title: Lea Salonga

text: In her popular music releases, Salonga has sung "simple love songs," which are common in Original Pilipino Music.


title: Lea Salonga

text: Salonga's style and music has been inspired by musical artists such as ABBA, the Carpenters (particularly Karen Carpenter), Olivia Newton-John, the Osmonds, Elaine Paige, and Barbra Streisand. She has noted that these performers provided "clear voices that really helped the listener focus on the lyrics besides the tone and music."


title: Lea Salonga

text: Salonga has repeatedly praised Streisand as one of her favorites for her "mammoth" career in singing, acting, producing, and arranging. During her January 15, 2000 concert at the Philippine International Convention Center, Salonga called Streisand one of her idols.


title: Lea Salonga

text: Salonga has been praised for her absolute pitch and control over her powerful vocals, which can evoke a wide array of emotion and soundscapes. Her voice has been described as "golden" by Marilyn Stasio for "Variety" magazine and "clear and as sparkling as Baccarat crystal" by Rex Reed for "Observer".


title: Lea Salonga

text: Due to her vocal versatility, it is often debated on what her vocal range and type classifications are. When Salonga performed as Kim in "Miss Saigon", she was expected to utilize most of her range, hitting notes as low as E and as high as D. In both Disney Princess singing roles, Jasmine and Mulan, Salonga uses head tones that reach up to F. Salonga has been recorded singing notes ranging from D to C


title: Lea Salonga

text: On October 15, 2010, Salonga was appointed Goodwill Ambassador for the Food and Agriculture Organization (FAO) of the United Nations.


title: Lea Salonga

text: Salonga has been openly supportive of LGBT equality for many years. On October 12, 2009, during a benefit concert held at The Philippine Center's Kalayaan Hall for the victims of Typhoon Ondoy, Salonga referenced the National Equality March in Washington, D.C. and stated, "I believe that every single human being has the fundamental right to marry whoever they want." In 2011, "The Advocate" called her a "major gay icon." In February 2016, Salonga criticized Filipino politician and former professional boxer Manny Pacquiao via Twitter for his views on homosexuality and same-sex marriage.


title: Lea Salonga

text: On March 29, 2021, Salonga condemned the rise of violent attacks on Asian Americans during the COVID-19 pandemic. On April 21, 2021, she appeared with actress Lucy Liu, politician and First Lady Hillary Clinton, and others in the #AAPI Women Strong: Organizing Beyond A Hashtag forum to share their experiences and spread awareness on anti-Asian hate.


title: Lea Salonga

text: After performing in the 2000 Manila production of "They're Playing Our Song", Salonga began a relationship with Korean-American co-star Michael K. Lee. The relationship ended in mid-2001.


title: Lea Salonga

text: In November 2001, while performing in the Los Angeles production of "Flower Drum Song" at the Mark Taper Forum, Salonga met Robert "Rob" Charles Chien, an American entrepreneur of Chinese and Japanese heritage. On January 10, 2004, Salonga and Chien married at the Our Lady of the Angels Cathedral. During the wedding ceremony, Salonga performed the song "Two Words," composed by Louie Ocampo and Freddie Santos, given to her as an early wedding present. The wedding was aired as a two-hour television special, which was directed by Bobby Garcia and hosted by Boy Abunda, on ABS-CBN in late January 2004.


title: Lea Salonga

text: Salonga has notable relatives around the world, including Filipino musical conductor and arranger Gerard Salonga (brother), ballerina Maniya Barredo (first cousin), and Canadian actress and model Shay Mitchell (cousin).


title: Lea Salonga

text: One of the most prolific actresses since her career's inception in 1978, Salonga has appeared in numerous international theatre productions, television shows, films, and video games.


title: Lea Salonga

text: In Manila, Salonga has appeared in theatre productions such as "The King and I" (1978), "Cat on a Hot Tin Roof" (1978), "Fiddler on the Roof" (1978), "Annie" (1980), "The Sound of Music" (1980), "The Rose Tattoo" (1980), "The Bad Seed" (1981), "The Goodbye Girl" (1982), "The Paper Moon" (1983), "Annie" (1984), "The Fantasticks" (1988), "My Fair Lady" (1994), "Grease" (1995), "They're Playing Our Song" (2000), "Miss Saigon" (2000), "Proof" (2002), "Baby" (2004), "Cats" (2010), "God of Carnage" (2012), "Fun Home" (2016), and "" (2019). In London's West End, she has appeared in "Miss Saigon" (1989–1990, 1999) and "Les Misérables" (1996). On Broadway, she has appeared in "Miss Saigon" (1991–1992, 1993, 1999, 2001), "Les Misérables" (1993), "Flower Drum Song" (2002–2003), "Something Good: A Broadway Salute to Richard Rogers on His 100th Birthday" (2002), "Les Misérables" (2007), "Allegiance" (2015–2016), and "Once on This Island" (2017–2018, 2018–2019). Salonga has also appeared in "Into the Woods" (1994), "They're Playing Our Song" (1999), "God of Carnage" (2012), and "" (2019) in Singapore, "Les Misérables" (1996) in Honolulu during the third U.S. national tour, Rodgers and Hammerstein's "Cinderella" (2008), "Allegiance" (2012) in San Diego, "Annie" (2018) at the Hollywood Bowl in Los Angeles, and the and anniversary concerts of "Les Misérables" at the Royal Albert Hall and The O2 Arena, respectively.


title: Lea Salonga

text: Salonga made her film debut in 1981 in the Filipino comedy "Tropang Bulilit". She went on to appear in the films "Like Father, Like Son" (1985), "Ninja Kids" (1986), "Captain Barbell" (1986), "Pik Pak Boom" (1988), "Dear Diary" (1989), "The Heat Is On" (1989), "Aladdin" (1992), "Bakit Labis Kitang Mahal" (1992), "Sana Maulit Muli" (1995), "Mulan" (1998), "" (1998), "My Neighbor Totoro" (2004), "Mulan II" (2004), "" (2007), "" (2010), "Miss Saigon: 25th Anniversary" (2016), "Allegiance" (2016), "Expedition Reef" (2018), and "Yellow Rose" (2019).


title: Lea Salonga

text: In 1983, Salonga began hosting her own variety show entitled "Love, Lea", which ended its run in 1985. She went on to appear in "That's Entertainment" (1986), "Olsen Twins Mother's Day Special" (1993), "Sesame Street" (1993), "Reading Rainbow" (1993, 2001), "Redwood Curtain" (1995), "Aladdin on Ice" (1995), "ASAP" (1997–present), "ER" (2001), "As the World Turns" (2001, 2003), "Johnny Bravo" (2004), "Miss Universe 2011" (2011), "Sofia the First" (2012, 2014), "The Voice of the Philippines" (2013, 2014–15), "The Voice Kids" (2014–2019), "Crazy Ex-Girlfriend" (2016), "Nature Is Speaking" (2016), "91st Macy's Thanksgiving Day Parade" (2017), "The Voice Teens" (2017, 2020), "Centaurworld" (2021), "American Experience" (2022), "" (2022), and "Little Demon" (2022).


title: Lea Salonga

text: Salonga gained national recognition in the Philippines at a young age, winning Best Child Performer at the Aliw Awards in 1980, 1981, and 1982. For her success as a child singer and actress, she was known as the "Shirley Temple of the Philippines."


title: Lea Salonga

text: For her performance as the leading role of Kim in "Miss Saigon", Salonga won Outstanding Performance of the Year by an Actress in a Musical at the 1990 Laurence Olivier Awards. After her return to the Philippines, she won Outstanding Performer at the Aliw Awards. In the same year, she received a Presidential Medal of Merit from President Corazon Aquino for her services to the arts. For reprising her role as Kim in the Broadway production of "Miss Saigon", Salonga was awarded Outstanding Actress in a Musical at the 1991 Drama Desk Awards, Outstanding Actress in a Musical at the 1991 Outer Critics Circle Awards, Best Actress in a Musical at the 1991 Theatre World Awards, and Best Performance by an Actress in a Musical at the 45th Annual Tony Awards. She made history as the first Asian actress to win a Tony Award and the second-youngest actress to win for Best Performance by a Leading Actress in a Musical. She later became the first Asian actress to portray the role of Éponine when she joined the Broadway production in early 1993. In 1993, she also became the first Filipino artist to sign with an international record label when she signed with Atlantic Records.


title: Lea Salonga

text: In 2004, Salonga won Entertainer of the Year at the Aliw Awards. She later won the Aliw Award for Best Major Concert (Female) in 2008. In 2007, President Gloria Arroyo honored Salonga with the rank of Commander of the Order of Lakandula in recognition of using her talents to benefit Philippine society and foster cultural exchange. The House of Representatives of the Philippines also awarded her with the Congressional Medal of Achievement for showing "the extent and depth of the Filipino musical talent" and "opening the way for other Filipino artists to break into the finest theaters in the world."


title: Lea Salonga

text: In 2011, Salonga was declared a "Disney Legend" for her work with the Walt Disney Company, providing the singing voices for Princess Jasmine in "Aladdin" and Fa Mulan in "Mulan" and "Mulan II". In September 2022, Salonga was recognized by "TIME" magazine at the TIME100 Impact Awards for being a "life-long role model for children of color." Salonga has been cited as an influence for several singers and actors, especially those of Asian descent, including Ali Ewoldt, Kimiko Glenn, Rachelle Ann Go, Bella Poarch, Nicole Scherzinger, and Phillipa Soo.


title: Amrita Singh

text: Amrita Singh (born 9 February 1958) is an Indian actress. Through her films such as "Betaab" and "Mard", she gained popularity and became a well-known and popular actress in the 1980s. She took a break from acting in the early 1990s for a decade and returned to acting in 2002, occasionally playing supporting roles . She also made her debut on television in 2005. Amrita keeps a low public profile and gives seldom interviews, only on occasional basis.


title: Amrita Singh

text: Amrita Singh was born on 9 February 1958 to a Punjabi Muslim Awan mother, Rukhsana Sultana and a Punjabi Jat Sikh father, army officer Shivinder Singh Virk, from a noble family with roots tracing back to the 17th-century Sikh martyr Bhai Sangat Singh. Her mother was a political associate of Sanjay Gandhi during the Indian Emergency in the 1970s, who became known for leading Sanjay Gandhi's sterilisation campaign in Muslim areas of Old Delhi. Through her paternal grandmother Mohinder Kaur, Amrita is the great-granddaughter of Sobha Singh, one of the builders of New Delhi, the grandniece of the late novelist Khushwant Singh, and great-grandniece of politician Ujjal Singh. The actress Begum Para is her great-aunt and her husband was Nasir Khan, who is the brother of Dilip Kumar. Actor Ayub Khan is her uncle (second cousin once removed). Singh was a childhood friend of Shah Rukh Khan. Their mothers often worked together in the Old Delhi area and Singh attended the same school as Khan's sister, Shahnaz.


title: Amrita Singh

text: Singh made her Bollywood debut in 1983 with "Betaab", an highly successful romantic drama in which she was paired with Sunny Deol. This was quickly followed by a succession of hits, such as "Sunny" (1984), "Mard" (which was the biggest hit of 1985) and "Saaheb" (also 1985), "Chameli Ki Shaadi" and "Naam" (both 1986), "Khudgarz" (1987), and "Waaris" (1988). Singh made a successful pair in several films, not only with Sunny Deol, Sanjay Dutt, and Raj Babbar, but also with Jeetendra, Vinod Khanna, Anil Kapoor and Amitabh Bachchan, some of the leading actors of the 1980s. As well as playing leading roles, she also played supporting negative roles in films such as "Raju Ban Gaya Gentleman" (1992), "Suryavanshi" (1992) and "Aaina" (1993), winning the Filmfare Award for Best Supporting Actress for the lattermost. Her comic timings in films such as "Saaheb" and "Chameli Ki Shaadi" are still remembered. She decided to retire into family life and quit acting after her appearance in "Rang" (1993).


title: Amrita Singh

text: Singh returned to acting in 2002 with "", in which she played the mother of Bhagat Singh (played by Bobby Deol). She joined the television industry with Ekta Kapoor's family drama "Kavyanjali", which aired on Star Plus in 2005. In the show, Singh was seen in a negative role that soon gained immense popularity. Later that year, she won acclaim for her performance in yet another negative role for the film "Kalyug". In 2007, Singh played the role of gangster Maya Dolas' mother, Ratnaprabha Dolas, in the Sanjay Gupta film "Shootout at Lokhandwala", directed by Apoorva Lakhia - Vivek Oberoi played the role of Maya Dolas. Later on, she appeared in the anthology film "Dus Kahaniyaan," where she appeared in the short story "Poornmasi".


title: Amrita Singh

text: Continuing her acting journey, Singh was seen in "Kajraare" (2010), and also appeared in "Aurangzeb" (2012) under the Yash Raj Films banner, where she was paired with Jackie Shroff after almost two decades, after having paired together in "Aaina". In 2014, she was seen in "2 States", produced by Dharma Productions, portraying the role of co-actor Arjun Kapoor's mother. The film was released on 18 April 2014, and was a critical and commercial success, and also earned Singh a nomination for the Filmfare Award for Best Supporting Actress. In 2016, she appeared in "Flying Jat" playing Tiger Shroff's mother. In 2017, she appeared in the comedy-drama "Hindi Medium" as a school principal. In 2019, she appeared in Sujoy Ghosh's "Badla", her first time working with Amitabh Bachchan in 18 years. "Badla" met with highly positive reviews, and Singh's performance received high critical acclaim. The film proved to be a commercial success, and Singh's performance earned her a nomination for the Filmfare Award for Best Supporting Actress.


title: Amrita Singh

text: Singh married actor Saif Ali Khan in January 1991. Singh, who was raised as a Sikh, converted to Islam before marriage and the couple had an Islamic wedding. 12 years younger, Khan is the son of former Indian test cricket captain Mansoor Ali Khan Pataudi, the ninth Nawab of Pataudi and actress Sharmila Tagore and is a member of the royal family of the erstwhile Bhopal State and Pataudi State . Despite controversies, they remained married. She gave up acting after her marriage to Khan. After thirteen years of marriage, the couple divorced in 2004. Their daughter Sara Ali Khan Pataudi was born on 12 August 1995. and son Ibrahim Ali Khan Pataudi on 5 March 2001. Sara graduated from Columbia University and their son, Ibrahim Ali Khan is studying in England.


title: Neo-noir

text: Neo-noir is a revival of film noir, a genre that had originally flourished during the post-World War II era in the United Statesroughly from 1940 to 1960. The French term, "film noir", translates literally to English as "black film", indicating sinister stories often presented in a shadowy cinematographic style. Neo-noir has a similar style but with updated themes, content, style, and visual elements.


title: Neo-noir

text: The neologism neo-noir, using the Greek prefix for the word "new", is defined by Mark Conard as "any film coming after the classic noir period that contains noir themes and noir sensibility". Another definition describes it as later noir that often synthesizes diverse genres while foregrounding the scaffolding of "film noir".


title: Neo-noir

text: "Film noir" was coined by critic Nino Frank in 1946 and popularized by French critics and Etienne Chaumeton in 1955. The term revived in general use beginning in the 1980s, with a revival of the style.


title: Neo-noir

text: The classic "film noir" era is usually dated from the early 1940s to the late 1950s. The films were often adaptations of American crime novels, which were also described as "hardboiled". Some authors resisted these terms. For example, James M. Cain, author of "The Postman Always Rings Twice" (1934) and "Double Indemnity" (1944), is considered to be one of the defining authors of hard-boiled fiction. Both novels were adapted as crime films, the former more than once. Cain is quoted as saying, "I belong to no school, hard-boiled or otherwise, and I believe these so-called schools exist mainly in the imagination of critics, and have little correspondence in reality anywhere else."


title: Neo-noir

text: Neo-noir film directors refer to 'classic noir' in the use of Dutch angles, interplay of light and shadows, unbalanced framing; blurring of the lines between good and bad and right and wrong, and thematic motifs including revenge, paranoia, and alienation.


title: Neo-noir

text: Typically American crime dramas or psychological thrillers, films noirs had common themes and plot devices, and many distinctive visual elements. Characters were often conflicted antiheroes, trapped in a difficult situation and making choices out of desperation or nihilistic moral systems. Visual elements included low-key lighting, striking use of light and shadow, and unusual camera placement. Sound effects helped create the noir mood of paranoia and nostalgia.


title: Neo-noir

text: Few major films in the classic "film noir" genre have been made since the early 1960s. These films usually incorporated both thematic and visual elements reminiscent of "film noir". Both classic and neo-noir films are often produced as independent features.


title: Neo-noir

text: After 1970, film critics took note of "neo-noir" films as a separate genre. Noir and post-noir terminology (such as "hard-boiled", "neo-classic" and the like) are often rejected by both critics and practitioners.


title: Neo-noir

text: Robert Arnett stated, "Neo-noir has become so amorphous as a genre/movement, any film featuring a detective or crime qualifies." Screenwriter and director Larry Gross identifies Jean-Luc Godard's "Alphaville", alongside John Boorman’s "Point Blank" (1967) and Robert Altman’s "The Long Goodbye" (1973), based on Raymond Chandler's 1953 novel, as neo-noir films. Gross believes that they deviate from classic noir in having more of a sociological than a psychological focus. Neo noir features characters who commit violent crimes, but without the motivations and narrative patterns found in "film noir".


title: Neo-noir

text: Neo noir assumed global character and impact when filmmakers began drawing elements from films in the global market. For instance, Quentin Tarantino's works have been influenced by Ringo Lam's "City on Fire". This was particularly the case for the noir-inflected "Reservoir Dogs", which was instrumental in establishing Tarantino in October 1992.


title: Sickle cell disease

text: Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person's parents. The most common type is known as sickle cell anaemia. It results in an abnormality in the oxygen-carrying protein haemoglobin found in red blood cells. This leads to a rigid, sickle-like shape under certain circumstances. Problems in sickle cell disease typically begin around 5 to 6 months of age. A number of health problems may develop, such as attacks of pain (known as a sickle cell crisis), anemia, swelling in the hands and feet, bacterial infections and stroke. Long-term pain may develop as people get older. The average life expectancy in the developed world is 40 to 60 years.


title: Sickle cell disease

text: Sickle cell disease occurs when a person inherits two abnormal copies of the β-globin gene ("HBB") that makes haemoglobin, one from each parent. This gene occurs in chromosome 11. Several subtypes exist, depending on the exact mutation in each haemoglobin gene. An attack can be set off by temperature changes, stress, dehydration, and high altitude. A person with a single abnormal copy does not usually have symptoms and is said to have sickle cell trait. Such people are also referred to as carriers. Diagnosis is by a blood test, and some countries test all babies at birth for the disease. Diagnosis is also possible during pregnancy.


title: Sickle cell disease

text: The care of people with sickle cell disease may include infection prevention with vaccination and antibiotics, high fluid intake, folic acid supplementation, and pain medication. Other measures may include blood transfusion and the medication hydroxycarbamide (hydroxyurea). A small percentage of people can be cured by a transplant of bone marrow cells.


title: Sickle cell disease

text: , about 4.4 million people have sickle cell disease, while an additional 43 million have sickle cell trait. About 80% of sickle cell disease cases are believed to occur in Sub-Saharan Africa. It also occurs to a lesser degree in parts of India, Southern Europe, West Asia, North Africa and among people of African origin (sub-Saharan) living in other parts of the world. In 2015, it resulted in about 114,800 deaths. The condition was first described in the medical literature by American physician James B. Herrick in 1910. In 1949, its genetic transmission was determined by E. A. Beet and J. V. Neel. In 1954, the protective effect against malaria of sickle cell trait was described.


title: Sickle cell disease

text: Signs of sickle cell disease usually begin in early childhood. The severity of symptoms can vary from person to person. Sickle cell disease may lead to various acute and chronic complications, several of which have a high mortality rate.


title: Sickle cell disease

text: The terms "sickle cell crisis" or "sickling crisis" may be used to describe several independent acute conditions occurring in patients with SCD, which results in anaemia and crises that could be of many types, including the vaso-occlusive crisis, aplastic crisis, splenic sequestration crisis, haemolytic crisis, and others. Most episodes of sickle cell crises last between five and seven days. "Although infection, dehydration, and acidosis (all of which favor sickling) can act as triggers, in most instances, no predisposing cause is identified."


title: Sickle cell disease

text: The vaso-occlusive crisis is caused by sickle-shaped red blood cells that obstruct capillaries and restrict blood flow to an organ, resulting in ischaemia, pain, necrosis, and often organ damage. The frequency, severity, and duration of these crises vary considerably. Painful crises are treated with hydration, analgesics, and blood transfusion; pain management requires opioid drug administration at regular intervals until the crisis has settled. For milder crises, a subgroup of patients manages on nonsteroidal anti-inflammatory drugs such as diclofenac or naproxen. For more severe crises, most patients require inpatient management for intravenous opioids; patient-controlled analgesia devices are commonly used in this setting. Vaso-occlusive crisis involving organs such as the penis or lungs are considered an emergency and treated with red blood cell transfusions. Incentive spirometry, a technique to encourage deep breathing to minimise the development of atelectasis, is recommended.


title: Sickle cell disease

text: The spleen is frequently affected in sickle cell disease, as the sickle-shaped red blood cells cause narrowing of blood vessels and reduced function in clearing the defective cells. It is usually infarcted before the end of childhood in individuals with sickle cell anaemia. This spleen damage increases the risk of infection from encapsulated organisms; preventive antibiotics and vaccinations are recommended for those lacking proper spleen function.


title: Sickle cell disease

text: Splenic sequestration crises are acute, painful enlargements of the spleen, caused by intrasplenic trapping of red cells and resulting in a precipitous fall in haemoglobin levels with the potential for hypovolemic shock. Sequestration crises are considered an emergency. If not treated, patients may die within 1–2 hours due to circulatory failure. Management is supportive, sometimes with blood transfusion. These crises are transient; they continue for 3–4 hours and may last for one day.


title: Sickle cell disease

text: Acute chest syndrome is defined by at least two of these signs or symptoms: chest pain, fever, pulmonary infiltrate or focal abnormality, respiratory symptoms, or hypoxemia. It is the second-most common complication and it accounts for about 25% of deaths in patients with SCD. Most cases present with vaso-occlusive crises, and then develop acute chest syndrome. Nevertheless, about 80% of people have vaso-occlusive crises during acute chest syndrome.


title: Sickle cell disease

text: Aplastic crises are instances of an acute worsening of the patient's baseline anaemia, producing pale appearance, fast heart rate, and fatigue. This crisis is normally triggered by parvovirus B19, which directly affects production of red blood cells by invading the red cell precursors and multiplying in and destroying them. Parvovirus infection almost completely prevents red blood cell production for two to three days. In normal individuals, this is of little consequence, but the shortened red cell life of SCD patients results in an abrupt, life-threatening situation. Reticulocyte counts drop dramatically during the disease (causing reticulocytopenia), and the rapid turnover of red cells leads to the drop in haemoglobin. This crisis takes 4 to 7 days to disappear. Most patients can be managed supportively; some need a blood transfusion.


title: Sickle cell disease

text: Haemolytic crises are acute accelerated drops in haemoglobin level. The red blood cells break down at a faster rate. This is particularly common in people with coexistent G6PD deficiency.Another influence of hemolytic crises in Sickle Cell Disease is oxidative stress on the erythrocytes, leukocytes, and platelets. When there is not enough red blood cell production in the bone marrow, the oxygen that the body receives, processes, and transports is unbalanced with the body’s antioxidants. There is an imbalance in the oxygen reactive species in the cells, which leads to more production of red blood cells that are not properly oxygenated or formed. Oxidative stress may lead to anemia because of the imbalance of oxygen in the tissue.


title: Sickle cell disease

text: One of the earliest clinical manifestations is dactylitis, presenting as early as six months of age, and may occur in children with sickle cell trait. The crisis can last up to a month. Given that pneumonia and sickling in the lung can both produce symptoms of acute chest syndrome, the patient is treated for both conditions. It can be triggered by painful crisis, respiratory infection, bone-marrow embolisation, or possibly by atelectasis, opiate administration, or surgery. Hematopoietic ulcers may also occur.


title: Sickle cell disease

text: Normally, humans have haemoglobin A, which consists of two alpha and two beta chains, haemoglobin A2, which consists of two alpha and two delta chains, and haemoglobin F (HbF), consisting of two alpha and two gamma chains in their bodies. Of these three types, haemoglobin F dominates until about 6 weeks of age. Afterwards, haemoglobin A dominates throughout life. In people diagnosed with sickle cell disease, at least one of the β-globin subunits in haemoglobin A is replaced with what is known as haemoglobin S. In sickle cell anaemia, a common form of sickle cell disease, haemoglobin S replaces both β-globin subunits in the haemoglobin.


title: Sickle cell disease

text: Sickle cell disease has an autosomal recessive pattern of inheritance from parents. The types of haemoglobin a person makes in the red blood cells depend on what haemoglobin genes are inherited from her or his parents. If one parent has sickle cell anaemia and the other has sickle cell trait, then the child has a 50% chance of having sickle cell disease and a 50% chance of having sickle cell trait. When both parents have sickle cell trait, a child has a 25% chance of sickle cell disease; 25% do not carry any sickle cell alleles, and 50% have the heterozygous condition.


title: Sickle cell disease

text: Sickle cell gene mutation probably arose spontaneously in different geographic areas, as suggested by restriction endonuclease analysis. These variants are known as Cameroon, Senegal, Benin, Bantu, and Saudi-Asian. Their clinical importance is because some are associated with higher HbF levels, e.g., Senegal and Saudi-Asian variants, and tend to have milder disease.


title: Sickle cell disease

text: The gene defect is a single nucleotide mutation (see single-nucleotide polymorphism – SNP) (GAG codon changing to GTG) of the β-globin gene, which results in glutamate (E/Glu) being substituted by valine (V/Val) at position 6 (E6V substitution). Haemoglobin S with this mutation is referred to as HbS, as opposed to the normal adult HbA. This is normally a benign mutation, causing no apparent effects on the secondary, tertiary, or quaternary structures of haemoglobin in conditions of normal oxygen concentration. However, under low oxygen concentration, HbS polymerizes and forms fibrous precipitates because the deoxy form of haemoglobin exposes a hydrophobic patch on the protein between the E and F helices (Phe 85, Leu 88).


title: Sickle cell disease

text: In people heterozygous for HbS (carriers of sickling haemoglobin), the polymerisation problems are minor because the normal allele can produce half of the haemoglobin. In people homozygous for HbS, the presence of long-chain polymers of HbS distort the shape of the red blood cell from a smooth, doughnut-like shape to ragged and full of spikes, making it fragile and susceptible to breaking within capillaries. Carriers have symptoms only if they are deprived of oxygen (for example, while climbing a mountain) or while severely dehydrated.


title: Sickle cell disease

text: The allele responsible for sickle cell anaemia can be found on the short arm of chromosome 11, more specifically 11p15.5. A person who receives the defective gene from both father and mother develops the disease; a person who receives one defective and one healthy allele remains healthy, but can pass on the disease and is known as a carrier or heterozygote. Heterozygotes are still able to contract malaria, but their symptoms are generally less severe.


title: Sickle cell disease

text: Due to the adaptive advantage of the heterozygote, the disease is still prevalent, especially among people with recent ancestry in malaria-stricken areas, such as Africa, the Mediterranean, India, and the Middle East. Malaria was historically endemic to southern Europe, but it was declared eradicated in the mid-20th century, with the exception of rare sporadic cases.


title: Sickle cell disease

text: The malaria parasite has a complex lifecycle and spends part of it in red blood cells. In a carrier, the presence of the malaria parasite causes the red blood cells with defective haemoglobin to rupture prematurely, making the "Plasmodium" parasite unable to reproduce. Further, the polymerization of Hb affects the ability of the parasite to digest Hb in the first place. Therefore, in areas where malaria is a problem, people's chances of survival actually increase if they carry sickle cell traits (selection for the heterozygote).


title: Sickle cell disease

text: In the United States, with no endemic malaria, the prevalence of sickle cell anaemia among people of African ancestry is lower (about 0.25%) than among people in West Africa (about 4.0%) and is falling. Without endemic malaria, the sickle cell mutation is purely disadvantageous and tends to decline in the affected population by natural selection, and now artificially through prenatal genetic screening. However, the African American community descends from a significant admixture of several African and non-African ethnic groups and also represents the descendants of survivors of slavery and the slave trade. Thus, a degree of genetic dilution via crossbreeding with non-African people and high health-selective pressure through slavery (especially the slave trade and the frequently deadly Middle Passage) may be the most plausible explanations for the lower prevalence of sickle cell anaemia (and, possibly, other genetic diseases) among African Americans compared to West Africans. Another factor that limits the spread of sickle cell genes in North America is the relative absence of polygamy. In polygamous societies, affected males may father many children with multiple partners.


title: Sickle cell disease

text: The loss of red blood cell elasticity is central to the pathophysiology of sickle cell disease. Normal red blood cells are quite elastic and have a biconcave disc shape, which allows the cells to deform to pass through capillaries. In sickle cell disease, low oxygen tension promotes red blood cell sickling and repeated episodes of sickling damage the cell membrane and decrease the cell's elasticity. These cells fail to return to normal shape when normal oxygen tension is restored. As a consequence, these rigid blood cells are unable to deform as they pass through narrow capillaries, leading to vessel occlusion and ischaemia.


title: Sickle cell disease

text: The actual anaemia of the illness is caused by haemolysis, the destruction of the red cells, because of their shape. Although the bone marrow attempts to compensate by creating new red cells, it does not match the rate of destruction. Healthy red blood cells typically function for 90–120 days, but sickled cells only last 10–20 days.


title: Sickle cell disease

text: In HbS, the complete blood count reveals haemoglobin levels in the range of 6–8 g/dl with a high reticulocyte count (as the bone marrow compensates for the destruction of sickled cells by producing more red blood cells). In other forms of sickle cell disease, Hb levels tend to be higher. A blood film may show features of hyposplenism (target cells and Howell-Jolly bodies).


title: Sickle cell disease

text: Sickling of the red blood cells, on a blood film, can be induced by the addition of sodium metabisulfite. The presence of sickle haemoglobin can also be demonstrated with the "sickle solubility test" (also called "sickledex"). A mixture of haemoglobin S (HbS) in a reducing solution (such as sodium dithionite) gives a turbid appearance, whereas normal Hb gives a clear solution.


title: Sickle cell disease

text: Abnormal haemoglobin forms can be detected on haemoglobin electrophoresis, a form of gel electrophoresis on which the various types of haemoglobin move at varying speeds. Sickle cell haemoglobin (HgbS) and haemoglobin C with sickling (HgbSC)—the two most common forms—can be identified from there. The diagnosis can be confirmed with high-performance liquid chromatography. Genetic testing is rarely performed, as other investigations are highly specific for HbS and HbC.


title: Sickle cell disease

text: An acute sickle cell crisis is often precipitated by infection. Therefore, a urinalysis to detect an occult urinary tract infection, and chest X-ray to look for occult pneumonia should be routinely performed.


title: Sickle cell disease

text: People who are known carriers of the disease or at risk of having a child with sickle cell anemia may undergo genetic counseling. Genetic counselors work with families to discuss the benefits, limitations, and logistics of genetic testing options as well as the potential impact of testing and test results on the individual. During pregnancy, genetic testing can be done on either a blood sample from the fetus or a sample of amniotic fluid. During the first trimester of pregnancy, chorionic villus sampling (CVS) is also a technique used for SCD prenatal diagnosis. Since taking a blood sample from a fetus has greater risks, the latter test is usually used. Neonatal screening sometimes referred to as newborn screening, provides not only a method of early detection for individuals with sickle cell disease but also allows for the identification of the groups of people who carry the sickle cell trait. Genetic counselors can help individuals of colour and their families tackle the racial and ethnic disparities that exist in healthcare.


title: Sickle cell disease

text: In 2010, there was significant consideration and debate in the US surrounding comprehensive screening of athletes for SCD. The American Society of Hematology concluded in a statement in 2012 that they do not support testing or disclosure of sickle cell trait status as a prerequisite for participation in athletic activities due to lack of scientific evidence, inconsistency with good medical practice, and inconsistency with public health ethics. They recommended universal interventions to reduce exertion-related injuries and deaths effective for all athletes irrespective of their sickle cell status.


title: Sickle cell disease

text: Treatment involves a number of measures. While it has been historically recommended that people with sickle cell disease avoid exercise, regular exercise may benefit people. Dehydration should be avoided. A diet high in calcium is recommended but the effectiveness of vitamin D supplementation remains uncertain. L-glutamine use was supported by the FDA starting at the age of five, as it decreases complications.


title: Sickle cell disease

text: From birth to five years of age, penicillin daily, due to the immature immune system that makes them more prone to early childhood illnesses, is recommended. Dietary supplementation of folic acid had been previously recommended by the WHO. A 2016 Cochrane review of its use found "the effect of supplementation on anaemia and any symptoms of anaemia remains unclear" due to a lack of medical evidence.


title: Sickle cell disease

text: The protective effect of sickle cell trait does not apply to people with sickle cell disease; in fact, they are more vulnerable to malaria, since the most common cause of painful crises in malarial countries is infection with malaria. People with sickle cell disease living in malarial countries should receive lifelong medication for prevention.


title: Sickle cell disease

text: Most people with sickle cell disease have intensely painful episodes called vaso-occlusive crises. However, the frequency, severity, and duration of these crises vary tremendously. Painful crises are treated symptomatically with pain medications; pain management requires opioid drug administration at regular intervals until the crisis has settled. For milder crises, a subgroup of patients manages on NSAIDs (such as diclofenac or naproxen). For more severe crises, most patients require inpatient management for intravenous opioids.


title: Sickle cell disease

text: Extra fluids, administered either orally or intravenously, are a routine part of treatment of vaso-occlusive crises but the evidence about the most effective route, amount and type of fluid replacement remains uncertain.


title: Sickle cell disease

text: Crizanlizumab, a monoclonal antibody target towards p-selectin was approved in 2019 in the United States to reduce the frequency of vaso-occlusive crisis in those 16 years and older.


title: Sickle cell disease

text: Transcranial Doppler ultrasound (TCD) can detect children with sickle cell that have a high risk for stroke. The ultrasound test detects blood vessels partially obstructed by sickle cells by measuring the rate of blood into the brain, as blood flow velocity is inversely related to arterial diameter, and consequently, high blood-flow velocity is correlated with narrowing of the arteries. In 2002 the National Institute of Health (NIH) issued a statement recommending that children with sickle cell get the Transcranial Doppler ultrasound screen annually, and in 2014 a panel of experts convened by the NIH issued guidelines reiterating the same recommendation. One review of medical records, by hematologist Dr. Julie Kanter at the University of Alabama at Birmingham, showed that on average only 48.4 percent of children with sickle cell get the recommended ultrasound test.


title: Sickle cell disease

text: A 1994 NIH study showed that children at risk for strokes who received blood transfusions had an annual stroke rate of less than 1 percent, whereas those children who did not receive blood transfusions had a 10 percent stroke rate per year. (Also see 1998 study in the "New England Journal of Medicine".) In addition to ultrasounds and blood transfusions, the inexpensive generic drug hydroxyurea can reduce the risk of irreversible organ and brain damage. Guidelines from NIH published in 2014 state that all children and adolescents should take hydroxyurea, as should adults with serious complications or three or more pain crises in a year.


title: Sickle cell disease

text: Management is similar to vaso-occlusive crisis, with the addition of antibiotics (usually a quinolone or macrolide, since cell wall-deficient ["atypical"] bacteria are thought to contribute to the syndrome), oxygen supplementation for hypoxia, and close observation. In the absence of high quality evidence regarding the effectiveness of antibiotics for acute chest syndrome in people with sickle cell disease, there is no standard antibiotic treatment as of 2019. It is recommended that people with suspected acute chest syndrome should be admitted to the hospital with worsening A-a gradient an indication for ICU admission.


title: Sickle cell disease

text: Should the pulmonary infiltrate worsen or the oxygen requirements increase, simple blood transfusion or exchange transfusion is indicated. The latter involves the exchange of a significant portion of the person's red cell mass for normal red cells, which decreases the level of haemoglobin S in the patient's blood. However, there is currently uncertain evidence about the possible benefits or harms of blood transfusion for acute chest syndrome in people with sickle cell disease.


title: Sickle cell disease

text: Hydroxyurea, also known as hydroxycarbamide, probably reduces the frequency of painful episodes and the risk of life-threatening illness or death but there is currently insufficient evidence regarding the risk of adverse effects. Hydroxyurea and phlebotomy combined may be more effective than transfusion and chelation combined in terms of pain, life-threatening illness and risk of death.


title: Sickle cell disease

text: It was the first approved drug for the treatment of sickle cell anaemia, and was shown to decrease the number and severity of attacks in 1995 and shown to possibly increase survival time in a study in 2003. This is achieved, in part, by reactivating fetal haemoglobin production in place of the haemoglobin S that causes sickle cell anaemia. Hydroxyurea had previously been used as a chemotherapy agent, and some concern exists that long-term use may be harmful, but this risk is either absent or very small and the benefits likely outweigh the risks.


title: Sickle cell disease

text: Voxelotor was approved in the United States in 2019 to increase hemoglobin in people with SS disease.


title: Sickle cell disease

text: Blood transfusions are often used in the management of sickle cell disease in acute cases and to prevent complications by decreasing the number of red blood cells (RBCs) that can sickle by adding normal red blood cells. In children, preventive RBC transfusion therapy has been shown to reduce the risk of first stroke or silent stroke when transcranial Doppler ultrasonography shows abnormal cerebral blood flow. In those who have sustained a prior stroke event, it also reduces the risk of recurrent stroke and additional silent strokes.


title: Sickle cell disease

text: Bone marrow transplants have proven effective in children; they are the only known cure for SCD. However, bone marrow transplants are difficult to obtain because of the specific HLA typing necessary. Ideally, a close relative (allogeneic) would donate the bone marrow necessary for transplantation. Some gene therapies are under development that would alter the patient's own bone marrow stem cells "ex vivo," which can then be transplanted back into the patient after chemotherapy eliminates the original unmodified cells.


title: Sickle cell disease

text: When treating avascular necrosis of the bone in people with sickle cell disease, the aim of treatment is to reduce or stop the pain and maintain joint mobility. Current treatment options include resting the joint, physical therapy, pain-relief medicine, joint-replacement surgery, or bone grafting. High quality, randomized, controlled trials are needed to assess the most effective treatment option and determine if a combination of physical therapy and surgery is more effective than physical therapy alone.


title: Sickle cell disease

text: Psychological therapies such as patient education, cognitive therapy, behavioural therapy, and psychodynamic psychotherapy, that aim to complement current medical treatments, require further research to determine their effectiveness.


title: Sickle cell disease

text: About 90% of people survive to age 20, and close to 50% survive beyond age 50. In 2001, according to one study performed in Jamaica, the estimated mean survival for people was 53 years for men and 58 years for women with homozygous SCD. The specific life expectancy in much of the developing world is unknown. In 1975 about 7.3% of people with SCD died before their 23rd birthday; while in 1989 2.6% of people with SCD died by the age of 20.


title: Sickle cell disease

text: The highest frequency of sickle cell disease is found in tropical regions, particularly sub-Saharan Africa, tribal regions of India, and the Middle East. Migration of substantial populations from these high-prevalence areas to low-prevalence countries in Europe has dramatically increased in recent decades and in some European countries, sickle cell disease has now overtaken more familiar genetic conditions such as haemophilia and cystic fibrosis. In 2015, it resulted in about 114,800 deaths.


title: Sickle cell disease

text: Sickle cell disease occurs more commonly among people whose ancestors lived in tropical and subtropical sub-Saharan regions where malaria is or was common. Where malaria is common, carrying a single sickle cell allele (trait) confers a heterozygote advantage; humans with one of the two alleles of sickle cell disease show less severe symptoms when infected with malaria.


title: Sickle cell disease

text: This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.


title: Sickle cell disease

text: Three-quarters of sickle cell cases occur in Africa. A recent WHO report estimated that around 2% of newborns in Nigeria were affected by sickle cell anaemia, giving a total of 150,000 affected children born every year in Nigeria alone. The carrier frequency ranges between 10 and 40% across equatorial Africa, decreasing to 1–2% on the North African coast and <1% in South Africa.


title: Sickle cell disease

text: Studies in Africa show a significant decrease in infant mortality rate, ages 2–16 months, because of the sickle cell trait. This happened in areas of predominant malarial cases.


title: Sickle cell disease

text: Uganda has the fifth-highest sickle cell disease burden in Africa. One study indicates that 20 000 babies per year are born with sickle cell disease with the sickle cell trait at 13·3% and with disease 0·7%.


title: Sickle cell disease

text: The number of people with the disease in the United States is about 100,000 (one in 3,300), mostly affecting Americans of sub-Saharan African descent. In the United States, about one out of 365 African-American children and one in every 16,300 Hispanic-American children have sickle cell anaemia. The life expectancy for men with SCD is approximately 42 years of age while women live approximately six years longer. An additional 2 million are carriers of the sickle cell trait. Most infants with SCD born in the United States are identified by routine neonatal screening. As of 2016 all 50 states include screening for sickle cell disease as part of their newborn screen. The newborn's blood is sampled through a heel-prick and is sent to a lab for testing. The baby must have been eating for a minimum of 24 hours before the heel-prick test can be done. Some states also require a second blood test to be done when the baby is two weeks old to ensure the results. Sickle cell anemia is the most common genetic disorder among African Americans. Approximately 8% are carriers and 1 in 375 are born with the disease. Patient advocates for sickle cell disease have complained that it gets less government and private research funding than similar rare diseases such as cystic fibrosis, with researcher Elliott Vichinsky saying this shows racial discrimination or the role of wealth in health care advocacy.


title: Sickle cell disease

text: As a result of population growth in African-Caribbean regions of overseas France and immigration from North and sub-Saharan Africa to mainland France, sickle cell disease has become a major health problem in France. SCD has become the most common genetic disease in the country, with an overall birth prevalence of one in 2,415 in metropolitan France, ahead of phenylketonuria (one in 10,862), congenital hypothyroidism (one in 3,132), congenital adrenal hyperplasia (one in 19,008) and cystic fibrosis (one in 5,014) for the same reference period.


title: Sickle cell disease

text: Since 2000, neonatal screening of SCD has been performed at the national level for all newborns defined as being "at-risk" for SCD based on ethnic origin (defined as those born to parents originating from sub-Saharan Africa, North Africa, the Mediterranean area (South Italy, Greece, and Turkey), the Arabic peninsula, the French overseas islands, and the Indian subcontinent).


title: Sickle cell disease

text: In the United Kingdom, between 12,000 and 15,000 people are thought to have sickle cell disease with an estimated 250,000 carriers of the condition in England alone. As the number of carriers is only estimated, all newborn babies in the UK receive a routine blood test to screen for the condition. Due to many adults in high-risk groups not knowing if they are carriers, pregnant women and both partners in a couple are offered screening so they can get counselling if they have the sickle cell trait. In addition, blood donors from those in high-risk groups are also screened to confirm whether they are carriers and whether their blood filters properly. Donors who are found to be carriers are then informed and their blood, while often used for those of the same ethnic group, is not used for those with sickle cell disease who require a blood transfusion.


title: Sickle cell disease

text: In Saudi Arabia, about 4.2% of the population carry the sickle cell trait and 0.26% have sickle cell disease. The highest prevalence is in the Eastern province, where approximately 17% of the population carry the gene and 1.2% have sickle cell disease.


title: Sickle cell disease

text: In 2005, Saudi Arabia introduced a mandatory premarital test including HB electrophoresis, which aimed to decrease the incidence of SCD and thalassemia.


title: Sickle cell disease

text: In Bahrain, a study published in 1998 that covered about 56,000 people in hospitals in Bahrain found that 2% of newborns have sickle cell disease, 18% of the surveyed people have the sickle cell trait, and 24% were carriers of the gene mutation causing the disease. The country began screening of all pregnant women in 1992 and newborns started being tested if the mother was a carrier. In 2004, a law was passed requiring couples planning to marry to undergo free premarital counseling. These programs were accompanied by public education campaigns.


title: Sickle cell disease

text: Sickle cell disease is common in some ethnic groups of central India, where the prevalence has ranged from 9.4 to 22.2% in endemic areas of Madhya Pradesh, Rajasthan, and Chhattisgarh. It is also endemic among Tharu people of Nepal and India; however, they have a sevenfold lower rate of malaria despite living in a malaria infested zone.


title: Sickle cell disease

text: In Jamaica, 10% of the population carry the sickle cell gene, making it the most prevalent genetic disorder in the country.


title: Sickle cell disease

text: The first modern report of sickle cell disease may have been in 1846, where the autopsy of an executed runaway slave was discussed; the key finding was the absence of the spleen. Reportedly, African slaves in the United States exhibited resistance to malaria, but were prone to leg ulcers. The abnormal characteristics of the red blood cells, which later lent their name to the condition, was first described by Ernest E. Irons (1877–1959), intern to Chicago cardiologist and professor of medicine James B. Herrick (1861–1954), in 1910. Irons saw "peculiar elongated and sickle-shaped" cells in the blood of a man named Walter Clement Noel, a 20-year-old first-year dental student from Grenada. Noel had been admitted to the Chicago Presbyterian Hospital in December 1904 with anaemia. Noel was readmitted several times over the next three years for "muscular rheumatism" and "bilious attacks" but completed his studies and returned to the capital of Grenada (St. George's) to practice dentistry. He died of pneumonia in 1916 and is buried in the Catholic cemetery at Sauteurs in the north of Grenada. Shortly after the report by Herrick, another case appeared in the "Virginia Medical Semi-Monthly" with the same title, "Peculiar Elongated and Sickle-Shaped Red Blood Corpuscles in a Case of Severe Anemia." This article is based on a patient admitted to the University of Virginia Hospital on 15 November 1910. In the later description by Verne Mason in 1922, the name "sickle cell anemia" is first used. Childhood problems related to sickle cells disease were not reported until the 1930s, despite the fact that this cannot have been uncommon in African-American populations.


title: Sickle cell disease

text: Memphis physician Lemuel Diggs, a prolific researcher into sickle cell disease, first introduced the distinction between sickle cell disease and trait in 1933, although until 1949, the genetic characteristics had not been elucidated by James V. Neel and E.A. Beet. 1949 was the year when Linus Pauling described the unusual chemical behaviour of haemoglobin S, and attributed this to an abnormality in the molecule itself. The molecular change in HbS was described in 1956 by Vernon Ingram. The late 1940s and early 1950s saw further understanding in the link between malaria and sickle cell disease. In 1954, the introduction of haemoglobin electrophoresis allowed the discovery of particular subtypes, such as HbSC disease.


title: Sickle cell disease

text: Large-scale natural history studies and further intervention studies were introduced in the 1970s and 1980s, leading to widespread use of prophylaxis against pneumococcal infections amongst other interventions. Bill Cosby's Emmy-winning 1972 TV movie, "To All My Friends on Shore", depicted the story of the parents of a child with sickle cell disease. The 1990s had the development of hydroxycarbamide, and reports of cure through bone marrow transplantation appeared in 2007.


title: Sickle cell disease

text: Effective 15 September 2017, the U.S. Social Security Administration issued a Policy Interpretation Ruling providing background information on sickle cell disease and a description of how Social Security evaluates the disease during its adjudication process for disability claims.


title: Sickle cell disease

text: In the U.S., there are stigmas surrounding SCD that discourage people with SCD from receiving necessary care. These stigmas mainly affect people of African American and Latin American ancestries, according to the National Heart, Lung, and Blood Institute. People with SCD experience the impact of stigmas of the disease on multiple aspects of life including social and psychological well-being. Studies have shown that those with SCD frequently feel as though they must keep their diagnosis a secret to avoid discrimination in the workplace and also among peers in relationships. In the 1960s, the US government supported initiatives for workplace screening for genetic diseases in an attempt to be protective towards people with SCD. By having this screening, it was intended that employees would not be placed in environments that could potentially be harmful and trigger SCD.


title: Sickle cell disease

text: Uganda has the 5th highest sickle cell disease (SCD) burden in the world. In Uganda, social stigma exists for those with sickle cell disease because of the lack of general knowledge of the disease. The general gap in knowledge surrounding sickle cell disease is noted among adolescents and young adults due to the culturally sanctioned secrecy about the disease. While most people have heard generally about the disease, a large portion of the population is relatively misinformed about how SCD is diagnosed or inherited. Those who are informed about the disease learned about it from family or friends and not from health professionals. Failure to provide the public with information about sickle cell disease results in a population with a poor understanding of the causes of the disease, symptoms, and prevention techniques. The differences, physically and socially, that arise in those with sickle cell disease, such as jaundice, stunted physical growth, and delayed sexual maturity, can also lead them to become targets of bullying, rejection, and stigma.


title: Sickle cell disease

text: The data compiled on sickle cell disease in Uganda has not been updated since the early 1970s. The deficiency of data is due to a lack of government research funds, even though Ugandans die daily from SCD. Data shows that the trait frequency of sickle cell disease is 20% of the population in Uganda. This means that 66 million people are at risk of having a child who has sickle cell disease. It is also estimated that about 25,000 Ugandans are born each year with SCD and 80% of those people don't live past five years old. SCD also contributes 25% to the child mortality rate in Uganda. The Bamba people of Uganda, located in the southwest of the country, carry 45% of the gene which is the highest trait frequency recorded in the world. The Sickle Cell Clinic in Mulago is only one sickle cell disease clinic in the country and on average sees 200 patients a day.


title: Sickle cell disease

text: The stigma around the disease is particularly bad in regions of the country that are not as affected. For example, Eastern Ugandans tend to be more knowledgeable of the disease than Western Ugandans, who are more likely to believe that sickle cell disease resulted as a punishment from God or witchcraft. Other misconceptions about SCD include the belief that it is caused by environmental factors but, in reality, SCD is a genetic disease. There have been efforts throughout Uganda to address the social misconceptions about the disease. In 2013, the Uganda Sickle Cell Rescue Foundation was established to spread awareness of sickle cell disease and combat the social stigma attached to the disease. In addition to this organization's efforts, there is a need for the inclusion of sickle cell disease education in preexisting community health education programs in order to reduce the stigmatization of sickle cell disease in Uganda.


title: Sickle cell disease

text: The deeply rooted stigma of SCD from society causes families to often hide their family members' sick status for fear of being labeled, cursed, or left out of social events. Sometimes in Uganda, when it is confirmed that a family member has sickle cell disease, intimate relationships with all members of the family are avoided. The stigmatization and social isolation people with sickle cell disease tend to experience is often the consequence of popular misconceptions that people with SCD should not socialize with those free from the disease. This mentality robs people with SCD of the right to freely participate in community activities like everyone else SCD-related stigma and social isolation in schools, especially, can make a life for young people living with sickle cell disease extremely difficult. For school-aged children living with SCD, the stigma they face can lead to peer rejection. Peer rejection involves the exclusion from social groups or gatherings. It often leads the excluded individual to experience emotional distress and may result in their academic underperformance, avoidance of school, and occupational failure later in life. This social isolation is also likely to negatively impact people with SCD's self-esteem and overall quality of life.


title: Sickle cell disease

text: Mothers of children with sickle cell disease tend to receive disproportionate amounts of stigma from their peers and family members. These women will often be blamed for their child's diagnosis of SCD, especially if SCD is not present in earlier generations, due to the suspicion that the child's poor health may have been caused by the mother's failure to implement preventative health measures or promote a healthy environment for her child to thrive. The reliance on theories related to environmental factors to place blame on the mother reflects many Ugandan's poor knowledge of how the disease is acquired as it is determined by genetics, not environment. Mothers of children with sickle cell disease are also often left with very limited resources to safeguard their futures against the stigma of having SCD. This lack of access to resources results from their subordinating roles within familial structures as well as the class disparities that hinder many mothers' ability to satisfy additional childcare costs and responsibilities.


title: Sickle cell disease

text: Women living with SCD who become pregnant often face extreme discrimination and discouragement in Uganda. These women are frequently branded by their peers as irresponsible for having a baby while living with sickle cell disease or even engaging in sex while living with SCD. The criticism and judgement these women receive, not only from healthcare professionals but also from their families, often leaves them feeling alone, depressed, anxious, ashamed, and with very little social support. Most pregnant women with SCD also go on to be single mothers as it is common for them to be left by their male partners who claim they were unaware of their partner's SCD status. Not only does the abandonment experienced by these women cause emotional distress for them, but this low level of parental support can be linked to depressive symptoms and overall lower quality of life for the child once they are born.


title: Sickle cell disease

text: In 2021 many patients were found to be afraid to visit hospitals so purchasing pain relief to treat themselves outside the NHS, such was the level of ignorance among staff. They were often waiting a long time for pain relief, and sometimes suspected of “drugs-seeking” behaviour. Delays to treatment, failure to inform the hospital haematology team and poor pain management had caused deaths. Specialist haematology staff prefer to work in bigger, teaching hospitals, leading to shortages of expertise elsewhere. In 2021 the NHS initiated its first new treatment in 20 years for Sickle Cell. This involved the use of Crizanlizumab, a drug given via transfusion drips, which reduces the number of visits to A and E by sufferers. The treatment can be accessed, via consultants, at any of ten new hubs set up around the country. In the same year, however, an All-Party Parliamentary Group produced a report on Sickle Cell and Thalassaemia entitled 'No-one is listening'. Partly in response to this, on 19 June 2022, World Sickle Cell Day, the NHS launched a campaign called " Can you tell it's sickle cell?". The campaign had twin aims. One was to increase awareness of the key signs and symptoms of the blood disorder so that people are as alert to signs of a sickle cell crisis as they are to an imminent heart attack or stroke. The second aim was to set up a new training programme to help paramedics, Accident and Emergency staff, carers and the general public to care effectively for sufferers in crisis.


title: Sickle cell disease

text: While umbilical cord blood transplant can potentially cure the condition, a suitable donor is available in only 10% of people. About 7% of people also die as a result of the procedure and graft versus host disease may occur.


title: Sickle cell disease

text: Diseases such as sickle cell disease for which a person's normal phenotype or cell function may be restored in cells that have the disease by a normal copy of the gene that is mutated, may be a good candidate for gene therapy treatment. The risks and benefits related to gene therapy for sickle cell disease are not known.


title: Sickle cell disease

text: In 2001, sickle cell disease reportedly had been successfully treated in mice using gene therapy. The researchers used a viral vector to make the mice—which have essentially the same defect that causes human sickle cell disease—express production of fetal haemoglobin (HbF), which an individual normally ceases to produce shortly after birth. In humans, using hydroxyurea to stimulate the production of HbF has been known to temporarily alleviate sickle cell disease symptoms. The researchers demonstrated that this gene therapy method is a more permanent way to increase therapeutic HbF production.


title: Sickle cell disease

text: Phase 1 clinical trials of gene therapy for sickle cell disease in humans were started in 2014. The clinical trials will assess the safety of lentiviral vector-modified bone marrow for adults with severe sickle cell disease. As of 2020, however, no randomized controlled trials have been reported. A case report for the first person treated was published in March 2017, with a few more people being treated since then.


title: Sickle cell disease

text: Gene editing platforms like CRISPR/Cas9 have been used to correct the disease-causing mutation in hematopoietic stem cells taken from a person with the condition. In July 2019 the gene-editing tool CRISPR was used to edit bone marrow cells from a person with SCD to "turning on" the gene for fetal haemoglobin. A number of researchers have considered the ethical implications of SCD being one of the first potential applications of CRISPR technology, given the historical abuses and neglect of the African American community by the medical field.


title: Sickle cell disease

text: In 2017 twelve clinical trials were focusing on gene therapy to treat sickle cell anemia. Of those 12 trials, four of them replaced the mutated HBB gene with a healthy one. Three trials used Mozobil, a medication used to treat types of cancer, to determine whether the increase of stem cells can be used for gene therapy. One trial focused on analyzing bone marrow samples from patients with sickle cell anemia. Another trial experimented with using umbilical cord blood from babies both with and without sickle cell anemia to develop gene therapy.


title: Sickle cell disease

text: There is no strong medical evidence to determine the risks and potential benefits related to treating people with sickle cell disease with hematopoietic stem cell transplantations.


title: Lauren London

text: Lauren Nicole London is an American actress. London is known for her roles in films and televisions shows including "ATL" (2006), "This Christmas" (2007), "Madea’s Big Happy Family" (2011), "Baggage Claim" (2013), "The Game" (2013-2015), "Games People Play" (2019), and "Without Remorse" (2021).


title: Lauren London

text: In 2022, London and PUMA collaborated on the L.A Love Story project. The footwear and apparel collection is inspired by her hometown, Los Angeles. Items also feature her late boyfriend Nipsey Hussle, who was fatally shot on March 31, 2019 in Los Angeles.


title: Lauren London

text: London was born to an African-American mother and an Ashkenazi Jewish father in Los Angeles. After attending Palisades Charter High School into her second year, London was homeschooled.


title: Lauren London

text: London appeared in music videos for artists such as Tyrese, Ludacris, Pharrell ("Frontin'") and Snoop Dogg. Her breakout year came in 2006, where she made her television debut in the "Everybody Hates Funerals" episode of the sitcom "Everybody Hates Chris". That same year, London landed her first film role as well, playing hip-hop artist T.I.'s romantic lead in the film "ATL". For her work, London was nominated for "Best Supporting Actress" at the Black Movie Awards. In 2007, London landed a role on the HBO comedy series "Entourage", playing the character Turtle's (Jerry Ferrara) love interest. Based on her performance in "ATL", London was given her role in 2007's "This Christmas" without having to audition. London, along with pop/R&B singers Cassie and Asia Nitollano. She also became one of the spokesmodels for the Sean John woman's collection in 2007.


title: Lauren London

text: In 2008, London landed the role of the character Christina in the first season of the show "90210", originally thought to be a possible romantic interest of Tristan Wilds' character "Dixon Wilson". London's next film role was the character "Ivy" in the 2009 release "Next Day Air". That same year, she played the character Cammy Alcott in the Chris Columbus film "I Love You, Beth Cooper". London also appeared on the covers of magazines such as "King" and "Jewel".


title: Lauren London

text: She appeared in "Tyler Perry's Madea's Big Happy Family", which was released on April 22, 2011. She also made a cameo appearance in the premiere of VH1's "Single Ladies". London joined the cast of the hit BET show "The Game" as a series regular from the sixth season until the series finale. She played a character named Kiera, "a former child star who starred in a "Cosby Show"-esque sitcom". London co-starred, alongside Paula Patton, Jill Scott, and Derek Luke, in "Baggage Claim" (2013), the film adaptation of playwright and director David E. Talbert's 2005 novel. In 2016, London co-starred in the film "The Perfect Match" as "Ginger". In 2018, London starred in the Lifetime Movies "Always & 4Ever" and "Poinsettias for Christmas".


title: Lauren London

text: In 2019, London played the lead character, "Vanessa King", in the BET show "Games People Play." In 2021 Lauren starred in the movie Without Remorse. The film was released on Prime Video on April 30, 2021. According to Samba TV, the film was watched in 4.8 million households in its first 30 days of release. She also starred in the American drama limited series drama limited series which premiered on November 24, 2021 on Netflix.


title: Lauren London

text: London dated Lil Wayne on and off. The couple's son, Kameron Carter, was born September 9, 2009. In May 2011, London said of her relationship with Wayne, "I met Wayne when I was 15 years old. I’ve known him a very long time, and we were in a relationship that didn’t make it. We tried more than once to revive it, and we were engaged briefly years ago, but we eventually parted ways. People see the 'Lil Wayne' personality and think they know who he really is. My son’s father is an intelligent, loving, and lovable person who will always be a dear friend. And that will never change. That is all." Lil Wayne's second verse of the song 'Young'n Blues" explains how he met London and refers to her as "young Cali sweet thang". Lil Wayne's "California Love" lyric "now I've got an actress sticking' by my hip...shorty is reddish" is also about London, and how he proposed to her and then broke it off "and in dat box it's a ring...somebody call that thing and tell her shawty give me back my ring". From 1999 to 2003, Lil Wayne had "Lauren" tattooed on his right arm, but he wrote "Carter" over it shortly before his marriage to his now ex-wife.


title: Lauren London

text: London dated Ermias Asghedom, better known as American rapper Nipsey Hussle, from 2013 until his murder on March 31, 2019. Nipsey and London were thought to have become engaged, but it was later revealed that their engagement photos were for a "GQ" photoshoot. The couple's son Kross Ermias Asghedom was born August 31, 2016.


title: Wong Kar-wai

text: Wong Kar-wai (born 17 July 1958) is a Hong Kong film director, screenwriter, and producer. His films are characterised by nonlinear narratives, atmospheric music, and vivid cinematography involving bold, saturated colours. A pivotal figure of Hong Kong cinema, Wong is considered a contemporary auteur, and ranks third on "Sight & Sound"s 2002 poll of the greatest filmmakers of the previous 25 years. His films frequently appear on best-of lists domestically and internationally.


title: Wong Kar-wai

text: Born in Shanghai, Wong emigrated to British Hong Kong as a child with his family. He began a career as a screenwriter for soap operas before transitioning to directing with his debut, the crime drama "As Tears Go By" (1988). While "As Tears Go By" was fairly successful in Hong Kong, Wong moved away from the contemporary trend of crime and action movies to embark on more personal filmmaking styles. "Days of Being Wild" (1990), his first venture in such a direction, did not perform well at the box office. It however received critical acclaim, and won Best Film and Best Director at the 1991 Hong Kong Film Awards. His next film, "Ashes of Time" (1994), met with a mixed reception because of its vague plot and atypical take on the genre.


title: Wong Kar-wai

text: Exhausted by the time-consuming filming and post-production of "Ashes of Time", Wong directed "Chungking Express" (1994), a smaller film that he hoped would rekindle his love of cinema. The film, expressing a more lighthearted atmosphere, catapulted Wong to international prominence, and won Best Film and Best Director at the 1995 Hong Kong Film Awards. Wong followed up with the crime thriller "Fallen Angels" in 1995. Although it was initially tepidly received by critics, "Fallen Angels" has since come to be considered a cult classic of the Golden Age of Hong Kong cinema, being especially representative of Wong’s style. Wong would go on to consolidate his worldwide reputation with the 1997 drama "Happy Together", for which he won Best Director at the Cannes Film Festival.


title: Wong Kar-wai

text: The 2000 drama "In the Mood for Love", revered for its lush visuals and subtle storytelling, concretely established Wong's trademark filmmaking styles. Among his other work are "2046" (2004) and "The Grandmaster" (2013), both of which received awards and nominations worldwide.


title: Wong Kar-wai

text: Wong Kar-wai was born on 17 July 1958 in Shanghai, the youngest of three siblings. His father was a sailor and his mother was a housewife. By the time Wong was five years old, the seeds of the Cultural Revolution were beginning to take effect in China and his parents decided to relocate to British-ruled Hong Kong. The two older children were meant to join them later, but the borders closed before they had a chance and Wong did not see his brother or sister again for ten years. In Hong Kong, the family settled in Tsim Sha Tsui, and his father got work managing a night club. Being an only child in a new city, Wong has said he felt isolated during his childhood; he struggled to learn Cantonese and English, only becoming fluent in these new languages when he was a teenager.


title: Wong Kar-wai

text: As a youth, Wong was frequently taken to the cinema by his mother and exposed to a variety of films. He later said: "The only hobby I had as a child was watching movies". At school he was interested in graphic design, and earned a diploma in the subject from Hong Kong Polytechnic in 1980. After graduating, Wong was accepted onto a training course with the TVB television network, where he learned the processes of media production.


title: Wong Kar-wai

text: He soon began a screenwriting career, firstly with TV series and soap operas, such as "Don't Look Now" (1981), before progressing to film scripts. He worked as part of a team, contributing to a variety of genres including romance, comedy, thriller, and crime. Wong had little enthusiasm for these early projects, described by the film scholar Gary Bettinson as "occasionally diverting and mostly disposable", but continued to write throughout the 1980s on films including "Just for Fun" (1983), "Rosa" (1986), and "The Haunted Cop Shop of Horrors" (1987). He is credited with ten screenplays between 1982 and 1987, but claims to have worked on about fifty more without official credit. Wong spent two years writing the screenplay for Patrick Tam's action film "Final Victory" (1987), for which he was nominated at the 7th Hong Kong Film Awards.


title: Wong Kar-wai

text: By 1987 the Hong Kong film industry was at a peak, enjoying a considerable level of prosperity and productivity. New directors were needed to maintain this success, and – through his links in the industry – Wong was invited to become a partner on a new independent company, In-Gear, and given the opportunity to direct his own picture. Gangster films were popular at the time, in the wake of John Woo's highly-successful "A Better Tomorrow" (1986), and Wong decided to follow suit. Specifically, unlike Hong Kong's other crime films, he chose to focus on young gangsters. The film, named "As Tears Go By", tells the story of a conflicted youth who has to watch over his hot-headed friend.


title: Wong Kar-wai

text: Because he was well acquainted with the producer, Alan Tang, Wong was given considerable freedom in the making of "As Tears Go By". His cast included what he considered some of "the hottest young idols in Hong Kong": singer Andy Lau, Maggie Cheung, and Jacky Cheung. "As Tears Go By" was released in June 1988 and was popular with audiences. Several journalists named Wong among the "Hong Kong New Wave". While it was a conventional crime film, critic David Bordwell said that Wong "[stood] out from his peers by abandoning the kinetics of comedies and action movies in favour of more liquid atmospherics." "As Tears Go By" received no attention from Western critics upon its initial release, but it was selected to be screened during the Directors' Fortnight of the 1989 Cannes Film Festival.


title: Wong Kar-wai

text: For his next film, Wong decided to move away from the crime trend in Hong Kong cinema, to which he felt indifferent. He was eager to make something unique, and the financial success of "As Tears Go By" made this possible. Developing a more personal project than his previous film, Wong picked the 1960s as a setting – evoking an era that he remembered well and had a "special feeling" for. "Days of Being Wild" focuses on a disillusioned young adult named Yuddy and those around him. There is no straightforward plot or obvious genre, but Stephen Teo sees it as a film about the "longing for love". Andy Lau, Maggie Cheung, and Jacky Cheung rejoined Wong for his second film, while Leslie Cheung was cast in the central role. Hired as cinematographer was Christopher Doyle, who became one of Wong's most important collaborators, photographing his next six films.


title: Wong Kar-wai

text: With its popular stars, "Days of Being Wild" was expected to be a mainstream picture; instead it was a character piece, more concerned with mood and atmosphere than narrative. Released in December 1990, the film earned little at the box office and divided critics. Despite this, it won five Hong Kong Film Awards, and received some attention internationally. With its experimental narrative, expressive camerawork, and themes of lost time and love, "Days of Being Wild" is described by film critic Peter Brunette as the first typical "Wong Kar-wai film". It has since gained a reputation as one of Hong Kong's finest releases. Its initial failure was disheartening for the director, and he could not gain funding for his next project – a planned sequel.


title: Wong Kar-wai

text: Struggling to get support for his work, Wong formed his own production company, Jet Tone Films, with Jeff Lau in 1992. In need of further backing, Wong accepted a studio's offer that he make a (ancient martial arts) film based on the popular novel "The Legend of the Condor Heroes" by Jin Yong. Wong was enthusiastic about the idea, claiming he had long wanted to make a costume drama. He eventually took little from the book other than three characters, and in 1992 began experimenting with several different narrative structures to weave what he called "a very complex tapestry". Filming began with another all-star cast: Leslie, Maggie, and Jacky Cheung returned alongside Brigitte Lin, Carina Lau, Charlie Young, and Tony Leung Chiu-wai − the latter of which became one of Wong's key collaborators.


title: Wong Kar-wai

text: Set during the Song dynasty, "Ashes of Time" concerns a desert-exiled assassin who is called upon by several different characters while nursing a broken heart. It was a difficult production and the project was not completed for two years, at a cost of HK$47 million. Upon release in September 1994, audiences were confused by the film's vague plotting and atypical take on . The film scholar Martha P. Nochimson has called it "the most unusual martial arts film ever made", as fast-paced action scenes are replaced with character ruminations, and story becomes secondary to the use of colour, landscape, and imagery. As such, "Ashes of Time" was a commercial failure, but critics were generally appreciative of Wong's "refusal to be loyal to [the ] genre". The film won several local awards, and competed at the Venice Film Festival where Doyle won Best Cinematography. In 2008, Wong reworked the film and re-released it as "Ashes of Time Redux".


title: Wong Kar-wai

text: During the long production of "Ashes of Time", Wong faced a two-month break as he waited for equipment to re-record sound for some scenes. He was in a negative state, feeling heavy pressure from his backers and worrying about another failure, and so decided to start a new project: "I thought I should do something to make myself feel comfortable about making films again. So I made "Chungking Express", which I made like a student film." Conceived and completed within only six weeks, the new project ended up being released two months before "Ashes of Time".


title: Wong Kar-wai

text: "Chungking Express" is split into two distinct parts – both set in contemporary Hong Kong and focusing on lonely policemen (Takeshi Kaneshiro and Tony Leung Chiu-wai) who each fall for a woman (Brigitte Lin and Faye Wong). Wong was keen to experiment with "two crisscrossing stories in one movie" and worked spontaneously, filming at night what he had written that day. Peter Brunette notes that "Chungking" is considerably more fun and lighthearted than the director's previous efforts, but deals with the same themes. At the 1995 Hong Kong Film Awards it was named Best Picture, and Wong received Best Director. Miramax acquired the film for American distribution, which, according to Brunette, "catapulted Wong to international attention". Stephen Schneider includes it in his book "1001 Movies You Must See Before You Die" with the summary: "While other films by Wong may pack more emotional resonance, "Chungking Express" gets off on sheer innocence, exuberance, and cinematic freedom, a striking triumph of style over substance".


title: Wong Kar-wai

text: Wong continued to work without break, expanding his ideas from "Chungking Express" into another film about alienated young adults in contemporary Hong Kong. "Chungking Express" had originally been conceived as three stories, but when time ran out, Wong developed the third as a new project, "Fallen Angels", with new characters. Wong conceived both films as complementary studies of Hong Kong: "To me "Chungking Express" and "Fallen Angels" are one film that should be three hours long."


title: Wong Kar-wai

text: "Fallen Angels" is broadly considered a crime thriller, and contains scenes of extreme violence, but is atypical of the genre and heavily infused with Wong's fragmented, experimental style. The loose plot again involves two distinct, subtly overlapping narratives, and is dominated by frantic visuals. The film mostly occurs at night and explores the dark side of Hong Kong, which Wong planned intentionally to balance the sweetness of "Chungking": "It's fair to show both sides of a coin". Takeshi Kaneshiro and Charlie Young were cast again, but new to Wong's films were Leon Lai, Michelle Reis and Karen Mok. Upon release in September 1995, several critics felt that the film was too similar to "Chungking Express" and some complained that Wong had become self-indulgent. However, as time went on, critics would go on to have a significant re-appraisal of the film, and it has amassed a large cult following, becoming one of Wong’s most popular and iconic films. "Fallen Angels" has often been stated as one of the director’s most stylish films, and it has also been received with praise for its non-conventional, fragmented plot. Film historians Zhang Yingjin and Xiao Zhiwei commented: "While not as groundbreaking as its predecessors, the film is still different and innovative enough to confirm [Wong's] presence on the international scene."


title: Wong Kar-wai

text: While his reputation grew steadily throughout the early 1990s, Wong's international standing was "thoroughly consolidated" with the 1997 romantic drama "Happy Together" (1997). Its development was influenced by the handover of Hong Kong from Britain to China, which occurred that year. Wong was widely expected to address the event in his next film; instead, he avoided the pressure by choosing to shoot in Argentina. The issues of the handover were nevertheless important: knowing that homosexuals in Hong Kong faced uncertainty after 1997, Wong decided to focus on a relationship between two men. He was keen to present the relationship as ordinary and universal, as he felt Hong Kong's previous LGBT films had not.


title: Wong Kar-wai

text: "Happy Together" tells the story of a couple (Tony Leung Chiu-wai and Leslie Cheung) who travel to Buenos Aires in an effort to save their relationship. Wong decided to change the structure and style from his previous films, as he felt he had become predictable. Teo, Brunette, and Jeremy Tambling all see "Happy Together" as a marked change from his earlier work: the story is more linear and understandable, there are only three characters (with no women at all), and while it still has Doyle's "exuberant" photography, it is more stylistically restrained. After a difficult production period – where a six-week shoot was dragged out to four months – the film was released in May 1997 to great critical acclaim. It competed for the Palme d'Or at the Cannes Film Festival, where Wong became Hong Kong's first winner of the Best Director Award (an achievement he downplayed: "it makes no difference, it’s just something you can put on an ad.")


title: Wong Kar-wai

text: In his 2005 monograph, Brunette opines that "Happy Together" marked "a new stage in [Wong's] artistic development", and along with its successor – "In the Mood for Love" (2000) – showcases the director at "the zenith of his cinematic art." The latter film emerged from a highly complicated production history that lasted two years. Several different titles and projects were planned by Wong before they evolved into the final result: a romantic melodrama set in 1960s Hong Kong that is seen as an unofficial sequel to "Days of Being Wild". Wong decided to return to the era that fascinated him, and reflected his own background by focusing on Shanghainese émigrés.


title: Wong Kar-wai

text: Maggie Cheung and Tony Leung Chiu-wai play the lead characters, who move into an apartment building on the same day in 1962 and discover that their spouses are having an affair; over the next four years they develop a strong attraction. Teo writes that the film is a study of "typical Chinese reserve and repressed desire", while Schneider describes how the "strange relationship" is choreographed with "the grace and rhythm of a waltz" and depicted in "a dreamlike haze by an eavesdropping camera".


title: Wong Kar-wai

text: The shoot lasted 15 months, with both Cheung and Leung reportedly driven to their breaking points. Wong shot more than 30 times the footage he eventually used, and only finished editing the film the morning before its Cannes premiere. At the festival, "In the Mood for Love" received the Technical Grand Prize and Best Actor for Leung. It was named Best Foreign Film by the National Society of Film Critics. Wong said after its release: ""In the Mood for Love" is the most difficult film in my career so far, and one of the most important. I am very proud of it." In subsequent years it has been included on lists of the greatest films of all time.


title: Wong Kar-wai

text: While "In the Mood for Love" took two years to complete, its sequel – "2046" – took double that time. The film was actually conceived first, when Wong picked the title as a reference to the final year of China's "One country, two systems" promise to Hong Kong. Although his plans changed and a new film developed, he simultaneously shot material for "2046", with the first footage dating back to December 1999. Wong immediately continued with the project once "In the Mood for Love" was complete, reportedly becoming obsessed with it. In Bettinson's account, it "became a behemoth, impossible to finish".


title: Wong Kar-wai

text: "2046" continues the story of Chow Mo-wan, Leung's character from "In the Mood for Love", though he is considered much colder and very different. Wong found that he did not want to leave the character, and commenced where he left off in 1966; nevertheless, he claimed: "It's another story, about how a man faces his future due to a certain past". His plans were vague and according to Teo, he set "a new record in his own method of free-thinking, time-extensive and improvisatory filmmaking" with the production. Scenes were shot in Beijing, Shanghai, Hong Kong, Macau, and Bangkok. Actresses Zhang Ziyi and Gong Li were cast to play the women who consume Mo-wan, as the character plans a science fiction novel titled "2046". The film premiered at the 2004 Cannes Film Festival, but Wong delivered the print 24 hours late and still was not happy: he continued editing until the film's October release. It was Wong's most expensive and longest-running project to date. "2046" was a commercial failure in Hong Kong, but the majority of western critics gave it positive reviews. Ty Burr of "The Boston Globe" praised it as an "enigmatic, rapturously beautiful meditation on romance and remembrance", while Steve Erikson of "Los Angeles Magazine" called it Wong's masterpiece.


title: Wong Kar-wai

text: Before starting on his next feature, Wong worked on the anthology film "Eros" (2004), providing one of three short films (the others directed by Michelangelo Antonioni and Steven Soderbergh) that centre on the theme of lust. Wong's segment, titled "The Hand", starred Gong Li as a 1960s call girl and Chang Chen as her potential client. Although "Eros" was not well received, Wong's segment was often called the most successful.


title: Wong Kar-wai

text: Following the difficult production of "2046", Wong wanted his next feature to be a simple, invigorating experience. He decided to make an English-language film in America, later justifying this by explaining: "It’s a new landscape. It’s a new background, so it’s refreshing." After hearing a radio interview with the singer Norah Jones he immediately decided to contact her, and she signed on as the lead. Wong's understanding of America was based only on short visits and what he had seen in films, but he was keen to depict the country accurately. As such, he co-wrote the film (one of the rare times a screenplay was pre-prepared) with author Lawrence Block. Titled "My Blueberry Nights", it focused on a young New Yorker who leaves for a road trip when she learns that her boyfriend has been unfaithful. Cast as the figures she meets were Jude Law, Natalie Portman, Rachel Weisz and David Strathairn.


title: Wong Kar-wai

text: Filming on "My Blueberry Nights" took place over seven weeks in 2006, on location in Manhattan, Memphis, Las Vegas, and Ely, Nevada. Wong produced it in the same manner as he would in Hong Kong, and the themes and visual style – despite Doyle being replaced by cinematographer Darius Khondji – remained the same. Premiering in May 2007, "My Blueberry Nights" was Wong's fourth consecutive film to compete for the Palme d'Or at Cannes. Although he considered it a "special experience", the film did not receive positive critical reviews. With common complaints that the material was thin and the product uneven, "My Blueberry Nights" became Wong's first critical failure.


title: Wong Kar-wai

text: Wong's next film was not released for five years, as he underwent another long and difficult production on "The Grandmaster" (2013) – a biographical film of the martial arts teacher Ip Man. The idea had occurred to him in 1999, but he did not commit to it until the completion of "My Blueberry Nights". Ip Man is a legendary figure in Hong Kong, known for training actor Bruce Lee in the art of Wing Chun, but Wong decided to focus on an earlier period of Ip's life (1936–1956) that covered the turmoil of the Second Sino-Japanese War and World War II. He set out to make "a commercial and colourful film". After considerable research and preparation, filming began in 2009. Tony Leung Chui-wai rejoined Wong for their seventh film together, having spent 18 months being trained in Wing Chun. The "gruelling" production lasted intermittently for three years, twice interrupted by Leung fracturing his arm, and is Wong's most expensive to date.


title: Wong Kar-wai

text: "The Grandmaster" is described by Bettinson as a mixture of popular and arthouse traditions, with form, visuals, and themes consistent with Wong's previous work. Three different versions of the film exist, as Wong shorted it from its domestic release for the 2013 Berlin Film Festival, and again for its US distribution by the Weinstein Company. Described in "Slant Magazine" as Wong's most accessible film since his debut, "The Grandmaster" won twelve Hong Kong Film Awards, including Best Film and Best Director, and received two Academy Award nominations (Cinematography and Production Design). Critics approved of the film, and with a worldwide gross of US$64 million it is Wong's most lucrative film to date.


title: Wong Kar-wai

text: When asked about his career in 2014, Wong told "The Independent", "To be honest with you, I feel I’m only halfway done." In November 2016, he was announced as taking over an upcoming film about the murder of Maurizio Gucci from previous director Ridley Scott, but commented in October 2017 that he was no longer involved in the project. In September 2017, Amazon Video issued a straight-to-series order for "Tong Wars", a television drama to be directed by Wong. It focuses on the gang wars that occurred in nineteenth-century San Francisco, but Amazon later dropped the series. Regarding his next film, the Asian media has reported that it will be titled "Blossoms" and based on Jin Yucheng's book of the same name, which focuses on numerous characters in Shanghai from the 1960s to the 2000s. "Blossoms" is also slated to become a web series for Tencent in which Wong produces.


title: Wong Kar-wai

text: In May 2019, Wong announced the 4K restoration of his entire filmography, which was released in 2021 in celebration of the 20th anniversary of "In the Mood for Love". The restoration was carried out by the Cineteca di Bologna's film restoration laboratory L'Immagine Ritrovata. Criterion Collection released Wong's restored filmography as a box set in the United States in March 2021.


title: Wong Kar-wai

text: Wong and his wife, Esther, have one child – a son named Qing. The director is known for always appearing in sunglasses, which James Motram of "The Independent" says adds "to the alluring sense of mystery that swirls around the man and his movies."


title: Wong Kar-wai

text: In 2009, Wong signed a petition in support of director Roman Polanski following his arrest in relation to his 1977 sexual abuse charges, who had been detained while traveling to a film festival, which the petition argued would undermine the tradition of film festivals as a place for works to be shown "freely and safely", and that arresting filmmakers traveling to neutral countries could open the door "for actions of which no-one can know the effects."


title: Wong Kar-wai

text: Wong is wary of sharing his favourite directors, but has stated that he watched a range of films growing up, from Hong Kong genre films to European art films. They were never labelled as such, and so he approached them equally and was broadly influenced. The energy of the Hong Kong films had a "tremendous" impact according to Brunette. Art professor Giorgio Biancorosso commented that Wong's international influences include Martin Scorsese, Michelangelo Antonioni, Alfred Hitchcock, and Bernardo Bertolucci. Some of his favorite contemporary filmmakers include Scorsese, Christopher Nolan, and Quentin Tarantino. He is often compared with French New Wave director Jean-Luc Godard. Wong's most direct influence was his colleague Patrick Tam, who was an important mentor and likely inspired his use of colour.


title: Wong Kar-wai

text: Outside of cinema, Wong has been heavily influenced by literature. He has a particular affinity for Latin American writers, and the fragmentary nature of his films came primarily from the "scrapbook structures" of novels by Manuel Puig and Julio Cortázar, which he attempted to emulate. Haruki Murakami, particularly his novel "Norwegian Wood", also provided inspiration, as did the writing of Liu Yichang. The television channel MTV was a further influence on Wong. He said in a 1998 interview: "In the late eighties, when [MTV] was first shown in Hong Kong, we were all really impressed with the energy and the fragmented structure. It seemed like we should go in this direction."