Pope Pius XII , on the occasion of the 100th anniversary of Pius IX's institution of the feast, instructed the entire Latin Church at length on the devotion to the Sacred Heart in his encyclical letter  Haurietis aquas  of 15 May 1956. On 15 May 2006, the 50th anniversary of that encyclical,  Pope Benedict XVI  sent a letter to  Peter Hans Kolvenbach , the  Superior General of the Society of Jesus , reaffirming the importance of the devotion to the Sacred Heart of Jesus. On 24 October 2024,  Pope Francis  published his fourth encyclical, the 28,000-word  Dilexit nos  ("He loved us"), which reflects on the philosophical and theological meaning of "the heart" and addresses the importance of the devotion to the Sacred Heart in a contemporary context. [ 34 ] [ 35 ]


Worship of the Sacred Heart mainly consists of several  devotions , practices,  consecrations ,  hymns , the salutation of the Sacred Heart, and the  Litany of the Sacred Heart . It is common in Roman Catholic services.


Since  c.  1850 , groups, congregations, and countries have  consecrated  themselves to the Sacred Heart.


By a law voted on 24 July 1873, the  Basilica of the Sacred Heart  of Montmartre known as  National Vow , is declared of public utility by the  National Assembly  of 1871. On 16 June 1875, the  Archbishop of Paris , Cardinal Guibert layed the first stone of the basilica, honoring after two hundred years the fourth request of Jesus reported by Margaret Mary Alacoque from 16 June 1675. [ 36 ]


On 25 March 1874, by petition of president  Gabriel García Moreno  and  archbishop  José Ignacio Checa y Barba,  Ecuador  was the first country in the world to be  consecrated to the Sacred Heart  by legislative decree. [ 37 ] [ 38 ] [ 39 ] [ 40 ]  Since then, more than twenty countries have followed and consecrated themselves either by decree or at the initiative of their respective national Church, some of which renewed their consecration a few times. [ 41 ] [ 42 ]  On 22 June 1902,  Colombia  was consecrated by decree with the agreement of president  José Manuel Marroquín . [ 43 ] [ 44 ] [ 45 ]  On 30 May 1919,  Spain  was officially consecrated to the Sacred Heart by  King Alfonso XIII . [ 46 ] [ 47 ] [ 48 ] [ 49 ]


In the  Catholic tradition , the Sacred Heart has been closely associated with  Acts of Reparation to Jesus Christ . In his  encyclical   Miserentissimus Redemptor ,  Pope Pius XI  stated: "The spirit of expiation or reparation has always had the first and foremost place in the worship given to the Most Sacred Heart of Jesus." [ 50 ]  The  Golden Arrow Prayer  directly refers to the Sacred Heart.


The  Feast of the Sacred Heart  is a  solemnity  in the  liturgical calendar  of the  Latin Church . It is celebrated on the third Friday after  Pentecost , which was up until the changes in the  General Roman Calendar of Pope Pius XII  referred to as the Friday after the  octave  of Corpus Christi. It is the last feast day of the year that is dependent on the date of  Easter . The acts of  consecration ,  reparation , and  devotion  were introduced when the feast of the Sacred Heart was declared. Some Anglican Franciscans keep the feast under the name  (The) Divine Compassion of Christ . [ 51 ]


The month of June is traditionally devoted in a special way to the veneration of the Sacred Heart. [ 52 ] [ 53 ] [ 54 ]  Masses, novenas, and the recitation of devotional prayers in honor of the Sacred Heart are traditionally observed.


A personal  prayer of consecration to the Sacred Heart  was written by Saint  Margaret Mary Alacoque , [ 55 ]  allegedly under the inspiration of Jesus, which she wrote to the priest John Croiset, recommending that he include it in the book he was to publish about her revelations "It comes from Him, and He would not agree to its omission." [ 56 ]


On 25 May 1899,  Pope Leo XIII  wrote an  Act of Consecration of the Human Race to the Sacred Heart  in his  encyclical  letter  Annum sacrum , [ 57 ]  with the influence of  Mary of the Divine Heart  and in response to demands received over 25 years.


On 19 May 1908, a particular family consecration prayer known as the Act of Consecration of the Family to the Sacred Heart was approved and granted with an indulgence by  Pope Pius X . [ 58 ] [ 59 ]


The  First Fridays Devotion  is a devotion to offer  reparations for sins  to the  Eucharist  and in honor of the Sacred Heart, which had its origin in the  apparitions of Christ  reported by  Margaret Mary Alacoque . This devotion to the Sacred Heart of Jesus was fully approved by the Catholic Church [ 33 ]  and a "Great Promise" of final penance was made to those who practice the First Fridays Devotion. The devotion consists of several practices that are performed on the first Fridays of nine consecutive months. On these days, a person is to attend  Mass  and receive the Eucharist. If the need arises, in order to receive communion in a state of grace, a person should also make use of the  sacrament of penance  before attending Mass. [ 60 ]


Alacoque stated that she received a vision of Jesus in which she was instructed to spend an hour every Thursday night as a reparation and to pray and meditate on his  agony in the Garden of Gethsemane . [ 61 ]  This practice later became widespread among Roman Catholics and became the devotion of the  Holy Hour , a devotional tradition of spending an hour in prayers or in  Eucharistic adoration  in the presence of the Eucharist.


The act of enthroning the Sacred Heart entails placing an image of the Sacred Heart of Jesus in a place of honor in the home after a time of prayerful preparation. [ 62 ]  Many families will also place an image of the Immaculate Heart of Mary in tandem with the Sacred Heart image. [ 63 ] [ a ]


The practice of the home enthronement of the Sacred Heart was started by R. Mateo Crawley-Boevey, a priest of the  Congregation of the Sacred Hearts of Jesus and Mary , in 1907, having visited the apparition chapel in  Paray-le-Monial . [ 66 ]


Enthronement of the Sacred Heart is promoted by the National Enthronement Center in Fairhaven, Massachusetts, [ 67 ]  the Sacred Heart Apostolate of Knoxville, Tennessee, Sacred Heart Columbus in Columbus, Ohio, [ 68 ]  and the Sacred Heart Enthronement Network, a 501(c)(3) located in Columbus, Ohio. [ 69 ]  It is also endorsed by the  World Apostolate of Fátima .


The  Scapular of the Sacred Heart  and the  Scapular of the Sacred Hearts of Jesus and Mary  are  devotional articles  worn by some  Catholics . [ 70 ]


An early form of the Scapular of the Sacred Heart were cloth  badges  bearing an image of the Heart of Jesus. made and distributed by Margaret Mary Alacoque. [ 70 ]  Following the claims by Estelle Faguette that the  Virgin Mary had appeared  to her at  Pellevoisin  in 1876 and requested a scapular of the Sacred Heart of Jesus, a scapular of the proposed design was approved by the Congregation of Rites in 1900. It bears the representation of the Sacred Heart of Jesus on one side and that of the Virgin Mary under the title of Mother of Mercy on the other side. [ 71 ]


The  Litany of the Sacred Heart of Jesus  is common in Roman Catholic services and occasionally is found in  Anglican  services.


There is also a  Morning offering  to the Sacred Heart.


The " Alliance of the Hearts of Jesus and Mary " is a phrase coined by  Pope John Paul II  during his Angelus Address of September 15, 1985 when he mentioned that devotion to the  Sacred Heart of Jesus  and to the  Immaculate Heart of Mary , "...though distinct, they are interrelated...." [ 72 ]  symposia were held on the concept during the 1980s and 1990s. [ 73 ]


It was not until the seventeenth century when devotion to the Immaculate Heart of Mary was popularized by  John Eudes . Although Eudes always associated the two Hearts, he began his devotional teachings with the Heart of Mary, and then extended it to the Sacred Heart of Jesus. [ 74 ]


In the eighteenth and nineteenth centuries both devotions grew, particularly through the popularity of the  Miraculous Medal , depicting the Heart of Jesus thorn-crowned and the Heart of Mary pierced with a sword. [ 75 ]  The devotions and associated prayers grew into the twentieth century through the reported messages of  Our Lady of Fátima  saying that the Heart of Jesus wishes to be honored together with the Heart of Mary. [ 76 ]  In the 1956 encyclical  Haurietis aquas , Pope Pius XII encouraged both devotions.


The Sacred Heart crowned with thorns is depicted on the reverse side of the  Miraculous Medal , [ 77 ]


The Carillon-Sacré-Coeur flag has been adopted by the  Société Saint-Jean-Baptiste  in Québec.


Religious imagery depicting the Sacred Heart is frequently featured in homes. Ireland was consecrated to the Sacred Heart on  Passion Sunday  1873 by the bishops of Ireland, which led to the  Sacred Heart lamp  becoming a common devotional object in Irish homes. [ 78 ]  Sometimes the image is part of a set, along with the  Immaculate Heart of Mary . However, the  Sacred Congregation of Rites  stated in 1879 that images of the hearts of Jesus or Mary were not appropriate for being placed on the  altar  for Mass, although are appropriate for "private devotion". [ 79 ]


Sacred Heart  is a name used for many Catholic institutions, including schools, colleges, and hospitals in many countries. It is also the name of many Catholic parishes, and religious congregations.


Peter Coudrin  of France founded the  Congregation of the Sacred Hearts of Jesus and Mary  on 24 December 1800. A  religious order  of the Latin Church, the order carried out  missionary  work in  Hawaii . [ 80 ]


Clelia Merloni from  Forlì  (Italy) founded the  Congregation of the Apostles of the Sacred Heart of Jesus  in  Viareggio , Italy, on 30 May 1894. [ 81 ]


Devotion to the Sacred Heart may be found in some  Eastern Catholic Churches , particularly the  Ukrainian . [ 82 ]  Others see it as an example of  liturgical Latinisation . Many Eastern churches observe a comparable feast of "Jesus, Lover of Mankind", celebrated on July 17.


Heart: A History  is a 2018 book by  Sandeep Jauhar . In the book Jauhar discusses the historical experiments and procedures done in the past and how innovations can be taken for granted. [ 1 ]


The book begins with Jauhar discussing his personal health and family history, focusing on heart-related issues. He gives his opinion and talks about the advances in technology that have come about in the past few decades and how they have shaped the way doctors practice  cardiology  today.  Jauhar also discusses the old views that people had about the heart and why this was the last organ that was operated upon due to cultural perspectives and the level of difficulty.  He further notes several of his personal experiences as a cardiologist and states that the heart is still the center of attention of the body. Jauhar mentions research and experiments conducted on animals and humans, which he sees as unethical by modern standards while stating that without them society would not have the experience or procedures that are currently used.


Jauhar also covers the effects of emotions on the heart and how he believes stressors can significantly damage a person's heart. He states that doctors have lowered the risk of dying from a heart attack in a hospital to 3 percent, which he does not believe can be improved much further. He notes the difficulty for physicians to help patients prevent common stressors and that it has become easy to prescribe medicine for cholesterol. Finally, Jauhar advises that  yoga , meditation, and activities that help emotions should be taught in schools and the medical field.


Critical reception for the book has been positive, [ 2 ] [ 3 ] [ 4 ]  and received reviews from  The New Statesman ,  The Globe and Mail ,  and  Financial Express . [ 5 ] [ 6 ] [ 7 ]   The Washington Post  and  Business Standard  both wrote favorable reviews, with the former stating that it was "a fascinating education for those of us who harbor this most hallowed organ but know little about it.” [ 8 ] [ 9 ]


Interbeat interval  ( IBI ) is a scientific term used in the study of the  mammalian   heart .


Interbeat interval is a scientific term used in reference to the time interval between individual beats of the  mammalian   heart . Interbeat interval is abbreviated "IBI" and is sometimes written with a hyphen, "inter-beat interval". It is also sometimes referred to as a "beat-to-beat" interval.


IBI is generally measured in units of milliseconds. In normal heart function, each IBI value varies from beat to beat. This natural variation is known as  heart rate variability  (HRV). However, certain cardiac conditions may cause the individual IBI values to become nearly constant, resulting in the HRV being nearly zero. This can happen, for example, during periods of exercise as the heart rate increases and the beats become regular. Certain illnesses can cause the heart rate to increase and become uniform as well, such as when a subject is afflicted by an infection.


A number of instruments have been developed for specifically recording individual IBI values. Generally, the instruments are used in basic cardiology research, as there is yet no specific condition whose IBI statistics can be used to diagnose the condition or guide treatment for the condition. However, HRV is an active field of research, and IBI analysis can yield a rich amount of data that holds promise for future medical applications.


" Lady & Peebles " is the nineteenth episode of the  fourth season  of the American  animated television series   Adventure Time . The episode was written and storyboarded by Cole Sanchez and  Rebecca Sugar , from a story by Patrick McHale,  Kent Osborne , and  Pendleton Ward . It originally aired on  Cartoon Network  on August 20, 2012. The episode guest stars  George Takei  as Ricardio.


The series follows the adventures of  Finn  (voiced by  Jeremy Shada ), a human boy, and his best friend and adoptive brother  Jake  (voiced by  John DiMaggio ), a dog with magical powers to change shape and grow and shrink at will. In this episode,  Princess Bubblegum  (voiced by  Hynden Walch ) and Lady Rainicorn (voiced by  Niki Yang ) go searching for Finn and Jake, who have been missing for three weeks after fighting with the  Ice King  (voiced by  Tom Kenny ). It is revealed that Ricardio, the Ice King's living heart, has trapped them and wishes to marry Bubblegum. Bubblegum eventually defeats Ricardio in hand-to-hand combat, and saves the day.


"Lady & Peebles" featured the return of Takei, who had previously voiced Ricardio in the  first season  episode, " Ricardio the Heart Guy ". Several video games inspired elements of the episode, including  The Legend of Zelda: Majora's Mask ,  Eternal Darkness: Sanity's Requiem  and  Amnesia: The Dark Descent . "Lady & Peebles" was watched by 2.754 million people and received largely positive critical attention, with Oliver Sava of  The A.V. Club  praising Takei's voice acting, and Richard Whittaker of  The Austin Chronicle  applauding the female-centric nature of the episode. The episode was later nominated for an  Annie Award .


Princess Bubblegum and Lady Rainicorn investigate a mysterious black ice cave, fearing that Finn and Jake may have been captured by the Ice King on a routine expedition. Once inside the cave, Lady and Bubblegum enter into a biologically-engineered dungeon and are attacked by mysterious hand-like creatures that attempt to grab them. Lady manages to phase through a wall, and the two hear the Ice King's voice coming from a  ventilation shaft . Inside the shaft, the two are attacked by a giant tongue before they enter into a room covered with eyes. As Bubblegum and Lady approach the room's exit, the eyes activate and shoot laser at the duo, incapacitating Lady.


Bubblegum plods on in the dark, carrying an unconscious Lady around her shoulders. Suddenly, she stumbles upon the  disemboweled  body of the oblivious Ice King. From the dark, Ricardio, the living heart of the Ice King, introduces himself, tossing an unconscious Finn and Jake into the light. Ricardio reveals that he built himself both a body as well as the dungeon complex in an attempt to impress Bubblegum. He reveals that he wishes to marry her; Bubblegum agrees to marry Ricardio if he can beat her in  hand-to-hand combat . After a short fight, Bubblegum disarms Ricardio and forces him to flee, wounded, into the darkness. Later, at the Candy Kingdom, Finn, Jake, the Ice King, and Lady recover, and Lady reveals to Jake that she is pregnant.


"Lady & Peebles" was storyboarded by  Rebecca Sugar  and Cole Sanchez, from a story by Patrick McHale,  Kent Osborne , and  Pendleton Ward . It was directed by  Larry Leichliter  with  Adam Muto  serving as creative director and  Nick Jennings  serving as art director. [ 2 ]  Sugar, the eventual creator of the Cartoon Network series  Steven Universe , began working on said program's pilot episode while she was storyboarding this episode. [ 3 ]


The episode features the return of the anthropomorphic heart villain Ricardio, played by  George Takei , a character that  Tom Kenny  called "the valentine from Hell". [ 4 ]  Takei had previously played the role in the  season one  episode " Ricardio the Heart Guy ". [ 5 ]  In the commentary track for the episode, Sugar explained that she saw Bubblegum as the victim of sexual harassment by Ricardio, and that the only way for her to solve the problem was for her to turn the situation around and somehow overcome Ricardio's chauvinism. In the episode, this was metaphorically depicted by having Bubblegum best him in combat. Sugar reveled in the fact that she got to draw Bubblegum ripping off Ricardio's leg and beating him with, noting that she had been wanting to featuring such a scene in her art since she was in high school. [ 6 ]   Robert Ryan Cory , a character designer most known for his work on the  Nickelodeon  series  SpongeBob SquarePants , storyboarded the panels featuring Princess Bubblegum stomping on Ricardio and grinding her foot into his face. Because he drew the panels, lead character designer Andy Ristaino also allowed Cory to finalize the character designs for the scene. He later posted them on his official  Flickr  account. [ 7 ]


The episode reveals that Lady Rainicorn is pregnant with Jake's children. This plot point would later be revisited in the  fifth season  episode "Jake the Dad". [ 5 ] [ 8 ]  In the first draft of the ending, Lady Rainicorn was supposed to break up with Jake because he was causing her to be too stressed. However, the crew decided this was a bad idea, and it was changed to Rainicorn telling Jake that she is pregnant. [ 9 ]  As with all of Lady's dialogue, it was originally planned for the pregnancy revelation to be in Korean, but the crew felt that such a revelation would be lost on most of the audience. [ 6 ]


Several video games inspired elements of the episode. Ricardio's bio-engineered body was based on the finale incarnation of  Majora , a character from the eponymous video game  The Legend of Zelda: Majora's Mask  (2000).  The general look of Ricardio's dungeon was inspired by the video games  Eternal Darkness: Sanity's Requiem  (2002) and the game  Amnesia: The Dark Descent  (2010). [ 10 ]  The climactic scene with Ricardio was also supposed to have featured more  body imagery ; for instance, Ricardio was originally slated to have been seated on a giant hand-throne, and the hole in the Ice King's chest was to have been more graphic. [ 6 ]


"Lady & Peebles" first aired on  Cartoon Network  on August 8, 2012. The episode was viewed by 2.754 million viewers and scored a 0.5  Nielsen rating  in the 18- to 49-year-old demographic. Nielsen ratings are  audience measurement  systems that determine the audience size and composition of  television programming  in the United States, which means that the episode was seen by 0.5 percent of all households aged 18 to 49 years old were watching television at the time of the episode's airing. [ 11 ]  The episode first saw physical release as part of the 2013  Fionna and Cake  DVD, which included 16 episodes from the series' first three seasons. [ 12 ]


Critical reception to the episode was largely positive. Sava awarded the episode a "B+", and wrote that Ricardio is "always welcome on this series, largely due to Takei’s delightful voice work." [ 5 ]  Furthermore, he praised the way that Takei delivered his lines, noting that "there’s a theatrical smarminess to his vocals that is a stark contrast to the Ice King’s nasality", and that "Takei always sounds like he’s having a great time reading the ridiculous lines that are written for him." [ 5 ]  Sava also wrote positively of Bubblegum's character, noting that she "dominates this episode" and that the "episode reveals a side of her that we rarely see, and hopefully we’ll get more of badass PB in the future." [ 5 ]


Richard Whittaker of  The Austin Chronicle  wrote that the episode is "Princess Bubblegum-centric", which, along with the  third season  episode " Fionna and Cake ", provides the female fans of the show an opportunity to see female characters acting in situations normally reserved for Finn and Jake. [ 13 ]  The  Entertainment Examiner  named the episode as one of the "memorable" episodes that appeared on the 2013 DVD release  Fionna and Cake . [ 14 ]  The episode was nominated for an  Annie Award  for "Storyboarding in an Animated Television/Broadcast Production" at the  40th Annie Awards , although the episode did not win. [ 15 ]


Lateral hearts , also known as  pseudohearts  or  commissural vessels , are blood vessels on either side of the alimentary canal of some  annelids  that pump blood from the dorsal vessel to the ventral vessel.


The lateral hearts of  Lumbricus terrestris  are located in body segments 6–11. [ 1 ]


This  annelid -related article is a  stub . You can help Wikipedia by  expanding it .


A  heart–lung transplant  is a procedure carried out to replace both failing  heart  and  lungs  in a single operation. Due to a shortage of suitable donors and because both heart and lung have to be transplanted together, it is a rare procedure; only about a hundred such transplants are performed each year in the United States. [ United States-centric ]


The patient is  anesthetised . When the donor organs arrive, they are checked for fitness; if any organs show signs of damage, they are discarded and the operation cancelled.


Once suitable donor organs are present, the surgeon makes an incision starting above and finishing below the sternum, cutting all the way to the bone. The skin edges are retracted to expose the sternum. Using a bone saw, the sternum is cut down the middle. Rib spreaders are inserted in the cut, and spread the ribs to give access to the heart and lungs of the patient.


The patient is connected to a  heart–lung machine , which circulates and oxygenates blood. The surgeon removes the failing heart and lungs. Most surgeons endeavour to cut blood vessels as close as possible to the heart to leave room for trimming, especially if the donor heart is of a different size than the original organ.


The donor heart and lungs are positioned and sewn into place. As the donor organs warm up to body temperature, the lungs begin to inflate. The heart may  fibrillate  at first – this occurs because the  cardiac muscle  fibres are not contracting synchronously. Internal paddles can be used to apply a small electric shock to the heart to restore proper rhythm.


Once the donor organs are functioning normally, the heart–lung machine is withdrawn, and the chest is closed.


Most candidates for heart–lung transplants have life-threatening damage to both their heart and lungs. In the US, most prospective candidates have between twelve and twenty-four months to live. At any one time, there are about 250 people registered for heart–lung transplantation at the  United Network for Organ Sharing  (UNOS) in the US, of which around forty will die before a suitable donor is found. [ citation needed ]


Conditions which may necessitate a heart–lung transplant include:


Candidates for a heart–lung transplant are usually required to be:


Most patients spend several days in  the intensive care unit  after the operation. If there are no complications (e.g.,  infection ,  rejection ), some are able to return home after just two weeks in hospital. Patients will be given  anti-rejection drugs  and  antibiotics  to prevent infection as the anti-rejection drugs weakens the immune system. A schedule of frequent follow up visits is necessary.


The success rate of heart–lung transplants has improved significantly in recent years. The British  National Health Service  states that the survival rate is now around 85%, one year after the transplant was performed. [ 1 ]


In 2004, there were only 39 heart–lung transplants performed in the entire United States and only 75 worldwide. By comparison, in that same year there were 2,016 heart and 1,173 lung transplants. [ 2 ]


Norman Shumway  laid the groundwork for heart lung transplant with his experiments into heart transplant at  Stanford  in the mid-1960s. [ citation needed ]  Shumway conducted the first adult heart transplant in the US in 1968. [ 3 ]


The first successful heart transplant was performed in South Africa in 1967. [ 4 ]  The first successful heart–lung transplant was performed at Stanford in the United States, by  Bruce Reitz  on  Mary Gohlke  in 1981. [ 5 ]


Magdi Yacoub  performed the first heart-lung transplant in the United Kingdom in 1983. [ 6 ]


Australia's first heart-lung transplant was conducted by  Victor Chang  at  St Vincent's Hospital, Sydney  in 1986. [ 7 ]  Iran's first heart-lung transplant was performed in Tehran in 2002. [ 8 ]


The  moderator band  (also known as  septomarginal trabecula [ 1 ] ) is a band of  cardiac muscle  found in the right  ventricle  of the  heart . [ 2 ] [ 3 ] [ 4 ]  It is well-marked in  sheep  and some other animals, including humans. It extends from the base of the anterior  papillary muscle  of the  tricuspid valve  to the  ventricular septum . [ 2 ]


The moderator band is located in the right ventricle. [ 2 ] [ 3 ]  The moderator band connects the base of the anterior papillary muscles of the tricuspid valve to the ventricular septum. [ 2 ]


The moderator band is important because it carries part of the right bundle branch of the  atrioventricular bundle  of the  conduction system of the heart  to the anterior  papillary muscle . [ 1 ]  This shortcut across the chamber of the ventricle ensures equal conduction time in the left and right ventricles, allowing for coordinated contraction of the anterior papillary muscle. [ 1 ]


The moderator band is often used by  radiologists  and  obstetricians  to more easily identify the  right ventricle  in  prenatal   ultrasound .


From its attachments it was thought to prevent overdistension of the  ventricle , and was named the "moderator band". It was first described by  Leonardo da Vinci  in his exploration of human anatomy.


The  Egyptian hieroglyph  for "perfect, complete" (with the extended meanings of "good, pleasant, well,  beautiful ") in  Gardiner's sign list  is numbered  F35 ; its phonetic value is  nfr , with a reconstructed pronunciation of  [nafir] [ 2 ]  and a  conventional Egyptological vocalization  of  nefer .


The  triliteral Egyptian hieroglyph  F35 ('nfr') has sometimes been explained as a representation of a  lute ; however, Egyptologists today no longer consider this hypothesis likely. Rather than a lute, the hieroglyph is actually a representation of the  heart  and  trachea . [ 1 ]  It originally may have been the  esophagus  and heart. The striations of the  windpipe  only appear in the hieroglyph following the  Old Kingdom of Egypt . The lower part of the sign has always clearly been the heart, for the markings clearly follow the form of a  sheep 's heart. [ 3 ]


The term  nfr  has been incorporated into many names in Ancient Egypt. Examples include  Nefertiti ,  Nefertari , and  Neferhotep .


Some scholars suggest that it was used in ancient Egyptian construction where 'nfrw' was used to denote 'level zero' of a building and in accounting where 'nfr' would refer to a zero balance. [ 4 ]


This  ancient Egypt  biographical article is a  stub . You can help Wikipedia by  expanding it .


The  heart of the Brazilian emperor  Dom Pedro I  has been preserved since his death in 1834. The organ is kept in a glass jar, with  formaldehyde , in the  Church of Our Lady of Lapa  [ pt ] . The container is kept in an urn, locked under lock and key. [ 1 ]  The heart is considered a relic by the Portuguese government. [ 2 ]


Dom Pedro I's body is buried in  São Paulo , in the crypt of the  Monument to Independence . By decision of the monarch himself, as one of his last requests in life, the heart was separated and kept in Portugal. [ 1 ]  Dom Pedro I asked that the heart be preserved in  Porto  because of the relevance of the city in the  dispute  for the Portuguese throne between Dom Pedro I (known as Dom Pedro IV in Portugal) and his brother  Dom Miguel . [ 3 ]


After the emperor's death from tuberculosis in September 1834, a series of royal and ecclesiastical agreements were made so that, in February 1835, the heart was finally sent to Porto, kept in a gilded silver vase, wrapped in a black velvet-lined case, inside the Church of Our Lady of Lapa. [ 4 ]


In 2022, after its exhibition in the context of the  Bicentennial of Brazil's Independence  [ pt ] , it was reported that the organ has a swollen appearance, possibly due to the material initially used in its conservation by the doctor  João Fernandes Tavares  [ pt ] , before being kept in formaldehyde. [ 5 ]  The conditions of the heart are the subject of research in the field of  forensic anthropology . [ 3 ]


On September 23, 1834, on the eve of his death, Dom Pedro I wrote a  letter  addressed to the Brazilian public, [ a ]  in which he declares his wish regarding the fate of his remains after death: [ 6 ]


Brazilians! I leave my heart to the heroic City of  Porto , theater of my true glory, and the rest of my mortal spoils to the City of  Lisbon , place of my birth; but you possess the most precious relic, the living emanation of my being,  my son ! My only son! [ 7 ]


Dom Pedro was not the first monarch to determine, while he was still alive, that his heart should be separated from his body and preserved or buried. Even during the  Middle Ages , monarchs such as  Robert I of Scotland ,  Richard I of England , and  Henry I of England  had their hearts buried in different locations than the rest of their bodies. [ 8 ] [ 9 ] [ 10 ]


After Dom Pedro died of tuberculosis, his daughter,  Maria II of Portugal , decided to fulfill her father's wish. [ 11 ]  As narrated by  Amélie of Leuchtenberg , Dom Pedro's widow, in a letter to her daughter  Januária of Bragança , an autopsy of the body was performed, revealing a swollen and heavy right lung and an enlarged-looking heart. [ 12 ] [ 13 ]  The exhumation of D. Pedro's remains, performed in 2013 by a team from the  Museum of Archaeology and Ethnology at the University of São Paulo  [ pt ] , determined that part of the ribs on the right side of the body had been cut, probably for the removal of the heart during the time of autopsy and embalming. [ 14 ]


However, the late emperor had not made it clear in which part of the city of Porto his heart should be kept, and soon a dispute ensued. The queen, Maria II, and the then bishop of Lisbon,  Francisco de São Luís , had chosen the  Lapa Church , which had been frequented frequently by Pedro. However, the  Porto City Council  [ pt ]  had favored the chapel of São Vicente in the  Sé of Porto . [ 15 ]


Finally, the decision was made in February 1836 that the relic of the heart would finally be kept at Lapa. On February 4, the heart set sail across the  Tagus  River toward the city of Porto aboard the warship  Jorge IV , commanded by Colonel  Baltazar de Almeida Pimentel  [ pt ]  and a guard of honor composed of 70 soldiers. [ 15 ]


Arriving in  Ribeira  [ pt ]  after a 3-day trip, the delegation was received with an official ceremony, where the urn containing the heart was handed over to the Chamber of Porto, along with its key. [ 16 ]


The original urn was composed of an outer part made of  mahogany  and an inner part made of silver. Later, the heart was placed inside a hermetically sealed glass vase, which is contained inside the silver urn. [ 16 ]


In the context of the bicentennial celebrations of the  Independence of Brazil , Dom Pedro I's heart was transported to Brazil and exhibited in  Brasília . [ 17 ]


The coming of the body to Brazil was idealized by  Nise Yamaguchi  in the first half of 2022, in dialogue with President  Jair Bolsonaro , and the descendants of Dom Pedro, Federal Deputy  Luiz Philippe de Orléans e Bragança  and  Bertrand of Orléans-Braganza . [ 18 ]  The deputy, great-great-great-grandson of Dom Pedro I, is said to have traveled to Porto, where he made contact with those responsible for the Lapa Church and with members of the City Council. [ 18 ]  The  Brazilian Embassy in Lisbon  [ pt ]  and the Brazilian consulate got involved in the negotiation, proposing that the heart be temporarily loaned for the bicentennial festivities. [ 19 ]


Both the City Council and the Third Order of Lapa showed no opposition to the proposal, provided that the safety of the heart was ensured. The  President of the Portuguese Republic ,  Marcelo Rebelo de Sousa , had been consulted, and suggested that the loan of the relic be in fact carried out. [ 19 ]  To ensure that the heart would not be damaged during transport to Brazil, an expert study was ordered by the National Institute of Legal Medicine, conducted by researchers from the  Faculty of Medicine of the University of Porto  [ pt ]  and the  Abel Salazar Biomedical Sciences Institute . [ 19 ] [ 20 ]  The study concluded that there would be no risk to the relic, provided it was transported in a pressurized chamber on the plane. [ 19 ]


Thus, in a session on July 18, the Porto City Council unanimously approved the proposal for the loan of the heart. The approved proposal considers that all costs related to transport will be the responsibility of the  Brazilian government , and establishes the legal basis for the effective transfer of the relic. [ 20 ]


On July 22, the heart was brought from Portugal in a  Brazilian Air Force  plane, and received with honors as head of state, transported in the presidential  Rolls-Royce Silver Wraith , and escorted by the  1st Cavalry Regiment of Guards  [ pt ] . Finally, an official session was held with President Jair Bolsonaro on the ramp of the  Planalto Palace . [ 21 ]


The solemnity and the exposition of Dom Pedro I's heart were criticized, especially for the cost of the transfer and the morbidity of the tributes. [ 22 ]  It was also criticized the fact that, with the coming of the organ to Brazil, Dom Pedro I's last request was not respected, since he had asked for the heart to remain in Portugal. [ 5 ]


Media related to  Pedro I's heart  at Wikimedia Commons


Psychai  are the diminutive, winged  shades  of the dead in  Greek mythology  and some fifth century BC funerary lekythoi. [ 1 ]  Although commonly translated as " soul " today, in the epics of  Homer , it meant "life" [ 2 ]  and did not have any connection to consciousness or psychological functions in the living. It is only later, at the end of the fifth century BC in the works of other poets such as  Pindar , that the word acquires its meaning relating to being the principal seat of intellect, emotion, and will. [ 3 ]  From there, it became possible to translate  psyche  as "heart" or "soul". [ 4 ]


In  Islamic philosophy , the  qalb  ( Arabic :  قلب ) or heart is the center of the human personality. The  Quran  mentions "qalb" 132 times and its root meaning suggests that the heart is always in a state of motion and transformation. According to the Quran and the  traditions of Muhammad , the heart plays a central role in human existence, serving as the source of good and evil, right and wrong. In  Islam ,  God  is more concerned with the motives of one's heart than their actions. The heart is also a medium for God's  revelations  to human beings, and is associated with virtues such as  knowledge ,  faith ,  purity ,  piety , love, and  repentance . Without purification, however, the heart can become plagued with negative attributes such as  sickness , sinfulness, evil, and hate.


Theologically, the heart is regarded as the  barzakh  or  isthmus  between  this world  and  the next , and between the visible and invisible worlds, the human realm, and the realm of the  Spirit .


The Quran frequently employs the term "qalb" (heart), which appears 132 times, and at times substitutes it with similar terms. The word's root meaning denotes concepts of change, transformation, and fluctuation, implying that the heart is constantly in motion and may undergo reversal or alteration. [ 2 ]  The Quran uses the term "heart" in various ways that highlight its central role in human existence. These diverse uses of the word imply that its original meaning - involving ideas of turning, changing, and overturning - remains relevant, as the heart is regarded as the source of good and evil, right and wrong. The Quran teaches that both believers and non-believers possess hearts. [ 2 ]  In general, the Quran portrays the heart "as the locus of that which makes a human being human, the center of the human personality". This importance of the heart is due to the profound relationship between humans and God, with the heart being the point of convergence where they can meet God. This interaction is multidimensional, encompassing both cognitive and moral dimensions. [ 2 ]


God pays special attention to the heart, as it is viewed as the true center of a person. Quranic verses highlight that God is more concerned with the motives of one's heart than their actions. While mistakes can be forgiven, the intentions of the heart are critical. [ 2 ]  For example, in 33:5 the Quran states: "There is no fault in you if you make mistakes, but only in what your hearts premeditate". In 2:225, it says: "God will
not take you to task for a slip in your oaths; but He will take you to task for what your hearts have earned; and God is Forgiving, Clement" (cf. 2:118, 8:70). [ 2 ]


According to the Quran, the heart serves as a medium for God's revelations to human beings. Prophets receive revelations in their hearts, and it is also a place for vision, understanding, and remembrance. The heart plays a crucial role in fostering faith and directing guidance towards the right path. However, it can also serve as a breeding ground for doubt, denial, unbelief, and misguidance, which Satan may try to instill. The heart is associated with virtues such as purity, piety, love, and repentance, but these virtues are not inherent and must be instilled and nurtured by God. Without God's purification, the heart can become plagued with negative attributes such as sickness, sinfulness, evil, and hate. [ 3 ]  The heart is meant to be open and receptive to the divine guidance, light, and love. However, the hearts of those who do wrong can become hard and harsh. The Quran teaches that God has sent down a beautiful scripture, and those who fear Him tremble when they read it, causing their skin and hearts to soften. However, if the heart is not receptive, it can become hard like stone, or even harder, as the hearts of some have become. [ 4 ]


Muhammad frequently used supplications, where he called upon God as the one who makes hearts fluctuate or turn about. He described the heart as being like a feather in the desert, blown by the wind to and fro. One of his wives reported that he used to pray for his heart to be fixed in God's religion, and when she asked him about it, he explained that every person's heart lies between two fingers of God and that God can make it go straight or swerve as He wishes. [ 5 ]


The Prophet (peace and blessings of Allah be upon him) said, A Muslim is the brother of another Muslim.  He will not oppress him.  Don't look down on him.   Taqwa  resides here ( Qalb ).  With this he pointed three times towards his chest.  It is enough for a man to be evil that he despises his Muslim brother.  It is forbidden for every Muslim to take one another's blood, his wealth and his honor.


In Islamic thought, the heart is considered the core of human being, encompassing not only physical and emotional aspects but also intellectual and spiritual aspects. It serves as a connection between individuals and the larger, transcendent realms of existence. According to  Seyyed Hossein Nasr , modern society rejects the importance of heart-knowledge because it fails to recognize the existence of individuals beyond their individualistic levels of being. [ 6 ]


The heart is not a center of our being; it is the supreme center, its uniqueness resulting from the metaphysical principle that for any specific realm of manifestation there must exist a principle of unity. The heart is the barzakh or isthmus between this world and the next, between the visible and invisible worlds, between the human realm and the realm of the Spirit, between the horizontal and vertical dimensions of existence. [ 6 ]


The assessment of the  regional function of the heart  is a good tool for early detection of deterioration in certain parts of the  heart  wall before a cardiac arrest is  diagnosed . One of the most accurate measures of changes in regional function is the use of  strain  as a measure of the regional function of  cardiac muscle .


One of the most important indicators of heart problems is described as the  weakening  of  cardiac function . This means that the heart's ability to circulate blood throughout the body is diminished. Before this becomes a problem for other organs of the body, it is beneficial to detect early progress of the disease in the heart wall muscle itself. This can be detected, when the proper device is used, as weakening of the contractility of a part of the heart muscle. Hence, it is described as a change in regional function. The weakening of regional function does not always lead to a weakening in overall cardiac function. This will depend on a number of factors, including the degree of regional weakening and its extent inside the wall.


The myocytes of the heart (also called the myocardial fibers) are arranged in a general circumferential direction in the ventricles. In the  left ventricle  (LV), the fiber will change gradually in direction from a certain longitudinal-circumferential direction in the outer layer of the heart (epicardium) to another angulated direction almost orthogonal in the inner wall (endocardium), becoming overwhelmingly circumferential somewhere halfway in the middle of the wall. It is, therefore, perceived that measuring the strain in the circumferential direction is a good indicator of the contractility of the fibers.


There are different ways to measure the regional function of the wall. It has been proposed to measure the speed of the LV wall motion, the thickening of the wall, or other changes in the shape of small regions of the wall as it contracts and relaxes. The latter is best measured using the mechanical quantity called “strain."  Strain can be described as the percentile change in spacing between two points on a deforming object.


Because strain is measured between two points, that strain, therefore, describes the change in distance along the direction connecting the two points. If we think of a rubber band that is stretched, the strain along the band will have a positive value for stretching, i.e., when selecting two points placed along the band length. At the same time, the bandwidth will decrease, resulting in a negative strain orthogonal to the band's length. In the case of the heart, it has become conventional to use certain directions for measuring strain:


This is the strain measured along the thickness of the wall. In fact, it measures the wall thickening. In a normal heart, the radial strain is positive as measured from end-diastole.


For the LV and RV, it is the strain that measured the shortening (or relaxation) of the wall muscle from the base of the ventricles to the apex. In a normal heart, the longitudinal strain is negative as measured from end diastole.


This is the third strain component whose direction is orthogonal to both the radial and longitudinal. One way to see it is the reduction of the circumference of the LV chamber as seen in a short-axis view. The annular shape of the LV wall will change and become thicker (radial strain) with a smaller inner circle (circumferential strain). In a normal heart, the circumferential strain or positives negative as measured from end-diastole.


Note that:


Peak contraction:  This is the point of time when the rubber band is smallest. In the case of the LV of the heart, it can be identified as end-systole. However, end-systole describes a global change in the chamber, which is the sum of the contraction of the regions. Because of the different timing of activation of the wall region and other factors, the end-systole does not coincide exactly with the peak contractions of the regions. In a normal heart, these times should be close enough for efficient pumping by the heart, but they are not exactly the same. When the variance in time exceeds a certain degree, the heart becomes more dyssynchronous.


Peak stretching:  Similar to peak contraction, peak stretching is the instant when the rubber band is at its maximum length. In the case of the LV, it will correspond with end-diastole, and with the same comment about the variance in end-systole.


Strain can be measured by various medical imaging modalities. Of special interest is using  echocardiography  or  magnetic resonance imaging (MRI) . In echocardiography, strain can be measured by using  Tissue Doppler Imaging (TDI)  or  Speckle Tracking Echocardiography (STE) . Using MRI, strain and deformation can be measured, noninvasively, using MRI Tagging and  Harmonic Phase Analysis (HARP) , [ 1 ]   Strain Encoding (SENC) , or Tissue Tracking. The latter is similar to STE, although the MRI images do not show significant heterogeneity within the tissue to track.


One of the applications is using peak circumferential strain to the viability of the myocardium. [ 2 ] [ 3 ]  The figure shows this relation, as well as converting the strain value into the typical qualitative assessment as normal, hypokinetic, akinetic, and dyskinetic for the wall motion.


Redirect to:


" Ricardio the Heart Guy " is the seventh episode of the  first season  of the American  animated television series   Adventure Time . The episode was written and storyboarded by Bert Youn  and Sean Jimenez, from a story by  Merriwether Williams ,  Tim McKeon  and  Adam Muto . It originally aired on  Cartoon Network  on April 26, 2010. The episode guest stars  George Takei  as the title character, Ricardio.


The series follows the adventures of  Finn  (voiced by  Jeremy Shada ), a human boy, and his best friend and adoptive brother  Jake  (voiced by  John DiMaggio ), a dog with magical powers to change shape and grow and shrink at will. In this episode, Finn believes that Princess Bubblegum's (voiced by  Hynden Walch ) new friend, a heart named Ricardio, is evil, and is proven right after learning that Ricardio is the heart of the  Ice King  (voiced by  Tom Kenny ). Ricardio reveals that he wants to "make out" with Bubblegum's heart, but he is defeated by Finn and Jake.


Ricardio would become a minor recurring villain, reappearing in the  fourth season  entry " Lady & Peebles ". After the episode aired, series composer Casey James Basichis posted a video explaining his inspiration and the method in which he produced the music featured in the episode. Basichis largely scored the episode with opera music, because he felt the genre suited Ricardio. "Ricardio the Heart Guy" was watched by 1.91 million people and received largely positive critical attention, with many reviews praising Takei's voice work.


After the Ice King captures Princess Bubblegum, Finn and Jake manage to save her. Bubblegum is so happy that she decides to throw a party for Finn as a thank you. Finn makes a Paper Crane for Bubblegum as a gift, but Jake says that Finn has a crush on her, which Finn denies. When they arrive at the party, however, no one notices them; everyone, including Bubblegum, is too preoccupied with a heart-shaped man named Ricardio. He and Bubblegum begin discussing scientific topics on the dance floor, which leaves Finn feeling jealous.


Finn begins to think that Ricardio is a villain, but Jake just notes that Finn is jealous. However, the two spy on Ricardio to see if he is evil or not. They see Ricardio going into a dumpster and acquiring a rope and broken bottles. Then they see him throwing the Ice King into the dumpster, so they decide to question Ricardio about being a super-villain. Finn punches Ricardio right when Bubblegum comes. Mad and upset, she takes Ricardio away. However, the Ice King soon crawls toward Finn and Jake, looking sickly. He reveals that Ricardio is actually his own heart, which gained sentience after the Ice King performed a failed love spell. Ricardio desires to cut out Bubblegum's heart and make it his bride.


Finn and Jake race to Bubblegum's castle and find her tied to a chair, with Ricardio about to rip her heart out. Finn and Jake then fight Ricardio and manage to beat him up. The Ice King crawls into the castle and places Ricardio back into his chest. Later during dinner, Bubblegum tells Finn that he does not need to be jealous anymore, but Finn denies that he was jealous in the first place.


"Ricardio the Heart Guy" was written and  storyboarded  by Bert Youn and Sean Jimenez, from a story by  Merriwether Williams , Tim McKeon, and Adam Muto. Directed by  Larry Leichliter , the episode introduces the recurring villain Ricardio, played by  George Takei , a character that  Tom Kenny  later called "the valentine from Hell". [ 2 ]  Takei later reprised the role in the season four episode "Lady and Peebles". [ 3 ]  Initial drafts of the character featured him looking more like an anthropomorphic heart, complete with arteries and ventricles. [ 4 ]  Ricardio is one of the few individuals in the  Adventure Time  universe to have a highly detailed face; during the commentary for the episode, his design was compared to that of the face on the moon in the 1902 French silent film  Le Voyage dans la Lune , based on  H.G. Wells 's 1901 novel  The First Men in the Moon . [ 5 ]


After the episode aired, series composer Casey Basichis posted a video explaining his inspiration and method of producing the music featured in the episode. According to the video, Basichis created a "skeleton" of the score in his shower using his voice and a ukulele; the audio was captured on a phone. Originally, the score was going to have a " New York City , taxi, and  jazz " feel, but Basichis was unhappy with the genre choice, and changed the feel. [ 6 ]  For the music that played while the Ice King interacted with Ricardio, Basichis was inspired by the score from the original  seven-minute short . In addition, opera singer Karen Vuong lent her voice to the episode. According to Basichis, Vuong was able to record her vocals successfully in one take. Basichis chose opera because he knew it had a reputation for being "sickeningly intellectual" and "preoccupied with murder", traits that he felt suited Ricardio. [ 6 ]


"Ricardio the Heart Guy" first aired on  Cartoon Network  on April 26, 2010. The episode was watched by 1.91 million viewers, and scored a 1.3/2 percent  Nielsen household rating , meaning that it was seen by 1.3 percent of all households and 2 percent of all households watching television at the time of the episode's airing. [ 7 ]  The episode first saw physical release as part of the 2011  Adventure Time: My Two Favorite People  DVD, which included 12 episodes from the series' first two seasons. [ 8 ]  It was later re-released as part of the complete first season DVD in July 2012; commentary for the episode was also included on the DVD. [ 9 ] [ 10 ]


The episode garnered mostly positive reviews from critics. Matt Fowler of  IGN , in a review of the  My Two Favorite People  DVD, noted that while "the idea of a walking, talking heart named Ricardio […] who plans to cut out Princess Bubblegum's heart is potent nightmare fuel", the show nevertheless "finds a way to make that grim idea accessible and fun." [ 11 ]


Takei's appearance as Ricardio gained critical favor. Charlie Anders of  io9  named Takei's appearance in the episode as one of his "greatest moments", noting, "how could we have missed that Takei did the voice for this sleazy science-talking heart on  Adventure Time , our new favorite show?" [ 12 ]  Tyler Foster of  DVD Talk  called Ricardio one of the highlights of the season. [ 13 ]   The A.V. Club  reviewer Oliver Sava, in a review for "Lady & Peebles", wrote that Ricardio is "always welcome on this series, largely due to Takei’s delightful voice work." [ 3 ]  Furthermore, he praised the way that Takei delivered his lines, noting that "there’s a theatrical smarminess to his vocals that is a stark contrast to the Ice King’s nasality", and that "Takei always sounds like he’s having a great time reading the ridiculous lines that are written for him." [ 3 ]


The  Seven Countries Study  is an  epidemiological   longitudinal study  directed by  Ancel Keys  at what is today the  University of Minnesota  Laboratory of Physiological Hygiene & Exercise Science (LPHES). Begun in 1956 with a yearly grant of US$200,000 from the  U.S. Public Health Service , the study was first published in 1978 and then followed up on its subjects every five years thereafter.


As the world's first multicountry epidemiological study, it systematically examined the relationships between lifestyle, diet,  coronary heart disease  and  stroke  in different populations from different regions of the world. It directed attention to the causes of coronary heart disease and stroke, but also showed that an individual’s risk can be changed.


Writing in 1975, project officer Henry Blackburn identified two "strikingly polar attitudes", characterising them as persisting "academic" and "pragmatic" views with "much talk from each and little listening between." [ 1 ]


In the 1940s, a University of Minnesota researcher,  Ancel Keys , postulated that the apparent epidemic of heart attacks in middle-aged American men was related to their mode of life and possibly modifiable physical characteristics. He first explored this idea in a group of Minnesota business and professional men (executives aged 45 to 55) that he recruited into a prospective study in 1947, the first of many  cohort studies  eventually mounted internationally. The U.S. Public Health Service agreed to fund the study (and then set up and proceeded to fund the  Framingham Heart Study  on a larger scale). The Minnesota men were followed through 1981 and the first major report appeared in 1963 after the fifteen-year follow-up study. [ 2 ] [ 3 ]


The study contributed much to survey methods and confirmed larger studies that reported earlier on the predictive value for heart attack of several characteristics, the now-traditional risk factors of  blood pressure  and blood  cholesterol  level and cigarette  smoking . Keys traveled widely with his wife Margaret who tested people's serum cholesterol. They sent their samples back to Minnesota for analysis. In 1952, Keys's hypothesis that coronary heart disease could be related to diet was first published in  Voeding  in The Netherlands. [ 4 ]  His work in post-wartime  Naples  led him to seek organization and funding for studies of different populations, as did his subsequent work in  Uganda ;  Cape Town , South Africa;  Sardinia ;  Bologna ; and  Ilomantsi , Finland; and with Japanese men living in  Hawaii  and in  Japan . He decided to concentrate on men living in  villages , rather than those in cities where the population moved around frequently. [ 3 ]


In the mid-1950s, with improved methods and design, Keys recruited collaborating researchers in seven countries to mount the first cross-cultural comparison of heart attack risk in populations of men engaged in traditional occupations in cultures contrasting in diet, especially in the proportion of fat calories of different composition, the Seven Countries Study still under observation today.


The Seven Countries Study was formally started in fall 1958 in  Yugoslavia . In total, 12,763 males, 40–59 years of age, were enrolled as 16 cohorts, in seven countries, in four regions of the world (United States, Northern Europe, Southern Europe, Japan). One cohort is in the United States, two cohorts in Finland, one in the Netherlands, three in Italy, five in Yugoslavia (two in  Croatia , and three in  Serbia ), two in Greece, and two in Japan. The entry examinations were performed between 1958 and 1964 with an average participation rate of 90%, lowest in the US, with 75% and highest in one of the Japanese cohorts, with 100%. [ 5 ]  The study has continued for more than 50 years.


The Seven Countries Study suggested that the risk and rates of  heart attack and stroke  (CVR), both at the population level and at the individual level,  correlated  directly and independently to the level of total serum cholesterol, in seven sampled out countries. It demonstrated that the correlation between blood cholesterol level and coronary heart disease (CHD) risk from 5 to 40 years follow-up is found consistently across different specially selected cultures in these seven countries. Cholesterol and obesity correlated with increased mortality from cancer. [ 6 ] [ 7 ] [ 8 ]  The Seven Countries Study suggested that elevated blood pressure ( hypertension ) was correlated with risk of coronary heart disease and stroke. It showed that the  mortality rate  after a coronary heart disease event or stroke was associated with the level of hypertension. In several cohorts of the study, stroke deaths exceeded deaths from coronary heart disease. [ 9 ] [ 10 ]  It hinted that differences in overall mortality between the different regions of the seven countries are largely associated with variation in cardiovascular mortality. [ 11 ]  Coronary deaths in the United States and Northern Europe greatly exceeded those in Southern Europe, even when controlled for age, cholesterol, blood pressure, smoking, physical activity, and weight.


The Seven Countries Study was investigated further in regard to an eating pattern loosely characterized as the  Mediterranean Diet . [ 12 ] [ 13 ] [ 14 ] [ 11 ] [ 15 ]  What exactly is meant by "Mediterranean Diet" today, was detailed by  Antonia Trichopoulou  (wife of  Dimitrios Trichopoulos ), [ 16 ]  and Anna Ferro-Luzzi. [ 17 ]  The diet was publicized and popularized by Greg Drescher of the Oldways Preservation and Exchange Trust and by  Walter Willett  of the  Harvard School of Public Health . [ 18 ] [ 19 ] [ 20 ] [ 21 ] [ 22 ]


The Seven Countries Study also showed that the slowly changing habits of a population in the Mediterranean region, from a healthy, active lifestyle and diet, to a less active lifestyle and a diet influenced by the  Western pattern diet , significantly correlated with increased risk of heart disease. [ 23 ] [ 24 ]  Meanwhile, it has been confirmed by other researchers that there is an inverse association between adherence to the  Mediterranean Diet  and the incidence of fatal and non- fatal heart disease in initially healthy middle-aged adults in the Mediterranean region. [ 25 ]


The Seven Countries Study, along with other studies, e.g., the  Framingham Heart Study  and the  Nurses' Health Study , showed the importance of  overweight ,  obesity  and regular  exercise  as health issues. [ 26 ] [ 27 ] [ 28 ] [ 29 ]  It showed a correlation between good cardiovascular health and dementia in the general population. It also showed that cardiovascular risk factors in mid life are significantly associated with increased risk of dementia death later in life. [ 30 ]  It indicated that cigarette smoking is a highly significant predictor of the development of coronary heart disease, leading to excess rates of  angina pectoris ,  myocardial infarction  (MI) and coronary death, along with other studies about smoking, e.g., the Framingham Heart Study and the  British Doctors Study . [ 31 ] [ 32 ] [ 33 ] [ 34 ]


Initial results from the Seven Countries Study in North Karelia (Finland) prompted public pressure for the authorities to act to reduce historically high levels of chronic disease in the region. The results influenced a subsequent public health program, the  North Karelia Project , which ran from 1972 until 1997, and which had among its aims a reduction in levels of peoples' saturated fat intake. [ 35 ]


Subcutaneous implantable cardioverter defibrillator , or  S-ICD,  is an implantable medical device for detecting and terminating   ventricular tachycardia  and  ventricular fibrillation  in patients at risk of sudden cardiac arrest. [ 1 ]  It is a type of  implantable cardioverter defibrillator  but unlike the transvenous ICD, the S-ICD lead is placed just under the skin, leaving the heart and veins untouched.


The S-ICD was developed to reduce the risk of complications associated with transvenous leads. [ 2 ]  Potential complications, such as infections in the bloodstream and the need to remove or replace the leads in the heart, are minimised or entirely eliminated with the S-ICD system.


The generator is smaller than the S-ICD generator, which may result in a less visible implanted device. This could improve the time needed to get used to the implantable device, although this is subjective. The procedure can usually be done under local anesthesia and light sedation. The transvenous ICD is capable of  pacing  for  bradycardia  and delivering  antitachycardia pacing  (ATP).   However, device-related complications were numerically more frequent in patients with transvenous ICDs, inappropriate shocks are less frequent that in those with subcutaneous ICDs. [ 3 ]


The leads go into the vein and heart and will grow into the heart wall over time. This may increase the chance of complications if the leads need to be removed or replaced, as the procedure to extract an intracardiac leads can be a challenge. Because the leads need to go into the heart they need to be relatively thin and flexible, since they have to pass through (and remain in) the heart valve(s) and need to flex with every heartbeat. This makes the leads more vulnerable to lead fracture (and therefore complications). It has been demonstrated that  device-related complications were numerically more frequent in patients with transvenous ICDs. [ 3 ]  Due to the position of the pulse generator under the collarbone, it can be more visible with clothing with low neckline.


Patients who are relatively older, who need ICD for secondary prevention, or who have concomitant bradycardia requiring pacing, or heart failure requiring  cardiac resynchronisation therapy  are more suitable for transvenous ICD implantation. An older patient with ischemic cardiomyopathy and documented symptomatic ventricular tachycardia is a typical example. [ 4 ]


The lead does not go into the heart, which means it leaves the veins and the heart completely intact. This reduces chance of complications (e.g. systemic infections). Because the lead does not go into the heart it can be thicker and more robust. This minimizes / reduces the chance of lead fracture. In the event the system needs to be explanted, the procedure is a relatively simple surgical procedure.


The pulse generator is larger than most transvenous ICD pulse generators. This could result in a longer time needed to get used to it, although this is subjective. Depending on the physique of a person, the S-ICD may be more visible with bare chest. The procedure usually requires deep sedation or general anaesthesia, as creating a larger pocket between the muscles and tunnelling the lead over the sternum, as well as performing defibrillation threshold testing, can be quite painful. The S-ICD can deliver only temporary post-shock pacing, but cannot otherwise address bradycardia and cannot deliver anti-tachycardia pacing.  Inappropriate shocks were numerically more frequent in those with subcutaneous ICDs. [ 3 ]  Defibrillation testing has traditionally been considered mandatory in patients with subcutaneous implantable cardioverter–defibrillator to confirm appropriate ventricular fibrillation detection. [ 5 ]  However, PRAETORIAN-DFT  randomised clinical trial  is aiming to demonstrate non-inferiority of omitting DFT in patients undergoing S-ICD implantation in which the S-ICD system components are optimally positioned by calculated PRAETORIAN score. [ 6 ]


Patients who are relatively younger, who need ICD for primary prevention, and who do not require pacing or cardiac resynchronisation therapy, are more suitable for S-ICD implantation. A young survivor of aborted  sudden cardiac death  is a typical example.


Vagal tone  is activity of the  vagus nerve  (the 10th  cranial nerve ) and a fundamental component of the  parasympathetic  branch of the  autonomic nervous system . This branch of the nervous system is not under conscious control and is largely responsible for the regulation of several body compartments at rest. Vagal activity results in various effects, including:  heart rate  reduction,  vasodilation/constriction  of  vessels , glandular activity in the  heart ,  lungs , and  digestive tract , liver, immune system regulation as well as control of gastrointestinal sensitivity, motility and inflammation. [ 1 ]


In this context, tone specifically refers to the continual nature of baseline parasympathetic action that the vagus nerve exerts. While baseline vagal input is constant, the degree of stimulation it exerts is regulated by a balance of inputs from  sympathetic  and  parasympathetic  divisions of the autonomic nervous system, with parasympathetic activity generally being dominant.  Vagal tone is frequently used to assess heart function, and is also useful in assessing emotional regulation and other processes that alter, or are altered by, changes in parasympathetic activity. [ 2 ] [ 3 ]


Measurements of vagal tone can be performed by means of either invasive or noninvasive procedures. Invasive procedures are in the minority and include vagus nerve stimulation by specific manual, breathing or electrical techniques. Noninvasive techniques mainly rely on the investigation of  heart rate  and  heart rate variability . [ 4 ] [ 5 ] [ 6 ]


In most cases, vagal tone is not measured directly. Instead the processes affected by the  vagus nerve  – specifically heart rate and heart rate variability – are measured and used as a surrogate for vagal tone. Increased vagal tone (and thus vagal action) is generally associated with a lower heart rate and increased heart rate variability. However, during  graded orthostatic tilt , vagal tone withdrawal is an indirect indicator of cardiovascular fitness. [ 7 ]


Heart rate  is largely controlled by the heart's internal pacemaker activity. In a healthy heart, the main pacemaker is a collection of cells on the border of the  atria  and  vena cava  called the  sinoatrial node . Heart cells exhibit automaticity, the ability to generate  electrical activity  independent of external stimulation. The electrical activity spontaneously generated by the sinoatrial node sets the pace for the rest of the heart. [ 1 ]


In absence of  external stimuli, sinoatrial pacing generally, while awake, maintains the heart rate in the range of 60–100 beats per minute (bpm). [ 8 ]  The two branches of the  autonomic nervous system  work together to increase or slow the heart rate. The vagus nerve acts on the sinoatrial node, slowing its conduction and modulating vagal tone, via the  neurotransmitter   acetylcholine  and downstream changes to  ionic currents  and calcium of heart cells. [ 4 ]   Because of its effect on heart rate, and cardio health, vagal tone can be measured and understood by examining its correlation to heart rate modulation and  heart rate variability . [ 5 ]


Respiratory sinus arrhythmia (RSA) is typically a benign, normal variation in heart rate that occurs during each breathing cycle: the heart rate increases when breathing in and decreases when breathing out. [ 1 ]  RSA was first recognized by  Carl Ludwig  in 1847 [ 9 ]  but is still imperfectly understood. [ 10 ]  It has been observed in humans from the early stages of life through adulthood, [ 11 ] [ 1 ]  and is found in several different species. [ 12 ] [ 13 ] [ 14 ]


During  inhalation , the  intra-thoracic pressure  lowers due to the contraction and downward movement of the  diaphragm  and the expansion of the chest cavity.  Atrial pressure  is also lowered as a result, causing increased blood flow to the heart, which in turn decreases  baroreceptors  firing response which diminishes vagal tone. This causes an increase in heart rate. [ 1 ]


During  exhalation , the diaphragm relaxes, moving upward, and decreases the size of the chest cavity, causing an increase in intrathoracic pressure. This increase in pressure inhibits  venous return  to the heart resulting in both reduced atrial expansion and increased activation of baroreceptors. This relieves the suppression of vagal tone and leads to a decreased heart rate. [ 1 ]


Respiratory sinus arrhythmia (RSA) is frequently used as a noninvasive method for investigating vagal tone, in physiological, behavioral, and several clinical studies. [ 16 ] [ 17 ] [ 18 ]  This can be done using  electrocardiography  (ECG) recording, [ 19 ]  although other methods are also being developed that take advantage of the interactions between ECG and  respiration . [ 20 ] [ 15 ]  Interpretation of RSA measurements must be done with care, however, as several factors including differences between individuals can change the relationship between RSA and vagal tone. [ 21 ]


It has been suggested that RSA may have evolved to save energy for both cardiac and respiratory systems by reducing the heart rate [ 22 ]  and by suppressing ineffective ventilation during the ebb of  perfusion  (delivery of blood from arteries to capillaries for oxygenation and nutrition). [ 23 ] [ 24 ]


RSA has been found to increase in subjects in resting state and to decrease in states of stress or tension. It is increased in supine position and decreased in prone position, and is on average higher and more pronounced during the day as compared to the night. [ 22 ]   RSA has also been extensively used to quantify vagal tone withdrawal in  graded orthostatic tilt . [ 7 ] [ 25 ]


Typically, expression of RSA decreases with age. [ 26 ]   However, adults in excellent cardiovascular health, such as endurance runners, swimmers, and cyclists, are likely to have a more pronounced RSA. Professional athletes on average maintain very high vagal tone and consequently higher RSA levels. RSA is less prominent in individuals with diabetes and cardiovascular disease. [ 27 ]


Vagal tone research has the potential to offer insight into social behavior, social interactions, and human psychology.  Much of this work has been focused on  newborns  and  children . [ 26 ]  Baseline vagal tone can be used either as a potential predictor of behavior or as a signal of mental health (particularly  emotion regulation ,  anxiety , and  internalizing  and  externalizing disorders ). [ 28 ] [ 29 ]


The  polyvagal theory  by  Porges  is an influential model of how the vagal pathways respond to novelty and to stressful external stimuli. [ 30 ] [ 31 ] [ 32 ]  The theory proposes that there are two vagal systems, one that is shared with  reptiles  and  amphibia  and a second, more recent, system that is unique to  mammals . The two pathways behave differently and can work against each other. This theory can account for several  psychophysiological  phenomena and  psychosomatic illnesses . [ 30 ] [ 26 ]  However, recent studies indicate that the vagal "system" described by Porges as being unique to mammals existed long before the evolution of mammals. [ 33 ] [ 34 ]


There are several methods of estimating vagal tone other than measuring RSA, including:


Vena amoris  is a  Latin  name meaning, literally, "vein of love."  It describes a special blood vein that was once believed to flow directly from the   fourth finger  of the left hand to the  heart . [ 1 ]  This belief has been cited in Western cultures as one of the reasons the  engagement ring  and/or  wedding ring  was placed on the fourth finger, or " ring finger ". This myth dates back to the  Medieval Ages .


While science now accepts that all blood veins flow to the heart, this was not understood at the time and would not be proven until the 17th century by the physician  William Harvey . [ 2 ]


The earliest known occurrence of the phrase  vena amoris  was from  Henry Swinburne , an English ecclesiastical lawyer whose work covering marriage, "A Treatise of Espousal or Matrimonial Contracts", was published posthumously in 1686.  Swinburne identifies the  vena amoris  as a vein of blood passing to the heart, found in the fourth finger of the left hand. He states that a wedding ring on that finger signifies that "as they give their hands each to other, so likewise they should give their hearts also, whereunto that vein is extended." [ 3 ]  He cites unnamed ancient sources for this belief and purports an Egyptian connection, most likely referring to a work by the fourth century Roman writer  Macrobius .


Macrobius, in Saturnalia VII, refers to the connection between the ring finger and the heart but implies that it is a nerve rather than a vein. In this work, the belief is stated to have originated in Egypt.


...after turning up some books on anatomy, I discovered the truth: that there is a certain nerve which has its origin in the heart and runs from there to the finger next to the little finger of the left hand, where it ends entwined with the rest of the nerves of that finger; and that this is the reason why it seemed good to the men of old to encircle that finger with a ring, as though to honor it with a crown. [ 4 ]


Another early reference, not specifying the hand, was by  Isidore of Seville  in his 7th century work  De ecclesiasticis officiis  XX, 8:


Men have begun to wear a ring on their fourth finger starting from the thumb, since there is a vein here which links it to the heart—something which the ancients thought worth noting and honouring.
 [ 5 ]


References to this vein continue in England until the 17th century, when more came to be understood about the circulatory system. Until then, the  vena amoris  figured into various remedies affecting the heart. Some thought that the simple wearing of a ring on this finger, or pinching the finger, would alleviate ailments. [ 6 ]  It was sometimes referred to as the  leech-finger  due to blood-letting practices.


While the placement of wedding rings has varied greatly over time and place, the  vena amoris  has always been identified in the fourth finger, next to the little finger. [ 1 ]
Most sources point to it being in the left hand, but some, like Isidore of Seville, do not specify a hand. Today many western countries follow a tradition of placing wedding rings on the fourth finger of the right hand instead. [ 7 ]


Venous hum  is a benign  auscultatory  phenomenon caused by the normal flow of blood through the  jugular veins . [ 1 ]  At rest, 20% of cardiac output flows to the brain via the internal carotid and vertebral arteries; this drains via the  internal jugular veins . The rush of blood from these veins to the  brachiocephalic vein  can cause the vein walls to vibrate, creating a humming noise which can often be heard by the subject.


Typically, a peculiar humming sound is heard in the upper chest near the  clavicle , emanating from the  supraclavicular fossa  just lateral to the  sternocleidomastoid muscle , usually more obviously on the right side than on the left. The sound may radiate to the upper sternal border on either side. [ 2 ]  Though the exact mechanism is still unclear, it has been suggested that the hum occurs when otherwise silent laminar flow through the internal jugular vein is disturbed by deformation of this vessel at the level of the  transverse process  of the  atlas  during head rotation. [ 3 ]


The venous hum is heard throughout the  cardiac cycle , though is typically louder during  diastole . It may be easier to hear when sitting, when the chin is elevated, or when the head is rotated contralaterally (away from the location of the sound); deep inspiration and hyperkinetic circulatory states (e.g.  hyperthyroidism ) can also increase its intensity. [ 2 ]  It may be loud enough to result in audible  pulsatile tinnitus . It is by far the most common type of normal continuous murmur, universal in healthy children, and frequently present in healthy young adults, especially during pregnancy. [ 4 ]


The humming may be confused with a  heart murmur , which may be a symptom of a potentially serious condition. The difference is easily detected by placing light pressure on the internal jugular vein when listening to the heart, which will immediately abolish or change the venous hum, whereas a true heart murmur will be unaffected by this maneuver. The murmur also disappears when the patient is in the  supine position  or may disappear if the subject turns their head to one side. It is also known by the names "nun's murmur" and "bruit de diable" (noise of devils).


While a venous hum may provoke consultation with a healthcare professional, the hum itself is entirely harmless and is the product of ordinary cardiac physiology. Abnormal and potentially serious conditions such as  thyrotoxicosis  and  anemia , by augmenting blood flow through the jugular veins, can nonetheless initiate or reinforce the venous hum, making it more noticeable, [ 4 ]  and manipulation of the sound with various maneuvers has often helped physicians discover and diagnose cardiovascular disorders. [ 5 ]


Acquired non-inflammatory myopathy (ANIM)  is a neuromuscular disorder primarily affecting skeletal muscle, most commonly in the limbs of humans, resulting in a weakness or dysfunction in the muscle. [ 1 ]  A  myopathy  refers to a problem or abnormality with the  myofibrils , which compose muscle tissue. In general, non-inflammatory myopathies are a grouping of muscular diseases not induced by an  autoimmune -mediated  inflammatory  pathway. These muscular diseases usually arise from a  pathology  within the muscle tissue itself rather than the nerves innervating that tissue. ANIM has a wide spectrum of causes which include drugs and toxins, nutritional imbalances, acquired metabolic dysfunctions such as an acquired defect in protein structure, and infections. [ 1 ]


Acquired non-inflammatory myopathy is a different diagnosis than  inflammatory myopathy . Inflammatory myopathies are a direct result of some type of autoimmune mediated pathway whereas ANIM is not the result of a dysfunction of the immune system. [ 2 ]  In addition, the cause of inflammatory myopathy is relatively unknown, whereas many causal agents for ANIM have been discovered which typically affect the structural integrity and function of the muscle fibers. [ 2 ]


Most myopathies are typically first diagnosed and classified as an  idiopathic  inflammatory myopathy. [ 2 ] [ 3 ] [ 4 ] [ 5 ]  However, a diagnosis of ANIM occurs when the cause of the myopathy is found to not arise from an autoimmune mechanism. [ 1 ]


Patients with acquired non-inflammatory myopathy typically experience weakness, cramping, stiffness, and  tetany , most commonly in skeletal muscle surrounding the limbs and upper shoulder girdle. [ 1 ]


The most commonly reported symptoms are:


Acquired non-inflammatory myopathy can be caused by a variety of factors including metabolic abnormalities, drugs, nutritional deficiency, trauma, and upstream abnormalities resulting in decreased function.  Two of the most common causes of ANIM are  hyperthyroidism  and excessive steroid use, while many drugs used to treat  rheumatism  are known to be inducing agents.  Most cases of ANIM can be linked to drugs or dietary abnormalities. [ citation needed ]


It is not uncommon for drugs to damage muscle fibers. Particular families of drugs are known to induce myopathies on the molecular level, thus altering organelle function such as the mitochondria. Use of multiple drugs from these families in conjunction with one another can increase the risk of developing a myopathy. [ 6 ]  Many of the drugs associated with inducing myopathies in patients are found in rheumatology practice. [ citation needed ]


Many dietary factors and aberrations can induce ANIM.  Chemical imbalances brought on by abnormal diets may either affect the muscle directly or induce abnormal functionality in upstream pathways.


Trauma  to any muscle is also a common cause for acute ANIM.  This is due to muscular contusions and partial or complete loss of function for affected muscle groups. [ 2 ]


A patient's history is one of the key factors in diagnosing acquired non-inflammatory myopathy. The history is used not only to analyze the time frame with which the patient began to express symptoms, but to also see if the disease is within the patient's family history, to check medication or drug use history, and to see if the patient has had any trauma due to illness or infection. Basic exams will test for where the muscle weakness is and how weak it is. This is performed by testing for proximal and distal muscle strength, as well as testing for any signs of  neurogenic  symptoms such as impaired sensation, deep tendon reflexes, and atrophy. [ 1 ]


If needed, more advanced equipment can be used to help determine whether a patient has ANIM. This includes:


When examining the serum levels of muscle enzymes, the relative levels of  creatine kinase ,  aldolase ,  aspartate aminotransferase ,  alanine aminotransferase , and  lactate dehydrogenase  are closely examined. Abnormal levels of these proteins are indicative of both  inflammatory myopathy  and ANIM. [ 1 ]


EMGs are particularly useful in locating the affected muscle groups, as well as determining the distribution of the myopathy throughout the cell. EMGs measure several indicators of myopathies such as: [ 1 ]


Magnetic Resonance Imaging will elicit edema in inflammatory patients, but it will most likely show nothing in patients with ANIM and if it does, it will show some  atrophy . [ 1 ]


If an individual's ANIM is a result of a metabolite defect, then additional tests are required. These tests are directed at enzyme function at rest and during exercise, and enzyme intermediates. Molecular  genetic testing  is often used to determine if there was any predisposition to the expressed symptoms. [ 1 ]


During vigorous  ischemic  exercise, skeletal muscle functions anaerobically, generating lactate and ammonia a coproduct of muscle myoadenylate deaminase (AMPD) activity. The forearm ischemic exercise test takes advantage of this physiology and has been standardized to screen for disorders of glycogen metabolism and AMPD deficiency. Patients with a glycogen storage disease manifest a normal increase in ammonia but no change from baseline of lactate, whereas in those with AMPD deficiency, lactate levels increase but ammonia levels do not. If ischemic exercise testing gives an abnormal result, enzyme analysis must be performed on muscle to confirm the putative deficiency state because false-positive results can occur. [ citation needed ]


Treatment for acquired noninflammatory myopathy is directed towards resolution of the underlying condition, pain management, and muscle rehabilitation.
Drug induced ANIMs can be reversed or improved by tapering off of the drugs and finding alternative care. [ 6 ]   Hyperthyroidism induced ANIM can be treated through anti-thyroid drugs, surgery, and not eating foods high in Iodine such as kelp.  Treatment of the hyperthyroidism results in complete recovery of the myopathy. [ 7 ]    ANIM caused by  vitamin D deficiency  can easily be resolved by taking vitamin supplements and increasing one's exposure to direct sunlight. [ 8 ]


Pain can be managed through massaging affected areas and the use of  nonsteroidal anti-inflammatory drugs  (NSAIDs).
Exercise, physical therapy, and occupational therapy can be used to rehabilitate affected muscle areas and resist the  atrophy  process. [ 2 ]  The use of walkers, canes, and braces may assist with the mobility of the affected individual. [ citation needed ]


A diagnostic test for statin-associated auto-immune necrotizing myopathy will be available soon in order to differentiate between different types of myopathies during diagnosis. The presence of abnormal spontaneous electrical activity in the resting muscles indicates an irritable myopathy and is postulated to reflect the presence of an active necrotising myopathic process or unstable muscle membrane potential. However, this finding has poor sensitivity and specificity for predicting the presence of an  inflammatory myopathy  on biopsy. Further research into this spontaneous electrical activity will allow for a more accurate differential diagnosis between the different myopathies. [ 1 ]


Currently a muscle biopsy remains a critical test, unless the diagnosis can be secured by genetic testing. Genetic testing is a less invasive test and if it can be improved upon that would be ideal. Molecular genetic testing is now available for many of the more common metabolic myopathies and muscular dystrophies. These tests are costly and are thus best used to confirm rather than screen for a diagnosis of a specific myopathy. It is the hope of researchers that as these testing methods improve in function, both costs and access will become more manageable [ 6 ]


The increased study of muscle pathophysiology is of importance to researchers as it helps to better differentiate inflammatory versus non-inflammatory and to aim treatment as part of the differential diagnosis. Certainly classification schemes that better define the wide range of myopathies will help clinicians to gain a better understanding of how to think about these patients. Continued research efforts to help appreciate the pathophysiology will improve clinicians ability to administer the most appropriate therapy based on the particular variety of myopathy. [ 2 ]


The mechanism for myopathy in individuals with low vitamin D is not completely understood. A decreased availability of 250HD leads to mishandling of cellular calcium transport to the sarcoplasmic reticulum and mitochondria, and is associated with reduced actomyosin content of myofibrils. [ 8 ]


Amyotrophy  is progressive wasting of  muscle  tissues. Muscle pain is also a symptom. It can occur in middle-aged males with  type 2 diabetes . It also occurs with  motor neuron disease .


The following are considered  differential diagnosis  for amyotrophy: [ 1 ]


A  compartment syndrome  is an increased pressure within a muscular compartment [ 1 ]  that compromises the circulation to the muscles.


Diffuse tightness and tenderness over the entire belly of the tibialis anterior muscle that does not respond to elevation or  pain medication  can be early warning signs and suggestive of Anterior Compartment Syndrome.  Other common symptoms include excessive swelling that causes the  skin  to become hot, stretched and glossy.  Pain,  paresthesias , and tenderness in both the ischemic muscles and the region supplied by the deep  common fibular nerve  are exhibited by patients with this condition.  Sensitivity to passive stretch and active contraction are common, and tend to increase the symptoms. [ citation needed ]


A compartment space is anatomically determined by an unyielding  fascial  (and  osseous ) enclosure of the muscles.  The anterior compartment syndrome of the  lower leg  (often referred to simply as anterior compartment syndrome), can affect any and all four muscles of that compartment:  tibialis anterior ,  extensor hallucis longus ,  extensor digitorum longus , and  peroneus tertius . [ citation needed ]


This term is often mistakenly used to describe various related/proximal conditions, including Anterior  Shin Splints .  It is important to distinguish between the two, as shin splints rarely causes serious health problems, while Anterior Compartment Syndrome can lead to irreversible damage. [ citation needed ]


The true compartment syndrome arises due to increased  pressure within the unyielding  anterior compartment of the leg .  The pressure obstructs venous outflow, which causes further swelling and increased pressure.  The resultant  ischemia  leads to  necrosis  (death of tissue) of the muscles and nerves.  The process can begin with swelling of the tibialis anterior, extensor hallucis longus, extensor digitorum longus, and/or the peroneus tertius muscles in response to strong  eccentric contractions  sufficient to produce postexercise soreness. [ citation needed ]


If these symptoms are observed/experienced it is important to contact a physician specializing in  sports medicine  ( MD / DO ), a  doctor of podiatric medicine  (DPM), or other qualified health care professional immediately so as to get the appropriate advice/treatment before serious damage occurs. [ citation needed ]


The 5 Ps of Anterior Compartment Syndrome:


The only option to treat acute compartment syndrome is surgery. The procedure, called a fasciotomy, involves a surgeon cutting open the skin and the fascia to relieve the pressure. Options to treat chronic compartment syndrome include physiotherapy, shoe inserts, and anti-inflammatory medications. [ citation needed ]


Benign acute childhood myositis  (BACM) is a syndrome characterized by muscle weakness and pain in the lower limbs that develop in children after a recent viral illness. It is transient with a spontaneous clinical resolution within 1 week. [ 1 ] [ 2 ]


Prodromal symptoms are typically fever, cough, and rhinorrhea. BACM symptoms that follow are most frequently calf pain, gait complaints, and inability to walk. [ 2 ]  The condition is self-limited and full restitution can be expected. In very rare cases, however,  rhabdomyolysis  may develop. [ 1 ]


Affected are preschool and school-age children with a male predominance. [ 2 ]  In one study, the median age was 6 years (range 2–13.2 years). [ 1 ]  It has been estimated that BACM has an incidence of 2.69 cases per 100,000 children (<18 years) during epidemic seasons and 0.23 cases during non-epidemic seasons. [ 3 ]


The history of a preceding influenza-like infection followed by the typical symptoms of acute onset of symmetrical calf pain and gait problems together with an isolated finding of a high level of  creatine kinase  suggests the diagnosis of BACM. [ 4 ]   Myoglobinuria  is rare and points to the possibility of the development of rhabdomyolysis and kidney failure. [ 2 ] [ 5 ]


Guillain-Barré syndrome  (GBS) is the main consideration in the differential diagnosis. It needs to be quickly excluded as early intervention in GBS is indicated. Other conditions under possible consideration are  dermatomyositis ,  muscular dystrophy ,  juvenile idiopathic arthritis ,  transient synovitis of the hip ,  osteomyelitis , and  myalgia . [ 1 ]


Few muscle biopsies have been conducted. Results may show normal findings or features of inflammation and necrosis. [ 1 ]


A number of different preceding viral infections have been reported, most commonly  influenza A  and  B . The condition appears to be more prevalent during late fall, winter, and spring. [ 2 ]  Other virus infections that have been linked to BACM are those caused by  Parainfluenza ,  Coxsackievirus ,  Adenovirus ,  Echovirus , and  Mycoplasma pneumonia . [ 1 ]
Viral myositis after viral infections may also occur in adults, and viruses, such as COVID-19, have been reported as a rare cause of myositis. [ 6 ]


BACM may be alarming to parents and lead to unnecessary extensive tests. [ 4 ]  Treatment consists of oral analgesics, rest, and adequate hydration. [ 1 ]  Hospitalization is usually not necessary. Full recovery can be expected within a week, however, recurrences can occur.


in 1957 Lundberg reported on a group of patients with a condition he named  myalgia cruris epidemica , [ 7 ]  seemingly the first description of BACM. Other terms later used include  influenza-associated myositis, viral myositis, acute myositis [ 2 ]  Middleton and colleagues reported on BACM as  severe myositis after influenza  in 1970. [ 8 ]  Viral myositis may occur also in later years.


Cataplexy  is a sudden and transient episode of muscle weakness accompanied by full conscious awareness, typically triggered by emotions such as laughing, crying, or terror. [ 1 ]  Cataplexy is the first symptom to appear in about 10% of cases of  narcolepsy , [ 2 ]  caused by an autoimmune destruction of hypothalamic neurons that produce the neuropeptide  hypocretin  (also called orexin), which regulates  arousal  and has a role in stabilization of the transition between wake and sleep states. [ 3 ]  Cataplexy without narcolepsy is rare and the cause is unknown.


The term cataplexy originates from the  Greek  κατά ( kata , meaning "down"), and πλῆξις ( plēxis , meaning "strike") [ 4 ]   and it was first used around 1880 in German physiology literature to describe the phenomenon of tonic immobility also known as " playing possum " (in reference to the  opossum 's behavior of feigning death when threatened). [ 4 ]  In the same year the French neuropsychiatrist Jean-Baptiste Gélineau coined the term 'narcolepsy' and published some clinical reports that contained details about two patients who had similar conditions to those of current narcoleptic cases. [ 5 ]  Nevertheless, the onset that he reported was in adulthood, as compared to current cases reported in childhood and adolescence. [ 6 ]  Even if he preferred the term 'astasia' instead of 'cataplexy', the case that he described remains iconic for the diagnosis of full narcoleptic  syndrome . [ 4 ]


Cataplexy manifests itself as muscular  weakness  which may range from a barely perceptible slackening of the facial  muscles  to complete muscle  paralysis  with postural collapse. [ 7 ]  Attacks are brief, most lasting from a few seconds to a couple of minutes, and typically involve dropping of the jaw, neck weakness, and/or buckling of the knees. Even in a full-blown collapse, people are usually able to avoid injury because they learn to notice the feeling of the cataplectic attack approaching and the fall is usually slow and progressive. [ 8 ]  Speech may be slurred and  vision  may be impaired (double vision, inability to focus), but hearing and  awareness  remain normal. [ citation needed ]


Cataplexy attacks are self-limiting and resolve without the need for medical intervention. If the person is reclining comfortably, they may transition into sleepiness,  hypnagogic hallucinations , or a period of  REM  sleep. While cataplexy worsens with fatigue, it is different from  narcoleptic sleep attacks  and is usually, but not always, triggered by strong emotional reactions such as  laughter ,  anger ,  surprise ,  awe , and  embarrassment , or by sudden physical effort, especially if the person is caught off guard. [ 9 ]  One well-known example of this was the reaction of  1968 Olympic   long jump  medalist  Bob Beamon  on learning that he had broken the previous world record by over 0.5 meters (almost 2 feet). [ 10 ] [ additional citation(s) needed ] [ medical citation needed ]  Cataplectic attacks may occasionally occur spontaneously, with no identifiable emotional trigger. [ 11 ]


Cataplexy is considered secondary when it is due to specific lesions in the brain that cause a depletion of the hypocretin neurotransmitter. Secondary cataplexy is associated with specific lesions located primarily in the lateral and posterior hypothalamus. Cataplexy due to  brainstem  lesions is uncommon particularly when seen in isolation. The lesions include tumors of the brain or brainstem and arterio-venous malformations. Some of the tumors include  astrocytoma ,  glioblastoma ,  glioma , and  subependymoma . These lesions can be visualized with brain imaging, however in their early stages they can be missed. Other conditions in which cataplexy can be seen include  ischemic  events,  multiple sclerosis ,  head injury ,  paraneoplastic syndromes , infections such as  encephalitis , and more rarely  Niemann Pick disease . Cataplexy may also occur transiently or permanently due to lesions of the hypothalamus that were caused by surgery, especially in difficult tumor resections. These lesions or generalized processes disrupt the hypocretin neurons and their pathways. The neurological process behind the lesion impairs pathways controlling the normal inhibition of muscle tone drop, consequently resulting in  muscle atonia . [ 12 ]


A phenomenon of  REM sleep , muscular paralysis, occurs at an inappropriate time. This loss of  tonus  is caused by massive inhibition of  motor neurons  in the spinal cord. When this happens during waking, the patient who had a cataplectic attack loses muscular control. As in REM sleep, the person continues to breathe and is able to control eye movements. [ 9 ]


The hypothalamus region of the brain regulates basic functions of hormone release, emotional expression and sleep. One study concluded that the neurochemical  hypocretin , also known as orexin, which is regulated by the hypothalamus, was significantly reduced in study participants with symptoms of cataplexy. Hypocretin regulates sleep and states of arousal. Hypocretin deficiency is further associated with decreased levels of  histamine  and  epinephrine , chemicals important in promoting wakefulness, arousal and alertness. [ 13 ]


The diagnosis of narcolepsy and cataplexy is usually made by symptom presentation. Presenting with the tetrad of symptoms (excessive daytime sleepiness, sleep-onset paralysis, hypnagogic hallucinations, and cataplexy symptoms) is strong evidence of the diagnosis of narcolepsy. A multiple sleep latency test [ clarification needed ]  is often conducted to quantify daytime sleepiness. [ 14 ]


Cataplexy can sometimes be misdiagnosed as a  seizure disorder , and people with narcolepsy are often misdiagnosed with other conditions such as  psychiatric disorders  or  emotional problems , it can take years for someone to get the proper diagnosis. [ 2 ]


Cataplexy is treated with medications. Treatment for narcolepsy and cataplexy can be divided to those that act on the excessive daytime sleepiness (EDS) and those that improve cataplexy. Most patients require lifelong use of medications. [ 15 ]  Most treatments in humans will act only symptomatically and do not target the loss of the orexin-producing neurons. [ 16 ]