title: Larry Eyler

text: Following Stock's closing argument, David Schippers began his own presentation before the jury, promising to "talk sense" regarding the case and the felony charges against his client, before stating: "Where is the evidence Danny Bridges was kidnapped by anyone?" Referencing the welt marks upon the decedent's wrists and ankles, Schippers speculated that as Eyler held a penchant for bondage, Bridges may have willingly submitted to this act. Speculating Eyler may not have been the actual murderer, Schippers hearkened to Dobrovolskis's testimony regarding Robert Little being at Eyler's apartment as late as 2:45 a.m. on August 20 and the convenience in his choosing to pay a tax bill not due for two months later that day in a possible effort to build himself an alibi. Schippers then referenced the state's acceptance of Little's version of events and a lack of any investigation into his potential culpability, adding: "Well, if Little says it, it must be true."


title: Larry Eyler

text: Mark Rakoczy delivered a brief rebuttal argument in which he argued the evidence presented overwhelmingly attested to Eyler's guilt before the state rested its case. Judge Urso then informed the jury of the factors to consider in reaching their deliberations, adding they should allow neither prejudice or sympathy to influence their verdicts. The jurors then retired to consider their verdict.


title: Larry Eyler

text: The jury deliberated for three hours before returning their verdict. Eyler was found guilty of the aggravated kidnapping, unlawful restraint and murder of Daniel Bridges, in addition to the concealment of the teenager's body. His face displayed little emotion as the verdict was announced, although his hands clenched the legs of the attorneys sitting either side of him.


title: Larry Eyler

text: On September 30, both prosecution and defense attorneys outlined their arguments in relation to the sentence to be imposed upon Eyler before Judge Urso; these arguments concluded the following day.


title: Larry Eyler

text: Prosecutor Richard Stock introduced four individuals who each testified to instances in which they had been assaulted and, in one case, left for dead by Eyler between 1978 and 1981. Outlining the similarities in Eyler's restraining or immobilizing these individuals to the restraint and torture Bridges had endured before he was "finally put out of his misery", Stock added: "There is nothing, Your Honor, that can mitigate the tears and the agony that Larry Eyler has caused in his entire life, thirty-three years, and he has caused more tears than anyone [...] a sentence other than death will be giving him his freedom."


title: Larry Eyler

text: On October 1, David Schippers introduced four character witnesses (Eyler's mother, stepfather, sister, and a Catholic chaplain) to testify to the kindness and decency they had observed in Eyler's character, with Eyler's mother, Shirley DeKoff, referencing her son's emotionally difficult childhood and her frequently marrying and divorcing a succession of abusive husbands as she constantly sought stability for her children. Both Eyler's mother and sister wept as they pleaded with Judge Urso to spare Eyler's life.


title: Larry Eyler

text: Schippers outlined his belief the death penalty should be inappropriate by stating the evidence presented before the jury asserting his client had committed murder was based upon circumstantial evidence. He also referenced historical cases where witnesses had provided false testimony and cases where juries had incorrectly returned guilty verdicts against innocent defendants. Schippers closed his argument before Judge Urso by emphasizing the existence of mitigating factors regarding Eyler's culpability in the actual act of homicide before requesting his client's sentence be life imprisonment.


title: Larry Eyler

text: Upon hearing the counsels' closing arguments, Judge Urso announced he would return his decision at 10:00 a.m. on October 3. On this date, Judge Urso formally sentenced Eyler to death by lethal injection. Emphasizing his decision had been difficult for him to reach due to his religious beliefs, Urso explained: "The senseless and barbaric murder of a 16-year-old boy, a killing which was so brutal it defies description, shows me your complete disregard for human life. If there ever was a person or a situation for which the death penalty is appropriate, it is you. You are an evil person. You truly deserve to die for your acts. I thereby sentence you to death for the murder of Danny Bridges, committed during the course of his aggravated kidnapping."


title: Larry Eyler

text: Following his sentencing, Eyler was transferred to the Pontiac Correctional Center, where he remained incarcerated on death row. Within this facility, Eyler underwent several psychiatric evaluations. These tests concluded Eyler suffered from a severe borderline personality disorder. Noting Eyler's pathological sensitivity to feelings of abandonment, experts theorized Eyler had killed in response to real or perceived feelings of rejection from his lover, discharging his rage upon his victims. Furthermore, these experts believed he had also murdered in order to maintain a sense of control.


title: Larry Eyler

text: In May 1988, Eyler filed a formal appeal against his conviction, contending that although he had dismembered Bridges' body and disposed of the remains, the actual murder itself had been committed by Robert Little in his absence, and this contention had not been rebutted by the prosecution at his trial. This appeal further contended Bridges had been driven to Eyler's apartment by Robert Little (whose vehicle had not been subjected to a forensic examination), and that his alibi had never been corroborated.


title: Larry Eyler

text: This appeal was heard on May 10, 1989, and later dismissed on October 25. An initial execution date was set for March 14, 1990.


title: Larry Eyler

text: On November 5, 1990, an attorney named Kathleen Zellner was appointed by the Illinois Appellate Defender's office to represent Eyler in his ongoing appeals against his conviction.


title: Larry Eyler

text: In November 1990, a Vermillion County prosecutor named Larry Thomas obtained the physical evidence retrieved against Eyler in relation to the murder of Ralph Calise (previously ordered suppressed by Judge William Block) with the intention of presenting the evidence before an Indiana grand jury to determine whether sufficient evidence existed to charge Eyler with the December 1982 murder of Steven Agan.


title: Larry Eyler

text: Upon being informed of his impending indictment in Agan's murder, Eyler agreed to voluntarily confess to his culpability, although he insisted this particular murder had been committed with the assistance of Robert Little. He agreed to confess to his guilt and testify against his alleged accomplice on the condition he be given a fixed term of imprisonment as opposed to a further death sentence. His offer was accepted, and Eyler provided his attorney with a seventeen-page confession on December 4.


title: Larry Eyler

text: On December 13, Eyler pleaded guilty to the murder of Steven Agan before Judge Don Darnell, additionally testifying Robert Little had been a knowing and willing participant in this murder. (An independent polygraph test conducted prior to Little's trial indicated the authenticity of this assertion, and to Eyler's further claim that Little had been the individual who had actually murdered Daniel Bridges.)


title: Larry Eyler

text: Eyler received a sentence of 60 years' imprisonment on December 28, to be served concurrently with his existing sentence. Little (aged 53) was arrested on December 18 and formally charged with Agan's first-degree murder, facing a sentence of 60 years' imprisonment if convicted.


title: Larry Eyler

text: The following month, Kathleen Zellner offered a deal on behalf of her client whereby Eyler would confess to his culpability in twenty further homicides committed across ten counties in Illinois and Indiana if the state of Illinois would commute his death sentence to one of life imprisonment without parole. According to Zellner, her client had offered until the end of January for this deal to be accepted or he would "take his secrets to the grave". Although authorities in eight of these ten jurisdictions readily agreed to offer Eyler a lengthy prison sentence in exchange for his confession, and a ninth jurisdiction indicated a potential willingness but awaited the official response from Cook County, the Cook County State's Attorney, Jack O'Malley, ultimately rejected Eyler's offer.


title: Larry Eyler

text: Robert Little was brought to trial on April 11, 1991. He was tried in Vermillion County before Judge Don Darnell, and entered a formal plea of not guilty on this date.


title: Larry Eyler

text: Eyler testified against his alleged accomplice at this trial; claiming he and Little had both committed the murder of Agan on December 19, 1982. According to Eyler, the two had regularly socialized within Indianapolis's gay community, occasionally bringing young men to Little's home to engage in sex, with Little frequently photographing the sexual acts.


title: Larry Eyler

text: Testimony from Eyler asserted that on the date of the murder, Little had suggested the two "do a scene", which he had understood to mean commit a murder for sexual pleasure as Little photographed the event with a Polaroid camera. He and Little had lured Agan—whom Eyler had vaguely known through frequenting the car wash where Agan had worked—into Little's vehicle in Terre Haute, initially with the promise of Agan simply drinking with the two. Although Agan was heterosexual, he agreed to participate in a bondage and photography session for money.


title: Larry Eyler

text: The two men had initially driven Agan to a location close to the Terre Haute Regional Airport, where a guardsman ordered the three off airport grounds. Eyler then drove toward an abandoned shed close to Indiana State Road 63. At this location, Agan's hands were tied above a beam before he was gagged and bound. According to Eyler, Little then shouted, "Get out the knife" before he had proceeded to stab Agan. Eyler further testified Little had repeatedly masturbated while photographing him as he had bound and repeatedly stabbed Agan, and that Little had also stabbed the young man before stating to Eyler, "Okay, kill the motherfucker." Little had taken Agan's undershirt from the crime scene, and had later complained to Eyler the overall murder ritual had been too fast for his liking.


title: Larry Eyler

text: Upon cross-examination, one of Little's defense attorneys, Dennis Zahn, asserted that because Little had appeared as a witness for the prosecution at Eyler's earlier trial for the murder of Daniel Bridges, he was simply implicating Little in a further murder he had committed as a form of revenge. In support of this contention, Zahn questioned Eyler in regard to fifteen other alleged victims of his; on each occasion, Eyler exercised his Fifth Amendment rights and suggested Little's attorneys could ask their client about those homicides. When questioned as to whether he had dismembered the body of Daniel Bridges, Eyler admitted that he had committed this act, although he denied responsibility for the teenager's actual murder.


title: Larry Eyler

text: Further questioned as to why no photographs had been found depicting Agan's restraint and murder in police searches of Little's home in either 1983 or 1990, Eyler stated Little had disposed of the photographs following the 1983 search of his home, adding the pictures had been inside a closet in Little's bedroom, which had not been searched.


title: Larry Eyler

text: On April 12, Dr. John Pless recounted the autopsy he had performed upon Agan's body on December 28, 1982. Dr. Pless testified as to having viewed several eviscerated bodies in his career, before stating: "This is the [most extensively mutilated body] I've seen without the body being cut into pieces." Pless testified that many of the beating, stabbing, and slashing injuries had been inflicted after Agan was already deceased, although numerous deep wounds to the neck and groin had been inflicted while the young man was still alive. He further testified that he could not conclusively pinpoint the actual time of Agan's death, but stated his belief the young man had been killed prior to December 21.


title: Larry Eyler

text: Defense attorney James Voyles claimed his client had not been in Indiana in the week before Christmas on any year between 1958 and 1989. To support this contention, Little's mother testified she had relocated from Indiana to Florida in 1958; that her son had first visited her home approximately a week before Christmas that year; and that he had "never missed a Christmas" at her home on any year since. Furthermore, he had invariably stayed at her home until New Year's Day. However, this claim had earlier been discredited by prosecutor Mark Greenwell, who had introduced into evidence ledger records proving Little's vehicle had been brought to a Terre Haute garage for minor repair work on December 21, 1982, and a phone bill proving a call had been made from Little's home on the same day before the prosecutors had rested their case on April 15.


title: Larry Eyler

text: Although Little had been prepared to testify in his own defense, his attorneys advised him not to do so on April 16; explaining their belief his mother's testimony had made an impression on the jurors' minds and that if he testified, his sexuality would largely be on trial.


title: Larry Eyler

text: Both prosecution and defense attorneys delivered their closing arguments before the jury on April 17. Mark Greenwell described the murder as being "a performance" orchestrated at Little's instruction, adding that the murder had been committed to satisfy the defendant's lust for sadomasochistic bondage. Greenwell also inferred Eyler had nothing to personally gain by asserting Little had actively participated in this murder, adding Eyler had readily admitted to physically taking the decedent's life.


title: Larry Eyler

text: Dennis Zahn described his client as an individual victimized because of his sexuality and portrayed Eyler as a convicted murderer cynically fabricating accusations against his client in a "last ditch" effort to have his death sentence commuted. Referencing the twenty-four occasions in which Eyler had exercised his Fifth Amendment rights in response to questioning by the defense, Zahn ended his closing argument by asking the jurors: "Would you convict an honorable man on the word of Larry Eyler?"


title: Larry Eyler

text: After deliberating for over seven hours, the jury found Little not guilty of all charges on April 17. Little grinned as the verdict was read before hugging his attorney as Steven Agan's brother and parents ran out of the courtroom. Following his acquittal, Little held a press conference in which he informed reporters: "I'm just so happy the ordeal is over", before stating his intentions to return to his teaching position at the Indiana State University.


title: Larry Eyler

text: Larry Eyler died in the infirmary of the Pontiac Correctional Center on March 6, 1994. His death was due to AIDS-related complications; he had been seriously ill for approximately ten days prior to his death.


title: Larry Eyler

text: At the time of Eyler's death, his attorney, Kathleen Zellner, had prepared a further appeal disputing her client's conviction in the Bridges murder. This appeal was pending in the Illinois Supreme Court, and Zellner remained confident Eyler's conviction would have been overturned.


title: Larry Eyler

text: The appeal itself maintained that one of Eyler's defense attorneys, David Schippers, had a conflict of interest as he had received a payment of $16,875 from Robert Little to assist in Eyler's defense at his trial for the murder of Daniel Bridges, although Little had appeared as a witness for the prosecution. Schippers had informed Judge Urso he was offering his legal services free of charge; adding he would inform the court if these circumstances changed. As such, the appeal contended Schippers had been guilty of attorney misconduct and that Eyler's conviction had therefore been unsafe. Zellner maintained her conviction that a conflict of interest of this magnitude would undoubtedly have resulted in Eyler securing a retrial. This appeal further claimed that Little had been the individual who had actually murdered Daniel Bridges.


title: Larry Eyler

text: Shortly after her client's death, Zellner confirmed that she would proceed with filing the appeal to clarify various outstanding legal issues pertaining to a lack of police investigation into Robert Little as a potential culprit in Bridges' abduction and murder and regarding documents negating her client's aggravated kidnapping conviction, which had not been made available to Eyler's defense attorneys either prior to or after his trial.


title: Larry Eyler

text: Two days after Eyler's death, Kathleen Zellner called a press conference in which she revealed the names and/or descriptions of seventeen individuals whom her client confessed to having personally murdered, and naming four other individuals—Steven Crockett, Steven Agan, an unidentified Caucasian murdered in late-May 1983, and a further unidentified Caucasian male murdered in April 1984—whom Eyler claimed had been murdered with the assistance of Robert Little (who Zellner referred to in this press conference as "an unnamed individual still living in Indiana"). Zellner emphasized her client's insistence Little had been the individual who had actually murdered Daniel Bridges.


title: Larry Eyler

text: According to Zellner, her client had been an emotionally insecure individual who had viewed Robert Little as something of the father figure he had never had in his life, and this had left Eyler vulnerable to manipulation, with Little using him as a means of facilitating his own access to young males for sexual purposes in return for the financial support he provided. Zellner further asserted Eyler's paraphilia had inadvertently increased his penchant for violence and that Little had begun to encourage her client to project his extreme self-hatred regarding his homosexuality and the conflict between his sexual preference and his religious beliefs onto other males approximately six months before the two had abducted and murdered Steven Crockett. Furthermore, Eyler had been actively encouraged, aided and abetted in all his subsequent murders by Little, who had known of all of his crimes.


title: Larry Eyler

text: Emphasizing her belief in Eyler's confessions, Zellner elaborated that her client had been formally diagnosed with AIDS in March 1991 and therefore "knew when he testified at [Little's] trial in the Steven Agan murder that he was dying. I believe Larry was truthful. Larry had no incentive to lie to anyone."


title: Larry Eyler

text: In his posthumous confession, Eyler stated he had typically lured his victims—who had been both heterosexual and homosexual—with promises of drugs, alcohol, money, or transport and that, immediately prior to stabbing several of his victims, he had pressed the blade of his knife against their abdomen before informing his victim to "make peace with God". Furthermore, Eyler claimed he had never engaged in sex with any of his victims, and he had frequently given his victims' T-shirts to Robert Little to use in masturbatory fantasies.


title: Larry Eyler

text: Zellner stated Eyler had begun compiling a list of his victims shortly after she had been appointed as his legal representative in November 1990 in an effort to obtain a plea bargain whereby his sentence would be commuted to one of life imprisonment. With his health in gradual decline, Eyler had authorized his attorney to publicly release his confessions after his death, with his explanation being that the families of his victims would know he had confessed to the murders of their relatives.


title: Larry Eyler

text: Eyler's posthumous confession revealed he had murdered twenty-one teenage boys and young men between 1982 and 1984, being assisted by his alleged accomplice Robert Little in four of these murders. He denied any culpability in the physical murder of Daniel Bridges, although he admitted to the dismemberment and disposal of the teenager's body. Investigators strongly believe Eyler is also responsible for two further homicides committed in Wisconsin and Kentucky in 1983.


title: Larry Eyler

text: In his formal confession, Eyler claimed to have committed his murders in part as a means of relieving internal frustrations frequently triggered by fights with his lover, and to his achieving a sense of relief after the act. His victims were hitchhikers, male prostitutes, or individuals he had generally encountered by happenstance. Each victim would be plied with alcohol and sedatives and driven to a remote area where Eyler would typically wait for an opportune moment to handcuff his victim. He would then overpower, gag, blindfold, and bind his victim hand and foot before proceeding to bludgeon and lash his victim before murdering him.


title: Larry Eyler

text: Of these twenty further victims to which Eyler posthumously confessed, ten had been committed in Indiana, and ten in Illinois. Furthermore, according to Eyler, the body of one of these victims—an Uptown male prostitute known as "Cowboy" killed in his Rogers Park apartment in April 1984—had never been found.


title: Larry Eyler

text: In April 2021, one of the four victims discovered alongside an oak tree close to an abandoned farmhouse in Lake Village, Indiana on October 18, 1983 was positively identified using DNA and genetic genealogy as John Brandenburg Jr. of Chicago. One victim recovered from this location remains unidentified. A further victim, discovered in Jasper County, Indiana on October 15, 1983, was identified in December 2021 as William Lewis of Peru, Indiana.


title: Larry Eyler

text: Four of Eyler's victims still remain unidentified, the body of one of whom has never been found. The bodies of two of these unidentified decedents were discovered in Indiana, with one further victim discovered in Illinois. Each unidentified decedent is listed below in order of body discovery, with the final entry being an entry within Eyler's posthumous confession to one further murder he claimed to have committed with the assistance of Robert Little in 1984.


title: Larry Eyler

text: Following Eyler's arrest and subsequent conviction for the murder of Daniel Bridges, Lake County Circuit Judge William Block suffered political repercussions as a result of his decision to suppress evidence pertaining to Eyler's guilt in the murder of Ralph Calise and to reduce his bond sum to $10,000. Block later unsuccessfully bid to be appointed to the Illinois Appellate Court. He remained a circuit court judge in Waukegan.


title: Larry Eyler

text: Eyler's lover, John Dobrovolskis, relocated to California shortly after his arrest. He later returned to live with his wife, Sally, in Chicago. Dobrovolskis died of AIDS in January 1990 at the age of 29.


title: Larry Eyler

text: Shortly after his 1991 acquittal of the murder of Steven Agan, Robert Little returned to the teaching position he had held at the Indiana State University since 1971, and continued to maintain his lack of knowledge of and innocence in any murders Eyler had committed.


title: Larry Eyler

text: On the day Eyler's posthumous confession was revealed by his attorney, a spokesman for the Cook County State's Attorney stated to the media that despite Eyler's claims to have been assisted by Little in four murders, and that Little had actually murdered Daniel Bridges, insufficient real evidence existed to substantiate Eyler's admissions and that no further investigation into Little's alleged participation in Eyler's murders would ensue.


title: Larry Eyler

text: Kathleen Zellner continues to practice law in Downers Grove, Illinois. Her firm specializes in the overturning of wrongful convictions. Shortly after Eyler confessed his guilt in twenty-one homicides to her in 1990, Zellner resolved she would never again knowingly defend another guilty individual.


title: Yukio (comics)

text: She was portrayed by Rila Fukushima in the 2013 film "The Wolverine", and an alternate teenage version by Shioli Kutsuna in the 2018 film "Deadpool 2".


title: Yukio (comics)

text: Yukio's first full appearance was in "Wolverine" #2 (September 1982), created by writer Chris Claremont and artist Frank Miller.


title: Yukio (comics)

text: The X-Men's first encounter with Yukio occurred when Wolverine had his struggle with Shingen Yashida, father of Wolverine's girlfriend Mariko Yashida. At that time Yukio worked for Shingen, and one of her tasks was to kill Wolverine. Instead she developed a crush on him and subsequently aided him in bringing about Shingen's downfall.


title: Yukio (comics)

text: Later, Wolverine invited his team to Japan for his wedding to Mariko, which Yukio joined subsequently. Viper and the Silver Samurai poisoned the X-Men during a dinner that Logan hosted for them. Logan, tasting the poison, warned Ororo and knocked the cup from her hand before she could drink it. While the others were recuperating from the attack, Storm, Wolverine, Rogue (who had been largely unaffected), and Yukio went after Viper and the Silver Samurai to stop his plot to assassinate Mariko, who was his half-sister. Yukio posed as a decoy, disguising herself as Mariko to lead them away from her. During their altercation with Viper and Silver Samurai, Storm found her powers inexplicably going out of control, endangering her life. Yukio knocked Storm into the nearby bay, enabling them to escape from the Silver Samurai. (These events had actually been brought about and influenced by the mutant villain Mastermind, who was conducting a revenge campaign against the X-Men at the time. He was also responsible for the subsequent halting of Wolverine's and Mariko's wedding). Storm, inspired by what she called Yukio's "madness" and lust for life, changed her image dramatically and adopted a new look: a mohawk haircut, studded collar, and black leather clothing.


title: Yukio (comics)

text: Yukio later met up, once again, with Wolverine to help him fight the ninja master Ogun. She developed a rivalry with the X-Man Gambit: Both being thieves, they often tried to steal the same object. Yukio once framed Gambit for a crime she committed. Yukio is also part of Professor X's secret information network of humans and mutants, known as the Mutant Underground (not to be confused with Cable's Underground).


title: Yukio (comics)

text: After the death of Mariko Yashida, Wolverine sent his adopted daughter, Amiko Kobayashi, to a foster family. He later discovered that her new foster parents were abusive and only interested in the money. Wolverine took Amiko away from them and asked Yukio to raise her. This unofficial adoption was under the protection of the Silver Samurai, now an ally of Wolverine. Yukio trained Amiko in the martial arts and to her own surprise she enjoyed her new role as a mother. When Sabretooth targeted Wolverine's friends and family, he hired Omega Red and Lady Deathstrike to kidnap Amiko. Yukio fought the two, but was overpowered and seriously injured, and left her in a wheelchair. She asked Wolverine to kill her, but Wolverine refused and saved Amiko shortly afterwards. Yukio reappeared and was fully recovered from her previous injuries. She teamed up with Storm again to enter the Arena, a fight club for mutants. In the end, Yukio, Storm, and Callisto took over the Arena.


title: Yukio (comics)

text: Later, Yukio and Amiko were attacked by Hellverine (a demonic being who had taken over Wolverine's body in order to kill his loved ones) on the behest of Marduk Kurios. Her confusion over the fake Wolverine's behavior earned Yukio serious injuries, but Amiko returned from school just in time to save them both from Hellverine. When Wolverine goes back to Japan to stop a war between the Hand and the Yakuza, Yukio is shown to be once again in a wheelchair due to Hellverine's attack.


title: Yukio (comics)

text: As part of the "All-New, All-Different Marvel" event, Yukio is shown running an illegal nightclub in Osaka, Japan when it is visited by War Machine where he asks her about the tech-based ninjas. Yukio states that she cannot say anything if she wants her business to stay afloat. After being threatened with the prospect of having the Avengers storming the place, Yukio points War Machine to a rather big and muscular man in a tuxedo who leaves the nightclub with two ladies entering the car with him.


title: Yukio (comics)

text: Within the context of the stories, Yukio is an occasional thief by profession, as well as a rōnin, a masterless samurai. Yukio has been portrayed as a free spirit with an almost careless disregard for personal safety. According to her own philosophy of life, living in danger is the ultimate adventure, while the peace of death is the final prize that awaits for every person who has truly lived. In 2011, UGO Networks featured her on their list of 25 Hot Ninja Girls, commenting: "While her short, black haircut and skin-tight leather outfit make her come off as a nefarious addition to the X-Men world, Yukio has proven to be quite a helpful non-mutant to Wolverine and his friends."


title: Yukio (comics)

text: While Yukio is highly skilled in the martial arts, her specialty weapons are scalpel-like shuriken, of which she can hurl up to three at a time with deadly accuracy. Wolverine once joked that Yukio's real first name was "Yukiko".


title: Yukio (comics)

text: In the limited series, "", a Skrull masquerades as Yukio on a mission from the Shi'ar to eliminate Storm and Wolverine. It is killed by Storm's ice powers.


title: Yukio (comics)

text: In 2011, UGO Networks featured her on their list of 25 Hot Ninja Girls, commenting: "While her short, black haircut and skin-tight leather outfit make her come off as a nefarious addition to the X-Men world, Yukio has proven to be quite a helpful non-mutant to Wolverine and his friends."


title: Yukio (comics)

text: Christy Lemire, writing for the website of Roger Ebert, described Yukio in "The Wolverine" as "frisky and fearless" and a "manga-inspired dream girl", writing that actress Fukushima "more than holds her own opposite the veteran Jackman in both the elaborate fight scenes and the quieter moments". With respect to her appearance in "Deadpool 2", Sergio Pereira, writing for "Screen Rant", felt that Kutsuna's portrayal of Yukio was bad for the character and the franchise, stating that "[a]ll of the character development and progress from "The Wolverine" is washed away as Yukio becomes a parody of herself". Writing for "Bustle", Olivia Truffaut-Wong said that the "Deadpool 2" Yukio "doesn't really seem to have a life outside of being one half of the first gay superhero couple onscreen... nor does she have a personality that goes beyond typical depictions of a cute Japanese anime character", although she does note the significance of the character appearing as being in a relationship.


title: Tết

text: Tết (), short for Tết Nguyên Đán (Chữ Hán: 節元旦), Spring Festival, Lunar New Year, or Vietnamese Lunar New Year is one of the most important celebrations in Vietnamese culture. The colloquial term "Tết" is a shortened form of , with Old Vietnamese origins meaning "Festival of the First Morning of the First Day". Tết celebrates the arrival of spring based on the Vietnamese calendar, which usually has the date on January or February in the Gregorian calendar.


title: Tết

text: "Tết Nguyên Đán" (Spring Festival or Lunar New Year) is not to be confused with "Tết Trung Thu" (Mid-Autumn Festival), which is also known as "Children's Festival" in Vietnam. "Tết" itself only means festival, but is often nominally known as "Lunar New Year Festival" in Vietnamese, as it is often seen as the most important festival amongst the Vietnamese diaspora, with "Children's Festival" (Tết Trung Thu) often regarded as the second-most important.


title: Tết

text: Vietnamese people celebrate Tết annually, which is based on a lunisolar calendar (calculating both the motions of Earth around the Sun and of the Moon around Earth). Tết is generally celebrated on the same day as Chinese New Year (also called Spring Festival), except when the one-hour time difference between Vietnam and China results in the new moon occurring on different days. It takes place from the first day of the first month of the Vietnamese lunar calendar (around late January or early February) until at least the third day.


title: Tết

text: Tết is also an occasion for pilgrims and family reunions. They set aside the trouble of the past year and hope for a better and happier upcoming year. This festival can also be referred to as in vernacular Vietnamese, (festival - lễ hội, spring - mùa xuân).


title: Tết

text: Vietnamese people usually return to their families during Tết. Some return to worship at the family altar or visit the graves of their ancestors in their homeland. They also clear up the graves of their families as a sign of respect. Although Tết is a national holiday among all Vietnamese, each region and religion has its own customs.


title: Tết

text: Many Vietnamese and Hoa people prepare for Tết by cooking special holiday food and doing house cleaning. These foods include , , , , , dried young bamboo soup (), , and xôi (sticky rice). Many customs and traditions are practiced during Tết, such as visiting a person's house on the first day of the new year (), ancestor worship, exchanging New Year's greetings, giving lucky money to children and elderly people, opening a shop, visiting relatives, friends, and neighbors.


title: Tết

text: Tết can be divided into three periods, known as "Tất Niên" 畢年 (penultimate New Year's Eve), "Giao Thừa" 交承 (New Year's Eve), and "Tân Niên" 新年 (the New Year), representing the preparation before Tết, the eve of Tết, and the days of and following Tết, respectively.


title: Tết

text: The first day of Tết is reserved for the nuclear family. Children receive red envelopes containing money from their elders. This tradition is called "mừng tuổi" (happy new age) in the North region and "lì xì" in the South region. Usually, children wear their new clothes and give their elders the traditional Tết greetings before receiving money. Since the Vietnamese believe that the first visitor who a family receives in the year determines their fortune for the entire year, people never enter any house on the first day without being invited first. The action of being the first person to enter a house at Tết is called "xông đất", "xông nhà", or "đạp đất", which is one of the most important rituals during Tết. According to Vietnamese tradition, if good things come to a family on the first day of the lunar New Year, the entire following year will also be full of blessings. Usually, a person of good temper, morality, and success will be a lucky sign for the host family and be first invited into his house. However, just to be safe, the owner of the house will leave the house a few minutes before midnight and come back just as the clock strikes midnight to prevent anyone else from entering the house first who might potentially bring any unfortunate events in the new year, to the household.


title: Tết

text: Sweeping during Tết is taboo, or "xui" (unlucky), since it symbolizes sweeping the luck away; that is why they clean before the new year. It is also taboo for anyone who experienced a recent loss of a family member to visit anyone else during Tết.


title: Tết

text: During subsequent days, people visit relatives and friends. Traditionally but not strictly, the second day of Tết is usually reserved for friends, while the third day is for teachers, who command respect in Vietnam. Local Buddhist temples are popular spots because people like to give donations and get their fortunes told during Tết. Children are free to spend their new money on toys or on gambling games such as "bầu cua cá cọp", which can be found in the streets. Prosperous families can pay for dragon dancers to perform at their house. Also, public performances are given for everyone to watch.


title: Tết

text: These celebrations can last from a day up to the entire week, and the New Year is filled with people in the streets trying to make as much noise as possible using firecrackers, drums, bells, gongs, and anything they can think of to ward off evil spirits. This parade will also include different masks and dancers hidden under the guise of what is known as the "múa lân "or lion dancing. The "lân" is an animal between a lion and a dragon and is the symbol of strength in the Vietnamese culture that is used to scare away evil spirits. After the parade, families, and friends come together to have a feast of traditional Vietnamese dishes and share the happiness and joy of the New Year with one another. This is also the time when the elders will hand out red envelopes with money to the children for good luck in exchange for Tết greetings.


title: Tết

text: It is also a tradition to pay off your debts before the Vietnamese New Year for some Vietnamese families.


title: Tết

text: Traditionally, each family displays "cây nêu", an artificial New Year tree consisting of a bamboo pole long. The top end is usually decorated with many objects, depending on the locality, including good luck charms, origami fish, cactus branches, and more.


title: Tết

text: At Tết, every house is usually decorated by Yellow Apricot blossoms ("hoa mai") in the central and southern parts of Vietnam, peach blossoms ("hoa đào") in the northern part of Vietnam, or St. John's wort ("hoa ban") in the mountain areas. In the north, some people (especially the elite in the past) also decorate their house with plum blossoms (also called "hoa mơ" in Vietnamese but referring to a totally different species from mickey-mouse blossoms). In the north or central, the kumquat tree is a popular decoration for the living room during Tết. Its many fruits symbolize fertility and fruitfulness which the family hopes in the coming year.


title: Tết

text: Vietnamese people also decorate their homes with bonsai and flowers such as chrysanthemums ("hoa cúc"), marigolds ("vạn thọ") symbolizing longevity, cockscombs ("mào gà") in southern Vietnam, and paperwhites ("thủy tiên") and pansies ("hoa lan") in northern Vietnam. In the past, there was a tradition where people tried to make their paperwhites bloom on the day of the observance.


title: Tết

text: The traditional greetings are ""Chúc Mừng Năm Mới"" (祝𢜠𢆥㵋, Happy New Year) and ""Cung Chúc Tân Xuân"", (恭祝新春, gracious wishes of the new spring). People also wish each other prosperity and luck. Common wishes for Tết include the following:


title: Tết

text: In the Vietnamese language, to celebrate Tết is to "ăn Tết", literally meaning "eat Tết", showing the importance of food in its celebration. Some of the food is also eaten year-round, while other dishes are only eaten during Tết. Also, some of the food is vegetarian since it is believed to be good luck to eat vegetarian on Tết. Some traditional foods on Tết include the following:


title: Tết

text: People enjoy traditional games during Tết, including "bầu cua cá cọp", "cờ tướng", "ném còn", "chọi trâu", and "đá gà". They also participate in some competitions presenting their knowledge, strength, and aestheticism, such as the bird competition and "ngâm thơ" competition.


title: Tết

text: Fireworks displays have also become a traditional part of a Tết celebration in Vietnam. During New Year's Eve, fireworks displays at major cities, such as Hà Nội, Ho Chi Minh City, and Da Nang, are broadcast through multiple national and local TV channels, accompanied by New Year wishes of the incumbent president. In 2017 only, fireworks displays were prohibited due to political and financial reasons. In 2021, due to the COVID-19 epidemic, most provinces and cities canceled the fireworks displays; instead, the displays were only held in Hà Nội and several provinces with public gatherings prohibited. In Australia, Canada & the United States, there are fireworks displays at many of its festivals, although in 2021 they were either held virtually or canceled.


title: Tết

text: "Gặp nhau cuối năm" ("Year-end meet") is a nationally known satirical theatrical comedy show, broadcast on VTV on New Year's Eve.


title: Nanoparticle

text: A nanoparticle or ultrafine particle is usually defined as a particle of matter that is between 1 and 100 nanometres (nm) in diameter. The term is sometimes used for larger particles, up to 500 nm, or fibers and tubes that are less than 100 nm in only two directions. At the lowest range, metal particles smaller than 1 nm are usually called atom clusters instead.


title: Nanoparticle

text: Nanoparticles are usually distinguished from microparticles (1-1000 µm), "fine particles" (sized between 100 and 2500 nm), and "coarse particles" (ranging from 2500 to 10,000 nm), because their smaller size drives very different physical or chemical properties, like colloidal properties and ultrafast optical effects or electric properties.


title: Nanoparticle

text: Being more subject to the brownian motion, they usually do not sediment, like colloidal particles that conversely are usually understood to range from 1 to 1000 nm.


title: Nanoparticle

text: Being much smaller than the wavelengths of visible light (400-700 nm), nanoparticles cannot be seen with ordinary optical microscopes, requiring the use of electron microscopes or microscopes with laser. For the same reason, dispersions of nanoparticles in transparent media can be transparent, whereas suspensions of larger particles usually scatter some or all visible light incident on them. Nanoparticles also easily pass through common filters, such as common ceramic candles, so that separation from liquids requires special nanofiltration techniques.


title: Nanoparticle

text: The properties of nanoparticles often differ markedly from those of larger particles of the same substance. Since the typical diameter of an atom is between 0.15 and 0.6 nm, a large fraction of the nanoparticle's material lies within a few atomic diameters of its surface. Therefore, the properties of that surface layer may dominate over those of the bulk material. This effect is particularly strong for nanoparticles dispersed in a medium of different composition since the interactions between the two materials at their interface also becomes significant.


title: Nanoparticle

text: Nanoparticles occur widely in nature and are objects of study in many sciences such as chemistry, physics, geology and biology. Being at the transition between bulk materials and atomic or molecular structures, they often exhibit phenomena that are not observed at either scale. They are an important component of atmospheric pollution, and key ingredients in many industrialized products such as paints, plastics, metals, ceramics, and magnetic products. The production of nanoparticles with specific properties is a branch of nanotechnology.


title: Nanoparticle

text: In general, the small size of nanoparticles leads to a lower concentration of point defects compared to their bulk counterparts, but they do support a variety of dislocations that can be visualized using high-resolution electron microscopes. However, nanoparticles exhibit different dislocation mechanics, which, together with their unique surface structures, results in mechanical properties that are different from the bulk material.


title: Nanoparticle

text: Non-spherical nanonparticles (e.g., prisms, cubes, rods etc.) exhibit shape-dependent and size-dependent (both chemical and physical) properties (anisotropy). Non-spherical nanoparticles of gold (Au), silver (Ag), and platinum (Pt) due to their fascinating optical properties are finding diverse applications. Non-spherical geometries of nanoprisms give rise to high effective cross-sections and deeper colors of the colloidal solutions. The possibility of shifting the resonance wavelengths by tuning the particle geometry allows using them in the fields of molecular labeling, biomolecular assays, trace metal detection, or nanotechnical applications. Anisotropic nanoparticles display a specific absorption behavior and stochastic particle orientation under unpolarized light, showing a distinct resonance mode for each excitable axis.


title: Nanoparticle

text: In its 2012 proposed terminology for biologically related polymers, the IUPAC defined a nanoparticle as "a particle of any shape with dimensions in the 1 × 10 and 1 × 10 m range". This definition evolved from one given by IUPAC in 1997.


title: Nanoparticle

text: In another 2012 publication, the IUPAC extends the term to include tubes and fibers with only two dimensions below 100 nm.


title: Nanoparticle

text: According to the International Standards Organization (ISO) technical specification 80004, a nanoparticle is an object with all three external dimensions in the nanoscale, whose longest and shortest axes do not differ significantly, with a significant difference typically being a factor of at least 3.


title: Nanoparticle

text: "Nanoscale" is usually understood to be the range from 1 to 100 nm because the novel properties that differentiate particles from the bulk material typically develop at that range of sizes.


title: Nanoparticle

text: For some properties, like transparency or turbidity, ultrafiltration, stable dispersion, etc., substantial changes characteristic of nanoparticles are observed for particles as large as 500 nm. Therefore, the term is sometimes extended to that size range.


title: Nanoparticle

text: Nanoclusters are agglomerates of nanoparticles with at least one dimension between 1 and 10 nanometers and a narrow size distribution. Nanopowders are agglomerates of ultrafine particles, nanoparticles, or nanoclusters. Nanometer-sized single crystals, or single-domain ultrafine particles, are often referred to as nanocrystals.


title: Nanoparticle

text: The terms colloid and nanoparticle are not interchangeable. A colloid is a mixture which has particles of one phase dispersed or suspended within an other phase. The term applies only if the particles are larger than atomic dimensions but small enough to exhibit Brownian motion, with the critical size range (or particle diameter) typically ranging from nanometers (10 m) to micrometers (10 m). Colloids can contain particles too large to be nanoparticles, and nanoparticles can exist in non-colloidal form, for examples as a powder or in a solid matrix.


title: Nanoparticle

text: Nanoparticles are naturally produced by many cosmological, geological, meteorological, and biological processes. A significant fraction (by number, if not by mass) of interplanetary dust, that is still falling on the Earth at the rate of thousands of tons per year, is in the nanoparticle range; and the same is true of atmospheric dust particles. Many viruses have diameters in the nanoparticle range.


title: Nanoparticle

text: Nanoparticles were used by artisans since prehistory, albeit without knowledge of their nature. They were used by glassmakers and potters in Classical Antiquity, as exemplified by the Roman Lycurgus cup of dichroic glass (4th century CE) and the lusterware pottery of Mesopotamia (9th century CE). The latter is characterized by silver and copper nanoparticles dispersed in the glassy glaze.


title: Nanoparticle

text: Michael Faraday provided the first description, in scientific terms, of the optical properties of nanometer-scale metals in his classic 1857 paper. In a subsequent paper, the author (Turner) points out that: "It is well known that when thin leaves of gold or silver are mounted upon glass and heated to a temperature that is well below a red heat (~500 °C), a remarkable change of properties takes place, whereby the continuity of the metallic film is destroyed. The result is that white light is now freely transmitted, reflection is correspondingly diminished, while the electrical resistivity is enormously increased."


title: Nanoparticle

text: During the 1970s and 80s, when the first thorough fundamental studies with nanoparticles were underway in the United States (by Granqvist and Buhrman) and Japan (within an ERATO Project), researchers used the term ultrafine particles. However, during the 1990s, before the National Nanotechnology Initiative was launched in the United States, the term nanoparticle had become more common (for example, see the same senior author's paper 20 years later addressing the same issue, lognormal distribution of sizes).


title: Nanoparticle

text: Nanoparticles occur in a great variety of shapes, which have been given many informal names such as nanospheres, nanorods, nanochains, nanostars, nanoflowers, nanoreefs, nanowhiskers, nanofibers, and nanoboxes.


title: Nanoparticle

text: The shapes of nanoparticles may be determined by the intrinsic crystal habit of the material, or by the influence of the environment around their creation, such as the inhibition of crystal growth on certain faces by coating additives, the shape of emulsion droplets and micelles in the precursor preparation, or the shape of pores in a surrounding solid matrix. Some applications of nanoparticles may require specific shapes, as well as specific sizes or size ranges.


title: Nanoparticle

text: Semi-solid and soft nanoparticles have been produced. A prototype nanoparticle of semi-solid nature is the liposome. Various types of liposome nanoparticles are currently used clinically as delivery systems for anticancer drugs and vaccines.


title: Nanoparticle

text: The breakdown of biopolymers into their nanoscale building blocks is considered a potential route to produce nanoparticles with enhanced biocompatibility and biodegradability. The most common example is the production of nanocellulose from wood pulp. Other examples are nanolignin, nanchitin, or nanostarches.


title: Nanoparticle

text: Nanoparticles with one half hydrophilic and the other half hydrophobic are termed Janus particles and are particularly effective for stabilizing emulsions. They can self-assemble at water/oil interfaces and act as Pickering stabilizers.


title: Nanoparticle

text: Hydrogel nanoparticles made of N-isopropylacrylamide hydrogel core shell can be dyed with affinity baits, internally. These affinity baits allow the nanoparticles to isolate and remove undesirable proteins while enhancing the target analytes.


title: Nanoparticle

text: Nucleation lays the foundation for the nanoparticle synthesis. Initial nuclei play a vital role on the size and shape of the nanoparticles that will ultimately form by acting as templating nuclei for the nanoparticle itself. Long-term stability is also determined by the initial nucleation procedures. Homogeneous nucleation occurs when nuclei form uniformly throughout the parent phase and is less common. Heterogeneous nucleation, however, forms on areas such as container surfaces, impurities, and other defects. Crystals may form simultaneously if nucleation is fast, creating a more monodisperse product. However, slow nucleation rates can cause formation of a polydisperse population of crystals with various sizes. Controlling nucleation allows for the control of size, dispersity, and phase of nanoparticles.


title: Nanoparticle

text: The process of nucleation and growth within nanoparticles can be described by burst nucleation, Ostwald ripening or the two-step mechanism-autocatalysis model.


title: Nanoparticle

text: The original theory of nucleation in nanoparticle synthesis believed that the changes in particle size could be described by burst nucleation alone. There are three portions to the LaMer mechanism: 1. Rapid increase in the concentration of free monomers in solution, 2. Burst nucleation of the monomer characterized by explosive growth of particles, 3. Growth of particles controlled by diffusion of the monomer. This model describes that the growth on the nucleus is spontaneous but limited by diffusion of the precursor to the nuclei surface. The LaMer mechanism alone does not explain certain kinetic and thermodynamic of nucleation such as gold sol formation.


title: Nanoparticle

text: Ostwald ripening is a process typically avoided in nanoparticle synthesis as it is known to negatively impact the functionality of nanoparticles. In this process, large particles grow at the expense of the smaller particles due to diffusion of disperse phase molecules through the continuous phase.


title: Nanoparticle

text: In later years, another theory of nucleation in nanoparticles was introduced by Watzky and Finke. This theory suggested that constant slow nucleation occurs far from supersaturation followed by autocatalytic growth where dispersity of nanoparticles is largely determined. Discovered by Watzky and Finke, this model provides a firmer mechanistic basis for the design of nanoparticles with a focus on size, shape, and dispersity control.


title: Nanoparticle

text: Recent work has begun to look at modeling the early stages of nucleation as well as the rates associated with nucleation through multiscale computational modeling. This includes exploration into an improved kinetic rate equation model as well as density function studies using the phase-field crystal model.


title: Nanoparticle

text: The classical nucleation theory explains that the nucleation rate will correspond to the driving force One method for measuring the nucleation rate is through the induction time method. This process uses the stochastic nature of nucleation and determines the rate of nucleation by analysis of the time between constant supersaturation and when crystals are first detected. Another method includes the probability distribution model, analogous to the methods used to study supercooled liquids, where the probability of finding at least one nucleus at a given time is derived.


title: Nanoparticle

text: The properties of a material in nanoparticle form are unusually different from those of the bulk one even when divided into micrometer-size particles. Many of them arise from spatial confinement of sub-atomic particles (i.e. electrons, protons, photons) and electric fields around these particles. The large surface to volume ratio is also significant factor at this scale.


title: Nanoparticle

text: The properties of a nanoparticle are heavily influenced by the initial nucleation stages of the synthesis process. Nucleation, for example, is vital to the size of the nanoparticle. A critical radius must be met in initial stages of solid formation, or the particles will redissolve into the liquid phase. The final shape of a nanoparticle is also controlled by nucleation. Possible final morphologies created by nucleation can include spherical, cubic, needle-like, worm-like, and more particles. Nucleation can be controlled predominately by time and temperature as well as the supersaturation of the liquid phase and the environment of the synthesis overall.


title: Nanoparticle

text: A bulk materials (>100 nm in size) are expected to have constant physical properties (such as thermal and electrical conductivity, stiffness, density, and viscosity) regardless of its size, for nanoparticle, however, this is different: the volume of the surface layer (few atomic diameters-wide) becomes a significant fraction of the particle's volume; whereas that fraction is insignificant for particles with diameter of one micrometer or more. In other words, the surface area/volume ratio impacts certain properties of the nanoparticles more prominently than in bulk particles.


title: Nanoparticle

text: For nanoparticles dispersed in a medium of different composition, the interfacial layer — formed by ions and molecules from the medium that are within a few atomic diameters of the surface of each particle — can mask or change its chemical and physical properties. Indeed, that layer can be considered an integral part of each nanoparticle.


title: Nanoparticle

text: Suspensions of nanoparticles are possible since the interaction of the particle surface with the solvent is strong enough to overcome density differences, which otherwise usually result in a material either sinking or floating in a liquid.


title: Nanoparticle

text: Nanoparticles often develop or receive coatings of other substances, distinct from both the particle's material and of the surrounding medium. Even when only a single molecule thick, these coatings can radically change the particles' properties, such as and chemical reactivity, catalytic activity, and stability in suspension.


title: Nanoparticle

text: The high surface area of a material in nanoparticle form allows heat, molecules, and ions to diffuse into or out of the particles at very large rates. The small particle diameter, on the other hand, allows the whole material to reach homogeneous equilibrium with respect to diffusion in a very short time. Thus many processes that depend on diffusion, such as sintering can take place at lower temperatures and over shorter time scales inducing catalysis.


title: Nanoparticle

text: The small size of nanoparticles affects their magnetic and electric properties. The ferromagnetic materials in the micrometer range is a good example: widely used in magnetic recording media, for the stability of their magnetization state, those particles smaller than 10 nm are unstable and can change their state (flip) as the result of thermal energy at ordinary temperatures, thus making them unsuitable for that application.


title: Nanoparticle

text: The reduced vacancy concentration in nanocrystals can negatively affect the motion of dislocations, since dislocation climb requires vacancy migration. In addition, there exists a very high internal pressure due to the surface stress present in small nanoparticles with high radii of curvature. This causes a lattice strain that is inversely proportional to the size of the particle, also well known to impede dislocation motion, in the same way as it does in the work hardening of materials. For example, gold nanoparticles are significantly harder than the bulk material. Furthermore, the high surface-to-volume ratio in nanoparticles makes dislocations more likely to interact with the particle surface. In particular, this affects the nature of the dislocation source and allows the dislocations to escape the particle before they can multiply, reducing the dislocation density and thus the extent of plastic deformation.


title: Nanoparticle

text: There are unique challenges associated with the measurement of mechanical properties on the nanoscale, as conventional means such as the universal testing machine cannot be employed. As a result, new techniques such as nanoindentation have been developed that complement existing electron microscope and scanning probe methods. Atomic force microscopy (AFM) can be used to perform nanoindentation to measure hardness, elastic modulus, and adhesion between nanoparticle and substrate. The particle deformation can be measured by the deflection of the cantilever tip over the sample. The resulting force-displacement curves can be used to calculate elastic modulus. However, it is unclear whether particle size and indentation depth affect the measured elastic modulus of nanoparticles by AFM.


title: Nanoparticle

text: Adhesion and friction forces are important considerations in nanofabrication, lubrication, device design, colloidal stabilization, and drug delivery. The capillary force is the main contributor to the adhesive force under ambient conditions. The adhesion and friction force can be obtained from the cantilever deflection if the AFM tip is regarded as a nanoparticle. However, this method is limited by tip material and geometric shape. The colloidal probe technique overcomes these issues by attaching a nanoparticle to the AFM tip, allowing control oversize, shape, and material. While the colloidal probe technique is an effective method for measuring adhesion force, it remains difficult to attach a single nanoparticle smaller than 1 micron onto the AFM force sensor.


title: Nanoparticle

text: Another technique is "in situ" TEM, which provides real-time, high resolution imaging of nanostructure response to a stimulus. For example, an "in situ" force probe holder in TEM was used to compress twinned nanoparticles and characterize yield strength. In general, the measurement of the mechanical properties of nanoparticles is influenced by many factors including uniform dispersion of nanoparticles, precise application of load, minimum particle deformation, calibration, and calculation model.


title: Nanoparticle

text: Like bulk materials, the properties of nanoparticles are materials dependent. For spherical polymer nanoparticles, glass transition temperature and crystallinity may affect deformation and change the elastic modulus when compared to the bulk material. However, size-dependent behavior of elastic moduli could not be generalized across polymers. As for crystalline metal nanoparticles, dislocations were found to influence the mechanical properties of nanoparticles, contradicting the conventional view that dislocations are absent in crystalline nanoparticles.


title: Nanoparticle

text: A material may have lower melting point in nanoparticle form than in the bulk form. For example, 2.5 nm gold nanoparticles melt at about 300 °C, whereas bulk gold melts at 1064 °C.


title: Nanoparticle

text: Quantum mechanics effects become noticeable for nanoscale objects. They include quantum confinement in semiconductor particles, localized surface plasmons in some metal particles, and superparamagnetism in magnetic materials. Quantum dots are nanoparticles of semiconducting material that are small enough (typically sub 10 nm or less) to have quantized electronic energy levels.


title: Nanoparticle

text: Quantum effects are responsible for the deep-red to black color of gold or silicon nanopowders and nanoparticle suspensions. Absorption of solar radiation is much higher in materials composed of nanoparticles than in thin films of continuous sheets of material. In both solar PV and solar thermal applications, by controlling the size, shape, and material of the particles, it is possible to control solar absorption.


title: Nanoparticle

text: Core-shell nanoparticles can support simultaneously both electric and magnetic resonances, demonstrating entirely new properties when compared with bare metallic nanoparticles if the resonances are properly engineered. The formation of the core-shell structure from two different metals enables an energy exchange between the core and the shell, typically found in upconverting nanoparticles and downconverting nanoparticles, and causes a shift in the emission wavelength spectrum.


title: Nanoparticle

text: By introducing a dielectric layer, plasmonic core (metal)-shell (dielectric) nanoparticles enhance light absorption by increasing scattering. Recently, the metal core-dielectric shell nanoparticle has demonstrated a zero backward scattering with enhanced forward scattering on a silicon substrate when surface plasmon is located in front of a solar cell.


title: Nanoparticle

text: Nanoparticles of sufficiently uniform size may spontaneously settle into regular arrangements, forming a colloidal crystal. These arrangements may exhibit original physical properties, such as observed in photonic crystals.


title: Nanoparticle

text: Artificial nanoparticles can be created from any solid or liquid material, including metals, dielectrics, and semiconductors. They may be internally homogeneous or heterogenous, e.g. with a Core–shell structure.


title: Nanoparticle

text: There are several methods for creating nanoparticles, including gas condensation, attrition, chemical precipitation, ion implantation, pyrolysis and hydrothermal synthesis and biosynthesis.


title: Nanoparticle

text: Friable macro- or micro-scale solid particles can be ground in a ball mill, a planetary ball mill, or other size-reducing mechanism until enough of them are in the nanoscale size range. The resulting powder can be air classified to extract the nanoparticles.


title: Nanoparticle

text: Biopolymers like cellulose, lignin, chitin, or starch may be broken down into their individual nanoscale building blocks, obtaining anisotropic fiber- or needle-like nanoparticles. The biopolymers are disintegrated mechanically in combination with chemical oxidation or enzymatic treatment to promote breakup, or hydrolysed using acid.


title: Nanoparticle

text: Another method to create nanoparticles is to turn a suitable precursor substance, such as a gas (e.g. methane) or aerosol, into solid particles by combustion or pyrolysis. This is a generalization of the burning of hydrocarbons or other organic vapors to generate soot.


title: Nanoparticle

text: Traditional pyrolysis often results in aggregates and agglomerates rather than single primary particles. This inconvenience can be avoided by ultrasonic nozzle spray pyrolysis, in which the precursor liquid is forced through an orifice at high pressure.


title: Nanoparticle

text: Nanoparticles of refractory materials, such as silica and other oxides, carbides, and nitrides, can be created by vaporizing the solid with a thermal plasma, which can reach temperatures of 10,000 kelvin, and then condensing the vapor by expansion or quenching in a suitable gas or liquid. The plasma can be produced by dc jet, electric arc, or radio frequency (RF) induction. Metal wires can be vaporized by the exploding wire method.


title: Nanoparticle

text: In RF induction plasma torches, energy coupling to the plasma is accomplished through the electromagnetic field generated by the induction coil. The plasma gas does not come in contact with electrodes, thus eliminating possible sources of contamination and allowing the operation of such plasma torches with a wide range of gases including inert, reducing, oxidizing, and other corrosive atmospheres. The working frequency is typically between 200 kHz and 40 MHz. Laboratory units run at power levels in the order of 30–50 kW, whereas the large-scale industrial units have been tested at power levels up to 1 MW. As the residence time of the injected feed droplets in the plasma is very short, it is important that the droplet sizes are small enough in order to obtain complete evaporation.


title: Nanoparticle

text: Inert-gas condensation is frequently used to produce metallic nanoparticles. The metal is evaporated in a vacuum chamber containing a reduced atmosphere of an inert gas. Condensation of the supersaturated metal vapor results in creation of nanometer-size particles, which can be entrained in the inert gas stream and deposited on a substrate or studied in situ. Early studies were based on thermal evaporation. Using magnetron sputtering to create the metal vapor allows to achieve higher yields. The method can easily be generalized to alloy nanoparticles by choosing appropriate metallic targets. The use of sequential growth schemes, where the particles travel through a second metallic vapor, results in growth of core-shell (CS) structures.


title: Nanoparticle

text: Nanoparticles can also be formed using radiation chemistry. Radiolysis from gamma rays can create strongly active free radicals in solution. This relatively simple technique uses a minimum number of chemicals. These including water, a soluble metallic salt, a radical scavenger (often a secondary alcohol), and a surfactant (organic capping agent). High gamma doses on the order of 10 Gray are required. In this process, reducing radicals will drop metallic ions down to the zero-valence state. A scavenger chemical will preferentially interact with oxidizing radicals to prevent the re-oxidation of the metal. Once in the zero-valence state, metal atoms begin to coalesce into particles. A chemical surfactant surrounds the particle during formation and regulates its growth. In sufficient concentrations, the surfactant molecules stay attached to the particle. This prevents it from dissociating or forming clusters with other particles. Formation of nanoparticles using the radiolysis method allows for tailoring of particle size and shape by adjusting precursor concentrations and gamma dose.


title: Nanoparticle

text: Nanoparticles of certain materials can be created by "wet" chemical processes, in which solutions of suitable compounds are mixed or otherwise treated to form an insoluble precipitate of the desired material. The size of the particles of the latter is adjusted by choosing the concentration of the reagents and the temperature of the solutions, and through the addition of suitable inert agents that affect the viscosity and diffusion rate of the liquid. With different parameters, the same general process may yield other nanoscale structures of the same material, such as aerogels and other porous networks.


title: Nanoparticle

text: The nanoparticles formed by this method are then separated from the solvent and soluble byproducts of the reaction by a combination of evaporation, sedimentation, centrifugation, washing, and filtration.


title: Nanoparticle

text: Alternatively, if the particles are meant to be deposited on the surface of some solid substrate, the starting solutions can be by coated on that surface by dipping or spin-coating, and the reaction can be carried out in place.


title: Nanoparticle

text: The suspension of nanoparticles that result from this process is an example of colloid. Typical instances of this method are the production of metal oxide or hydroxide nanoparticles by hydrolysis of metal alkoxides and chlorides.


title: Nanoparticle

text: Besides being cheap and convenient, the wet chemical approach allows fine control of the particle's chemical composition. Even small quantities of dopants, such as organic dyes and rare earth metals, can be introduced in the reagent solutions end up uniformly dispersed in the final product.


title: Nanoparticle

text: Ion implantation may be used to treat the surfaces of dielectric materials such as sapphire and silica to make composites with near-surface dispersions of metal or oxide nanoparticles.


title: Nanoparticle

text: Many properties of nanoparticles, notably stability, solubility, and chemical or biological activity, can be radically altered by coating them with various substances — a process called functionalization. Functionalized nanomaterial-based catalysts can be used for catalysis of many known organic reactions.


title: Nanoparticle

text: For example, suspensions of graphene particles can be stabilized by functionalization with gallic acid groups.


title: Nanoparticle

text: For biological applications, the surface coating should be polar to give high aqueous solubility and prevent nanoparticle aggregation. In serum or on the cell surface, highly charged coatings promote non-specific binding, whereas polyethylene glycol linked to terminal hydroxyl or methoxy groups repel non-specific interactions.


title: Nanoparticle

text: Nanoparticles can be linked to biological molecules that can act as address tags, directing them to specific sites within the body specific organelles within the cell, or causing them to follow specifically the movement of individual protein or RNA molecules in living cells. Common address tags are monoclonal antibodies, aptamers, streptavidin or peptides. These targeting agents should ideally be covalently linked to the nanoparticle and should be present in a controlled number per nanoparticle. Multivalent nanoparticles, bearing multiple targeting groups, can cluster receptors, which can activate cellular signaling pathways, and give stronger anchoring. Monovalent nanoparticles, bearing a single binding site, avoid clustering and so are preferable for tracking the behavior of individual proteins.


title: Nanoparticle

text: It has been shown that catalytic activity and sintering rates of a functionalized nanoparticle catalyst is correlated to nanoparticles' number density


title: Nanoparticle

text: The chemical processing and synthesis of high-performance technological components for the private, industrial, and military sectors requires the use of high-purity ceramics (oxide ceramics, such as aluminium oxide or copper(II) oxide), polymers, glass-ceramics, and composite materials, as metal carbides (SiC), nitrides (Aluminum nitrides, Silicon nitride), metals (Al, Cu), non-metals (graphite, carbon nanotubes) and layered (Al + Aluminium carbonate, Cu + C). In condensed bodies formed from fine powders, the irregular particle sizes and shapes in a typical powder often lead to non-uniform packing morphologies that result in packing density variations in the powder compact.


title: Nanoparticle

text: Uncontrolled agglomeration of powders due to attractive van der Waals forces can also give rise to microstructural heterogeneity. Differential stresses that develop as a result of non-uniform drying shrinkage are directly related to the rate at which the solvent can be removed, and thus highly dependent upon the distribution of porosity. Such stresses have been associated with a plastic-to-brittle transition in consolidated bodies, and can yield to crack propagation in the unfired body if not relieved.


title: Nanoparticle

text: In addition, any fluctuations in packing density in the compact as it is prepared for the kiln are often amplified during the sintering process, yielding inhomogeneous densification. Some pores and other structural defects associated with density variations have been shown to play a detrimental role in the sintering process by growing and thus limiting end-point densities. Differential stresses arising from inhomogeneous densification have also been shown to result in the propagation of internal cracks, thus becoming the strength-controlling flaws.


title: Nanoparticle

text: Inert gas evaporation and inert gas deposition are free many of these defects due to the distillation (cf. purification) nature of the process and having enough time to form single crystal particles, however even their non-aggreated deposits have lognormal size distribution, which is typical with nanoparticles. The reason why modern gas evaporation techniques can produce a relatively narrow size distribution is that aggregation can be avoided. However, even in this case, random residence times in the growth zone, due to the combination of drift and diffusion, result in a size distribution appearing lognormal.


title: Nanoparticle

text: It would, therefore, appear desirable to process a material in such a way that it is physically uniform with regard to the distribution of components and porosity, rather than using particle size distributions that will maximize the green density. The containment of a uniformly dispersed assembly of strongly interacting particles in suspension requires total control over interparticle forces. Monodisperse nanoparticles and colloids provide this potential.


title: Nanoparticle

text: Nanoparticles have different analytical requirements than conventional chemicals, for which chemical composition and concentration are sufficient metrics. Nanoparticles have other physical properties that must be measured for a complete description, such as size, shape, surface properties, crystallinity, and dispersion state. Additionally, sampling and laboratory procedures can perturb their dispersion state or bias the distribution of other properties. In environmental contexts, an additional challenge is that many methods cannot detect low concentrations of nanoparticles that may still have an adverse effect. For some applications, nanoparticles may be characterized in complex matrices such as water, soil, food, polymers, inks, complex mixtures of organic liquids such as in cosmetics, or blood.


title: Nanoparticle

text: There are several overall categories of methods used to characterize nanoparticles. Microscopy methods generate images of individual nanoparticles to characterize their shape, size, and location. Electron microscopy and scanning probe microscopy are the dominant methods. Because nanoparticles have a size below the diffraction limit of visible light, conventional optical microscopy is not useful. Electron microscopes can be coupled to spectroscopic methods that can perform elemental analysis. Microscopy methods are destructive and can be prone to undesirable artifacts from sample preparation, or from probe tip geometry in the case of scanning probe microscopy. Additionally, microscopy is based on single-particle measurements, meaning that large numbers of individual particles must be characterized to estimate their bulk properties.


title: Nanoparticle

text: Spectroscopy, which measures the particles' interaction with electromagnetic radiation as a function of wavelength, is useful for some classes of nanoparticles to characterize concentration, size, and shape. X-ray, ultraviolet–visible, infrared, and nuclear magnetic resonance spectroscopy can be used with nanoparticles."Structural, functional and magnetic ordering modifications in graphene oxide and graphite by 100 MeV gold ion irradiation". Vacuum. 182: 109700. 2020-12-01. doi:10.1016/j.vacuum.2020.109700</ref> Light scattering methods using laser light, X-rays, or neutron scattering are used to determine particle size, with each method suitable for different size ranges and particle compositions. Some miscellaneous methods are electrophoresis for surface charge, the Brunauer–Emmett–Teller method for surface area, and X-ray diffraction for crystal structure, as well as mass spectrometry for particle mass, and particle counters for particle number. Chromatography, centrifugation, and filtration techniques can be used to separate nanoparticles by size or other physical properties before or during characterization.


title: Nanoparticle

text: Nanoparticles present possible dangers, both medically and environmentally. Most of these are due to the high surface to volume ratio, which can make the particles very reactive or catalytic. They are also thought to aggregate on phospholipid bilayers and pass through cell membranes in organisms, and their interactions with biological systems are relatively unknown. However, it is unlikely the particles would enter the cell nucleus, Golgi complex, endoplasmic reticulum or other internal cellular components due to the particle size and intercellular agglomeration. A recent study looking at the effects of ZnO nanoparticles on human immune cells has found varying levels of susceptibility to cytotoxicity. There are concerns that pharmaceutical companies, seeking regulatory approval for nano-reformulations of existing medicines, are relying on safety data produced during clinical studies of the earlier, pre-reformulation version of the medicine. This could result in regulatory bodies, such as the FDA, missing new side effects that are specific to the nano-reformulation. However considerable research has demonstrated that zinc nanoparticles are not absorbed into the bloodstream in vivo.


title: Nanoparticle

text: Concern has also been raised over the health effects of respirable nanoparticles from certain combustion processes. Preclinical investigations have demonstrated that some inhaled or injected noble metal nano-architectures avoid persistence in organisms. As of 2013 the U.S. Environmental Protection Agency was investigating the safety of the following nanoparticles:


title: Nanoparticle

text: As of 2016, the U.S. Environmental Protection Agency had conditionally registered, for a period of four years, only two nanomaterial pesticides as ingredients. The EPA differentiates nanoscale ingredients from non-nanoscale forms of the ingredient, but there is little scientific data about potential variation in toxicity. Testing protocols still need to be developed.


title: Nanoparticle

text: As the most prevalent morphology of nanomaterials used in consumer products, nanoparticles have an enormous range of potential and actual applications. Table below summarizes the most common nanoparticles used in various product types available on the global markets.


title: Nanoparticle

text: Scientific research on nanoparticles is intense as they have many potential applications in pre-clinical and clinical medicine, physics, optics, and electronics. The U.S. National Nanotechnology Initiative offers government funding focused on nanoparticle research.|The use of nanoparticles in laser dye-doped poly(methyl methacrylate) (PMMA) laser gain media was demonstrated in 2003 and it has been shown to improve conversion efficiencies and to decrease laser beam divergence. Researchers attribute the reduction in beam divergence to improved dn/dT characteristics of the organic-inorganic dye-doped nanocomposite. The optimum composition reported by these researchers is 30% w/w of SiO (~ 12 nm) in dye-doped PMMA. Nanoparticles are being investigated as potential drug delivery system. Drugs, growth factors or other biomolecules can be conjugated to nano particles to aid targeted delivery. This nanoparticle-assisted delivery allows for spatial and temporal controls of the loaded drugs to achieve the most desirable biological outcome. Nanoparticles are also studied for possible applications as dietary supplements for delivery of biologically active substances, for example mineral elements.


title: Nanoparticle

text: Clay nanoparticles, when incorporated into polymer matrices, increase reinforcement, leading to stronger plastics, verifiable by a higher glass transition temperature and other mechanical property tests. These nanoparticles are hard, and impart their properties to the polymer (plastic). Nanoparticles have also been attached to textile fibers in order to create smart and functional clothing.


title: Nanoparticle

text: The inclusion of nanoparticles in a solid or liquid medium can substantially change its mechanical properties, such as elasticity, plasticity, viscosity, compressibility.


title: Nanoparticle

text: Being smaller than the wavelengths of visible light, nanoparticles can be dispersed in transparent media without affecting its transparency at those wavelengths. This property is exploited in many applications, such as photocatalysis.


title: Nanoparticle

text: Asphalt modification through nanoparticles can be considered as an interesting low-cost technique in asphalt pavement engineering providing novel perspectives in making asphalt materials more durable.


title: Nanoparticle

text: Nanoscale particles are used in biomedical applications as drug carriers or imaging contrast agents in microscopy. Anisotropic nanoparticles are a good candidate in biomolecular detection. Moreover, nanoparticles for nucleic acid delivery offer an unprecedented opportunity to overcome some drawbacks related to the delivery, owing to their tunability with diverse physico-chemical properties, they can readily be functionalized with any type of biomolecules/moieties for selective targeting.


title: Nanoparticle

text: Titanium dioxide nanoparticles imparts what is known as the self-cleaning effect, which lend useful water-repellant and antibacterial properties to paints and other products. Zinc oxide nanoparticles have been found to have superior UV blocking properties and are widely used in the preparation of sunscreen lotions, being completely photostable though toxic.


title: Adrenal insufficiency

text: Adrenal insufficiency is a condition in which the adrenal glands do not produce adequate amounts of steroid hormones. The adrenal gland normally secretes glucocorticoids (primarily cortisol), mineralocorticoids (primarily aldosterone), and androgens. These hormones are important in regulating blood pressure, electrolytes, and metabolism as a whole. Deficiency of these hormones leads to symptoms ranging from abdominal pain, vomiting, muscle weakness and fatigue, low blood pressure, depression, mood and personality changes (in mild cases) to organ failure and shock (in severe cases). An adrenal crisis may occur if the body is subjected to stress, such as an accident, injury, surgery, or severe infection; this is a life-threatening medical condition resulting from severe deficiency of cortisol in the body. Death may quickly follow.


title: Adrenal insufficiency

text: Adrenal insufficiency can be caused by dysfunction of the adrenal gland itself, whether by destruction (e.g. Addison's disease), failure of development (e.g. adrenal dysgenesis), or enzyme deficiency (e.g. congenital adrenal hyperplasia). Adrenal insufficiency can also occur when the pituitary gland or the hypothalamus do not produce adequate amounts of the hormones that assist in regulating adrenal function. This is called secondary adrenal insufficiency (when caused by lack of production of adrenocorticotropic hormone (ACTH) in the pituitary gland) or tertiary adrenal insufficiency (when caused by lack of corticotropin-releasing hormone (CRH) in the hypothalamus).


title: Adrenal insufficiency

text: Signs and symptoms include: hypoglycemia, hyperpigmentation, dehydration, weight loss, and disorientation. Additional signs and symptoms include weakness, tiredness, dizziness, low blood pressure that falls further when standing (orthostatic hypotension), cardiovascular collapse, muscle aches, nausea, vomiting, and diarrhea. These problems may develop gradually and insidiously. Addison's disease can present with tanning of the skin that may be patchy or even all over the body. Characteristic sites of tanning are skin creases (e.g. of the hands) and the inside of the cheek (buccal mucosa). Goitre and vitiligo may also be present. Eosinophilia may also occur. Hyponatremia is a sign of secondary insufficiency.


title: Adrenal insufficiency

text: When functioning normally, the adrenal glands secrete glucocorticoids (primarily, cortisol) in the "zona fasciculata" and mineralocorticoids (primarily, aldosterone) in the "zona glomerulosa" to regulate metabolism, blood pressure, and electrolyte balance. Adrenal hormone production is controlled by the hypothalamic-pituitary-adrenal axis, in which the hypothalamus produces corticotropin-releasing hormone (CRH), which stimulates the pituitary gland to produce adrenocorticotropic hormone (ACTH), which stimulates the adrenal gland to produce cortisol. High levels of cortisol inhibit the production of both CRH and ACTH, forming a negative feedback loop. The types of adrenal insufficiency thus refer to the level of the axis in which the dysfunction originates: primary, secondary, and tertiary for adrenal glands, pituitary gland, and hypothalamus, respectively.


title: Adrenal insufficiency

text: In adrenal insufficiency, there is a deficiency in cortisol production which may be accompanied by a deficiency in aldosterone production (predominantly in primary adrenal insufficiency). Depending on the cause and type of adrenal insufficiency, the mechanism of the disease differs. Generally, the symptoms manifest through the systemic effects of cortisol and aldosterone. In secondary and tertiary adrenal insufficiency, there is no effect on the production of aldosterone within the "zona glomerulosa" as this process is regulated by the renin–angiotensin–aldosterone system (RAAS), not ACTH.


title: Adrenal insufficiency

text: Adrenal insufficiency can also affect the "zona reticularis" and disrupt production of androgens, which are precursors to testosterone and estrogen. This leads to a deficiency of sex hormones and can contribute to symptoms of depression and menstrual irregularities.


title: Adrenal insufficiency

text: Cortisol increases blood sugar by inducing gluconeogenesis (glucose production) in the liver, lipolysis (fat breakdown) in adipose tissue, and proteolysis (muscle breakdown) in muscle while increasing glucagon secretion and decreasing insulin secretion in the pancreas. Overall, these actions cause the body to use fat stores and muscle for energy. Deficiency results in hypoglycemia, with associated nausea, vomiting, fatigue, and weakness.


title: Adrenal insufficiency

text: Cortisol potentiates the effectiveness of angiotensin II and catecholamines such as norepinephrine in vasoconstriction. Thus, a deficiency can contribute to hypotension, though this effect is most pronounced in mineralocorticoid deficiency.


title: Adrenal insufficiency

text: In primary adrenal insufficiency, the lack of negative feedback from cortisol leads to increased production of CRH and ACTH. ACTH is derived from pro-opiomelanocortin (POMC), which is cleaved into ACTH as well as α-MSH, which regulates production of melanin in the skin. The overproduction of α-MSH leads to the characteristic hyperpigmentation of Addison's disease.


title: Adrenal insufficiency

text: Although the production of aldosterone occurs within the adrenal cortex, it is not induced by adrenocorticotropic (ACTH); instead, it is regulated by the renin–angiotensin-aldosterone system (RAAS). Renin production in the juxtaglomerular cells of the kidney is induced by decreased arterial blood pressure, decreased sodium content in the distal convoluted tubule, and increased sympathetic tone. Renin initiates the downstream sequence of cleavage of angiotensinogen to angiotensin I to angiotensin II, in which angiotensin II stimulates aldosterone production in the "zona glomerulosa". Thus, dysfunction of the pituitary gland or the hypothalamus does not affect the production of aldosterone. However, in primary adrenal insufficiency, damage to the adrenal cortex (e.g. autoimmune adrenalitis a.k.a. Addison's disease) can lead to destruction of the "zona glomerulosa" and therefore a loss of aldosterone production.


title: Adrenal insufficiency

text: Aldosterone acts on mineralocorticoid receptors on epithelial cells lining the distal convoluted tubule, activating epithelial sodium channels (ENaC) and the Na⁺/K⁺-ATPase pump. This results in the absorption of sodium (with resulting retention of fluid) and the excretion of potassium. Deficiency of aldosterone leads to urinary loss of sodium and effective circulating volume, as well as retention of potassium. This can cause hypotension (in severe cases, shock), dizziness (from orthostatic hypotension), dehydration, and salt craving.


title: Adrenal insufficiency

text: Differently from mineralocorticoid deficiency, glucocorticoid deficiency does not cause a negative sodium balance (in fact a positive sodium balance may occur).


title: Adrenal insufficiency

text: Causes of acute adrenal insufficiency are mainly sudden withdrawal of long-term corticosteroid therapy, Waterhouse–Friderichsen syndrome, and stress in people with underlying chronic adrenal insufficiency. The latter is termed critical illness–related corticosteroid insufficiency.


title: Adrenal insufficiency

text: For chronic adrenal insufficiency, the major contributors are autoimmune adrenalitis (Addison's Disease), tuberculosis, AIDS, and metastatic disease. Minor causes of chronic adrenal insufficiency are systemic amyloidosis, fungal infections, hemochromatosis, and sarcoidosis.


title: Adrenal insufficiency

text: Causes of adrenal insufficiency can be categorized by the mechanism through which they cause the adrenal glands to produce insufficient cortisol. These are adrenal destruction (disease processes leading to glandular damage), impaired steroidogenesis (the gland is present but is biochemically unable to produce cortisol), or adrenal dysgenesis (the gland has not formed adequately during development).


title: Adrenal insufficiency

text: Autoimmune adrenalitis (Addison's disease) is the most common cause of primary adrenal insufficiency in the industrialised world, causing 80-90% of cases since 1950. Autoimmune destruction of the adrenal cortex is caused by an immune reaction against the enzyme 21-hydroxylase (a phenomenon first described in 1992). This may be isolated or in the context of autoimmune polyendocrine syndrome (APS type 1 or 2), in which other hormone-producing organs, such as the thyroid and pancreas, may also be affected.


title: Adrenal insufficiency

text: Autoimmune adrenalitis may be part of Type 2 autoimmune polyglandular syndrome, which can include type 1 diabetes, hyperthyroidism, and autoimmune thyroid disease (also known as autoimmune thyroiditis, Hashimoto's thyroiditis, and Hashimoto's disease). Hypogonadism may also present with this syndrome. Other diseases that are more common in people with autoimmune adrenalitis include premature ovarian failure, celiac disease, and autoimmune gastritis with pernicious anemia.


title: Adrenal insufficiency

text: Adrenal destruction is a feature of adrenoleukodystrophy (ALD). Destruction also occurs when the adrenal glands are involved in metastasis (seeding of cancer cells from elsewhere in the body, especially lung), hemorrhage (e.g. in Waterhouse–Friderichsen syndrome or antiphospholipid syndrome), particular infections which can spread to the adrenal cortex (tuberculosis, histoplasmosis, coccidioidomycosis), or the deposition of abnormal protein in amyloidosis.


title: Adrenal insufficiency

text: To form cortisol, the adrenal gland requires cholesterol, which is then converted biochemically into steroid hormones. Interruptions in the delivery of cholesterol include Smith–Lemli–Opitz syndrome and abetalipoproteinemia.


title: Adrenal insufficiency

text: Of the synthesis problems, congenital adrenal hyperplasia is the most common (in various forms: 21-hydroxylase, 17α-hydroxylase, 11β-hydroxylase and 3β-hydroxysteroid dehydrogenase), lipoid CAH due to deficiency of StAR and mitochondrial DNA mutations. Some medications interfere with steroid synthesis enzymes (e.g. ketoconazole), while others accelerate the normal breakdown of hormones by the liver (e.g. rifampicin, phenytoin).


title: Adrenal insufficiency

text: Adrenal insufficiency can also result when a patient has a brain mass in the pituitary gland (e.g. pituitary adenoma, craniopharyngioma) which can take up space and interfere with the secretion of pituitary hormones such as ACTH, therefore leading to decreased adrenal stimulation (secondary adrenal insufficiency). The same can occur with masses in the hypothalamus (tertiary adrenal insufficiency).


title: Adrenal insufficiency

text: Use of high-dose steroids for more than a week begins to produce suppression of the person's adrenal glands because the exogenous glucocorticoids suppress release of hypothalamic corticotropin-releasing hormone (CRH) and pituitary adrenocorticotropic hormone (ACTH). With prolonged suppression, the adrenal glands atrophy (physically shrink), and can take months to recover full function after discontinuation of the exogenous glucocorticoid. During this recovery time, the person is vulnerable to adrenal insufficiency during times of stress, such as illness, due to both adrenal atrophy and suppression of CRH and ACTH release. Use of steroids joint injections may also result in adrenal suppression after discontinuation.


title: Adrenal insufficiency

text: All causes in this category are genetic, and generally very rare. These include mutations to the "SF1" transcription factor, congenital adrenal hypoplasia due to "DAX-1" gene mutations and mutations to the ACTH receptor gene (or related genes, such as in the Triple A or Allgrove syndrome). "DAX-1" mutations may cluster in a syndrome with glycerol kinase deficiency with a number of other symptoms when "DAX-1" is deleted together with a number of other genes.


title: Adrenal insufficiency

text: The first step of diagnosing adrenal insufficiency is confirming inappropriately low cortisol secretion. This is followed by determining the origin of dysfunction (adrenal glands, pituitary gland, or hypothalamus) and therefore the type of adrenal insufficiency (primary, secondary, or tertiary). After narrowing down the source, further testing can elucidate the cause of insufficiency.


title: Adrenal insufficiency

text: If a patient is suspected to be experiencing an acute adrenal crisis, immediate treatment with IV corticosteroids is imperative and should not be delayed for any testing, as the patient's health can deteriorate rapidly and result in death without replacing the corticosteroids. Dexamethasone should be used as the corticosteroid of choice in these cases as it is the only corticosteroid that will not affect diagnostic test results.


title: Adrenal insufficiency

text: To confirm inappropriately low cortisol secretion, testing can include baseline morning cortisol level in the blood or morning cortisol level in the saliva. Cortisol levels typically peak in the morning; thus, low values indicate true adrenal insufficiency. Urinary free cortisol can also be measured, but are not necessary for diagnosis.


title: Adrenal insufficiency

text: To determine the origin of dysfunction, the ACTH stimulation test is the best initial test as it can differentiate between primary and secondary adrenal insufficiency. If cortisol levels remain low following ACTH stimulation, then the diagnosis is primary adrenal insufficiency. If cortisol levels increase following ACTH stimulation, then the diagnosis is either secondary or tertiary adrenal insufficiency. The corticotropin-releasing hormone test can then differentiate between secondary and tertiary adrenal insufficiency. Additional testing can include basal plasma ACTH, renin, and aldosterone concentrations, as well as a blood chemistry panel to check for electrolyte imbalances.


title: Adrenal insufficiency

text: Depending on the type of adrenal insufficiency, there are many possible causes and therefore many different avenues of testing (see Causes above). For primary adrenal insufficiency, the most common cause is autoimmune adrenalitis (Addison's disease); therefore, 21-hydroxylase autoantibodies should be checked. Structural abnormalities of the adrenal glands can be detected on CT imaging. For secondary and tertiary adrenal insufficiency, an MRI of the brain can be obtained to detect structural abnormalities such as masses, metastasis, hemorrhage, infarction, or infection.


title: Adrenal insufficiency

text: In general, the treatment of adrenal insufficiency requires replacement of deficient hormones, as well as treatment of any underlying cause. All types of adrenal insufficiency will require glucocorticoid repletion. Many cases (typically, primary adrenal insufficiency) will also require mineralocorticoid repletion. In rarer cases, repletion of androgens may also be indicated, typically in female patients with mood disturbances and changes in well-being.


title: Adrenal insufficiency

text: Primary adrenal insufficiency predisposes to higher risk of death, mostly due to infection, cardiovascular disease, and adrenal crisis. Delayed diagnosis can impair quality of life, and lack of treatment brings high mortality. However, with proper diagnosis, monitoring, and treatment, people with adrenal insufficiency can live normally.