# List of Algerian football players in foreign leagues

## Abstract

This is a complete List of Algerian football players in foreign leagues, i.e. association football players who have played in foreign leagues.

For most of the twentieth century, most Algeria internationals played in the native Algerian Ligue Professionnelle 1; however, the national team has included some players based abroad from the beginning. While some in the 1960s and 1970s played for Algerian clubs, for example Hacène Lalmas and Mokhtar Khalem at CR Belcourt, others played in France, such as Sadek Boukhalfa with Nantes or Mustapha Zitouni with AS Monaco. Seven players of the squad for the 1982 FIFA World Cup came from a foreign club: Abdelmajid Bourebbou (Stade Lavallois), Mustapha Dahleb (Paris SG), Djamel Tlemcani (Stade de Reims), Djamel Zidane (KV Kortrijk), Karim Maroc (FC Tours), Faouzi Mansouri (Montpellier HSC) and Nourredine Kourichi (Girondins Bordeaux). By the time of the 1986 World Cup that number had increased to 11 (50% of the squad), and at the 2010 and 2014 tournaments almost all were playing abroad (there were three and two home-based players respectively in the 23-man squads).

## The history of Algerian players in Europe

A Large number of Algerian players have played in Europe as especially in France, the former colonial ruler of Algeria. The first Algerian player in Europe and first North African to play in France was Ali Benouna who joined Sète in 1930. He is the first Algerian player to win a European title, having won the French league and Coupe de France of the 1933–34 season with Sète. Benouna paved the way for more Algerians to soon taste the success of the French championship. This was done by Abdelkader Ben Bouali in the colors of Olympique de Marseille in the 1936–37 season, then Mohamed Firoud and Abdelaziz Ben Tifour on two consecutive occasions with Nice in 1950–51 and 1951–52, in addition to Rachid Mekhloufi in 1956–57 with Saint Etienne and Mohamed Maouche in the next season with Stade de Reims; all these titles came in the colonial era. As for the first player to win a title outside France, Mekhloufi holds that accolade for winning the Swiss League in 1962.

In relation to statistics, the most prominent of these are Rachid Mekhloufi, star of AS Saint-Étienne who scored 150 goals and won the league title four times. There is also Mustapha Dahleb, former star for Paris Saint-Germain where he achieved two Coupe de France victories and is one of the most popular players in the history of the club (310 matches and 98 goals in 10 seasons). Rabah Madjer was perhaps the best Algerian player to turn professional in Europe; he claimed ten trophies with FC Porto: three League, two Cup and two Super Cup on the domestic level and two continental titles on the level, including the European Cup in 1987 becoming the first Algerian and an African player to achieve this feat, and the Intercontinental Cup in Japan against Peñarol from Uruguay in which he scored the winning goal. In the 1970s and 1980s, Algerian players were generally not allowed to play professionally until they were over 28 years old which deprived many of the stars of the Algerian team at the time of a top-level career, especially after the 1982 FIFA World Cup, including Mehdi Cerbah, Hocine Yahi, Chaabane Merzekane, Fodil Megharia, Hacène Lalmas, Mahmoud Guendouz, Ali Bencheikh, Ali Fergani, Lakhdar Belloumi, Djamel Menad, Tedj Bensaoula and Omar Betrouni; some of them did play professionally but did not achieve much success because of their advancing age. There were some players allowed to moved abroad even though they had not reached the age of 28: Djamel Zidane, Rabah Madjer and Salah Assad.

Several other players have achieved prominent titles: Rafik Djebbour won eight titles, four League and 4 in the cu, followed by El Arbi Hillel Soudani with 7 titles including three league and three cup, then Madjid Bougherra who won six trophies with Glasgow Rangers. Ahmed Reda Madouni was the first Algerian Bundesliga champion in the colours of Borussia Dortmund in the 2001–02 season (subsequently his career involved a strange fluctuation). in Eastern Europe, Selim Bouadla was crowned Hungarian league winner with Debrecen twice in the 2011–12 and 2013–14 season, noting that La Liga and Serie A has not tasted the taste of any Algerian player so far and the nearest thing was the Runner-up in Serie A by Djamel Mesbah in 2012 and Faouzi Ghoulam in 2016. The English Premier League, was won by Riyad Mahrez with Leicester City. the 2012–13 season is considered the best for Algerian players, where they won 12 titles including three league, seven cups, three Super Cup and one league cup achieved by seven players are Djebbour, Soudani, Abdoun, Ghoulam, Rani, Sayoud and Benzia, In 2018–19, Riyad Mahrez achieved the English treble with Manchester City as the first Algerian to achieve this achievement. In the 2017–18 season, 161 Algerian players (including those of the diaspora who represent the national team) featured across all the leagues in Europe, and were present in 31 of the 55 leagues.

At the level of individual titles Mahrez won the 2016 PFA Players' Player of the Year award. He was the first African to earn the accolade. There is also Ali Benarbia achieved the best player award in the French league with Girondins de Bordeaux. Sofiane Hanni also won the best player award. in the Belgian league with Mechelen as the first Algerian player achieves this award, El Arabi Hillel Soudani also with Dinamo Zagreb he won his first trophy in Croatia as the best player in the Prva liga after a vote of all the captains of the Prva liga Croatian clubs. as for at the level scorers There are only two Algerian players have achieved the title of top scorer of the league is in Europe, namely Ahmed Oudjani in the French league and Jabbour in Greek league and there are also Madjer, who won the title top scorer in the European Cup 1987–88 season. as for Makhloufi is considered the best Algerian scorer in Europe with 170 goal, including 156 in the league, followed by Djebbour 132 goal which 110 in the league comes after Dahleb 115 goal, including 102 in the league. as for more than play games just in the leagues there Rachid Mekhloufi with 360 games, Abdelkader Ferhaoui 343, Ryad Boudebouz by 328, Mustapha Dahleb by 321 and finally Mohamed Salem 308 games. on the other hand more than hat-tricks record is Makhloufi 9 all hat-tricks with Saint-Étienne then Madjer by 5 and finally Ahmed Oudjani and El Arbi Hillel Soudani by 4 hat-tricks.

At the level of countries have made Algerians players 61 title in France which is sixteen league, twenty five cup, nine Coupe de la Ligue and eleven Trophée des Champions after that Luxembourg twenty title, fourteen League and six cups and finally Scotland thirteen title, five Premiership, four Cup and four League Cup. Other countries where the Algerians players at least won one title is the 17th state in the following figure Azerbaijan, Belgium, Bulgaria, Croatia, Cyprus, England, Finland, Germany, Greece, Hungary, Italy, Northern Ireland, Portugal, Romania, Switzerland, Czechoslovak and Turkey. the beginning of sparkling Algeria national team in 2009 began Algerian players Shares rise in Europe, such as El Arbi Hillel Soudani, who moved from ASO Chlef to Vitória Guimarães from Portugal. There are also Islam Slimani from CR Belouizdad to Sporting CP and then moved to Leicester City as the most expensive transfer deal for Algerian player in the history, The transfer fee paid to Sporting was reported as £28 million, a club record for Leicester. also there is the Paradou AC/JMG "El Ankaoui" Academy, which graduated many players to Europe and they are Ramy Bensebaini, Youcef Attal, Haithem Loucif, Farid El Mellali and Hicham Boudaoui who became the most expensive Algerian player has moved from an Algerian club to Europe with 4,000,000 euros.

## Gallery

### Algerian descent players played for other national teams

Due to Algeria's historic ties with France, there have been a number of Algerian players playing professionally in the French leagues, while the France national team has included players of Algerian heritage, most notably Zinedine Zidane, Karim Benzema and Samir Nasri.

- Zinedine Yazid Zidane (Arabic: زين الدين يزيد زيدان) was born on 23 June 1972 in La Castellane, Marseille, in Southern France. Zidane is of Algerian Kabyle descent. His parents, Smaïl and Malika, emigrated to Paris from the village of Aguemoune in the Berber-speaking region of Kabylie in northern Algeria in 1953 before the start of the Algerian War. The family, which had settled in the city's tough northern districts of Barbès and Saint-Denis, found little work in the region

- Karim Benzema was born in the city of Lyon, France, to French nationals of Algerian descent. As a practicing Muslim, he observes fasting during the Islamic holy month of Ramadan. His grandfather, Da Lakehal Benzema, lived in the village of Tigzirt, located in the northern town of Beni Djellil in Algeria before migrating to Lyon, where he eventually settled in the 1950s. Benzema's father, Hafid, was born in Tigzirt, while his mother, Wahida Djebbara, was born and raised in Lyon; her family originated from Oran. Benzema is the third youngest in the family and grew up with eight other siblings in Bron, an eastern suburb of Lyon. His younger brothers Gressy and Sabri are also footballers. The former currently plies his trade at the amateur level with Vaulx-le-Velin in the Division d'Honneur, the sixth division of French football, while the latter plays in the youth academy of a club in the family's hometown of Bron.

- Samir Nasri (Arabic: سمير نصري) was born in Septèmes-les-Vallons, a northern suburb of Marseille, to French nationals of Algerian descent. His mother, Ouassila Ben Saïd, and father, Abdelhafid Nasri, were both born in France; his father being born and raised in Marseille, while his mother being from nearby Salon-de-Provence. Nasri's grandparents emigrated to France from Algeria. His mother is a housewife and his father previously worked as a bus driver before becoming his son's personal manager. At the start of his football career, Nasri initially played under his mother's surname, Ben Saïd, before switching to Nasri, his father's surname, following his selection to the France under-16 team. He is the eldest of four children and is a non-practising Muslim.

- Nabil Fekir Having earned one cap at under-21 level for his native France, Fekir had been named in his ancestral Algeria 's squad for friendlies against Oman and Qatar in March 2015. However, he withdrew to take part in the French squad for friendlies against Brazil and Denmark. He made his debut on 26 March against the former at the Stade de France, replacing Antoine Griezmann for the final 16 minutes of a 1 – 3 defeat. He scored his first goal on 7 June, concluding a 3–4 home friendly defeat to Belgium. On 4 September, in a 1–0 away friendly win over Portugal, he ruptured three ligaments in his right knee, putting him out for an estimated six months.

- Karim Boudiaf (Arabic: كريم بوضياف) was born in France, and is of Moroccan-Algerian descent. On December 22, 2009, Boudiaf was called up to the Algeria Under-23 national team for a training camp in Algiers. Boudiaf acquired Qatari nationality and was called up to the Qatar national football team on November 13, 2013. He was capped in an unofficial friendly exhibition match against Saudi club Al Hilal. He made his official debut for the team on 25 December in the 2014 WAFF Championship in a 1–0 win against Palestine.

- Boualem Khoukhi (Arabic: بوعلام خوخي) was born and raised in Algeria. On November 9, 2010, Khoukhi was called up for the first time to the Algeria under–23 national team for a pair of friendlies against Tunisia. The Qatar Football Association attempted to naturalize Khoukhi shortly after he arrived in Qatar, however, he refused and claimed that he would not be naturalized for any amount of money. He stated his desire was to play with the senior Algeria national team. Subsequently, he received Qatari citizenship in order to assist in his club's foreign player quota. Despite his call up to Algeria's olympic team, he was called up to the Qatar B team on November 13, 2013, by compatriot Djamel Belmadi. When questioned about Khoukhi's call-up to the squad, Belmadi claimed that Khoukhi was naturalized prior to his call-up in order for his team, Al Arabi, to overcome the foreign player quota. Belmadi stated he was surprised when the QFA revealed Khoukhi was eligible to be called up to the Qatar national team. He made his official debut for the team on December 25 in the 2014 WAFF Championship in a 1–0 win against Palestine.

- Houssem Aouar (Arabic: حسام عوار) is eligible to feature for Algeria despite playing for the French youth teams at the U17 and U21 levels. In 2018, he was reported considering to represent Algeria at international level following a talk with former Lyon and current Real Madrid striker Karim Benzema. In January 2019, manager of Algeria Djamel Belmadi confirmed that he would visit Aouar and present the vision and project of the Desert Foxes in hope of convincing him to play in the upcoming Africa Cup of Nations. On 26 August 2020, Aouar received his first call-up for France to prepare for 2020–21 UEFA Nations League matches against Sweden and Croatia in early September. He made his debut on 7 October 2020 in a friendly against Ukraine. After years of back and forth rumours on his nationality change. In March 2023, Aouar switched his international allegiance from his birth country of France to the country of his parents, Algeria. In an interview with the Algerian Football Federation, he said, "the president held out his hand to me and it seemed like it was just meant to be. I had a second chance and I jumped on it." He also added that he "regretted" having played for France, saying that he felt he "hadn't made the best choice".

## European League

## List All-time top goalscorers in european Leagues

## Algerian players and European Competitions

Bold Still playing competitive football in Europe

Correct as of 1 June 2024 (UTC)

## List All-time top goalscorers for the Algerian players in european Competitions

Bold Still playing competitive football in Europe

Correct as of 1 June 2024 (UTC)

## List of Algerian players hat-tricks in european League

Position key: GK – Goalkeeper; DF – Defender; MF – Midfielder; FW – Forward; – Player scored four goals; – Player scored six goals; * – The home team

## Summary UEFA

## Individual Honours

## History of Algerian players in the rest of the world Leagues

Algerian players have played in all continents, most of them in Arab leagues in Africa and Asia, especially in the Persian Gulf, and Nadir Belhadj is the most successful player. played 214 matches in six seasons with the Qatari club Al-Sadd, and 43 matches in two seasons with Al-Sailiya. during which he won 5 titles including the AFC Champions League and participated in the FIFA Club World Cup. the first Algerian to Participates in this competition is Moussa Saïb with Al-Nassr in 2000 and scored one goal, At the level of titles Algerian players won 90 titles in twelve countries, namely Bahrain, Canada, Egypt, Kuwait, Mexico, Morocco, Saudi Arabia, Singapore, Thailand, United Arab Emirates and Tunisia the country where Algerian players have won the highest number of titles with 36, followed by Qatar with 23 titles. and more player won titles is Baghdad Bounedjah with seven, On the level of local league, Youcef Belaïli won with Espérance ST four league championships more than any other Algerian player. in 2010 witnessed the achievement of four Algerian players S.League and League Cup in Singapore, they are Khaled Kharroubi, Karim Boudjema, Nordine Talhi and Mansour Lakehal which has never happened before, The two brothers Mustapha and Abdelaziz Ben Tifour, first who won title outside Algeria by winning the Tunisian Cup twice in 1947 and 1948.

At the level of continental titles and start in Africa, where the Algerian players won eight titles in CAF Champions League, CAF Confederation Cup and CAF Super Cup, mostly with Tunisian clubs and the first to win the continental title is the international goalkeeper Nacerdine Drid with Moroccan club Raja Casablanca in 1989 led by Algerian coach Rabah Saâdane. On 9 November 2018, Twenty-two years later, Youcef Belaïli won the CAF Champions League and for the first time in its new version after winning the final against Al-Ahly, he is the fourth Algerian player to win this title. On the level of Asia, Nadir Belhadj won the AFC Champions League title for the first time for an Algerian player in 2011 and scored the decisive penalty kick.

The transfers of Algerian players in the rest of the world Leagues and the most prominent, Khaled Kharroubi is the first Algerian to play in South America and exactly in Brazil with Vitória where he played for one season. Aymen Tahar is the first Algerian to play in the J1 League, but has played only one match. also Karim Matmour is the first Algerian to play in Australia A-League where he joined to Adelaide United, but he left in December 2017, terminating his contract early after playing 11 games. Raïs M'Bolhi is also the first Algerian to play in Major League Soccer with a club Philadelphia Union. After playing in only 9 matches in the 2015 season, head coach, Jim Curtin said that M'Bolhi would never play again for Philadelphia. M'Bohli is rated as one of the worst signings in club history., On 22 January 2018, Saphir Taïder signed a three-year deal at Major League Soccer franchise Montreal Impact, starting with a two-year loan and the option of a fourth year. He joined as a Designated Player. and the first goal for an Algerian player in MLS was against Atlanta United FC in a 4–1 defeat away. in Africa, Farès Hachi is the first Algerian to play in South Africa when he joined African champion Mamelodi Sundowns. but played only 21 game in the Premier Soccer League in a season and a half and then left South Africa.

Also there is the French-born Chaher Zarour who spent the Vietnam League 1 with Sanna Khánh Hòa as the first Algerian player to play there. The first player to play in South Asia was Hamid Berguiga, when he joined Brunei DPMM in Brunei, who plays in the Singapore league and won the League Cup in 2009 first in this region for an Algerian player. In North America, Andy Delort became the first Algerian to win a title there with Mexican club Tigres UANL where Delort won Liga MX Apertura in 2016, although he did not have Algerian citizenship until 2019. Also his transfer deal was the highest for an Algerian player outside Europe where he signed a four-year contract while the transfer fee paid to Caen was reported as €8 million. Three years after Saphir Taïder achieved the Canadian Championship with Montreal Impact after winning against Toronto FC in the final first for an Algerian player.

On the level of statistics and awards, Algerian players won the top scorer in eight times, most notably Bounedjah four times one in Tunisia with Etoile du Sahel and three with Al-Sadd and is considered the same player the most recorded hat-tricks with thirteen. Bounedjah also won the CAF Confederation Cup top scorer with Etoile du Sahel in 2015. On 12 August 2018, Bounedjah broke the Qatar Stars League single-game goal record, scoring 7 goals in a 10–1 win against Al Arabi., Bounedjah continued his success at the individual level by winning the top scorer of the 2018 AFC Champions League with 13 goals to become the first Algerian and the first player from a Qatari club to achieve this award, The Al-Sadd forward matched the all-time single tournament record held by Muriqui who netted the same tally by the conclusion of Guangzhou Evergrande's 2013 campaign. On 7 December 2018, Bounedjah beats Qatar goal record with 28 goals after just 14 matches, He broke the record held by Brazilian striker Clemerson de Araújo, who scored 27 goals in 2007–08. On 23 February 2019, Bounedjah scored in the Qatari classico against Al-Rayyan his 100 goal in all leagues competitions to become the first Algerian player to reach him With one club outside Europe. After changing the laws in Tunisia and considering the players from North Africa local a large number of Algerian players Join the Tunisian Ligue Professionnelle 1.

## Rest of the world Leagues

## League statistics rest of the world

## Algerian players in the rest of the world intercontinental Competitions

Bold Still playing competitive football in the rest of the world

## List of Algerian players hat-tricks in the rest of the world Leagues

Position key: GK – Goalkeeper; DF – Defender; MF – Midfielder; FW – Forward; – Player scored four goals; – Player scored five goals; – Player scored seven goals; * – The home team

## List All-time top goalscorers in All the rest of the world Competitions

## Summary


CTDNEP1

# CTDNEP1

## Abstract

In cell biology, CTDNEP1 (CTD nuclear envelope phosphatase 1) is a protein coding gene involved in neural development. It is a member of DXDX(T/V) phosphatase family and is a potential regulator of neural tube development in Xenopus. The gene promotes neural development by inhibiting bone morphogenetic proteins (BMPs). The encoded protein is relatively small and only contains 244 amino acids.

## Description

CTDnep1, which stands for CTD nuclear envelope phosphatase 1. It is a protein coding gene, which include phosphatase activity and protein serine/threonine phosphatase activity. CTDnep1 encodes a protein serine/threonine phosphatase and dephosphorylates LPIN1 and LPIN2. LPIN1 and LPIN2 catalyze the reaction of the conversion of phosphatidic acid to diacylglycerol. The reaction can affect and change the lipid concentration of the endoplasmic reticulum and the nucleus.

## Dullard and BNP signaling

Neural development happens in the dorsal ectoderm. In the genus Xenopus, over expression of CTDNEP1 undergoes apoptosis in early development. CTDNEP1 helps promote Ubiquitin by proteosomal degradation. CTDNEP1 mRNA is derived from maternal genes and is localized within the animal neural hemisphere. Functioning negatively for the regulation of Bone Morphogenetic Proteins (BMPs), CTDNEP1 conserves the C-terminal region of NLI-IF, in which is fairly dominant in cellular functions. CTDNEP1 is essential for inhibiting BMP receptor activation during Xenopus neuralization.

## Human Dullard

Human CTDNEP1 has shown that the protein has two membrane spanning regions. One end is the N-terminal end, which helps localize the protein to the nuclear envelope. CTDNEP1 dephosphorylates the mammalian phosphatidic acid phosphatase, lipin. CTDNEP1 participates in a unique phosphatase cascade regulating nuclear membrane biogenesis, and that this cascade is conserved from yeast to mammals. There is belief that CTDNEP1 may have other targets that is not only associated with the nuclear envelope. In recent studies, CTDNEP1 interacts with BMP type 1 to inhibit dependent phosphorylation. This can conclude that it is a potential source for regulating the level of BMP signaling and can affect germ cell specification.

CTD nuclear envelope phosphatase 1 is a protein in humans that is encoded by the CTDNEP1 gene.


2024–25 Primeira Liga

# 2024–25 Primeira Liga

## Abstract

The 2024–25 Liga Portugal (also known as Liga Portugal Betclic for sponsorship reasons) is the 91st season of the Primeira Liga, the top professional league for Portuguese association football clubs and the fourth season under the current Liga Portugal title. This is the eighth Primeira Liga season to use video assistant referee (VAR). Sporting CP are the defending champions, having won their 20th title the previous season.

## Teams

### Changes

Santa Clara (after one year absence), Nacional (after three years absence) and AVS (promoted for the first time in their history), were promoted from the 2023–24 Liga Portugal 2, replacing Vizela, Chaves and Portimonense (relegated after three, two and seven years on the top flight, respectively).

## League table

## Results

### Positions by round

The table lists the positions of teams after each week of matches. In order to preserve chronological evolvements, any postponed matches are not included to the round at which they were originally scheduled, but added to the full round they were played immediately afterwards.

## Statistics

### Top goalscorers

#### Hat-tricks

(H) – Home team (A) – Away team

## Awards


Dejan Živković (footballer, born 1982)

# Dejan Živković (footballer, born 1982)

## Abstract

Dejan Živković (Serbian Cyrillic: Дејан Живковић; born 28 April 1982) is a Serbian professional footballer who plays as a midfielder.

## Honours

- Serbian First League: 2014–15


# Poisons or the World History of Poisoning

## Abstract

Poisons or the World History of Poisoning (Russian: Яды, или Всемирная история отравлений, romanized: Yady, ili vsemirnaya istoriya otravleniy) is a 2001 Russian fantastical absurdist comedy directed by Karen Shakhnazarov.

## Plot

Young family of Volkov's, Oleg and Katya, move to an apartment they bought and get acquainted with their neighbor, locksmith Arnold Sharapov. Right during a friendly dinner Katya cheats on her husband. Frustrated Oleg decides to drown his sorrows in alcohol, but at the bar accidentally meets Ivan Petrovich Prokhorov, pensioner, whose wife in his time was also unfaithful. In a conversation with the nice old man, Oleg learns that Prokhorov punished his wife by slipping poison into her yogurt. And now Ivan strongly persuades Oleg to also kill his unfaithful wife, using a small collection of poisons which Prokhorov constantly carries with him.

After some hesitation Oleg decides to do the terrible thing, but random interference from his mother-in-law Eugenia Ivanovna Kholodkova saves the wife of the hapless poisoner. As a result of a family quarrel, Oleg leaves the house and is a guest of Zoya, wife of Arnold, who in turn drove her traitor-husband out of the house. Oleg and Zoya fall in love with each other and decide to live together.

But the former spouses of the loving couple, consumed with anger and envy decide to destroy them. On the advice of the insidious mother-in-law Evgenia Ivanovna, Arnold and Katya want to invite Oleg and Zoya to dinner together and poison them by feeding them contaminated burgers. Learning this, Oleg first seeks the advice of experienced poisoner Prokhorov, who offers a number of retaliatory steps brilliant in their deviousness. But in the end Oleg decides to let go peacefully, both couples divorce, Oleg and Zoya begin together an existence full of love and mutual interests...

Throughout the action, under the influence of Prokhorov's stories about famous poisoners Oleg often "daydreams", imagining crimes of these villains. Central figure in Oleg's visions becomes Pope Alexander VI Borgia, the famous medieval poisoner and a victim of his own treachery...

## Cast

- Ignat Akrachkov as Oleg Volkov, actor

- Oleg Basilashvili as Ivan Petrovich Prokhorov, pensioner / Pope Alexander VI

- Zhanna Dudanova as Katya, Oleg's wife

- Aleksandr Bashirov as Arnold Sharapov, locksmith

- Olga Tumaykina as Zoya Filimonova, sportswoman, Arnold's wife

- Lyudmila Kasatkina as Eugenia Ivanovna Kholodkova, Oleg's mother-in-law

- Andrei Panin as Cesare Borgia

- Nikolay Afanasyev as Cardinal di Carnet

- Yuriy Osherov as Socrates

- Aleksandr Andreevich as Artaxerxes II of Persia

- Elena Fomina as Parysatis

- Veronika Nikolaeva as Stateira, Artaxerxes's wife

- Marina Kazankova as Lucrezia Borgia

- Ekaterina Klimova as Jeanne d'Albret

- Elena Obukhova as Madame de Brinvilliers

- Ivan Lakshin as Nero

- Fedor Shelenkov as Caligula

- Timur Matsiev as Khan Meñli I Giray

- Dmitri Dyuzhev as Dr. Edme Costa

- Yelena Zakharova as actress in the theater

## Awards

The film was awarded the Grand Prix at the Kinotavr film festival in Sochi. At the Karlovy Vary International Film Festival the picture was nominated for the Crystal Globe and was screened at the 51st Berlin International Film Festival.


Vedado

# Vedado

## Abstract

Vedado (Spanish: El Vedado, Spanish pronunciation:) is a central business district and urban neighborhood in the city of Havana, Cuba. Bordered on the east by Calzada de Infanta and Central Havana, and on the west by the Alemendares River and Miramar / Playa district, Vedado is a more modern part of the city than the areas to the east, developed in the first half of the 20th century, during the Republic period. In 2016 it was described by one commentator as the city's "most affluent" section. The main street running east to west is Calle 23, also known as "La Rampa". The northern edge of the district is the waterfront seawall known as the Malecón, a famous and popular place for social gatherings in the city. The area popularly referred to as 'Vedado' consists of the wards (consejos populares) of Vedado, Rampa, Vedado-Malecón and Carmelo, all in the municipality of Plaza de la Revolución.

## Notable sites

Among the notable sites in Vedado are the hotels: Hotel Nacional de Cuba (National Hotel), the Havana Libre (former Hilton), Melia Cohiba Hotel and Hotel Riviera.

In addition:

- Colon Cemetery

- FOCSA Building, tallest building in Cuba at 121 m

- Edificio del Seguro Médico, Havana

- López Serrano Building, first skyscraper in Cuba

- Radiocentro CMQ Building

- Coppelia (ice cream parlor)

- Embassy of the United States, Havana

- José Martí Anti-Imperialist Plaza

- Jewish religious centers include the Gran Sinagoga Bet Shalom and the Centro Hebreo Sefaradi

- John Lennon Park, named for the statue of Lennon located there

- Monument to the Victims of the USS Maine

- University of Havana

- National broadcast center for Cuban television.

- Cementerio Chino (The Chinese Cemetery)

Nearby neighborhoods include:

- To the east: Central Havana

- To the west: Miramar

## Economy

Aero Caribbean has its headquarters in Vedado.

The Venezuelan airline Conviasa has an office in the IACC Building in Vedado.

## Government and infrastructure

Instituto de Aeronáutica Civil de Cuba, Cuba's civil aviation authority, has its headquarters in Vedado.

## Culture

### Gay scene

23rd Street in Vedado is also the centerpoint of the city's gay scene in a country which now grants many rights to LGBT citizens. At night, 23rd St. is reminiscent of a gay district between the Cinema Yara and Coppelia ice cream parlor, and the foot of 23rd at the Malecón, with numerous gay entertainment options nearby such as the Bim Bom outdoor bar and the Las Vegas nightclub. Many of the casas particulares target LGBT clients as customers.


Hyaluronic acid

# Hyaluronic acid

## Abstract

Hyaluronic acid (/ ˌ h aɪ. ə l j ʊəˈr ɒ n ɪ k /; abbreviated HA; conjugate base hyaluronate), also called hyaluronan, is an anionic, nonsulfated glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues. It is unique among glycosaminoglycans as it is non-sulfated, forms in the plasma membrane instead of the Golgi apparatus, and can be very large: human synovial HA averages about 7 MDa per molecule, or about 20,000 disaccharide monomers, while other sources mention 3–4 MDa.

Medically, hyaluronic acid is used to treat osteoarthritis of the knee, dry eye, for wound repair, and as a cosmetic filler.

The average 70 kg (150 lb) person has roughly 15 grams of hyaluronan in the body, one third of which is turned over (i.e., degraded and synthesized) per day.

As one of the chief components of the extracellular matrix, it contributes significantly to cell proliferation and migration, and is involved in the progression of many malignant tumors. Hyaluronic acid is also a component of the group A streptococcal extracellular capsule, and is believed to play a role in virulence.

## Physiological function

Until the late 1970s, hyaluronic acid was described as a " goo " molecule, a ubiquitous carbohydrate polymer that is part of the extracellular matrix. For example, hyaluronic acid is a major component of the synovial fluid and was found to increase the viscosity of the fluid. Along with lubricin, it is one of the fluid's main lubricating components.

Hyaluronic acid is an important component of articular cartilage, where it is present as a coat around each cell (chondrocyte). When aggrecan monomers bind to hyaluronan in the presence of HAPLN1 (hyaluronic acid and proteoglycan link protein 1), large, highly negatively charged aggregates form. These aggregates imbibe water and are responsible for the resilience of cartilage (its resistance to compression). The molecular weight (size) of hyaluronan in cartilage decreases with age, but the amount increases.

A lubricating role of hyaluronan in muscular connective tissues to enhance the sliding between adjacent tissue layers has been suggested. A particular type of fibroblasts, embedded in dense fascial tissues, has been proposed as being cells specialized for the biosynthesis of the hyaluronan-rich matrix. Their related activity could be involved in regulating the sliding ability between adjacent muscular connective tissues.

Hyaluronic acid is also a major component of skin, where it is involved in repairing tissue. When skin is exposed to excessive UVB rays, it becomes inflamed (sunburn), and the cells in the dermis stop producing as much hyaluronan and increase the rate of its degradation. Hyaluronan degradation products then accumulate in the skin after UV exposure.

While it is abundant in extracellular matrices, hyaluronan also contributes to tissue hydrodynamics, movement, and proliferation of cells and participates in a number of cell surface receptor interactions, notably those including its primary receptors, CD44 and RHAMM. Upregulation of CD44 itself is widely accepted as a marker of cell activation in lymphocytes. Hyaluronan's contribution to tumor growth may be due to its interaction with CD44. Receptor CD44 participates in cell adhesion interactions required by tumor cells.

Although hyaluronan binds to receptor CD44, there is evidence hyaluronan degradation products transduce their inflammatory signal through toll-like receptor 2 (TLR2), TLR4, or both TLR2 and TLR4 in macrophages and dendritic cells. TLR and hyaluronan play a role in innate immunity.

There are limitations including the in vivo loss of this compound limiting the duration of effect.

### Wound repair

As a major component of the extracellular matrix, hyaluronic acid has a key role in tissue regeneration, inflammation response, and angiogenesis, which are phases of wound repair. As of 2023, however, reviews of its effect on healing for chronic wounds including burns, diabetic foot ulcers or surgical skin repairs show either insufficient evidence or only limited positive clinical research evidence. There is also some limited evidence to suggest that hyaluronic acid may be beneficial for ulcer healing and may help to a small degree with pain control. Hyaluronic acid combines with water and swells to form a gel, making it useful in skin treatments as a dermal filler for facial wrinkles; its effect lasts for about 6 to 12 months, and treatment has regulatory approval from the US Food and Drug Administration.

### Granulation

Granulation tissue is the perfused, fibrous connective tissue that replaces a fibrin clot in healing wounds. It typically grows from the base of a wound and is able to fill wounds of almost any size it heals. HA is abundant in granulation tissue matrix. A variety of cell functions that are essential for tissue repair may attribute to this HA-rich network. These functions include facilitation of cell migration into the provisional wound matrix, cell proliferation, and organization of the granulation tissue matrix. Initiation of inflammation is crucial for the formation of granulation tissue; therefore, the pro-inflammatory role of HA as discussed above also contributes to this stage of wound healing.

### Cell migration

Cell migration is essential for the formation of granulation tissue. The early stage of granulation tissue is dominated by a HA-rich extracellular matrix, which is regarded as a conducive environment for the migration of cells into this temporary wound matrix. HA provides an open hydrated matrix that facilitates cell migration, whereas, in the latter scenario, directed migration and control of related cell mechanisms are mediated via the specific cell interaction between HA and cell surface HA receptors. It forms links with several protein kinases associated with cell locomotion, for example, extracellular signal-regulated kinase, focal adhesion kinase, and other non-receptor tyrosine kinases. During fetal development, the migration path through which neural crest cells migrate is rich in HA. HA is closely associated with the cell migration process in granulation tissue matrix, and studies show that cell movement can be inhibited, at least partially, by HA degradation or blocking HA receptor occupancy.

By providing the dynamic force to the cell, HA synthesis has also been shown to associate with cell migration. Basically, HA is synthesized at the plasma membrane and released directly into the extracellular environment. This may contribute to the hydrated microenvironment at sites of synthesis, and is essential for cell migration by facilitating cell detachment.

### Skin healing

HA plays an important role in the normal epidermis. HA also has crucial functions in the reepithelization process due to several of its properties. These include being an integral part of the extracellular matrix of basal keratinocytes, which are major constituents of the epidermis; its free-radical scavenging function, and its role in keratinocyte proliferation and migration.

In normal skin, HA is found in relatively high concentrations in the basal layer of the epidermis where proliferating keratinocytes are found. CD44 is collocated with HA in the basal layer of epidermis where additionally it has been shown to be preferentially expressed on plasma membrane facing the HA-rich matrix pouches. Maintaining the extracellular space and providing an open, as well as hydrated, structure for the passage of nutrients are the main functions of HA in epidermis. A report found HA content increases in the presence of retinoic acid (vitamin A). The proposed effects of retinoic acid against skin photo-damage and photoaging may be correlated, at least in part, with an increase of skin HA content, giving rise to increased tissue hydration. It has been suggested that the free-radical scavenging property of HA contributes to protection against solar radiation, supporting the role of CD44 acting as a HA receptor in the epidermis.

Epidermal HA also functions as a manipulator in the process of keratinocyte proliferation, which is essential in normal epidermal function, as well as during reepithelization in tissue repair. In the wound healing process, HA is expressed in the wound margin, in the connective tissue matrix, and collocating with CD44 expression in migrating keratinocytes.

## Medical uses

Hyaluronic acid has been FDA-approved to treat osteoarthritis of the knee via intra-articular injection. A 2012 review showed that the quality of studies supporting this use was mostly poor, with a general absence of significant benefits, and that intra-articular injection of HA could possibly cause adverse effects. A 2020 meta-analysis found that intra-articular injection of high molecular weight HA improved both pain and function in people with knee osteoarthritis.

Hyaluronic acid has been used to treat dry eye. Hyaluronic acid is a common ingredient in skin care products. Hyaluronic acid is used as a dermal filler in cosmetic surgery. It is typically injected using either a classic sharp hypodermic needle or a micro-cannula. Some studies have suggested that the use of micro-cannulas can significantly reduce vessel embolisms during injections. Currently, hyaluronic acid is used as a soft tissue filler due to its bio-compatibility and possible reversibility using hyaluronidase. Complications include the severing of nerves and microvessels, pain, and bruising. Some side effects can also appear by way of erythema, itching, and vascular occlusion; vascular occlusion is the most worrisome side effect due to the possibility of skin necrosis, or even blindness in a patient. In some cases, hyaluronic acid fillers can result in a granulomatous foreign body reaction.

Hyaluronic acid is used to displace tissues away from tissues which are going to be subjected to radiation, for instance in one treatment option for some prostate cancers.

## Sources

Hyaluronic acid is produced on a large scale by extraction from animal tissues, such as chicken comb, and from Streptococci.

## Structure

Hyaluronic acid is a polymer of disaccharides, which are composed of D -glucuronic acid and N -acetyl- D -glucosamine, linked via alternating β-(1→4) and β-(1→3) glycosidic bonds. Hyaluronic acid can be 25,000 disaccharide repeats in length. Polymers of hyaluronic acid can range in size from 5,000 to 20,000,000 Da in vivo. The average molecular weight in human synovial fluid is 3–4 million Da, and hyaluronic acid purified from human umbilical cord is 3,140,000 Da; other sources mention average molecular weight of 7 million Da for synovial fluid. Hyaluronic acid also contains silicon, ranging 350–1,900 μg/g depending on location in the organism.

Hyaluronic acid is energetically stable, in part because of the stereochemistry of its component disaccharides. Bulky groups on each sugar molecule are in sterically favored positions, whereas the smaller hydrogens assume the less-favorable axial positions.

Hyaluronic acid in aqueous solutions self-associates to form transient clusters in solution. While it is considered a polyelectrolyte polymer chain, hyaluronic acid does not exhibit the polyelectrolyte peak, suggesting the absence of a characteristic length scale between the hyaluronic acid molecules and the emergence of a fractal clustering, which is due to the strong solvation of these molecules.

## Biological synthesis

Hyaluronic acid is synthesized by a class of integral membrane proteins called hyaluronan synthases, of which vertebrates have three types: HAS1, HAS2, and HAS3. These enzymes lengthen hyaluronan by repeatedly adding D -glucuronic acid and N -acetyl- D -glucosamine to the nascent polysaccharide as it is extruded via ABC-transporter through the cell membrane into the extracellular space. The term fasciacyte was coined to describe fibroblast-like cells that synthesize HA.

Hyaluronic acid synthesis has been shown to be inhibited by 4-methylumbelliferone (hymecromone), a 7-hydroxy-4-methylcoumarin derivative. This selective inhibition (without inhibiting other glycosaminoglycans) may prove useful in preventing metastasis of malignant tumor cells. There is feedback inhibition of hyaluronan synthesis by low-molecular-weight hyaluronan (<500 kDa) at high concentrations, but there is stimulation by high-molecular-weight hyaluronan (>500 kDa) when tested in cultured human synovial fibroblasts.

Bacillus subtilis recently has been genetically modified to culture a proprietary formula to yield hyaluronans, in a patented process producing human-grade product.

### Fasciacyte

A fasciacyte is a type of biological cell that produces hyaluronan-rich extracellular matrix and modulates the gliding of muscle fasciae.

Fasciacytes are fibroblast-like cells found in fasciae. They are round-shaped with rounder nuclei and have less elongated cellular processes when compared with fibroblasts. Fasciacytes are clustered along the upper and lower surfaces of a fascial layer.

Fasciacytes produce hyaluronan, which regulates fascial gliding.

## Biosynthetic mechanism

Hyaluronic acid (HA) is a linear glycosaminoglycan (GAG), an anionic, gel-like, polymer, found in the extracellular matrix of epithelial and connective tissues of vertebrates. It is part of a family of structurally complex, linear, anionic polysaccharides. The carboxylate groups present in the molecule make it negatively charged, therefore allowing for successful binding to water, and making it valuable to cosmetic and pharmaceutical products.

HA consists of repeating β4-glucuronic acid (GlcUA)-β3- N -acetylglucosamine (GlcNAc) disaccharides, and is synthesized by hyaluronan synthases (HAS), a class of integral membrane proteins that produce the well-defined, uniform chain lengths characteristic to HA. There are three existing types of HASs in vertebrates: HAS1, HAS2, HAS3; each of these contribute to elongation of the HA polymer. For an HA capsule to be created, this enzyme must be present because it polymerizes UDP-sugar precursors into HA. HA precursors are synthesized by first phosphorylating glucose by hexokinase, yielding glucose-6-phosphate, which is the main HA precursor. Then, two routes are taken to synthesize UDP-n-acetylglucosamine and UDP-glucuronic acid which both react to form HA. Glucose-6-phosphate gets converted to either fructose-6-phosphate with hasE (phosphoglucoisomerase), or glucose-1-phosphate using pgm (α-phosphoglucomutase), where those both undergo different sets of reactions.

UDP-glucuronic acid and UDP-n-acetylglucosamine get bound together to form HA via hasA (HA synthase).

### Synthesis of UDP-glucuronic acid

UDP-glucuronic acid is formed from hasC (UDP-glucose pyrophosphorylase) converting glucose-1-P into UDP-glucose, which then reacts with hasB (UDP-glucose dehydrogenase) to form UDP-glucuronic acid.

### Synthesis of N-acetyl glucosamine

The path forward from fructose-6-P utilizes glmS (amidotransferase) to form glucosamine-6-P. Then, glmM (Mutase) reacts with this product to form glucosamine-1-P. hasD (acetyltransferase) converts this into n-acetylglucosamine-1-P, and finally, hasD (pyrophosphorylase) converts this product into UDP-n-acetylglucosamine.

### Final step: Two disaccharides form hyaluronic acid

UDP-glucuronic acid and UDP-n-acetylglucosamine get bound together to form HA via hasA (HA synthase), completing the synthesis.

## Degradation

Hyaluronic acid can be degraded by a family of enzymes called hyaluronidases. In humans, there are at least seven types of hyaluronidase-like enzymes, several of which are tumor suppressors. The degradation products of hyaluronan, the oligosaccharides and very low-molecular-weight hyaluronan, exhibit pro- angiogenic properties. In addition, recent studies showed hyaluronan fragments, not the native high-molecular weight molecule, can induce inflammatory responses in macrophages and dendritic cells in tissue injury and in skin transplant.

Hyaluronan can also be degraded via non-enzymatic reactions. These include acidic and alkaline hydrolysis, ultrasonic disintegration, thermal decomposition, and degradation by oxidants.

## Etymology

Hyaluronic acid is derived from hyalos (Greek for vitreous, meaning ‘glass-like’) and uronic acid because it was first isolated from the vitreous humour and possesses a high uronic acid content. The term hyaluronate refers to the conjugate base of hyaluronic acid. Since the molecule typically exists in vivo in its polyanionic form, it is most commonly referred to as hyaluronan.

## History

Hyaluronic acid was first obtained by Karl Meyer and John Palmer in 1934 from the vitreous body in a cow's eye. The first hyaluronan biomedical product, Healon, was developed in the 1970s and 1980s by Pharmacia, and approved for use in eye surgery (i.e., corneal transplantation, cataract surgery, glaucoma surgery, and surgery to repair retinal detachment). Other biomedical companies also produce brands of hyaluronan for ophthalmic surgery.

Native hyaluronic acid has a relatively short half-life (shown in rabbits) so various manufacturing techniques have been deployed to extend the length of the chain and stabilise the molecule for its use in medical applications. The introduction of protein-based cross-links, the introduction of free-radical scavenging molecules such as sorbitol, and minimal stabilisation of the HA chains through chemical agents such as NASHA (non-animal stabilised hyaluronic acid) are all techniques that have been used to preserve its shelf life.

In the late 1970s, intraocular lens implantation was often followed by severe corneal edema, due to endothelial cell damage during the surgery. It was evident that a viscous, clear, physiologic lubricant to prevent such scraping of the endothelial cells was needed.

The name "hyaluronan" is also used for a salt.

## Other animals

Hyaluronan is used in treatment of articular disorders in horses, in particular those in competition or heavy work. It is indicated for carpal and fetlock joint dysfunctions, but not when joint sepsis or fracture are suspected. It is especially used for synovitis associated with equine osteoarthritis. It can be injected directly into an affected joint, or intravenously for less localized disorders. It may cause mild heating of the joint if directly injected, but this does not affect the clinical outcome. Intra-articularly administered medicine is fully metabolized in less than a week.

According to Canadian regulation, hyaluronan in HY-50 preparation should not be administered to animals to be slaughtered for horse meat. In Europe, however, the same preparation is not considered to have any such effect, and edibility of the horse meat is not affected.

## Research

Due to its accumulation in airway epithelial cells in various respiratory diseases, such as COVID-19, cystic fibrosis, influenza, and sepsis, hyaluronic acid is under study as a possible mediator of lung inflammatory mechanisms, as of 2022.

The high biocompatibility of hyaluronic acid and its common presence in the extracellular matrix of tissues indicate its possible use as a biomaterial scaffold in tissue engineering. In particular, research groups have found hyaluronan's properties for tissue engineering and regenerative medicine may be improved with cross-linking, producing a hydrogel. Crosslinking may allow a desired shape, as well as to deliver therapeutic molecules into a host. Hyaluronan can be crosslinked by attaching thiols (see thiomers) (trade names: Extracel, HyStem), hexadecylamides (trade name: Hymovis), and tyramines (trade name: Corgel). Hyaluronan can also be crosslinked directly with formaldehyde (trade name: Hylan-A) or with divinylsulfone (trade name: Hylan-B).

Due to its ability to regulate angiogenesis by stimulating endothelial cells to proliferate in vitro, hyaluronan can be used to create hydrogels to study vascular morphogenesis.

Research shows that abnormal hyaluronic acid (HA) metabolism is a major factor in tumor progression. HA and HA fragment-tumor cell interaction could activate the downstream signaling pathways, promoting cell proliferation, adhesion, migration and invasion, and inducing angiogenesis, lymphangiogenesis, epithelial-mesenchymal transition, stem cell-like property, and chemoradioresistance in digestive cancers.


Oocyte cryopreservation

# Oocyte cryopreservation

## Abstract

Oocyte cryopreservation is a procedure to preserve a woman's eggs (oocytes). This technique has been used to postpone pregnancy. When pregnancy is desired, the eggs can be thawed, fertilized, and transferred to the uterus as embryos. Several studies have shown that most infertility problems are due to germ cell deterioration related to aging. The procedure's success rate varies depending on the age of the woman, (with the odds of success being higher in younger women), as well as depending on health and genetic indicators. In 1986, the first human birth of oocyte cryopreservation was reported.

## Indications

Oocyte cryopreservation can increase the chance of a future pregnancy for four key groups of women:

- Those diagnosed with cancer who have not yet begun chemotherapy or radiotherapy Over 50,000 reproductive-age women are diagnosed with cancer each year in the United States. Chemotherapy and radiotherapy are toxic for oocytes, reducing the amount of viable eggs. Egg-freezing may be used in this case to preserve eggs.

- Over 50,000 reproductive-age women are diagnosed with cancer each year in the United States. Chemotherapy and radiotherapy are toxic for oocytes, reducing the amount of viable eggs. Egg-freezing may be used in this case to preserve eggs.

- Those undergoing treatment with assisted reproductive technologies who do not consider embryo freezing an option

- Those who would like to preserve their future ability to have children Women with a family history of early menopause may have an interest in fertility preservation to preserve viable eggs that could deteriorate at an earlier onset.

- Women with a family history of early menopause may have an interest in fertility preservation to preserve viable eggs that could deteriorate at an earlier onset.

- Those with ovarian diseases such as PCOS

Oocyte cryopreservation is one of many options for individuals undergoing IVF. In some cases, persons may prefer oocyte cryopreservation over other options, where freezing embryos is the primary procedure.

## Method

The egg retrieval process for oocyte cryopreservation is the same as that for in vitro fertilization. This includes one to several weeks of hormone injections that stimulate ovaries to ripen multiple eggs. When the eggs are mature, final maturation induction is performed, preferably by using a GnRH agonist rather than human chorionic gonadotrophin (hCG), since it decreases the risk of ovarian hyperstimulation syndrome with no evidence of a difference in live birth rate (in contrast to fresh cycles where usage of GnRH agonist has a lower live birth rate). The eggs are subsequently removed from the body by transvaginal oocyte retrieval. The procedure is usually conducted under sedation. The eggs are immediately frozen.

The egg is the largest cell in the human body and contains a large amount of water. When the egg is frozen, the ice crystals that form can destroy the integrity of the cell. To prevent this, the egg must be dehydrated before freezing. This is done using cryoprotectants which replace most of the water within the cell and inhibit the formation of ice crystals.

Eggs (oocytes) are frozen using either a controlled rate, a slow-cooling method, or a newer flash-freezing process known as vitrification. Vitrification is much faster but requires higher concentrations of cryoprotectants to be added. The result of vitrification is a solid glass-like cell, free of ice crystals. Vitrification has been developed and successfully applied in IVF treatment with the first live birth following the vitrification of oocytes achieved in 1999. Vitrification eliminates ice formation inside and outside of oocytes on cooling, during cryostorage, and as the oocytes warm. Vitrification is associated with higher survival rates and enhanced development compared to slow-cooling when applied to oocytes in metaphase II (MII). Vitrification has also become the method of choice for pronuclear oocytes, although prospective randomized controlled trials are still lacking.

During the freezing process, the zona pellucida, or shell of the egg can be modified preventing fertilization. Thus, when eggs are thawed and pregnancy is desired, a fertilization procedure known as ICSI (Intracytoplasmic Sperm Injection) is performed by an embryologist whereby sperm is injected directly into the egg with a needle rather than allowing sperm to penetrate naturally by placing it around the egg in a dish.

Immature oocytes have been grown until maturation in vitro, but it is not yet clinically available.

## Success rates

Early work investigating the percentage of transferred cycles showed lower frozen cycles compared with fresh cycles (approx. 30% and 50%), however more recent studies show "fertilization and pregnancy rates are similar to IVF/ICSI (or (in vitro fertilization/intracytoplasmic sperm injection) with fresh oocytes when vitrified and warmed oocytes are used as part of IVF/ICSI". These studies were completed mostly in young patients.

In a 2013 meta-analysis of more than 2,200 cycles using frozen eggs, scientists found the probability of having a live birth after three cycles was 31.5 percent for women who froze their eggs at age 25, 25.9 percent at age 30, 19.3 percent at age 35, and 14.8 percent at age 40.

Two 2000s studies showed that the rate of birth defects and chromosomal defects when using cryopreserved oocytes is consistent with that of natural conception.

Recent modifications in the protocol regarding cryoprotectant composition, temperature, and storage methods have had a large impact on the technology, and while it is still considered an experimental procedure, it is quickly becoming an option for women. Slow freezing traditionally has been the most commonly used method to cryopreserve oocytes and is the method that has resulted in the most babies born from frozen oocytes worldwide. Ultra-rapid freezing or vitrification represents a potential alternative freezing method.

In the fall of 2009, The American Society for Reproductive Medicine (ASRM) issued an opinion on oocyte cryopreservation concluding that the science holds "great promise for applications in oocyte donation and fertility preservation" because recent laboratory modifications have resulted in improved oocyte survival, fertilization, and pregnancy rates from frozen-thawed oocytes in IVF. The ASRM noted that from the limited research performed to date, there does not appear to be an increase in chromosomal abnormalities, birth defects, or developmental deficits in the children born from cryopreserved oocytes. The ASRM recommended that pending further research, oocyte cryopreservation should be introduced into clinical practice on an investigational basis and under the guidance of an Institutional Review Board (IRB). As with any new technology, safety and efficacy must be evaluated and demonstrated through continued research.

In October 2012, the ASRM lifted the experimental label from the technology for women with a medical need, citing success rates in live births, among other findings. However, they also warned against using it only to delay child-bearing.

In 2014, a Cochrane systematic review was published. It compared vitrification (the newest technology) versus slow freezing (the oldest one). Key results of that review showed that the clinical pregnancy rate was almost 4 times higher in the oocyte vitrification group than in the slow-freezing group, with moderate quality of evidence.

Immature oocytes have been grown until maturation in vitro at a 10% survival rate, but no experiment has been performed to fertilize such oocytes.

## Cost

The cost of the egg-freezing procedure (without embryo transfer) in the United States, the United Kingdom, and other European countries varies in between $5,000 and $12,000. The cost of egg storage can vary from $100 to more than $1,000. Provisional health programs do not cover social egg freezing. Furthermore, no provinces provide funding for IVF after social egg freezing.

Medical tourism may have lower costs than performing egg freezing in high-cost countries like the US. Some well-established medical tourism and IVF countries such as the Czech Republic, Ukraine, and Cyprus offer egg freezing at competitive prices. It is a lower-cost alternative to typical US options for egg freezing. Spain and the Czech Republic are popular destinations for this treatment.

Iranian insurance started to pay insurance incentives for women freezing their eggs in 2024.

## History

Cryopreservation itself has always played a central role in assisted reproductive technology. With the first cryopreservation of sperm in 1953 and of embryos twenty five years later, these techniques have become routine. Dr. Christopher Chen of Singapore reported the world's first pregnancy in 1986 using previously frozen oocytes. This report stood alone for several years followed by studies reporting success rates using frozen eggs to be much lower than those of traditional in vitro fertilization (IVF) techniques using fresh oocytes. Providing the lead to a new direction in cryobiology, Dr. Lilia Kuleshova was the first scientist to achieve vitrification of human oocytes that resulted in a live birth in 1999. Articles published in the journal Fertility and Sterility reported that pregnancy rates using frozen oocytes that were comparable to those of cryopreserved embryos and even fresh embryos.

## Elective oocyte cryopreservation

Elective oocyte cryopreservation, also known as social egg freezing, is non-essential egg freezing to preserve fertility for delayed child-bearing when natural conception becomes more problematic. The frequency of this procedure has steadily increased since October 2012 when the American Society for Reproductive Medicine (ASRM) lifted the 'experimental' label from the process. There was a spike in interest in 2014 when global corporations Apple and Facebook revealed they were introducing egg freezing as a benefit for their female employees. This announcement was controversial as some women found it empowering and practical, while others viewed the message these companies were sending to women trying to have a successful long-term career and a family as harmful and alienating. A string of "egg-freezing parties" hosted by third-party companies have also helped popularize the concept among young women. Social science research suggests that women use elective egg freezing to disentangle their search for a romantic partner from their plans to have children.

In 2016, then US Secretary of Defense Ash Carter announced that the Department of Defense would cover the cost of freezing sperm or eggs through a pilot program for active duty service members, to preserve their ability to start a family even if they sustain certain combat injuries.

There are still warnings for women using this technology to fall pregnant at an older age as the risk of pregnancy complications increases with a mother's age. However, studies have shown that the risk of congenital abnormalities in babies born from frozen oocytes is not increased further when compared to naturally conceived babies.

## Risks

The risks associated with egg freezing relate to the administration of medications to stimulate the ovaries and the procedure of egg collection.

The main risk associated with the administration of medications to stimulate the ovaries is ovarian hyperstimulation syndrome (OHSS). This is a transient syndrome in which there is increased permeability of the blood vessels, resulting in fluid loss from the vessels into the surrounding tissues. In most cases, the syndrome is mild, with symptoms such as abdominal bloating, mild discomfort, and nausea. In moderate OHSS there is increased abdominal bloating resulting in pain and vomiting. Reduced urine output may occur. Severe OHSS is serious with even further bloating so that the abdomen appears very distended, and thirst and dehydration occur with minimal urine output. There may be shortness of breath and there is an increased risk of DVT and/or pulmonary embolism. Kidney and liver function can be compromised. Hospitalization under specialist care is indicated. There is no treatment for OHSS, supportive care until the symptoms naturally resolve is required. If an hCG trigger has been used with no embryo transfer, OHSS usually resolves in 7–10 days. If an embryo transfer has occurred and pregnancy results, the symptoms may persist for several weeks. Doctors reduce the likelihood of OHSS occurring by decreasing the doses of gonadotropins (FSH) administered, using a GnRH agonist trigger (instead of an hCG trigger), and freezing all embryos for transfer rather than conducting a fresh embryo transfer.

Risks associated with the egg collection procedure relate to bleeding and infection. The collection procedure involves passing a needle through the wall of the vagina into vascular-stimulated ovaries. A small amount of bleeding is inevitable. In rare cases, there is excessive bleeding into the abdomen requiring surgery. Women undergoing the procedure must advise their specialist of all medications, including herbal supplements, they are using so the specialist can assess whether any of these medications will affect the ability of the blood to clot. Concerning infection, provided the woman does not have additional risk factors for infection (suppressed immune system, use of immuno-suppressive medications, or large ovarian endometriomas) the risk of infection is very low.

One additional risk of the ovaries being temporarily increased in size is ovarian torsion. Ovarian torsion occurs when an enlarged ovary twists around on itself, cutting off its blood supply. The condition is excruciatingly painful and requires urgent surgery to prevent the ischemic loss of the ovary.


2024 Texas Rangers season

# 2024 Texas Rangers season

## Abstract

The 2024 Texas Rangers season is the 64th of the Texas Rangers franchise overall, their 53rd in Arlington as the Rangers, and the fifth season at Globe Life Field. They entered the season as the defending World Series champions, after winning their first World Series title in franchise history, as well as the defending American League champions. The Rangers failed to improve on their 90–72 record from 2023 after their 9–2 loss to the Oakland Athletics on August 30th.

## Season standings

### American League West

### American League Wild Card

#### Record against opponents

Updated with the results of all games through September 12, 2024.

## Game Log

### Detailed records