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  • Correspondent: Joe Tundra Walker
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The biggest tech revolution of the 21st Century isn't digital, it's biological. A breakthrough called CRISPR has given us unprecedented control over the basic building blocks of life. It opens the door to curing diseases, reshaping the biosphere, and designing our own children. Human Nature is a provocative exploration of CRISPR's far-reaching implications, through the eyes of the scientists who discovered it, the families its affecting, and the bio-engineers who are testing its limits. How will this new power change our relationship with nature? What will it mean for human evolution? To begin to answer these questions we must look back billions of years and peer into an uncertain future

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112 M; Star - Sei Hiraizumi, Shun Oguri; writer - Makoto Shinkai; ; Genres - Fantasy, Family; release Date - 2019. Tenki no ko Movie online store. Tenki no ko Movie online ecouter. Tenki no ko movie online. Intro be like : NYAN NYAN NYAN NYAN NYAN NYAN. I want to eat your pancreas is shocked and agitated and really hungry for pancreas right now. Ver Weathering With You (2019) Pelicula Completa En Espanol Latino Ver película Weathering With You Dos completa en Español sin cortes y sin publicidad. Última actualización: HOY. Weathering With You Dos pelicula completa (2019) esta disponible, como siempre en Repelis. Nuestro contenido está adaptado al Español latino. El genero de Weathering With You Dos es Terror. Weathering With You Dos para ver la Pelicula Completa tiene una duración de 169 min. Nuestro contenido para ver online tenemos siempre es de la mejor calidad centrandonos en contenido HD, 1080, o 720. Ver Weathering With You PELICULA-COMPLETA Subtitulada Director: Makoto Shinkai Guión: Makoto Shinkai Protagonista: Daigo Tiger eliminando Lang / Sen siete platos / Oguri / Honda Wing / Baisho Chieko / Más … Tipo: Romance / Animación / Fantasía sistema País / Región: japonés Idioma: japonés Fecha de lanzamiento: 2019–07–19 (Japón) Duración: 114 minutos AKA: Weathering With You / Weather Child / Weather’s Child / Child of Weather Enlace de IMDb: tt9426210 Sinopsis de · · · · · · En el verano de Gaoyi, Fan Gao (la voz del tigre) se quedó en la ciudad natal de la isla y llegó solo a Tokio. La dura vida lo obligó a encontrar un trabajo, y finalmente llegó a una publicación especial de extrañas publicaciones sobrenaturales. El editor es escritor. Pronto, Tokio comenzó a llover durante mucho tiempo, como si implicara un futuro muy resbaladizo. En esta ciudad ocupada, las velas de todo el lugar se balancearon con el hermano menor, la increíble y hermosa niña Yangcai (hijo de siete platos doblados). “Espera, estará bien”, dijo Yangcai a la vela. Pronto, las nubes oscuras sobre la cabeza se dispersaron gradualmente, y el deslumbrante sol hizo añicos las calles … Resultó que Yangcai tenía la maravillosa capacidad de “cambiar el clima” … Tenki no Ko (Weathering With You) F U L L M O V I E English Subtítulos EL TIEMPO CONTIGO (SUBBED INGLÉS) [Subtítulos en inglés] Tenki no Ko (Weathering with You): anime EL TIEMPO CONTIGO Tenki no Ko CON SUBTÍTULOS EN INGLÉS Makoto Shinkai English Sub — Tenki No Ko: Weathering With You Vea Weathering with You PELÍCULA COMPLETA HD1080p Sub Inglés WeatheringwithYou movie transmisión de películas completas en línea El verano de su primer año de secundaria, Hodaka huye de su remota isla a Tokio, y rápidamente se ve empujado a sus límites financieros y personales. El clima es inusualmente sombrío y lluvioso todos los días, como para sugerir su futuro. Vive sus días aislado, pero finalmente encuentra trabajo como escritor para una misteriosa revista oculta. Entonces, un día, Hodaka se encuentra con Hina en una esquina concurrida. Esta chica brillante y de voluntad fuerte posee una habilidad extraña y maravillosa: el poder de detener la lluvia y despejar el cielo … EL TIEMPO CON TI PELÍCULA COMPLETA ENG SUB Tenki no Ko (Weathering With You) Subtítulos en inglés TIEMPO CONTIGO INGLÉS SUBBED EL TIEMPO CON USTED TRAILER CON SUBTÍTULOS EN INGLÉS Vea Weathering with You PELÍCULA COMPLETA HD1080p Sub Inglés Tenki no Ko: Weathering With You Theatrical Anime Film capeando contigo película completa eng sub Tráiler de Weathering With You: llora por la nueva película de Makoto Shinkai 天 気 の 子 — Envejeciendo contigo ENGLISH SUB Tenki No Ko (Weathering with You): La historia, los temas y la música Tenki no Ko (Weathering With You) MyAnimeList.

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I went to watch weathering with you after the movie got released in India due to petition from thousands of Indian fans(yes petitions work after all.
I was stunned by looking at all those beautiful animations. Really you can't do the same with live action. The CG used in fireworks citywide scene was particularly amazing. Animation and music in this movie were perfect.
Although I couldn't stop and compare it with other Makoto Shinkai films. Although this film is good but it is not Your Name or 5 cm per Second. You can certainly enjoy the film, it is packed with comedic and thrilling scenes.
That being said I hope anime movies from directors like Mamoru Hosoda get a release in India without fans needing to signing petition.(yes it doesn't work all the time, looking at you GoT s8.

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Inxs 3a baby live at wembley stadium funk. Inxs live baby live at wembley stadium dvd. Contains some strong language. A spectacular INXS concert filmed on 13 July 1991 at Wembley Stadium, London, featuring classic anthems New Sensation, Mystify and Need You Tonight.   Duration 57 mins First shown 11pm 28 Dec 2019 Available for 10 months. Myzcloud Цветовая тема RU English Русский Хиты Коллекции... ТОП-250 Альбомы Сборники Саундтреки Радио Плейлисты Хит-Парады Алфавит... A B C D E F G H I J K L M N O P Q R S T U V W X Y Z А Б В Г Д Е Ж З И К Л М Н О П Р С Т У Ф Х Ц Ч Ш Щ Э Ю Я # Топ жанров #Dance #Italo Disco #Alternative Metal #K-Pop #Death Metal #Instrumental #Drum'n'Bass #Chillout #Hip-Hop #Classic Rock #Industrial Metal #Melodic Death #Deep House #Ambient #Эстрада #Black Metal #Pop-Rock #Indie Rock #Breakbeat #Chanson Все жанры Топ исполнителей Imagine Dragons Pink Floyd Imany Кино Queen Scorpions Major Lazer The Beatles Robin Schulz Ария Все исполнители Главная Исполнители INXS Live Baby Live Wembley Stadium (Remastered) #Alternative Rock 2019 1 Guns In The Sky 03:44 320 Кб/с 156 2 New Sensation 03:54 87 3 I Send A Message 03:40 60 4 The Stairs 05:01 45 5 Know The Difference 03:46 30 6 Disappear 04:07 44 7 By My Side 03:17 52 8 Hear That Sound 27 9 Original Sin 05:36 39 10 Lately 06:41 29 11 The Loved One 12 Wild Life 03:36 28 13 Mystify 03:10 37 14 Bitter Tears 04:26 15 Suicide Blonde 04:36 51 16 What You Need 06:30 17 Kick 03:31 31 18 Need You Tonight 02:59 40 19 Mediate 05:38 22 20 Never Tear Us Apart 03:47 50 21 Who Pays The Price 24 Devil Inside 07:25 30.

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INXS: Live Baby Live at Wembley Stadium INXS: Live Baby Live at Wembley Stadium (UK, 2019) A 100 min Musical Trailer Sinopsis 1991 fue un año espectacular para INXS. Su álbum "X" había estado en las listas durante ocho meses, convirtiéndose en platino en el Reino Unido y doble platino en los Estados Unidos. Ganando dos premios Brit, INXS tocó actuaciones de espectáculos récord en su tierra natal australiana, encabezó Rock In Rio y emprendió una gira con entradas agotadas por los EE. Sin embargo, fueron los eventos del 13 de julio de 1991 los que llevaron a la banda a la estratosfera musical. Seis años hasta el día de Live Aid, y cinco años y un día, desde que la banda apoyó a Queen en el estadio de Wembley, INXS encabezó su propio espectáculo en el famoso lugar ante una multitud de 73, 791 fanáticos enloquecidos. El evento, llamado "Summer XS", fue inmortalizado en la película de conciertos más vendida "Live Baby Live", dirigida por David Mallet. Veintiocho años después, la película se ha restaurado minuciosamente durante un período de seis meses desde el negativo original de 35 mm a 4K Ultra HD. La película ahora se presenta en una gloriosa pantalla panorámica cinematográfica, creada al pasar por la película disparo a disparo y reposicionar cada una de ellas para obtener lo mejor del cuadro. Para acompañar la sorprendente mejora visual, el audio ahora se presenta en Dolby Atmos completo (y sonido envolvente 5. 1), creado por el productor ejecutivo de música de la banda, Giles Martin, en los estudios Abbey Road. Además, el proceso de restauración reveló una actuación "perdida", que no se incluyó en los lanzamientos originales - "Últimamente" del álbum "X". Ahora vuelve a su posición legítima en la lista de conciertos. Consulta más Horarios Cargando horarios:( Por el momento no hay horarios disponibles para esta película. :( Por favor selecciona un cine.

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Live at Wembley Stadium 1991 Live album by INXS Released 7 February 2014 Recorded 13 July 1991 Venue Wembley Stadium Genre Rock Label Petrol Electric INXS live chronology The Very Best (2011) Live at Wembley Stadium 1991 (2014) Mystify: A Musical Journey with Michael Hutchence (2019) "Live at Wembley Stadium 1991" is a live album recorded by Australian band INXS. Background and release [ edit] On 13 July 1991, INXS were filmed in concert at Wembley Stadium in London, performing to a sold-out mass of 72, 000 fans. This concert was filmed in 35 mm and directed by David Malle with no less than 17 cameras. [1] The album was released in February 2014 to coincide with the screening of INXS: Never Tear Us Apart, an Australian miniseries about INXS that commenced airing on 9 February 2014 and concluded the following week on 16 February on the Seven Network. [2] Track listing [ edit] The album was released as a digital download on 7 February 2014. [3] "Guns in the Sky" – 3:27 "New Sensation" – 3:54 "I Send a Message" – 3:41 "The Stairs" – 4:59 "Know the Difference" – 3:47 "Disappear" – 4:12 "By My Side" – 3:10 "Hear That Sound" – 3:44 "Original Sin" – 6:17 "The Loved One" – 4:06 "Wildlife" – 3:32 "Mystify" – 3:18 "Bitter Tears" – 4:12 "Suicide Blonde" – 4:32 "What You Need" – 6:30 "Kick" – 3:30 "Need You Tonight" – 2:57 "Mediate" – 5:32 "Never Tear Us Apart" – 3:47 "Who Pays the Price" – 3:39 "Devil Inside" – 7:13 "Shining Star" – 3:40 Charts [ edit] Live at Wembley Stadium 1991 was a commercial success, reaching #4 on the Australian iTunes albums chart before peaking at #17 on ARIA Albums Chart. [4] INXS: Live Baby Live Wembley Stadium [ edit] INXS: Live Baby Live Wembley Stadium Live album by INXS Released 15 November 2019 Recorded 13 July 1991 Venue Wembley Stadium Genre Rock Length 96: 44 INXS chronology INXS: Live Baby Live Wembley Stadium (2019) A fully restored film edition of the Wembley Stadium performance was released in 2019, with CD and vinyl editions. [7] "Guns in the Sky" "New Sensation" "I Send a Message" "The Stairs" "Know the Difference" "Disappear" "By My Side" "Hear That Sound" "Original Sin "Lately" (previously unreleased) "The Loved One" "Wild Life" "Mystify" "Bitter Tears" "Suicide Blonde" "What You Need" "Kick" "Need You Tonight" "Mediate" "Never Tear Us Apart" "Who Pays the Price" "Devil Inside" See also [ edit] INXS discography Live Baby Live References [ edit].

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Score - 1036 vote / Genre - Thriller / / actor - Veerle Baetens / runtime - 17 m / Writer - Delphine Girard. Free online une soeur en. "Une soeur" or "A Sister" is a Belgian French-language live action short film that premiered back in 2018 and was nominated at the 2020 Academy Awards almost 1.5 years later. The director is Delphine Girard, apparently still a relatively young filmmaker, and her effort here makes me curious about what we can expect from her once she makes the transition to full feature films. I got to watch all the five nominated live action short films last night before the Oscar ceremony and this one here was the first they showed and also my favorite from the bunch. At approximately 17 minutes, it as also the shortest from the nominees I believe, but the outcome here is a perfect example of how quantity does not equal quality because the other four are inferior, some even drastically. Shame this one probably never really had a chance to take home the prize. But that does not make it worse or anything. When and after watching, I still thought it was merely good, but after thinking a bit about it, I'd say it is even great and one of the finest short movies from its year and also deserving of the Oscar win. This partially has to do with lead actress Veerle Baetens here, who plays an emergency phone hotline operator. I already thought she was amazing on "The Broken Cicle Breakdown" wow... can't believe this one is already almost a decade old. so I recognized her immediately. This film reminded me of a Danish film from not too long ago that was also fairly close to being nominated for an Oscar, but that was a full feature film, so there were plot twwists and everything. This one here is just very focused and essential story-telling that almost feels a bit like a documentary from a police investigation. Fittingly, I read an article not too long ago about a case where a woman called such a hotline to report a case of domestic violence I think and that she (or somebody close to her) is in danger, but she could not speak freely, so she disguised her call as if she was calling to order a pizza. The hotline operator understood and realized it is not a prank and managed to help her to become hero of the day.
This film is at least slightly similar to that but it as made way before the event I just mentioned (became public) so it did not inspire this film. I think the moment you realize what's going on, namely when you find out that the hotline operator just received the call you saw before that from the perspective of the woman in the car, you are immediately in the middle of this film. And you won't leave until it is over. It is that good and had me on the edge of my seat more than most full feature movies. Of course, you will need subtitles unless you are fluent in French, but this should not keep you from watching. It is really essential that you understand all the dialogues. I also liked how they elaborated on what happened before that, probably that the woman was abused sexually and then abducted. You would not know how it ends, if there is a big car chase scene, the guy loses it and maybe kills his victim and/or himself or whatever else could happen, but Girard took the most likely and most realistic way out without any spectacular final sequence. Or I should say any spectacular showy sequence because the moment the police stops them, he gets out of the car and surrenders. Felt very authentic and realistic. So did everything else about the end, for example how she asks the woman on the phone if she is supposed to step out of the vehicle now as well. She trusted her to make the right decision for her the way she did before that by basically saving her. And at the very end, when Baetens' character asked for her name, we find out how anonymous this job really is and how you have to deliver acts that are much bigger than a simple "hello my name is. and still it stays a really lonely profession. The attention to detail in this film is nice too. Just one example how she steps away from the noise at her workplace when she is about to talk to the guy. She definitely is a pro knowing what needed to be done to do her best to save a life. There is no guarantee of course. Early on, there is also a brief moment of comedy when we find out about a guy who has been constantly calling for nothing that warrants calling. And finally, I would like to say that I think the title is a good choice as well. Very simple, but hits the nail right on the head. She is her sister that night, not only because of how she has to pretend she is, but also because the two women have a special connection. In the truest sense of the word. I highly recommend this film. Very well done.

Free online une soeur site. Free online une soeur de. Vengo luego de ver los Oscars. Lamentablemente este metraje no ganó, pero el corto es muy bueno la verdad. Free online une soeur meaning. Free online une soeur film. Free online une soeur du. J étais morte de rire a 5:25 quand Yassine a crié 😂😂😂. Free Online Une soeur marie. Free online une soeur l. Ta sœur ne fait pas du tout 19 ans sinon superbe video👌. Défi réussi ! vous êtes magnifiques ❤️ J'adore ce concept je vais faire pareil avec ma sœur jumelle ❤️ 😜.

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Free online une soeur un. Très touchant j' en ai les larmes aux je suis très contente 🤗💞 pour toi tu es si adorable souriante. Je te souhaite que du bonheur 😍😍 soulager que tu es retrouver ta sœur 🙏🙏🙏 paix à son âme pour ta maman. For other uses, see Sister (disambiguation). A Sister Directed by Delphine Girard Produced by Jacques-Henri Bronckart Written by Delphine Girard Starring Veerle Baetens Selma Alaoui Guillaume Duhesme Cinematography Juliette Van Dormael Edited by Damien Keyeux Production company Versus Production Release date 1 October 2018 Running time 16 minutes Country Belgium A Sister ( French: Une soeur) is a 2018 Belgian live-action short film directed by Delphine Girard. It has been selected and awarded at several film festivals including Rhode Island International Film Festival in August 2019 where it won the Oscar Qualifying Best Short Film Award [1]. The film was also nominated at the 9th Magritte Awards ceremony in February 2019 in Best Live Action Short Film category. [2] In January 2020, it was nominated for the 2020 Academy Award for Best Live Action Short Film. [3] Contents 1 Plot 2 Awards 3 References 4 External links Plot [ edit] A night. A car. Alie is in danger. To get by, she must make the most important phone call of her life. Awards [ edit] Since its launch, the film has been selected in many festivals around the world and has received several awards. Year Presenter/Festival Award/Category Status 2018 Festival International du Film Francophone de Namur Best Short Film Audience Award BeTV Award University of Namur Award Won [4] 2019 9th Magritte Awards Nominated [5] Saguenay International Short Film Festival Jury Award Won [6] [7] Palm Springs International Film Festival Best Short Film? Nominated [8] Rhode Island International Film Festival Won [9] Encounters Short Film and Animation Festival International Competition Nominated [10] Brussels Short Film Festival Best Short Nominated 2020 Academy Awards Best Live Action Short Film References [ edit] ^ "Scene Here: Festivals to the south — in Rhode Island and on the Vineyard - The Boston Globe".. Retrieved 2020-01-02. ^ " ' Girl, ' 'Above the Law' Lead Belgium Film Award Nominations". The Hollywood Reporter. Retrieved 2020-01-02. ^ "Oscars: Full List of Nominations". Retrieved 2020-01-16. ^ "33e Festival du Film Francophone de Namur: le palmarès". Cinopsis (in French). 2018-10-05. Retrieved 2020-01-03. ^ "Découvrez le palmarès complet des Magritte du Cinéma 2019". RTBF Culture (in French). 2019-02-02. Retrieved 2020-01-03. ^ Hervé, Jean-Baptiste (2019-03-18). "Festival Regard: l'animation à l'honneur". Journal Métro (in French). Retrieved 2020-01-03. ^ Smith, Justine (2019-03-20). "10 highlights from one of the best short film fests in the world". Cult MTL. Retrieved 2020-01-03. ^ "Under guidance of women programmers, ShortFest 2019 films to span #MeToo, ecology and sex". Desert Sun. Retrieved 2020-01-03. ^ "Ten of the best new short films at Encounters Film Festival 2019 | Sight & Sound". British Film Institute. Retrieved 2020-01-03. External links [ edit] A Sister on IMDb.

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Free Online Une soeurs. Free online une soeur french. Free online une soeur tv. Très émouvant la rencontre. Bien de choses à elle. Un article de Wikipédia, l'encyclopédie libre. Une sœur Roman graphique Scénario Bastien Vivès Dessin Lettrage Jean-François Rey Pays France Langue originale Français Éditeur Casterman Première publication 2017 ISBN 978-2-203-14716-4 Format normal Nb. de pages 212 Nb. d’albums 1 Site web modifier Une sœur est un roman graphique réalisé par Bastien Vivès, publié en 2017 chez Casterman. Synopsis [ modifier | modifier le code] Un été, en Bretagne, en vacances avec ses parents dans leur maison de l'Île aux Moines, au cœur du Golfe du Morbihan, Antoine, 13 ans, voit débarquer Hélène, 16 ans, la fille d'une amie de la famille qui se remet mal d'une fausse-couche. La jeune adolescente va partager la chambre et la vie d'Antoine et son jeune frère Titi. A eux trois, ils vont former une petite fratrie dans laquelle Hélène, jeune adolescente un peu angoissée, un peu perdue et un peu seule, va se sentir bien. Elle va aider Antoine à faire son éducation sentimentale. Historique [ modifier | modifier le code] L'auteur Bastien Vivès au Carrefour du Cinéma d'Animation 2017, au Forum des Images de Paris. La mère de Bastien Vivès a fait une fausse couche avant sa naissance et il a toujours regretté d'avoir manqué l'opportunité d'avoir une grande sœur qui aurait pu l'aider dans ses rapports avec les filles (difficiles pour cause de timidité et de surpoids) et lui donner une proximité féminine autre que celle de sa mère. Il a donc imaginé ce récit où une jeune fille fait irruption dans la vie d'un jeune adolescent et de son jeune frère pour reconstituer une relation totalement fantasmée sœur-frère. Une carte de tendre délicate et sensible. « – Y a beau avoir plein de monde, j'ai toujours l'impression d'être toute seule. – Même quand t'es avec nous? – Non, avec vous c'est chouette. » Le personnage d'Antoine est inspiré de Bastien Vivès enfant, plutôt solitaire et passant son temps à dessiner. Graphiquement, Bastien Vivès réalise un album en noir et blanc rehaussé de lavis de gris, avec la volonté de privilégier l'efficacité en choisissant par exemple de supprimer parfois les yeux des personnages pour ne pas parasiter la lecture et en sélectionnant avec attention les cadrages et les postures des personnages [ 1]. Publication [ modifier | modifier le code] 1ère édition: Casterman (212 pages, noir et blanc avec lavis gris), 3 mai 2017 (DL 05/2017 - ( ISBN   978-2-203-14716-4)) [ 2] Bibliographie [ modifier | modifier le code] Interview de Bastien Vivès et commentaires de l'auteur sur 4 planches in Casemate n° 103 (mai 2017) pages 50 à 59 Notes et références [ modifier | modifier le code] Portail de la bande dessinée francophone.

Free online une soeur video. Free online une soeur et. Free online une soeur le. Publié le 23 Mars 2017 par jean françois Je tiens a apporter ci une rectification, l'article paru hier sur le Blog a pris sa source dans le Blog Hiram Be et non dans Critica Masonica comme indiqué. Cette erreur a été relevée par Géplu et c'est bien normal, je lui fait une demande d'excuse. JF. Newsletter Abonnez-vous pour être averti des nouveaux articles publiés. Hébergé par Overblog. Free Online Une soeurette.

 

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Free full raise your voice movie. Free full rabid pictures. Free Full rapid'news. Rabies A dog with rabies in the paralytic (post-furious) stage Specialty Infectious disease Symptoms Fever, fear of water, confusion, excessive salivation, hallucinations, trouble sleeping, paralysis, coma [1] [2] Causes Rabies virus, Australian bat lyssavirus [3] Prevention Rabies vaccine, animal control, rabies immunoglobulin [1] Prognosis Nearly always death [1] Deaths 17, 400 (2015) [4] Rabies is a viral disease that causes inflammation of the brain in humans and other mammals. [1] Early symptoms can include fever and tingling at the site of exposure. [1] These symptoms are followed by one or more of the following symptoms: violent movements, uncontrolled excitement, fear of water, an inability to move parts of the body, confusion, and loss of consciousness. [1] Once symptoms appear, the result is nearly always death. [1] The time period between contracting the disease and the start of symptoms is usually one to three months, but can vary from less than one week to more than one year. [1] The time depends on the distance the virus must travel along peripheral nerves to reach the central nervous system. [5] Rabies is caused by lyssaviruses, including the rabies virus and Australian bat lyssavirus. [3] It is spread when an infected animal bites or scratches a human or other animal. [1] Saliva from an infected animal can also transmit rabies if the saliva comes into contact with the eyes, mouth, or nose. [1] Globally, dogs are the most common animal involved. [1] In countries where dogs commonly have the disease, more than 99% of rabies cases are the direct result of dog bites. [6] In the Americas, bat bites are the most common source of rabies infections in humans, and less than 5% of cases are from dogs. [1] [6] Rodents are very rarely infected with rabies. [6] The disease can be diagnosed only after the start of symptoms. [1] Animal control and vaccination programs have decreased the risk of rabies from dogs in a number of regions of the world. [1] Immunizing people before they are exposed is recommended for those at high risk, including those who work with bats or who spend prolonged periods in areas of the world where rabies is common. [1] In people who have been exposed to rabies, the rabies vaccine and sometimes rabies immunoglobulin are effective in preventing the disease if the person receives the treatment before the start of rabies symptoms. [1] Washing bites and scratches for 15 minutes with soap and water, povidone-iodine, or detergent may reduce the number of viral particles and may be somewhat effective at preventing transmission. [1] [7] As of 2016, only fourteen people had survived a rabies infection after showing symptoms. [8] [9] [10] Rabies caused about 17, 400 human deaths worldwide in 2015. [4] More than 95% of human deaths from rabies occur in Africa and Asia. [1] About 40% of deaths occur in children under the age of 15. [11] Rabies is present in more than 150 countries and on all continents but Antarctica. [1] More than 3 billion people live in regions of the world where rabies occurs. [1] A number of countries, including Australia and Japan, as well as much of Western Europe, do not have rabies among dogs. [12] [13] Many Pacific islands do not have rabies at all. [13] It is classified as a neglected tropical disease. [14] Signs and symptoms The period between infection and the first symptoms (incubation period) is typically 1–3 months in humans. [15] This period may be as short as four days or longer than six years, depending on the location and severity of the wound and the amount of virus introduced. [15] Initial symptoms of rabies are often nonspecific such as fever and headache. 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[18] Saliva production is greatly increased, and attempts to drink, or even the intention or suggestion of drinking, may cause excruciatingly painful spasms of the muscles in the throat and larynx. This can be attributed to the fact that the virus multiplies and assimilates in the salivary glands of the infected animal with the effect of further transmission through biting. The ability to transmit the virus would decrease significantly if the infected individual could swallow saliva and water. [19] Hydrophobia is commonly associated with furious rabies, which affects 80% of rabies-infected people. The remaining 20% may experience a paralytic form of rabies that is marked by muscle weakness, loss of sensation, and paralysis; this form of rabies does not usually cause fear of water. [18] Cause Drawing of the rabies virus. Rabies is caused by a number of lyssaviruses including the rabies virus and Australian bat lyssavirus. [3] Duvenhage lyssavirus may cause a rabies-like infection. [20] The rabies virus is the type species of the Lyssavirus genus, in the family Rhabdoviridae, order Mononegavirales. Lyssavirions have helical symmetry, with a length of about 180  nm and a cross-section of about 75 nm. [21] These virions are enveloped and have a single-stranded RNA genome with negative sense. The genetic information is packed as a ribonucleoprotein complex in which RNA is tightly bound by the viral nucleoprotein. The RNA genome of the virus encodes five genes whose order is highly conserved: nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G), and the viral RNA polymerase (L). [22] Once within a muscle or nerve cell, the virus undergoes replication. The trimeric spikes on the exterior of the membrane of the virus interact with a specific cell receptor, the most likely one being the acetylcholine receptor. The cellular membrane pinches in a procession known as pinocytosis and allows entry of the virus into the cell by way of an endosome. The virus then uses the acidic environment, which is necessary, of that endosome and binds to its membrane simultaneously, releasing its five proteins and single strand RNA into the cytoplasm. [23] The L protein then transcribes five mRNA strands and a positive strand of RNA all from the original negative strand RNA using free nucleotides in the cytoplasm. These five mRNA strands are then translated into their corresponding proteins (P, L, N, G and M proteins) at free ribosomes in the cytoplasm. Some proteins require post-translative modifications. For example, the G protein travels through the rough endoplasmic reticulum, where it undergoes further folding, and is then transported to the Golgi apparatus, where a sugar group is added to it ( glycosylation). [23] When there are enough viral proteins, the viral polymerase will begin to synthesize new negative strands of RNA from the template of the positive strand RNA. These negative strands will then form complexes with the N, P, L and M proteins and then travel to the inner membrane of the cell, where a G protein has embedded itself in the membrane. The G protein then coils around the N-P-L-M complex of proteins taking some of the host cell membrane with it, which will form the new outer envelope of the virus particle. The virus then buds from the cell. [23] From the point of entry, the virus is neurotropic, traveling along the neural pathways into the central nervous system. The virus usually first infects muscle cells close to the site of infection, where they are able to replicate without being 'noticed' by the host's immune system. Once enough virus has been replicated, they begin to bind to acetylcholine receptors at the neuromuscular junction. [24] The virus then travels through the nerve cell axon via retrograde transport, as its P protein interacts with dynein, a protein present in the cytoplasm of nerve cells. Once the virus reaches the cell body it travels rapidly to the central nervous system (CNS), replicating in motor neurons and eventually reaching the brain. [5] After the brain is infected, the virus travels centrifugally to the peripheral and autonomic nervous systems, eventually migrating to the salivary glands, where it is ready to be transmitted to the next host. [25]: 317 Transmission All warm-blooded species, including humans, may become infected with the rabies virus and develop symptoms. Birds were first artificially infected with rabies in 1884; however, infected birds are largely, if not wholly, asymptomatic, and recover. [26] Other bird species have been known to develop rabies antibodies, a sign of infection, after feeding on rabies-infected mammals. [27] [28] The virus has also adapted to grow in cells of cold-blooded vertebrates. [29] [30] Most animals can be infected by the virus and can transmit the disease to humans. Infected bats, [31] [32] monkeys, raccoons, foxes, skunks, cattle, wolves, coyotes, dogs, cats, and mongooses (normally either the small Asian mongoose or the yellow mongoose) [33] present the greatest risk to humans. Rabies may also spread through exposure to infected bears, domestic farm animals, groundhogs, weasels, and other wild carnivorans. However, lagomorphs, such as hares and rabbits, and small rodents such as chipmunks, gerbils, guinea pigs, hamsters, mice, rats, and squirrels, are almost never found to be infected with rabies and are not known to transmit rabies to humans. [34] Bites from mice, rats, or squirrels rarely require rabies prevention because these rodents are typically killed by any encounter with a larger, rabid animal, and would, therefore, not be carriers. [35] The Virginia opossum is resistant but not immune to rabies. [36] The virus is usually present in the nerves and saliva of a symptomatic rabid animal. [37] [38] The route of infection is usually, but not always, by a bite. In many cases, the infected animal is exceptionally aggressive, may attack without provocation, and exhibits otherwise uncharacteristic behavior. [39] This is an example of a viral pathogen modifying the behavior of its host to facilitate its transmission to other hosts. Transmission between humans is extremely rare. A few cases have been recorded through transplant surgery. [40] The only well-documented cases of rabies caused by human-to-human transmission occurred among eight recipients of transplanted corneas and among three recipients of solid organs. [41] In addition to transmission from cornea and organ transplants, bite and non-bite exposures inflicted by infected humans could theoretically transmit rabies, but no such cases have been documented, since infected humans are usually hospitalized and necessary precautions taken. Casual contact, such as touching a person with rabies or contact with non-infectious fluid or tissue (urine, blood, feces) does not constitute an exposure and does not require post-exposure prophylaxis. Additionally, as the virus is present in sperm or vaginal secretions, spread through sex may be possible. [42] After a typical human infection by bite, the virus enters the peripheral nervous system. It then travels along the afferent nerves toward the central nervous system. [43] During this phase, the virus cannot be easily detected within the host, and vaccination may still confer cell-mediated immunity to prevent symptomatic rabies. When the virus reaches the brain, it rapidly causes encephalitis, the prodromal phase, which is the beginning of the symptoms. Once the patient becomes symptomatic, treatment is almost never effective and mortality is over 99%. Rabies may also inflame the spinal cord, producing transverse myelitis. [44] [45] Diagnosis Rabies can be difficult to diagnose because, in the early stages, it is easily confused with other diseases or with aggressiveness. [46] The reference method for diagnosing rabies is the fluorescent antibody test (FAT), an immunohistochemistry procedure, which is recommended by the World Health Organization (WHO). [47] The FAT relies on the ability of a detector molecule (usually fluorescein isothiocyanate) coupled with a rabies-specific antibody, forming a conjugate, to bind to and allow the visualisation of rabies antigen using fluorescent microscopy techniques. Microscopic analysis of samples is the only direct method that allows for the identification of rabies virus-specific antigen in a short time and at a reduced cost, irrespective of geographical origin and status of the host. It has to be regarded as the first step in diagnostic procedures for all laboratories. Autolysed samples can, however, reduce the sensitivity and specificity of the FAT. [48] The RT PCR assays proved to be a sensitive and specific tool for routine diagnostic purposes, [49] particularly in decomposed samples [50] or archival specimens. [51] The diagnosis can be reliably made from brain samples taken after death. The diagnosis can also be made from saliva, urine, and cerebrospinal fluid samples, but this is not as sensitive or reliable as brain samples. [48] Cerebral inclusion bodies called Negri bodies are 100% diagnostic for rabies infection but are found in only about 80% of cases. [21] If possible, the animal from which the bite was received should also be examined for rabies. [52] Some light microscopy techniques may also be used to diagnose rabies at a tenth of the cost of traditional fluorescence microscopy techniques, allowing identification of the disease in less-developed countries. [53] A test for rabies, known as LN34, is easier to run on a dead animal's brain and might help determine who does and does not need post-exposure prevention. [54] The test was developed by the CDC in 2018. [54] Differential diagnosis The differential diagnosis in a case of suspected human rabies may initially include any cause of encephalitis, in particular infection with viruses such as herpesviruses, enteroviruses, and arboviruses such as West Nile virus. The most important viruses to rule out are herpes simplex virus type one, varicella zoster virus, and (less commonly) enteroviruses, including coxsackieviruses, echoviruses, polioviruses, and human enteroviruses 68 to 71. [55] New causes of viral encephalitis are also possible, as was evidenced by the 1999 outbreak in Malaysia of 300 cases of encephalitis with a mortality rate of 40% caused by Nipah virus, a newly recognized paramyxovirus. [56] Likewise, well-known viruses may be introduced into new locales, as is illustrated by the outbreak of encephalitis due to West Nile virus in the eastern United States. [57] Epidemiologic factors, such as season, geographic location, and the patient's age, travel history, and possible exposure to bites, rodents, and ticks, may help direct the diagnosis. Prevention Almost all human cases of rabies were fatal until a vaccine was developed in 1885 by Louis Pasteur and Émile Roux. Their original vaccine was harvested from infected rabbits, from which the virus in the nerve tissue was weakened by allowing it to dry for five to ten days. [58] Similar nerve tissue-derived vaccines are still used in some countries, as they are much cheaper than modern cell culture vaccines. [59] The human diploid cell rabies vaccine was started in 1967. Less expensive purified chicken embryo cell vaccine and purified vero cell rabies vaccine are now available. [52] A recombinant vaccine called V-RG has been used in Belgium, France, Germany, and the United States to prevent outbreaks of rabies in undomesticated animals. [60] Immunization before exposure has been used in both human and nonhuman populations, where, as in many jurisdictions, domesticated animals are required to be vaccinated. [61] The Missouri Department of Health and Senior Services Communicable Disease Surveillance 2007 Annual Report states the following can help reduce the risk of contracting rabies: [62] Vaccinating dogs, cats, and ferrets against rabies Keeping pets under supervision Not handling wild animals or strays Contacting an animal control officer upon observing a wild animal or a stray, especially if the animal is acting strangely If bitten by an animal, washing the wound with soap and water for 10 to 15 minutes and contacting a healthcare provider to determine if post-exposure prophylaxis is required 28 September is World Rabies Day, which promotes the information, prevention, and elimination of the disease. [63] Vaccinating other animals In Asia and in parts of the Americas and Africa, dogs remain the principal host. Mandatory vaccination of animals is less effective in rural areas. Especially in developing countries, pets may not be privately kept and their destruction may be unacceptable. Oral vaccines can be safely distributed in baits, a practice that has successfully reduced rabies in rural areas of Canada, France, and the United States. In Montreal, Quebec, Canada, baits are successfully used on raccoons in the Mount-Royal Park area. Vaccination campaigns may be expensive, and cost-benefit analysis suggests baits may be a cost-effective method of control. [64] In Ontario, a dramatic drop in rabies was recorded when an aerial bait-vaccination campaign was launched. [65] The number of recorded human deaths from rabies in the United States has dropped from 100 or more annually in the early 20th century to one or two per year due to widespread vaccination of domestic dogs and cats and the development of human vaccines and immunoglobulin treatments. Most deaths now result from bat bites, which may go unnoticed by the victim and hence untreated. [66] Treatment After exposure Treatment after exposure can prevent the disease if given within 10 days. The rabies vaccine is 100% effective if given early, and still has a chance of success if delivery is delayed. [21] [23] [67] Every year, more than 15 million people get vaccination after potential exposure. While this works well, the cost is significant. [68] In the US it is recommended people receive one dose of human rabies immunoglobulin (HRIG) and four doses of rabies vaccine over a 14-day period. [69] HRIG is expensive and makes up most of the cost of post exposure treatment, ranging as high as several thousand dollars. [70] As much as possible of this dose should be injected around the bites, with the remainder being given by deep intramuscular injection at a site distant from the vaccination site. [23] People who have previously been vaccinated against rabies do not need to receive the immunoglobulin, only the postexposure vaccinations on days 0 and 3. [71] The side effects of modern cell-based vaccines are similar to flu shots. The old nerve-tissue-based vaccinations required multiple injections into the abdomen with a large needle but is inexpensive. [52] It is being phased out and replaced by affordable World Health Organization intradermal-vaccination regimens. [52] Intramuscular vaccination should be given into the deltoid, not the gluteal area, which has been associated with vaccination failure due to injection into fat rather than muscle. In children less than a year old, the lateral thigh is recommended. [72] Thoroughly washing the wound as soon as possible with soap and water for approximately five minutes is effective in reducing the number of viral particles. [73] Povidone-iodine or alcohol is then recommended to reduce the virus further. [74] Awakening to find a bat in the room, or finding a bat in the room of a previously unattended child or mentally disabled or intoxicated person, is an indication for post-exposure prophylaxis (PEP). The recommendation for the precautionary use of PEP in bat encounters where no contact is recognized has been questioned in the medical literature, based on a cost–benefit analysis. [75] However, a 2002 study has supported the protocol of precautionary administering of PEP where a child or mentally compromised individual has been alone with a bat, especially in sleep areas, where a bite or exposure may occur with the victim being unaware. [76] After onset A treatment known as the Milwaukee protocol, which involves putting a person into a chemically induced coma and using antiviral medications, has been proposed but subsequently found not to be useful. [77] It initially came into use in 2003, following Jeanna Giese, a teenager from Wisconsin, becoming the first person known to have survived rabies without preventive treatments before symptom onset. [78] [79] She, however, already had antibodies against rabies when she initially arrived at hospital. [77] While this treatment has been tried multiple times more, there have been no further cases of survival. [77] The protocol has since been assessed as an ineffective treatment with concerns related to the costs and ethics of its use. [77] [80] Prognosis Vaccination after exposure, PEP, is highly successful in preventing the disease PEP against rabies. [67] In unvaccinated humans, rabies is almost always fatal after neurological symptoms have developed. [81] Epidemiology Deaths from rabies per million persons in 2012    0    1    2–4    5–9    10–17    18–69 Map of rabies-free countries and territories In 2010, an estimated 26, 000 people died from rabies, down from 54, 000 in 1990. [82] The majority of the deaths occurred in Asia and Africa. [81] As of 2015, India, followed by China (approximately 6, 000), and the Democratic Republic of the Congo (5, 600) had the most cases. [83] A 2015 collaboration between the World Health Organization, World Organization of Animal Health (OIE), Food and Agriculture Organization of the United Nation (FAO), and Global Alliance for Rabies Control has a goal of eliminating deaths from rabies by 2030. [84] India India has the highest rate of human rabies in the world, primarily because of stray dogs, [85] whose number has greatly increased since a 2001 law forbade the killing of dogs. [86] Effective control and treatment of rabies in India is hindered by a form of mass hysteria known as puppy pregnancy syndrome (PPS). Dog bite victims with PPS, male as well as female, become convinced that puppies are growing inside them, and often seek help from faith healers rather than medical services. [87] An estimated 20, 000 people die every year from rabies in India, more than a third of the global total. [86] Australia The rabies virus survives in widespread, varied, rural animal reservoirs. Despite Australia's official rabies-free status, [88] Australian bat lyssavirus (ABLV), discovered in 1996, is a strain of rabies prevalent in native bat populations. There have been three human cases of ABLV in Australia, all of them fatal. United States Rabies cases in humans and domestic animals — United States, 1938–2018 From 1960 to 2018, a total of 125 human rabies cases were reported in the United States; 36 (28%) were attributed to dog bites during international travel. [89] Among the 89 infections acquired in the United States, 62 (70%) were attributed to bats. [89] While canine-specific rabies does not circulate among dogs, about a hundred dogs become infected from other wildlife per year in the US. [90] [91] Rabies is common among wild animals in the United States. Bats, raccoons, skunks and foxes account for almost all reported cases (98% in 2009). Rabid bats are found in all 48 contiguous states. Other reservoirs are more limited geographically; for example, the raccoon rabies virus variant is only found in a relatively narrow band along the East Coast. Due to a high public awareness of the virus, efforts at vaccination of domestic animals and curtailment of feral populations, and availability of postexposure prophylaxis, incidence of rabies in humans is very rare. A total of 49 cases of the disease was reported in the country between 1995 and 2011; of these, 11 are thought to have been acquired abroad. Almost all domestically acquired cases are attributed to bat bites. [92] Europe Either no or very few cases of rabies are reported each year in Europe; cases are contracted both during travel and in Europe. [93] In Switzerland the disease was virtually eliminated after scientists placed chicken heads laced with live attenuated vaccine in the Swiss Alps. [65] The foxes of Switzerland, proven to be the main source of rabies in the country, ate the chicken heads and immunized themselves. [65] [94] Italy, after being declared rabies-free from 1997 to 2008, has witnessed a reemergence of the disease in wild animals in the Triveneto regions ( Trentino-Alto Adige/Südtirol, Veneto and Friuli-Venezia Giulia), due to the spreading of an epidemic in the Balkans that also affected Austria. An extensive wild animal vaccination campaign eliminated the virus from Italy again, and it regained the rabies-free country status in 2013, the last reported case of rabies being reported in a red fox in early 2011. [95] [96] Great Britain has been free of rabies since the beginning of the twentieth century except for a rabies-like virus in a few Daubenton's bats; there has been one, fatal, case of transmission to a human. There have been four deaths from rabies, transmitted abroad by dog bite, since 2000. The last infection in the UK occurred in 1922, and the last death from indigenous rabies was in 1902. [97] [98] Unlike the other countries of Europe it is protected by being an island, and by strict quarantine procedures. Mexico Mexico was certified by the World Health Organization as free of dog-transmitted rabies in 2019, since no case of dog-human transmission has been recorded in two years. [99] History Rabies has been known since around 2000 BC. [100] The first written record of rabies is in the Mesopotamian Codex of Eshnunna (circa 1930 BC), which dictates that the owner of a dog showing symptoms of rabies should take preventive measure against bites. If another person were bitten by a rabid dog and later died, the owner was heavily fined. [101] Ineffective folk remedies abounded in the medical literature of the ancient world. The physician Scribonius Largus prescribed a poultice of cloth and hyena skin; Antaeus recommended a preparation made from the skull of a hanged man. [102] Rabies appears to have originated in the Old World, the first epizootic in the New World occurring in Boston in 1768. [103] It spread from there, over the next few years, to various other states, as well as to the French West Indies, eventually becoming common all across North America. Rabies was considered a scourge for its prevalence in the 19th century. In France and Belgium, where Saint Hubert was venerated, the " St Hubert's Key " was heated and applied to cauterize the wound. By an application of magical thinking, dogs were branded with the key in hopes of protecting them from rabies. The fear of rabies was almost irrational, due to the number of vectors (mostly rabid dogs) and the absence of any efficacious treatment. It was not uncommon for a person bitten by a dog merely suspected of being rabid to commit suicide or to be killed by others. [104] In ancient times the attachment of the tongue (the lingual frenulum, a mucous membrane) was cut and removed as this was where rabies was thought to originate. This practice ceased with the discovery of the actual cause of rabies. [25] Louis Pasteur's 1885 nerve tissue vaccine was successful, and was progressively improved to reduce often severe side-effects. [15] In modern times, the fear of rabies has not diminished, and the disease and its symptoms, particularly agitation, have served as an inspiration for several works of zombie or similarly-themed fiction, often portraying rabies as having mutated into a stronger virus which fills humans with murderous rage or incurable illness, bringing about a devastating, widespread pandemic. [105] Etymology The term is derived from the Latin rabies, "madness". [106] This, in turn, may be related to the Sanskrit rabhas, "to rage". [107] The Greeks derived the word lyssa, from lud or "violent"; this root is used in the genus name of the rabies virus, Lyssavirus. [104] Other animals Rabies is infectious to mammals; three stages of central nervous system infection are recognized. The first stage is a one- to three-day period characterized by behavioral changes and is known as the prodromal stage. The second is the excitative stage, which lasts three to four days. This stage is often known as "furious rabies" for the tendency of the affected animal to be hyper-reactive to external stimuli and bite at anything near. The third is the paralytic stage and is caused by damage to motor neurons. Incoordination is seen, owing to rear limb paralysis, and drooling and difficulty swallowing is caused by paralysis of facial and throat muscles. Death is usually caused by respiratory arrest. [108] Research The outer shell of the rabies virus, stripped of its RNA contents and thus unable to cause disease, may be used as a vector for the delivery of unrelated genetic material in a research setting. It has the advantage over other pseudotyping methods for gene delivery that the cell targeting ( tissue tropism) is more specific for the central nervous system, a difficult-to-reach site, obviating the need for invasive delivery methods. 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External links Classification D ICD - 10: A82 ICD - 9-CM: 071 MeSH: D011818 DiseasesDB: 11148 External resources MedlinePlus: 001334 eMedicine: med/1374 eerg/493 ped/1974 Patient UK: Rabies Orphanet: 770 Wikimedia Commons has media related to Rabies. Look up rabies in Wiktionary, the free dictionary. Rabies at Curlie "Rabies". Retrieved 12 August 2012. Virus Pathogen Database and Analysis Resource (ViPR): Rhabdoviridae OIE's Rabies Portal Aerophobia and Hydrophobia in Rabies Videos " Rabies virus ". NCBI Taxonomy Browser. 11292.

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