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Opiate

Opiate is a term classically used in pharmacology to mean a drug derived from opium. Opioid, a more modern term, is used to designate all substances, both natural and synthetic, that bind to opioid receptors in the brain. Opiates are alkaloid compounds found in the opium poppy plant Papaver somniferum; the psychoactive compounds found in the opium plant include morphine and thebaine. Opiates have long been used for a variety of medical conditions with evidence of opiate trade and use for pain relief as early as the eighth century AD. Opiates are considered drugs with moderate to high abuse potential and are listed on various "Substance-Control Schedules" under the Uniform Controlled Substances Act of the United States of America. In 2014, between 13 and 20 million people used opiates recreationally. According to the CDC, from this population, there has been a recorded 47,000 deaths with a total of a half a million deaths from 2000-2014. In 2016, the World Health Organization reported that 27 million people suffer from opioid abuse disorder.

They reported that in 2015, 450,000 people died as a result of drug use, with between a third and a half of that number being attributed to opioids. Opiates belong to the large biosynthetic group of benzylisoquinoline alkaloids, are so named because they are occurring alkaloids found in the opium poppy; the major psychoactive opiates are morphine and thebaine. Papaverine, 24 other alkaloids are present in opium but have little to no effect on the human central nervous system. Alkaloids that have no effect on the central nervous system are not considered to be opiates. Small quantities of hydrocodone and hydromorphone are detected in assays of opium on rare occasions. Dihydrocodeine, oxycodone, oxymorphone and other derivatives of morphine and/or hydromorphone are found in trace amounts in opium. Despite morphine being the most medically significant opiate, larger quantities of codeine are consumed medically, most of it synthesized from morphine. Codeine has more predictable oral bioavailability, making it easier to titrate the dose.

Codeine has less abuse potential than morphine, because it is milder, larger doses of codeine are required. Opiate withdrawal syndrome effects are associated with the abrupt cessation or reduction of prolonged opiate usage; the manifestation of opiate dependence and abuse relies on a variety of factors, including the opiate's pharmacokinetic properties and the user's predisposition for addiction. While the full synthesis of opioids from naphthoquinone or other simple organic starting materials is possible, they are tedious and uneconomical processes. Therefore, most of the opiate-type analgesics in use today are either extracted from Papaver somniferum or synthesized from those opiates thebaine. In 2015 researches reported successful biosynthesis of thebaine and hydrocodone using genetically modified yeast. Once scaled for commercial use the process would cut production time from a year to several days and could reduce costs by 90%. Codeine is a prodrug, converted to morphine and acts on μ-opiate receptors.

It is converted to morphine by metabolism of CYP2D6 enzymes. Individuals who have lower CYP2D6 activity may not metabolize codeine efficiently enough to experience its analgesic effects. Conversely, individuals with higher CYP2D6 activity may metabolize the drug too and experience dose-related side effects such as sedation and respiratory depression. With the report of codeine-related deaths in children, codeine should no longer be prescribed due to its adverse effects and poor efficacy. Fentanyl is a synthetic opioid structurally similar arylpiperidines, it is a strong μ-receptor agonist, 80–100 times more potent to morphine, has a fast onset with a shorter duration of action than morphine. It is metabolized in the liver by CYP3A4 enzymes to an inactive drug. Heroin, the brand name for diacetylmorphine, is the first of several semi-synthetic opioids to be derived from morphine, a component of natural opium. Although it is derived from, rather than directly found in, natural opium, it is referred to as an opiate.

Heroin is a morphine prodrug. One of the major metabolites of heroin, 6-monoacetylmorphine, is a morphine prodrug. Hydromorphone is used as alternative to morphine, it has a high first-pass metabolism, is glucuronidated in the liver to hydromorphone-3-glucoronide. 75% of hydromorphone is renally excreted, with 7% excreted as the parent opiate. Meperidine is a synthetic opiate part of the arylpiperidine class, it is a strong μ-receptor agonist with 1/10th the potency of morphine. It is used to treat rigors, has a half-life of three to four hours, it is hepatically metabolized to the active metabolites of normeperidine, normepiridinic acid, medperidinic acid. Normeperidine at toxic levels can cause CNS seizures. Methadone has half life compared to morphine, it is metabolized to an inactive product by N-demethylation by CYP3A4 enzymes in the liver. It has high person to person variability because of varying levels of CYP3A4 in individuals, it is approved for treatment of moderate to severe pain as well as opioid dependence.

Because of its high risk of drug interactions, liver toxicity, patient variability, patients have to be monitored at methadone clinics. Nicomorphine (m

Björn Engels

Björn Lionel G. Engels is a Belgian professional footballer who plays as a centre back for Premier League club Aston Villa. Born in Kaprijke, Engels first played for FC Kaprijke-Bentille, FC Lembeke and Lokeren as a youth. In 2006, at the age of 12, he joined Club Brugge. After progressing through the ranks of the academy, Engels appeared as an unused substitute, in a match against Gent on 29 October 2011, which saw Club Brugge win 5–4. On 20 September 2012, he made his professional debut in the UEFA Europa League against Girondins de Bordeaux coming on at half-time for Thibaut Van Acker. Only one minute he scored an own goal. After the match, Engels described his Club Brugge debut as "very painful". Having finished the 2012–13 season with one appearance, Engels signed his first professional contract with Club Brugge, agreeing a three–year deal. Engels made his league debut on 4 August 2013 in the second game of the 2013–14 season against Oostende, he scored the opening goal in the third minute.

Club Brugge won the game with 2–1. After scoring his second against Kortrijk on 20 October 2013, Engels’ performance at the club earned him a contract extension in November 2013, which would keep him until 2017. In the 2013–14 season, Engels went on to score three more goals against Genk, Zulte Waregem and Lokeren. Despite being sidelined due to injury and suspension, he continued to be a first team regular and finished the 2013–14 season with 35 appearances and 5 goals in all competitions. For his performances he was nominated for the Young Professional Footballer of the Year, but lost out to Youri Tielemans. After missing out the opening game of the 2014–15 season, due to an injury, Engels managed to regain his first team position making his first appearance of the season against Brøndby, he scored against Anderlecht on 31 August 2014 and a brace against Oostende on 28 September 2014. In the next match against Standard Liège on 5 October 2014, which Club Brugge won 3–0, Engels suffered both a knee and an ankle injury despite playing the whole game.

Out between three and six weeks, Engels’ recovery was delayed throughout 2014. While recovering from both injuries, Engels signed a contract extension until 2019 in January 2015. In March, a scan revealed Engels’ recovery would be delayed again and he would be out for the rest of the season. Engels finished the 2014–15 season making twelve appearances and scoring three times in all competitions while winning the Belgian Cup. Ahead of the 2015–16 season, Engels appeared to have recovered from his injuries when he returned to training in the pre–season. However, at the start of the 2015–16 season, Engels’ hopes of returning suffered a setback when he was out for several months, delaying his return again following a scan, he returned to training from injury around October. On 10 December 2015, he made his first appearance in a year, coming on as a late substitute in a 1–1 draw against Midtjylland on matchday 6 of the UEFA Europa League Group stage. Engels made his first league appearance in a year against Anderlecht on 20 December 2015, where he set up a goal for the club in a 4–1 loss.

On 16 January 2016, Engels scored his first goal of the season, in a 3–0 win over Mouscron, followed up by scoring his second in the next game on 24 January 2016, in a 2–1 win over Waasland-Beveren. Despite suffering two separate injuries towards the end of the 2015–16 season, Engels helped the club win the league in the 2015–16 season, earning him the winner's medal, made 21 appearances and scoring twice in all competitions. Ahead of the 2016–17 season, Engels was linked a move away from Club Brugge, prompting a response from Filip Joos, who stated that Engels would be worth €60 million. Engels remained at the club and signed a contract extension with the club, keeping him until 2020. After being left out of the squad for the first three matches at the start of the season, including Belgium Super Cup, he scored his first goal of the season on 28 August 2016, in a 2–2 draw against Standard Liège. On 14 September 2016, he made his Champions League debut against Leicester City, earning a booking in the 35th minutes, in a 3–0 loss.

During the match, Engels was substituted in the 53rd minute. After the match, it was announced. On 18 December 2016, he made his return from injury, making his first start in months, in a 5–1 win over Kortrijk. After returning to the first team, Engels regained his place for the rest of the season despite suffering from an abductor injury and appearing on the substitute bench, he scored again on 24 February 2017, in a 5–0 win over Zulte Waregem. At the end of the 2016–17 season, Engels had scored twice in 23 appearances. In the 2017–18 season, Engels continued to remain in the first team, making five appearances by the end of August. In the summer transfer window of 2017, Engels was linked with a move to English sides Arsenal and Stoke City. Greek Superleague side Olympiacos agreed with the player's side on 29 August 2017, while Club Brugge agreed on the transfer with Olympiacos for an estimated €7.1 million fee on 30 August 2017. The following day, on 31 August 2017, Olympiacos announced the signing of Engels.

Upon joining Olympiacos, Engels said of the move, quoting: "this seems to me the perfect step in my career. Olympiakos is the most important team in Greece, I'm happy to be here." On 22 October 2017, Engels's goal earned the victory in the derby against rivals PAOK. Belgian centre-back struck six minutes after half-time, bundling the ball home after a Kostas Fortounis free-kick caused panic in the PAOK penalty box to win three vital points for the defending champions. On summer 2018, after being told he was not part of ne

Twelve Views of Bayu

Twelve Views of Bayu are popular scenic views in and around the city of Chongqing, China. Ba and Yu are old names of Chongqing in imperial time. Influenced by Eight Views of Xiaoxiang in Hunan Province, people in Chongqing listed their own most beloved views during the reign of Tianshun Emperor of Ming Dynasty. Scenic views in the list changed throughout the history; some scenic views appeared in earlier lists no longer exist in modern days due to the change of physical geography and land-uses. The first version of the list contains eight popular scenic views, the same number of views in the Xiaoxiang list. In the second year of Tianshun Emperor's reign, people carved the list on to the bronze bell in Chongyin Temple, a former buddhism temple located at current Chongqing No. 25 Middle School's campus. The eight views on the original list are: Jin Bi Xiang Feng: Jinbi Mountain is the highest peak of Mountain Ba, it is part of the Renmin Park in Yuzhong District. Jinbi means golden and blue. During Song Dynasty, a governor of Chongqing built a hall with golden and blue tiles on top of the mountain.

In Ming Dynasty, another governor of Chongqing raised many species of flowers on the mountain and made the air there smells balmiest. Hong Yan Di Cui: Hongyan means waterful cliff, it is located near the riverside area of modern Yuzhong District and close to the Chongqing CBD. Today it is known for the clustered Diaojiaolou buildings. There is a cave on the cliff, spring water flows out of the cave and drops down the cliff. Long Men Hao Yue: Long Men means Gate of Chinese Dragon. There used to be two giant rock in the near-shore shallow water of Yangtze River, on which there were two big Chinese characters Long Men carved in Song Dynasty. In clear nights, the inverted image of the moon will appear in between those two rocks and makes there to be a beautiful scene, it is now a part of Nanbin Park in Nan'an District. Huang Ge Wan Du: Huang Ge Ferry was a major ferry crossing the Yangtze River and connecting the main town of Chongqing and the Nanping Town in previous times. Huang Ge is the local name of a type of tree distributed in Asia and Australia.

The Shibanpo Yangtze River Bridge replaced Huang Ge Ferry in 1980s, so that the ferry no longer exists. However, this scene is still manually preserved and become a part of Nanbin Park in 2005. Fo Tu Ye Yu: Fotu Pass was located to the west of today's Chongqing CBD area, close to Pipa Mountain Park and Eling Park, it was an important military fort to defend Chongqing from the west in ancient times. Yeyu Temple was a major temple in Fotu Pass. Yeyu means raining at night. Years ago, there was a rock in the front of Yeyu Temple, water permeated out of the rock every night and made the air moist, as if it were rainy; as a result, people called the temple Yeyu Temple. Kong Dian Qiu Xiang: In Ming Dynasty, there was a Confucian temple in today's Chongqing No.29 Middle School's campus. During autumn, guihua flowers would bring fragrance to the temple. Jue Lin Xiao Zhong: Juelin Temple, located in the forest of Lianhua Mountain in Nan'an District, was built during Song Dynasty; every morning, monks in the temple would ring the bell, the sound of bell made people be joyful.

In last years of Ming Dynasty, the temple and the bell were destroyed in wars and chaos. In Qing Dynasty, the temple was rebuilt and turned to be more glorious, it had its own Eight Views, but the Jue Lin Xiao Zhong was removed from lists. Bei Zhen Jin Sha: The northern town refers to the old Jiangbei Town. Jiangbei Town was located near the place. At the northern bank of where the two river merge, there is a sandy beach. Under the sun, sands on the beach shines like gold. Chongqing is a major city with diverse landscapes and culture; the original eight views were not able to present all popular scenic views in Chongqing. Therefore, the number of views in the list was expanded from eight to twelve; the traditional twelve views of Chongqing was proposed in 1760 by Wang Erjian, a county-level governor of Chongqing during the reign of Qianlong Emperor in Qing Dynasty. In the new list, three of former eight views were removed due to various reasons, several other views in and around Chongqing were added.

The twelve views in Wang's list are: Jin Bi Liu Xiang: The same view as Jin Bi Xiang Feng in the original list of eight views. See previous section. Huang Ge Wan Du: See previous section. Tong Jing Xia Yuan: Tongjing Valley is a series of river valleys in Yubei District, about 65 kilometers away from the downtown Chongqing. Yulin River and Wentang River form several deep valleys. Since Qing Dynasty, Tongjing Valley has been known for large numbers of monkeys living in that area, it is known for hot springs. Ge Le Ling Yin: Geleshan is a mountain range in today's Shapingba District. Cur