of Africa across the world. By calibrating the mutation rate of M. tuberculosis to match this narrative, the study suggested that MTBC evolved 40,000–70,000 years ago. Applying this time scale, the study found that the M. tuberculosis effective population size expanded during the Neolithic Demographic Transition (around 10,000 years ago) and suggested that M. tuberculosis was able to adapt to changing human populations and that the historical success of this pathogen was driven at least in part by dramatic increases in human host population density. It has also been demonstrated that after emigrating from one continent to another, a human host's region of origin is predictive of which TB lineage they carry, which could reflect either a stable association between host populations and specific M. tuberculosis lineages and/or social interactions that are shaped by shared cultural and geographic histories.

Regarding the congruence between human and M. tuberculosis phylogenies, a study relying on M. tuberculosis and human Y chromosome DNA sequences to formally assess the correlation between them, concluded that they are not congruent. Also, a more recent study which included genome sequences from M. tuberculosis complex members extracted from three 1,000-year-old Peruvian mummies, estimated that the most recent common ancestor of the M. tuberculosis complex lived only 4,000 – 6,000 years ago. The M. tuberculosis evolutionary rate estimated by the Bos et al. study is also supported by a study on Lineage 4 relying on genomic aDNA sequences from Hungarian mummies more than 200 years old. In total, the evidence thus favors this more recent estimate of the age of the MTBC most recent common ancestor, and thus that the global evolution and dispersal of M. tuberculosis has occurred over the last 4,000–6,000 years.

Among the seven recognized lineages of M. tuberculosis, only two are truly global in their distribution: Lineages 2 and 4. Among these, Lineage 4 is the most well dispersed, and almost totally dominates in the Americas. Lineage 4 was shown to have evolved in or in the vicinity of Europe, and to have spread globally with Europeans starting around the 13th century. This study also found that Lineage 4 tuberculosis spread to the Americas shortly after the European discovery of the continent in 1492, and suggests that this represented the first introduction of human TB on the continent (although animal strains have been found in human remains predating Columbus. Similarly, Lineage 4 was found to have spread from Europe to Africa during the Age of Discovery, starting in the early 15th century.

It has been suggested that ancestral mycobacteria may have infected early hominids in East Africa as early as three million years ago.

DNA fragments from M. tuberculosis and tuberculosis disease indications were present in human bodies dating from 7000 BC found at Atlit-Yam in the Levant.

Antibiotic resistance (ABR)
M. tuberculosis is a clonal organism and does not exchange DNA via horizontal gene transfer. Despite an additionally slow evolution rate, the emergence and spread of antibiotic resistance in M. tuberculosis poses an increasing threat to global public health. In 2019, the WHO reported the estimated incidence of antibiotic resistant TB to be 3.4% in new cases, and 18% in previously treated cases. Geographical discrepancies exist in the incidence rates of drug-resistant TB. Countries facing the highest rates of ABR TB China, India, Russia, and South Africa. Recent trends reveal an increase in drug-resistant cases in a number of regions, with Papua New Guinea, Singapore, and Australia undergoing significant increases.

Multidrug-resistant Tuberculosis (MDR-TB) is characterised by resistance to at least the two front-line drugs isoniazid and rifampin. MDR is associated with a relatively poor treatment success rate of 52%. Isoniazid and rifampin resistance are tightly linked, with 78% of the reported rifampin-resistant TB cases in 2019 being resistant to isoniazid as well. Rifampin-resistance is primarily due to resistance-conferring mutations in the rifampin-resistance determining region (RRDR) within the rpoB gene. The most frequently observed mutations of the codons in RRDR are 531, 526 and 516. However, alternative more elusive resistance-conferring mutations have been detected. Isoniazid function occurs through the inhibition of mycolic acid synthesis through the NADH-dependent enoyl-acyl carrier protein (ACP)-reductase. This is encoded by the inhA gene. As a result, isoniazid resistance is primarily due to mutations within inhA and the KatG gene or its promoter region - a catalase peroxidase which is required to activate Isoniazid. As MDR in M. tuberculosis becomes increasingly common, the emergence of pre-extensively drug resistant (pre-XDR) and extensively drug resistant (XDR-) TB threatens to exacerbate the public health crisis. XDR-TB is characterised by resistance to both rifampin and Isoniazid, as well second-line fluoroquinolones and at least one additional front-line drug. Thus, the development of alternative therapeutic measures is of utmost priority.

An intrinsic contributor to the antibiotic resistant nature of M. tuberculosis is its unique cell wall. Saturated with long-chain fatty acids or mycolic acids, the mycobacterial cell presents a robust, relatively insoluble barrier. This has led to its synthesis being the target of many antibiotics - such as Isoniazid. However, resistance has emerged to the majority of them. A novel, promising therapeutic target is mycobacterial membrane protein large 3 (MmpL3). The mycobacterial membrane protein large (MmpL) proteins are transmembrane proteins which play a key role in the synthesis of the cell wall and the transport of the associated lipids. Of these, MmpL3 is essential; knock-out of which has been shown to be bactericidal. Due to its essential nature, MmpL3 inhibitors show promise as alternative therapeutic measures in the age of antibiotic resistance. Inhibition of MmpL3 function showed an inability to transport trehalose monomycolate - an essential cell wall lipid - across the plasma membrane. The recently reported structure of MmpL3 revealed resistance-conferring mutations to associate primarily with the transmembrane domain. Although resistance to pre-clinical MmpL3 inhibitors has been detected, analysis of the widespread mutational landscape revealed a low level of environmental resistance. This suggests that MmpL3 inhibitors currently undergoing clinical trials would face little resistance if made available. Additionally, the ability of many MmpL3 inhibitors to work synergistically with other antitubercular drugs presents a ray of hope in combatting the TB crisis.

Host genetics
The nature of the host-pathogen interaction between humans and M. tuberculosis is considered to have a genetic component. A group of rare disorders called Mendelian susceptibility to mycobacterial diseases was observed in a subset of individuals with a genetic defect that results in increased susceptibility to mycobacterial infection.

Early case and twin studies have indicated that genetic components are important in host susceptibility to M. tuberculosis. Recent genome-wide association studies (GWAS) have identified three genetic risk loci, including at positions 11p13 and 18q11. As is common in GWAS, the variants discovered have moderate effect sizes.

DNA repair
As an intracellular pathogen, M. tuberculosis is exposed to a variety of DNA-damaging assaults, primarily from host-generated antimicrobial toxic radicals. Exposure to reactive oxygen species and/or reactive nitrogen species causes different types of DNA damage including oxidation, depurination, methylation, and deamination that can give rise to single- and double-strand breaks (DSBs).

DnaE2 polymerase is upregulated in M. tuberculosis by several DNA-damaging agents, as well as during infection of mice. Loss of this DNA polymerase reduces the virulence of M. tuberculosis in mice. DnaE2 is an error-prone DNA repair polymerase that appears to contribute to M. tuberculosis survival during infection.

The two major pathways employed in repair of DSBs are homologous recombinational repair (HR) and nonhomologous end joining (NHEJ). Macrophage-internalized M. tuberculosis is able to persist if either of these pathways is defective, but is attenuated when both pathways are defective. This indicates that intracellular exposure of M. tuberculosis to reactive oxygen and/or reactive nitrogen species results in the formation of DSBs that are repaired by HR or NHEJ. However deficiency of DSB repair does not appear to impair M. tuberculosis virulence in animal models.

History
M. tuberculosis, then known as the "tubercle bacillus", was first described on 24 March 1882 by Robert Koch, who subsequently received the Nobel Prize in Physiology or Medicine for this discovery in 1905; the bacterium is also known as "Koch's bacillus".

M. tuberculosis has existed throughout history, but the name has changed frequently over time. In 1720, though, the history of tuberculosis started to take shape into what is known of it today; as the physician Benjamin Marten described in his A Theory of Consumption, tuberculosis may be caused by small living creatures transmitted through the air to other patients.

Vaccine
The BCG vaccine (bacille Calmette-Guerin), which was derived from M. bovis, while effective against childhood and severe forms of tuberculosis, has limited success in preventing the most common form of the disease today, adult pulmonary tuberculosis. Because of this, it is primarily used in high tuberculosis incidence regions, and is not a recommended vaccine in the United States due to the low risk of infection. To receive this vaccine in the United States, an individual is required to go through a consultation process with an expert in M. tuberculosis and is only given to those who meet the specific criteria.

Research indicates there may be a correlation between BCG vaccination and better immune response to COVID-19.

The DNA vaccine can be used alone or in combination with BCG. DNA vaccines have enough potential to be used with TB treatment and reduce the treatment time in future.

title: Mycobacterium tuberculosis


text:
Peter Dmytruk

Peter Dmytruk  (May 27, 1920 in Radisson, Saskatchewan – December 9, 1943 at Les Martres-de-Veyre, Puy-de-Dôme, Auvergne Province, Occupied France) was a Sergeant in the Royal Canadian Air Force who was killed fighting with the French Resistance during World War II.

Life
Peter Dmytruk was born in Radisson, Saskatchewan in 1920 to a Ukrainian immigrant family. At the outbreak of World War II, Peter Dmytruk was living in Wynyard, Saskatchewan when he joined the Royal Canadian Air Force in July 1941. Following his training, he was shipped overseas where he served as a Halifax tail gunner with 405 Squadron RCAF. During a mission over France, just east of Paris, Flight Sergeant Dmytruk's plane was hit by German anti-aircraft fire. He survived the crash and after hiding in the woods, he was protected by locals who put him in touch with members of the French Underground. Dmytruk was led south through German-occupied France towards the escape route through the Pyrenees into Spain. Along the way, he was deeply impacted by the plight of the French people under Nazi occupation and chose not to be smuggled out of the country. Instead, he joined the French Resistance, which dubbed him, "Pierre le Canadien."

Peter Dmytruk's duties for the Resistance brought him to the small village of Les Martres-de-Veyre, about 15 kilometers south of Clermont-Ferrand where he gained a reputation amongst his French colleagues as a fearless fighter, undeterred by the ever-present danger. Following the sabotage of a German troop and munitions train, the Germans sent troops into Les Martres-de-Veyre. Normally, the usual Wehrmacht reprisal for such sabotage incidents involved executing all the men in the village. However, on December 9, 1943, Peter Dmytruk was arrested and because it was believed that the notorious "Pierre le Canadien" was responsible for the train sabotage, he was executed on the spot. As a result, the German military believed they had broken the backbone of the local Resistance movement.

Aftermath
The people of Les Martres-de-Veyre buried the 23-year-old Peter Dmytruk with honours in the community cemetery. Because of the war, it would be more than a year before the Canadian government could confirm Dmytruk's death to his family. Following VE Day, however, he was amongst those individuals almost completely forgotten, as the Canadian people were anxious to put the War behind them.

However, acclaimed as a hero whose selfless courage helped bring freedom to France and whose death saved the life of many residents of Les Martres-de-Veyre, a street was named after him. The Fourth French Republic honoured Dmytruk with the Croix de Guerre and at the end of the War, beginning in 1946 and each year thereafter, the citizens of Les Martres-de-Veyre held a parade and memorial service at his monument.

Almost thirty years after his death, in August 1972, the surprised mayor of Wynyard, Saskatchewan received a letter from the mayor of Les Martres-de-Veyre, who proposed to honour the slain Canadian airman through the twinning of their two small towns and the creation of a new and larger memorial at Dmytruk's gravesite. On the thirtieth anniversary of his death, a 13-person delegation of Dmytruk's relatives and officials from Saskatchewan joined the French commemoration ceremony.

In 1999, Peter Dmytruk was awarded the "Nation Builders Awards" that honours the contributions of outstanding Ukrainian Canadians from the Province of Saskatchewan.

title: Peter Dmytruk