ñoños

10 dari hampir 30 hasil pencarian terdekat untuk kata kunci ñoños oleh administrator realrecipeses.fun akan membuatmu bahagia.

image of Viajar con bebés o niños pequeños

Viajar con bebés o niños pequeños

Jan 27, 2008 · Éstos tienden a desaparecer pero a la hora de un buen llanto, son una salvación. Oídos: Para evitar que les duela los oídos durante el descenso, dáles su chupón/chupeta/bobo, su biberón o algo para masticar..
From: www.bebeslatinos.com

CrA³nica de Una Meada AnunciadaaE¦

Alarma de la EnuresisPoco despuA©s de cumplir los 3 aA±os, mi hijo dejA³ el paA±al. Ya me habA­an dicho que los niA±os orinan mA¡s frecuentemente que las niA±as (a mi hija le fue muy fA¡cil dejar el paA±al definitivamente), asA­ que me pareciA³ normal que mi hijo tuviera accidentes varias veces a la semana. Me aguantA© las cambiadas de pijama y sA¡banas con esperanzas de que fuera mejorando, porque tampoco querA­a volver a ponerle paA±al. Trataba tambiA©n de limitar la cantidad de lA­quido antes de la hora de dormir, de hablar con A©l, pero no habA­a mucho progreso. Le llevA© a la pediatra, pero me dijo que orinarse hasta los 8 (ocho!) aA±os es normal, que no hay que preocuparse y que ya lo superarA¡.

A sugerencia de las abuelas (y otras amigas), empecA© a levantarlo y llevarlo al baA±o todas las noches antes de acostarme. Esto funcionA³, especialmente en dA­as de semana cuando mi hijo se despertaba mA¡s temprano para ir a la escuela. Los fines de semana eran otra historia, tendA­a a dormir mA¡s largo y siempre amanecA­a mojado. Tres aA±os despuA©s, seguA­amos en lo mismo.

A principios de este mes acabA³ Kinder, ya con 6 aA±os y medio estaba peor que nunca, orinA¡ndose dos o tres veces todas las noches. TambiA©n A©l, estaba ya un poco avergonzado, sabiendo que la mayorA­a de sus amiguitos ya no mojan la cama. Hace un tiempo habA­a leA­do en internet sobre una alarma que ayuda a los niA±os a no orinarse en la cama. Es una alarma que en inglA©s se llama «Malem Ultimate Bedwetting Alarm» (alarma para el tratamiento de la enuresis, marca Malem). DecidA­ no comprarla porque me pareciA³ muy cara (cien dA³lares!) y no creA­ que fuera a funcionar. EsperA© a que acabara el aA±o escolar y ya desesperada, cambiA© de opinion y la compre en Amazon. Hay otros modelos y marcas, pero leyendo me decidA­ por el modelo que tenA­a mejores comentarios.

CA³mo Funciona la Alarma?

BA¡sicamente la alarma tiene dos partes, un sensor y una cajita que suena y vibra. El sensor se prensa al calzoncillo y estA¡ conectado por medio de un cable a la cajita que se agarra con un clip a la camiseta (como a la altura del pecho). Cuando el niA±o se empieza a orinar y el sensor se moja, la cajita empieza a vibrar y a sonar. La idea es simple, que la alarma ayude al niA±o a despertarse cuando se estA¡ orinando y asA­ empezar a entrenar al cerebro a reaccionar cuando el niA±o tenga ganas de ir al baA±o, para que no se orine.

Todas las reseA±as y comentarios que leA­ sobre la alarma decA­an que toma tiempo y que hay que tener paciencia, que a veces los niA±os no se despiertan con la alarma o se despiertan sobresaltados. El consenso es que no es una soluciA³n rA¡pida, puede tomar varias semanas o meses para ver resultados definitivos.

Alarma a Prueba

La alarma la empezamos a usar el 6 de junio. Mi hijo es un poco miedoso de los ruidos fuertes y estaba receloso de usar la alarma. Sorprendentemente, las dos primeras noches no se orinA³! Creo que finalmente estaba mA¡s consciente de que si se orinaba habrA­an consecuencias (la alarma) y por miedo a que se prendiera, de alguna forma se aguantA³.

A partir de la tercera noche todo volviA³ a la normalidad, mi hijo volviA³ a orinarse. La alarma se empezA³ a prender, una, dos y hasta tres veces por noche. Mientras la alarma sonaba, A©l se trataba de despertar, pero yo tenA­a que ayudarlo a levantarse y caminar al baA±o. Aunque se habA­a mojado, terminaba de orinar en el baA±o, cosa que ya era un pequeA±o avance. SegAon las instrucciones, el niA±o tiene que despertarse lo suficiente para acordarse en la maA±ana de que fue al baA±o. A mi hijo le molestaba mucho el sonido y mA¡s que todo la vibraciA³n de la alarma en su pecho, entonces se lo empecA© a poner en la cintura del calzoncillo. AsA­ pasamos dos semanas, levantA¡ndonos varias veces en la noche, yo llevA¡ndolo al baA±o. Poco a poco empecA© a notar que cada vez se mojaba menos.

Por Fin Resultados!

De repente una noche no se prendiA³ la alarma. Me despertA© pensando que dormA­ tan profundo que no la oA­ y que seguramente mi hijo se habA­a dormido mojado, como a veces pasa. Cuando mi hijo vino a mi cuarto en la maA±ana, me lleve la sorpresa de verlo con la pijama seca! No oA­ la alarma porque nunca se prendiA³! Ya van seis noches seguidas en que no se ha orinado.

Hoy vamos tres semanas de lo que empezamos a usar la alarma (dos de levantarnos y una en la que no se ha orinado). TodavA­a no canto victoria, pero lo que mA¡s me gusta es que sA© que A©l sA­ puede aguantarse toda la noche, y A©l estA¡ feliz de amanecer seco todas las maA±anas. Es todo un logro para A©l.

ConclusiA³n

Por ahora esta alarma esta recomendadA­sima y ha valido la pena la inversiA³n. MA¡s que todo siento que ha sido una ayuda mental para mi hijo, que le ha permitido tener mA¡s control de su cuerpo. Por ahora este es el final, pero sigan pendientes porque estarA© revisando este artA­culo para contarles mA¡s acerca de A©sta alarma y este tema. Estoy segura que tendrA© mA¡s cosas que reportar. TambiA©n me gustarA­a saber si alguien mA¡s estA¡ usando alguna otra alarma o mA©todo, asA­ que los invito a comentar!


Fomentando la lectura en los niños

Jan 24, 2008 · Fomentando la lectura en los niños. Iniciar y fomentar la lectura en nuestros hijos es muy importante y mientras más temprano mejor. Cuando son bebés, los niños no entienden la historia o cuento pero lo que disfrutan es oir las voces de sus padres (o tío, abuelo, etc) al leer..
From: www.bebeslatinos.com

Iniciar y fomentar la lectura en nuestros hijos es muy importante y mientras mA¡s temprano mejor. Cuando son bebA©s, los niA±os no entienden la historia o cuento pero lo que disfrutan es oir las voces de sus padres (o tA­o, abuelo, etc) al leer. Cuando ya son un poco mA¡s grandes y pueden entender la historia, es importante leerles con frecuencia, preferiblemente con un horario o hacerlo como parte de la rutina diaria. A muchos padres e hijos les funciona el leer siempre antes de ir a dormir. Puede ser tambiA©n luego de comer o en algAon momento que quiera compartir un momento tranquilo y relajado con sus hijos. Es importante hacer de la lectura algo interactivo, donde los papA¡s den la oportunidad a sus hijos de comentar sobre la historia, de inventar algo nuevo sobre los personajes, un nuevo final, contestar preguntas o dejar que ellos le lean a uno el cuento.

A los niA±os no solo les gusta oA­r un cuento, sino tambiA©n ver los dibujos y las palabras escritas. Es de mucha ayuda cuando los padres leen seA±alando las palabras para que el niA±o aprenda a seguir la historia y a la vez el niA±o se enseA±a a sA­ mismo ciertas letras o palabras y la nociA³n de leer. Hay veces que los adultos no sentimos intimidados por los libros, asA­ sean infantiles, porque creemos que hay que leer lo que estA¡ ahA­ y punto como si Perrault o la misma Caperucita nos fueran a regaA±ar por cambiar la historia. Mientras sus hijos son pequeA±os y no saben leer, no importa de quA© es el cuento ni en quA© idioma estA¡. Es aquA­ cuando los papA¡s tienen que volverse creativos. Cuando mi hija era pequeA±a, querA­a que le lea un libro que estaba en inglA©s y por un momento no sabA­a si leerle en inglA©s o quA©. Pero para ella no habA­a diferencia, asA­ que le leA­ mi versiA³n en espaA±ol. Incluso algunos libros que tiene en espaA±ol yo los leo a mi manera, simplificando ciertas palabras o cambiando algunas por otras mA¡s comunes en mi paA­s. Y no se preocupe si algAon dA­a su hijo le pide que le lea algo que ‘no se puede leer’. Mi hija a veces me da fotos de un juguete o un libro de calcamonA­as y me pide que se lo lea. Una vez le dije que ahA­ no decA­a nada pero para ella habA­a toda una historia en esos dibujos, entonces me inventA© toda una historia con lo que habA­a. Y no tiene que ser nada complicado (a veces al final del dA­a lo que menos tenemos los adultos es imaginaciA³n de niA±o), con que describa a su hijo lo que esta viendo, eso ya es un ‘cuento’ para A©l.

AsA­ mismo, usted tiene que decidir quA© le lee a su hijo y quA© no. Yo tuve que esconder Hansel y Gretel porque me parece un cuento cruel y al ver los dibujos mi hija me preguntaba que por quA© el papA¡ les llevA³ a los hijos al bosque (para abandonarlos) y que por quA© el niA±o estaba en una jaula (la bruja lo estaba engordando para comA©rselo) y que por quA© la bruja estaba en una olla (final muy cruel). Por mA¡s que usaba mi imaginaciA³n, preferA­ leer algo mA¡s agradable.

Si ya estA¡ cansado de leerle el mismo cuento todas las noches y aunque es aburrido para uno, los niA±os disfrutan oyendo lo mismo porque ya saben lo que viene, pueden ellos tambiA©n completar las frases que ya se saben de memoria y les atrae tambiA©n la emociA³n o efectos especiales que muchas veces los papA¡s aA±adimos a las historias. AsA­ que su mueca o sonidos al leerle un cuento, el final emocionante que se inventA³ o las cosquillas o beso que le da al final puede ser lo que su hijo quiera ver u oA­r cada vez.
Si su hijo es de los que le pide que siga leyendo y alargando el cuento y ya se le acabA³ la creatividad, no tenga miedo de repetir la historia, o en el caso contrario, de saltarse unas pA¡ginas para acabar mA¡s pronto. Lo importante es que le dA© ese momento de lectura a su hijo preferiblemente todos los dA­as y que en esos minutos se olvide de sus problemas de trabajo, de familia, etc y le dedique ese momento a A©l.

Y no hay nada como el buen ejemplo. Si a usted le gusta leer y su hijo le ve leyendo, aprenderA¡ que se puede disfrutar y aprender de los libros. Es importante enseA±arles a respetar los libros, a no rayarlos ni romperlos sino se los estA¡ menospreciando y a la lectura tambiA©n (usted no dejarA­a que su hijo pinte y desinfle su balA³n de fAotbol si quiere que luego juegue un partido). EnsA©A±e a sus hijos que los libros son divertidos y regA¡lele uno de vez en cuando para A©l que vea que para usted un libro es algo digno de regalar. Y como toda buena historia, «colorA­n colorado, este cuento se ha acabado.»


image of Å - Wikipedia

Å - Wikipedia

The letter Å represents various sounds in several languages. It is a separate letter in Danish, Swedish, Norwegian, Finnish, North Frisian, Low Saxon, Walloon, Chamorro, Lule Sami, Pite Sami, Skolt Sami, Southern Sami, Ume Sami, and Greenlandic alphabets. Additionally, it is part of the alphabets used for some Alemannic and Austro-Bavarian dialects of German. Though Å is ….
From: en.wikipedia.org

Letter A with overring

The letter A (a in lower case) represents various (although often very similar) sounds in several languages. It is a separate letter in Danish, Swedish, Norwegian, Finnish, North Frisian, Low Saxon, Walloon, Chamorro, Lule Sami, Pite Sami, Skolt Sami, Southern Sami, Ume Sami, and Greenlandic alphabets. Additionally, it is part of the alphabets used for some Alemannic and Austro-Bavarian dialects of German.[citation needed]

Though A is derived from A by adding an overring, it is considered a separate letter. It developed as a form of semi-ligature of an A with a smaller o above it to denote a long and darker A, a process similar to how the umlaut mark developed from a small e written above certain letters.

Scandinavian languages[edit] Origin[edit]

The A-sound originally had the same origin as the long /aː/ sound in German Aal and Haar (Scandinavian al, har, English eel, hair).

Historically, the a derives from the Old Norse long /aː/ vowel (spelled with the letter a), but over time, it developed to an [ɔː] sound in most Scandinavian language varieties (in Swedish and Norwegian, it has eventually reached the pronunciation [oː]). Medieval writing often used doubled letters for long vowels, and the vowel continued to be written Aa.

In Old Swedish the use of the ligature AE and of O (originally also a variant of the ligature OE) that represented the sounds [ae] and [o] respectively were gradually replaced by new letters. Instead of using ligatures, a minuscule (that is, lower-case) E was placed above the letters A and O to create new graphemes. They later evolved into the modern letters A and O, where the E was simplified into the two dots now referred to as umlaut. A similar process was used to construct a new grapheme where an "aa" had previously been used. A minuscule O was placed on top of an A to create a new letter. It was first used in print in the Gustav Vasa Bible that was published in 1541 and replaced Aa in the 16th century.[1]

In an attempt to modernize the orthography, linguists tried to introduce the A to Danish and Norwegian writing in the 19th century. Most people felt no need for the new letter, although the letter group Aa had already been pronounced like A for centuries in Denmark and Norway. Aa was usually treated as a single letter, spoken like the present A when spelling out names or words. Orthography reforms making A official were carried out in Norway in 1917 and in Denmark in 1948. According to Jorgen Norby Jensen, senior consultant at Dansk Sprognaevn, the cause for the change in Denmark was a combination of anti-German and pro-Nordic sentiment.[2] Danish had been the only language apart from German and Luxembourgish to use capitalized nouns in the last decades, but abolished them at the same occasion.

In a few names of Danish cities or towns, the old spelling has been retained as an option due to local resistance, e.g. Aalborg and Aabenraa; however, Alborg and Abenra are the spellings recommended by the Danish Language Board.[3] Between 1948 and 2010, the city of Aarhus was officially spelled Arhus. However, the city has changed to the Aa spelling starting 2011, in a controversial decision citing internationalization and web compatibility advantages.

Icelandic and Faroese are the only North Germanic languages not to use the a. The Old Norse letter a is retained, but the sound it now expresses is a diphthong, pronounced [au] in Icelandic and [ɔa] in Faroese. The short variation of Faroese a is pronounced [ɔ], though.

Use in names[edit]

In some place names, the old Aa spelling dominates, more often in Denmark than in Norway (where it has been abolished in official use since 1917). Locals of Aalborg and Aabenraa resist the A, whereas Alesund is rarely seen with Aa spelling. Official rules allow both forms in the most common cases, but A is always correct. A as a word means "small river" in Danish, Swedish, and Norwegian and can be found in place names.

Before 1917, when spelling with the double A was common, some Norwegian place names contained three or four consecutive A letters: for instance Haaa (now Haa, a river) and Blaaaasen (Blaasen, 'the blue ("bla") ridge ("as")').

In family names, the bearer of the name uses Aa or A according to their choice, but since family names are inherited they are resistant to change and the traditional Aa style is often kept. For instance, the last name Aagaard is much more common than Agard. The surname Aa is always spelled with double A, never with the single a. However, given names - which are less commonly inherited - have largely changed to the use of the A. For instance, in Norway more than 12,000 male citizens spell their name Hakon, while only around 2,500 are named Haakon.

Company names are sometimes spelled with the double A by choice, usually in order to convey an impression of old-fashionedness or traditionality. The double A, representing a single sound, is usually kept in initials e.g. for people whose first, middle, and/or last name begins with the double A. Accordingly, a man named "Hans Aagard Hauge" would spell his initials "H. Aa. H." (not "H. A. H." nor "H. A. H."), while a woman named Aase Vestergaard would spell her initials "Aa. V." (not "A. V." nor "A. V.").

Alphabetization[edit] Danish and Norwegian[edit]

Correct alphabetization in Danish and Norwegian places A as the last letter in the alphabet, the sequence being AE, O, A. This is also true for the alternative spelling "Aa". Unless manually corrected, sorting algorithms of programs localised for Danish or Norwegian will place e.g., Aaron after Zorro.

In Danish the correct sorting of aa depends on pronunciation: If the sound is pronounced as one sound it is sorted as A regardless of the sound is 'a' or 'a'; thus, for example, the German city Aachen is listed under A, as well as the Danish city Aabenraa. (This is §3 in the Danish Retskrivningsreglerne.)

Swedish[edit]

In the Swedish and Finnish alphabets, A is sorted after Z, as the third letter from the end, the sequence being A, A, O. This is easiest to remember across the Nordic languages, that Danish and Norwegian follow Z first with E-mutated letters AE and O and then the symbol with a one-stroke diacritic A. Swedish and Finnish follow Z with a one-stroke diacritic A and then a two-stroke (or two-dot) diacritic A, O. A combined Nordic sorting mnemonic is AE, O, A, A, O.

International transcription[edit]

Alternative spellings of the Scandinavian A have become a concern because of globalization, and particularly because of the popularization of the World Wide Web. This is to a large extent due to the fact that prior to the creation of IDNA system around 2005, internet domains containing Scandinavian letters were not recognized by the DNS system, and anyway do not feature on keyboards adapted for other languages. While it is recommended to keep the A intact wherever possible, the next best thing is to use the older, double A spelling (e.g. "www.raade.com" instead of "www.rade.com"). This is because, as previously discussed, the A/Aa indicates a separate sound. If the A is represented as a common A without the overring (e.g. "www.rade.com") there is no indication that the A is supposed to represent another sound entirely. Even so, representing the A as just an A is particularly common in Sweden, as compared to Norway and Denmark, because the spelling Aa has no traditional use there.

Finnish[edit]

Because the Finnish alphabet is derived from the Swedish alphabet, A is carried over, but it has no native Finnish use and is treated as in Swedish. Its usage is limited to loanwords and names of Swedish, Danish or Norwegian origin. In Finland there are many Swedish-speaking as well as many Finnish-speaking people with Swedish surnames, and many Swedish surnames include A. In addition, there are many geographical places in the Finnish coastal areas that have a in their Swedish names, such as Krako and Langnas. The Finnish name for A is ruotsalainen O ("Swedish O"), and is pronounced identically to O, which has the value [o̞].

It is not advised to substitute aa for a in Finnish, as aa is already a common letter combination with the value [aː].

Emilian-Romagnol[edit]

In Emilian-Romagnol, a is used to represent the open-mid back unrounded vowel [ʌ], e.g. Modenese dialect amm, danna [ˈʌmː], [ˈdʌnːa] "man, woman";

e.g. Bolognese dialect Bulaggna, dapp [buˈlʌɲːa] [ˈdʌpː] "Bologna, later".

Walloon[edit]

A was introduced to some eastern local variants of Walloon at the beginning of the 16th century and initially noted the same sound as in Danish. Its use quickly spread to all eastern dialects, but the cultural influence Liege and covered three sounds, a long open o, a long close o or a long a, depending on the local varieties. The use of a single a letter to cover such pronunciations has been embraced by the new pan-Walloon orthography, with one orthography for words regardless of the local phonetic variations. The Walloon use of A became the most popular use outside a Scandinavian language, even being used in the International Phonetic Alphabet drafted by Otto Jespersen.

In standardized writings outside the Liege area, words containing a are written with uh, a or o. For example, the word majhon (house), in the standardized orthography is spelled mojo, mahon, mohone, maujon in dialectal writings.

Istro-Romanian[edit]

The Istro-Romanian alphabet is based on the standard Romanian alphabet with three additional letters used to mark sounds specific only to this language: a, l and n.

Chamorro[edit]

A and a are also used in the practical orthography of Chamorro, a language indigenous to the people of Northern Mariana Islands and Guam. The Chamorro name for Guam is Guahan, and its capital is called Hagatna.

Greenlandic[edit]

In Greenlandic, a is not used in native words, but is used in several loanwords from Danish, such as bandoptageri (Danish bandoptager) 'tape recorder'. Like in Danish, a is sorted last in the alphabet.

Symbol for angstrom[edit]

The letter "A" (U+00C5) is also used throughout the world as the international symbol for the non-SI unit angstrom, a physical unit of length named after the Swedish physicist Anders Jonas Angstrom. It is always upper case in this context (symbols for units named after persons are generally upper-case). The angstrom is a unit of length equal to 10−10 m (one ten-billionth of a meter) or 0.1 nm.

Unicode also has encoded U+212B Å ANGSTROM SIGN. However, that is canonically equivalent to the ordinary letter A. The duplicate encoding at U+212B is due to round-trip mapping compatibility with an East-Asian character encoding, but is otherwise not to be used.[4]

On computers[edit] Similarly styled trademarks[edit]

The logo of the Major League Baseball team known as the Los Angeles Angels is a capital "A" with a halo. Due to the resemblance, some Angels fans stylize the name as "Angels".

The logo of the Stargate series similarly features a stylized A with a circle above it, making it resemble an A as in Stargate; in Norwegian, gate means "riddle".

Cirque du Soleil's Kooza production uses this character in its logo, although it is pronounced by the main singer as a regular "a".

British producer and singer Lapsley uses it in her stage name.

See also[edit] Notes[edit] References[edit]


Schuhreparatur Hesse / Sattlerarbeiten - Home | Facebook

Schuhreparatur Hesse / Sattlerarbeiten, Sebnitz, Germany. 297 likes · 4 were here. Shoe Repair Shop.
From: www.facebook.com

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image of miRNA-296-5p functions as a potential tumor suppressor in ...

miRNA-296-5p functions as a potential tumor suppressor in ...

Background: The pathogenesis of osteosarcoma (OS) is still unclear, and it is still necessary to find new targets and drugs for anti-OS. This study aimed to investigate the role and mechanism of the anti-OS effects of miR-296-5p. Methods: We measured the expression of miR-296-5p in human OS cell lines and tissues. The effect of miR-296-5p and its target gene staphylococcal nuclease and …Our study indicates that miR-296-5p may function as a tumor suppressor by targeting SND1 in OS..
Keyword: pmid:33652459, PMC7929571, doi:10.1097/CM9.0000000000001400, Ya-Zeng Huang, Jun Zhang, You-Jia Xu, Bone Neoplasms* / genetics, Cell Line, Tumor, Cell Movement / genetics, Cell Proliferation / genetics, Endonucleases / genetics, Gene Expression Regulation, Neoplastic, Genes, Tumor Suppressor, Humans, MicroRNAs* / genetics, Osteosarcoma* / genetics, PubMed Abstract, NIH, NLM, NCBI, National Institutes of Health, National Center for Biotechnology Information, National Library of Medicine, MEDLINE
From: pubmed.ncbi.nlm.nih.gov

Background: The pathogenesis of osteosarcoma (OS) is still unclear, and it is still necessary to find new targets and drugs for anti-OS. This study aimed to investigate the role and mechanism of the anti-OS effects of miR-296-5p.

Methods: We measured the expression of miR-296-5p in human OS cell lines and tissues. The effect of miR-296-5p and its target gene staphylococcal nuclease and tudor domain containing 1 on proliferation, migration, and invasion of human OS lines was examined. The Student's t test was used for statistical analysis.

Results: We found that microRNA (miR)-296-5p was significantly downregulated in OS cell lines and tissues (control vs. OS, 1.802 ± 0.313 vs. 0.618 ± 0.235, t = 6.402, P < 0.01). Overexpression of miR-296-5p suppressed proliferation, migration, and invasion of OA cells. SND1 was identified as a target of miR-296-5p by bioinformatic analysis and dual-luciferase reporter assay. Overexpression of SND1 abrogated the effects induced by miR-296-5p upregulation (miRNA-296-5p vs. miRNA-296-5p + SND1, 0.294 ± 0.159 vs. 2.300 ± 0.277, t = 12.68, P = 0.003).

Conclusion: Our study indicates that miR-296-5p may function as a tumor suppressor by targeting SND1 in OS.


image of Blueberries Improve Pain, Gait Performance, and ...

Blueberries Improve Pain, Gait Performance, and ...

Jan 29, 2019 · 1. Introduction. Osteoarthritis (OA) can be defined by symptoms such as pain and decreased flexibility. It is typically evaluated or classified through radiographic X-ray [].It often affects joint cartilage and/or underlying bones, involving the articular surfaces of synovial joints [].Symptomatic OA is defined as the presence of radiographic OA in combination with symptoms …Osteoarthritis (OA) is the most common joint disorder in the world and is the most frequent cause of walking related disability among older adults in the US, which brings a significant economic burden and reduces quality of life. The initiation and development ....
From: www.ncbi.nlm.nih.gov

Osteoarthritis (OA) is the most common joint disorder in the world and is the most frequent cause of walking related disability among older adults in the US, which brings a significant economic burden and reduces quality of life. The initiation and development of OA typically involves degeneration or progressive loss of the structure and function of articular cartilage. Inflammation is one of the major drives of the progression of OA. Dietary polyphenols have been studied for their anti-inflammatory properties and potential anabolic effects on the cartilage cells. Blueberries are widely consumed and are high in dietary polyphenols, therefore regular consumption of blueberries may help improve OA. The purpose of the present study was to examine the effect of freeze dried whole blueberries on pain, gait performance, and inflammation in individuals with symptomatic knee OA. In a randomized, double-blind trial, adults age 45 to 79 with symptomatic knee OA, were randomized to either consume 40 g freeze-dried blueberry powder (n = 33) or placebo powder (n = 30) daily for four months. Blood draws and assessment of pain and gait were conducted at baseline, two months, and four months. Western Ontario McMaster Osteoarthritis Index (WOMAC) questionnaires were used to assess pain and GAITRite® electronic walkway was used to evaluate gait spatiotemporal parameters. WOMAC total score and sub-groups, including pain, stiffness, and difficulty to perform daily activities decreased significantly in the blueberry treatment group (p < 0.05), but improvement of WOMAC total score and difficulty to perform daily activities were not observed in the placebo group. Normal walking pace single support percentage for both limbs increased (p = or < 0.007), while double support percentage for both limbs decreased in the blueberry treatment group (p = or < 0.003). No significant changes were observed in plasma concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-10, IL-13, matrix metalloproteinases (MMP)-3, MMP-13, and monocyte chemoattractant protein-1 (MCP-1) in both treatment groups. However, an increasing trend for IL-13 concentration and a decreasing trend in MCP-1 concentration were noted in the blueberry group. The findings of this study suggest that daily incorporation of whole blueberries may reduce pain, stiffness, and difficulty to perform daily activities, while improving gait performance, and would therefore improve quality of life in individuals with symptomatic knee OA.

Blueberries are consumed worldwide. Besides their pleasing taste, they are a significant source of polyphenols [30]. The major polyphenols found in blueberries are anthocyanins. Both in vitro and in vivo studies on anthocyanin effects in joint tissue have shown an anti-inflammatory effect [31]. Studies have shown that flavonoids increase the cartilage anabolic activity by enhancing certain factors such as insulin-like growth factor-1 (IGF-1), osteocalcin, bone morphogenetic protein (BMP), etc. [32,33]. A few clinical trials have also shown that blueberries have a potential anti-inflammatory effect [34,35] and could improve functionality measured by gait parameters in older adults [36]. However, there have been no studies with blueberries investigating their effects on pain reduction, functionality improvement, and inflammation in individuals with OA. This study investigated the effects of daily consumption of whole blueberries in individuals with symptomatic OA.

There is a growing body of research demonstrating a relationship between increased consumption of dietary polyphenols and their protective benefit in reducing risk for chronic human diseases, such as cardiovascular disease, hypertension, cancers, diabetes, certain infectious diseases, and osteoarthritis [11]. The proposed mechanism by which polyphenols reduce the risk of chronic human disease involves their ability to accept electrons from free radicals, thereby disrupting chain oxidation reactions, and increasing cellular antioxidative capacity [12]. Numerous in vitro studies and animal studies, and a small number of clinical trials have demonstrated polyphenols’ chondroprotective and anti-inflammatory actions [13,14,15,16,17,18,19,20]. Inflammation plays a major role the initiation and the development of OA. Studies suggest that inflammation occurs at the earliest stage of OA and contributes to the progression of OA [21,22]. Inflammatory cytokines and MMPs such as TNF-α, IL-1β, IL-6, MMP-3, and MMP-13 have been shown to be elevated in patients with OA [23,24,25] and contribute to the progression of OA [26,27]. On the other hand, anti-inflammatory cytokines such as IL-10 and IL-13 have been shown to have chondroprotective effects which slow down the progression of OA [28,29].

Current treatments for OA include pharmacologic, non-pharmacologic, and surgical intervention. Common pharmacological agents used include acetaminophen and other anti-inflammatory medications [7,8]. Long-term use of these pharmacological agents has potential adverse effects that can lead to serious consequences, including gastrointestinal bleeding and adverse cardiac effects [9,10]. Current pharmacological interventions only have a palliative benefit relieving the symptoms of OA while not treating the underlying problem of cartilage breakdown. Nutraceutical supplements, such as glucosamine and chondroitin, have been used to treat OA and reduce symptoms. However, there is currently no convincing information for the efficacy of such supplements in treating OA. Therefore, alternative, natural, and effective methods of reducing symptoms along with promoting healing and repair of cartilage tissue are warranted.

Osteoarthritis (OA) can be defined by symptoms such as pain and decreased flexibility. It is typically evaluated or classified through radiographic X-ray [1]. It often affects joint cartilage and/or underlying bones, involving the articular surfaces of synovial joints [2]. Symptomatic OA is defined as the presence of radiographic OA in combination with symptoms attributable to OA [1]. The primary symptoms of OA are joint pain, aching, and stiffness. OA is the most common joint disorder in the world and is the most frequent cause for walking-related disability among older adults in the United States [1]. It has been identified as an inflammatory disease of synovial joints and due to the symptoms and pathogenesis related structural changes of OA, it impacts one’s gait performance, therefore limiting physical activities [3]. One of the latest OA prevalence studies conducted by Barbour et al. reported over 54 million adults (22.7% of the US population) suffering from doctor diagnosed OA and it is projected to affect 78.4 million adults by 2040 [4]. Factors that contribute to the development of knee OA include systemic risk factors and local biomechanical risk factors. The systemic risk factors include age, gender, race/ethnicity, genetics, obesity, osteoporosis, bone density, and nutrition, while the local biomechanical risk factors include joint injury, certain occupations, physical activities, limb-length inequality, neuromuscular factors, bone characteristics, and joint space [5]. Among all risk factors, obesity, aging and female gender appear to be the most significant ones [6].

Descriptive statistics were calculated for all variables, comprising means, standard deviations, minima, and maxima for all continuous variables. Frequencies and percentages were calculated for all categorical variables. Distributions of the response variables were examined to determine if statistical tests of hypotheses based on the assumption of normality were being met, and that parametric testing is appropriate. Extreme outliers were investigated for technical or clerical error. Baseline differences of dependent variables were tested using independent sample t-tests. Although dependent variables in each area are related to each other, due to the small sample size, repeated measures (ANOVAs) were conducted to examine outcome differences of pain, stiffness, difficulties to perform daily activities, gait performance parameters, and inflammation biomarkers between treatments over time at baseline, midpoint, and final. Most variables are normally distributed, and some variables contain outliers. Therefore, the analyses were done on outlier-removed data as well. The data was analyzed using SPSS 25.0.0. (IBM, Armonk, NY, USA) All p-value ≤ 0.05 were considered statistically significant.

Overnight fasting venous blood was collected in ethylenediaminetetraacetic acid (EDTA) at baseline, midpoint, and final visits by a trained phlebotomist. Blood was centrifuged at 3000 g for 10 min to separate plasma, which then was aliquoted into collection tubes and stored at −80 °C for subsequent analysis of IL-1β, IL-6, TNF- α, IL-10, IL-13, MMP-3, MMP-13, and MCP-1. Magnetic bead multiplex ELISA kits from Millipore were used to analyze blood biomarkers of inflammation. Three different panels were conducted. A human high sensitivity T cell panel was used to analyze IL-1β, IL-6, TNF- α, IL-10, and IL-13 with inter-assay CVs (coefficient of variation) of <20%, a human MMP panel was used for analyzing MMP-3 and MMP-13 with inter-assay CVs of <20%, and a human metabolic hormone panel was used for analyzing MCP-1 with inter-assay CVs of <25%. Luminex 200 software (Luminex Corporation, Austin, TX, USA) was used to analyze the raw data.

Pain was assessed by using the WOMAC questionnaire at baseline, midpoint, and final visits. These questionnaires have been validated and have been used in many research projects studying symptomatic knee osteoarthritis [38]. Gait and balance were analyzed using a GAITRite® system (CIR Systems, Inc., Franklin, NJ, USA), a portable electronic walkway. The 10-meter GAITRite® system was set up and utilized by trained research personnel. Subjects were instructed to walk three trials on the walkway at self-elected (usual) speed and instructed to walk another three trials on the walkway at the fastest speed that they can walk without running. Twenty seconds of rest/pause were allowed between each trial. An average of the three trials for each gait velocity was recorded for analysis. The gait parameters measured included cadence, velocity, right and left step and stride length, right and left single and double support percentage to one gait cycle. The GAITRite® system has been validated and used as a reliable tool to assess a myriad of spatio-temporal gait parameters [39].

Qualified subjects were invited to the study site for three visits during the four-month study period, which included a baseline visit, midpoint visit (at two months), and final visit (at four months). At the baseline visit, qualified subjects were provided with a written consent form and informed on all aspects of the study. After consent forms were signed, research proceeded according to procedure. The procedures in each visit included anthropometric measurements including weight, height, leg length, and blood pressure, along with obtaining fasting blood samples, performing gait test, and filling out a WOMAC questionnaire.

Eligible men and women were randomly assigned to one of two groups, a treatment group (n = 33) or a placebo group (n = 30). The treatment group received 40 g of freeze-dried whole blueberry powder daily, provided by the US Highbush Blueberry Council (Folsom, CA, USA). The powder was constituted by merely extracting water, while maintaining the composition of whole blueberries, then milling to fine powder [37]. The powder was packaged in 20 g packets, with participants in the treatment group requested to consume two packets per day. The placebo group was also asked to consume 40 g of control powder daily, divided into 20 g packages, consumed twice a day. The placebo powder was constituted of maltodextrins to mimic the carbohydrate composition of whole blueberries, but without whole blueberries. The appearance of the placebo powder, along with energy content, are similar to blueberry powder. Participants in the treatment and control groups were instructed to reconstitute their respective powders in 10–12 ounces of water, immediately followed by consumption. Participants were on the respective regimen for a period of four months. The study protocols were approved by the Institutional Review Board at Texas Woman’s University.

Identification of potential subjects included a short screening questionnaire completed by phone. This screening questionnaire included questions on demographic information, smoking history, medical history, current medications/supplements, special diet, food allergies, and blueberry consumption. The inclusion criteria were men and women aged 45 to 79 experiencing knee pain, and in relatively healthy condition. The exclusion criteria were men and women who smoke more than one pack of cigarettes per day, have uncontrolled diabetes, who were on an insulin regimen that does not allow additional carbohydrate as part of a routine diet, who have congestive heart failure, who have knee replacements on both knees, or those who were using prescribed COX-2 inhibitors, chondroitin sulfate, glucosamine sulfate, or glucosamine hydrochloride powder and were not willing to stop taking these medications/supplements during the study period. Those who were allergic to blueberries were also excluded from participation.

Using a double-blind randomized placebo-controlled pre-test and post-test design, a total of 63 men and women, between the ages of 45 and 79, with self-reported symptomatic osteoarthritis were recruited through the local Denton community, Texas Woman’s University, and local orthopedic clinics. Recruited participants agreed to not take any cyclooxygenase-2 (COX-2) inhibitors, chondroitin sulfate, glucosamine sulfate, or glucosamine hydrochloride powder, all of which are known to have anti-inflammatory effects and/or influence the symptoms of knee pain. In addition, participants agreed not to consume any blueberry products or blueberries during the study.

There were no changes in plasma concentration of inflammatory biomarkers in the blueberry group over the study period. In the placebo group, there was a significant increase in the plasma concentration of TNF-α at midpoint over baseline, but there was a decrease at the final point over midpoint (a). There was also an increase in IL-1β at midpoint over baseline with a decrease at final point over midpoint, and no change overall for final point over baseline (b). IL-6 concentration remained consistent over the study periods in the placebo group (c). For the anti-inflammatory biomarkers, the plasma concentration of IL-10 and IL-13 stayed the same over the study period for both treatment groups. However, there was an overall increase in concentration of IL-13 at final point over baseline (+0.30 pg/mL) in the blueberry group, while there was an overall decrease in the placebo group at final point over baseline (−0.46 pg/mL) (b). The concentration of MMP-3 and MMP-13 in the blueberry group showed a decrease at midpoint over baseline and continued to decrease at final point, but the decreases at both midpoint and final point over baseline did not reach statistical significance. The plasma concentration of MMP-13 stayed the same over the study period in the placebo group (b). The MMP-3 concentration decreased at midpoint over baseline but rebounded at the final point (a). A decrease in concentration of MCP-1 was observed in the blueberry group, while an increase in MCP-1 was observed in the placebo group (). However, the changes did not reach significance. No significant changes of the inflammatory biomarkers, anti-inflammatory biomarkers, and MMPs were observed in the female only population.

In the blueberry group, normal paced velocity increased significantly at final point over baseline, and final point over midpoint (p < 0.05). There was a significant increase in normal paced walking left single support percentage to one gait cycle at midpoint over baseline (p < 0.05), and at final point over both baseline and midpoint (p < 0.05). At the same time, the decrease in the normal paced walking left limb led double support percentage to one gait cycle was noted at midpoint over baseline (p < 0.05) and final point over baseline (p < 0.05). A similar pattern was also noted in the normal paced right limb led single and double support percentage to one gait cycle in the blueberry group. Meanwhile, in the placebo group, there was a significant increase in the normal paced walking left single support percentage at midpoint (p < 0.05) and final point (p < 0.05) over baseline, but there was no change in the normal paced right single support percentage. For double support for both limbs in the placebo group, there was no change at final point over baseline. There were no changes in fast-paced single and double support percentage to one gait cycle for either limb in both groups at final point over baseline. A baseline difference was noted on the normal paced walking double support percentage to one gait cycle only in the right limb between the two groups. Measurements of gait parameters are shown in . In addition, data analysis of gait parameters was conducted for female only data, no additional findings were observed in the female population.

The WOMAC questionnaire was used to assess pain, stiffness, and difficulty to perform daily activities during the study. There was no difference in baseline WOMAC total score, pain, stiffness, or difficulty to perform daily activities between the two treatment groups. The total WOMAC score significantly decreased at midpoint over baseline and at final point over baseline for the blueberry group (). There was no change in the total WOMAC score in the placebo group throughout the study. In the blueberry group, pain decreased significantly at midpoint over baseline and continued to decrease at final point over baseline. In the placebo group, pain was significantly reduced at final point as compared to baseline (a). For stiffness, in the blueberry group, there was a significant decrease at midpoint over baseline and at final point over baseline. In the placebo group, there were no significant changes in stiffness from baseline to midpoint, but a significant decrease in stiffness at final point over baseline was noted (b). Significant decreases in difficulty to perform daily activities were observed in the blueberry group for midpoint and final point over baseline. There was no significant change of difficulty in performing daily activities in the placebo group throughout the study (c). There was no difference between the blueberry and placebo group in pain, stiffness, and difficulty to perform daily activities at any time point of the study. Female only data was also analyzed for WOMAC and the results were consistent with the data analyzed for both groups.

For body weight, height, and BMI, there was no significant difference between treatment groups at baseline. The body weight increased significantly at final point over baseline and midpoint in the placebo group, whereas the blueberry group maintained their body weight throughout the study, as shown in (a). In the blueberry group, participants maintained their BMI throughout the study period, while participants in the placebo group had a significant increase in BMI at final point over baseline and midpoint (b). A significant difference in systolic blood pressure between the two treatment groups was noted at baseline, but not of diastolic blood pressure. In the blueberry group, participants’ systolic blood pressure decreased significantly at midpoint over baseline and remained at the reduced level at final point (a). Also, participants’ diastolic blood pressure dropped significantly at final point over baseline in the blueberry group (b). There were no significant changes of systolic and diastolic blood pressure in the placebo group throughout the study. Besides the baseline differences in systolic blood pressure, there was no significant difference between the blueberry and the placebo group in regard to weight, height, BMI, or systolic and diastolic blood pressure, at any time point.

A total of 103 individuals were screened for participation in the study. Of those screened, 63 qualified individuals were scheduled for the baseline visit. Over the course of the study, there were 14 individuals who withdrew from the study due to issues such as taste and palatability of treatment, lack of interest, lack of compliance, or conflicts in study visit scheduling. A total of 49 participants completed the study. Demographic data associated with study participants is provided in . The majority of the participants in this study were female, who comprised 71% of the whole population at final point.

4. Discussion

The findings of the present study demonstrated that freeze-dried whole blueberry powder consumption for a period of four months results in a reduction in pain, stiffness, and difficulty to perform daily activities, an improved normal walking paced gait performance, and a favorable impact to certain inflammatory and anti-inflammatory biomarkers. A growing body of research has demonstrated a positive relationship between increased consumption of polyphenols and its protective effects in reducing chronic human disease risk [11]. The positive effects are attributed to its antioxidant and anti-inflammatory properties [40]. Both in vitro and in vivo studies have investigated polyphenols’ protective effects on osteoarthritis. Polyphenols from green tea extract, turmeric, red wine, citrus fruits, and pomegranate have been extensively investigated with many studies showing some level of anti-inflammatory and cartilage protective polyphenol effects [41,42,43,44,45].

Results from the WOMAC identified decreased pain and stiffness, and improved ability to perform daily activities in the blueberry group after consuming freeze-dried whole blueberry after 60 days of treatment, with the effects continuing to 120 days. These results are encouraging as pain and stiffness are the major symptoms for individuals suffering from OA, limiting their functional ability and thus lowering quality of life. However, improvements during the blueberry treatment were not significantly different from the placebo group at any time point. In a randomized double-blind crossover study investigating the efficacy of a tart cherry juice blend in treatment of knee OA, investigators observed a similar significant reduction in WOMAC scores in the tart cherry juice treatment group. Once again, the differences between treatment and placebo were not significant [46].

There was significant improvement in normal paced walking gait performance in the blueberry group, indicated by increased cadence, velocity, step and stride length for both limbs, increased single support percentage to one gait cycle and decreased double support percentage to one gait cycle for both limbs. The improvement happened as early as 60 days and continued to improve through the end of the treatment period. Stride length and cadence are correlated with classification of knee OA severity. Lower stride length and cadence correlated with higher grade OA as classified by the Kellgren and Lawrence evaluation system [47]. Single limb support is strongly correlated with WOMAC pain and function, as well as velocity and step length, which correlates with WOMAC pain and function [48]. Due to double limb support and single limb support collectively forming one gait cycle, when single limb support percentage to one gait cycle decreases, double limb support percentage to one gait cycle increases. The findings of gait performance in normal walking pace are consistent with the WOMAC score changes. Similarly, no significant differences were observed between the blueberry group and placebo group at any time point throughout the study. These results may be compared with other plant-based nutraceuticals which have been studied for their functions of improving gait. Javaheri et al. found that treating mice with sulforaphane—commonly found in cruciferous vegetables—for three months, led to greater symmetry in gait [49]. Innes et al. investigated feeding extracts of Indian and Javanese turmeric, Curcuma domestica, and Curcuma xanthorrhiza to dogs with OA for eight weeks, and examined gait improvement post treatment. No significant improvement in gait performance was observed in the treatment group [50]. However, Schrager et al. found similar results in older adults (age > 60 years old) as compared to the current study. In particular, Schrager et al. found that consumption of two cups of frozen blueberries a day for six weeks improved gait speed, reduced the number of step errors during single task adaptive gait, and increased gait speed during dual task adaptive gait [36].

In contrast to the placebo group, the inflammatory cytokines TNF-α, IL-1β, and IL-6 did not change in the blueberry group throughout the study, but a non-significant decrease in concentration of MCP-1 was noted at final point as compared to baseline. TNF-α, IL-1β, and IL-6 have been found to increase during the worsening of OA and contribute to the progression of OA. MCP-1 has been shown to contribute to the initiation and progression of OA [51]. Thus, blueberry treatment was able to prevent worsening of inflammation. The anti-inflammatory effects of polyphenols have been studied extensively. Most positive results are reported in in vitro and animal studies. Shakibaei et al. showed that pretreatment of human primary articular chondrocytes with resveratrol for 4 h, followed by treatment with IL-1β and continued treatment of resveratrol results in a reduction of IL-1β induced apoptosis [52]. A limited number of randomized controlled clinical trials investigating polyphenols’ anti-inflammatory effects have reported inconsistent results [53]. Plasma concentrations of IL-10 and IL-13 as well as MMP-3 and MMP-13 did not change significantly during the study period, in either treatment group. IL-10 and IL-13 are anti-inflammatory cytokines. Very few studies have investigated the effect of polyphenols on these anti-inflammatory markers in humans. Most studies have focused on in vitro and animal studies. One in vitro study found that epicatechin gallate, epigallocatechin and epigallocatechin gallate, the major tea polyphenols, decreased the production of IL-1β and enhanced the production of IL-10 in human leukocytes [54]. In an in vitro study, Ahmed et al. showed that pomegranate extracts inhibited IL-1b-induced expression of MMP-1, MMP-3, and MMP-13 in human osteoarthritis chondrocytes [16]. In a mouse post-traumatic OA model, Leong et al. found that articular cartilage in the EGCG-treated mice exhibited reduced levels of MMP-1, -3, -8, -13, ADAMTS5, IL-1β, and TNF-α mRNA [41]. One parallel-designed, placebo-controlled clinical trial reported that intervention with an anthocyanin extract from blueberries (300 mg/d for three weeks) significantly reduced the plasma concentration of IL-4, IL-13, IL-8, and IFN-a in a group of 120 healthy men and women aged 40–74 years [55]. In one clinical trial, six-week consumption of pomegranate juice significantly decreased serum levels of MMP-13 [45]. However, no significant changes in IL-10, IL-13, MMP-3, and MMP-13 were observed in our present study, which is inconsistent with most results from in vitro and animal studies and the limited number of human trials. Factors other than polyphenols that can impact plasma concentrations of these biomarkers include dietary pattern, physical activity, or other inflammation issues. This could potentially explain why no changes were observed in the present study.

In the blueberry group, weight and BMI stayed the same throughout the study, while, in the placebo group, weight, and BMI increased significantly at final point over midpoint and baseline. One plausible explanation to this is that dietary polyphenols may affect neuroregulatory factors that control satiety, therefore mediating food intake and energy regulation [56]. In an animal study, investigators found that rats fed with blueberry extracts for six days had reduced food intake and weight reduction compared to rat fed with control meals due to satiety effects [57]. Systolic and diastolic blood pressure significantly reduced in the blueberry group at the final point over baseline, while there were no significant changes in the placebo group. The average systolic blood pressure of individuals in the blueberry group was significantly higher than in the placebo group. Participants were randomly assigned into two treatment groups, with the difference in systolic blood pressure at baseline differing by chance. Our results are consistent with other studies on the effect of polyphenols on blood pressure. Johnson et al. found that consuming 22 g of freeze-dried blueberry powder for eight weeks significantly lowered systolic and diastolic blood pressure among postmenopausal women with pre- and stage 1 hypertension [58]. Studies have also shown that compared with other types of foods, the intake of flavonoid-rich foods and drinks significantly reduces blood pressure [59,60]. In a double blind, placebo controlled parallel trial, Naruszewicz et al. reported that consumption of chokeberry flavonoid extract for a period of six weeks significantly reduced systolic and diastolic blood pressure by an average of 11 and 7.2 mmHg, respectively [61].

Concerning potential limitations to this study, the dropout rate was high, making it harder to detect significant changes. Larger sample sizes may be needed to meet the required statistical power for the study. Alternatively, intent-to-treat analysis may be used to preserve the sample size, but the analysis needs to be used with caution. In addition, most of the study participants were females, which was less representative of the whole population. This study was based on participant compliance with consumption of the blueberry or placebo powder. Calendars were provided to participants to help improve compliance, but the compliance was self-reported. Follow up calls were made in between study visits to encourage compliance. Participants were asked to mix the blueberry powder or placebo powder with water and consume right after mixing. A few participants reported that the palatability of the powder was less tolerable over time, so they mixed the powder with other drinks such milk or added the powder to their breakfast cereal, which could impact the bioavailability and absorption of polyphenols. Diet variations can potentially have an impact on the study outcomes. During the study period, participants were asked to not consume blueberry but did not have other requirements for their diet.


image of The Effect of Physical Activity on Passive Leg Movement ...

The Effect of Physical Activity on Passive Leg Movement ...

Methods: PLM was performed on four subject groups: young sedentary (Y, 23 ± 1 yr, n = 12), old sedentary (OS, 73 ± 2 yr, n = 12), old active (OA, 71 ± 2 yr, n = 10), and old endurance trained (OT, 72 ± 1 yr, n = 10) in the supine and upright-seated posture. Hemodynamics were measured using ultrasound Doppler and finger photoplethysmography.As PLM predominantly reflects NO-mediated vasodilation, these findings support the idea that augmenting physical activity and fitness can protect NO bioavailability, attenuating the deleterious effects of advancing age on vascular function..
Keyword: pmid:27031748, PMC4949157, doi:10.1249/MSS.0000000000000936, H Jonathan Groot, Matthew J Rossman, Russell S Richardson, Age Factors*, Aged, Exercise*, Fingers, Hemodynamics, Humans, Leg / blood supply*, Male, Movement, Nitric Oxide / blood, Photoplethysmography, Posture, Regional Blood Flow, Sedentary Behavior, Ultrasonography, Doppler, Vasodilation*, Young Adult, PubMed Abstract, NIH, NLM, NCBI, National Institutes of Health, National Center for Biotechnology Information, National Library of Medicine, MEDLINE
From: pubmed.ncbi.nlm.nih.gov

Introduction: Because of reduced nitric oxide (NO) bioavailability with age, passive leg movement (PLM)-induced vasodilation is attenuated in older sedentary subjects and, unlike the young subjects, cannot be augmented by posture-induced elevations in femoral perfusion pressure. However, whether vasodilator function assessed with PLM, and therefore NO bioavailability, is preserved in older individuals with greater physical activity and fitness is unknown.

Methods: PLM was performed on four subject groups: young sedentary (Y, 23 ± 1 yr, n = 12), old sedentary (OS, 73 ± 2 yr, n = 12), old active (OA, 71 ± 2 yr, n = 10), and old endurance trained (OT, 72 ± 1 yr, n = 10) in the supine and upright-seated posture. Hemodynamics were measured using ultrasound Doppler and finger photoplethysmography.

Results: In the supine posture, PLM-induced peak change in leg vascular conductance was significantly attenuated in the OS compared with the young subjects (OS = 4.9 ± 0.5, Y = 6.9 ± 0.7 mL·min·mm Hg) but was not different from the young in the OA and OT (OA = 5.9 ± 1.0, OT = 5.4 ± 0.4 mL·min·mm Hg). The upright-seated posture significantly augmented peak change in leg vascular conductance in all but the OS (OS = 4.9 ± 0.5, Y = 11.8 ± 1.3, OA = 7.3 ± 0.8, OT = 8.1 ± 0.8 mL·min·mm Hg), revealing a significant vasodilatory reserve capacity in the other groups (Y = 4.92 ± 1.18, OA = 1.37 ± 0.55, OT = 2.76 ± 0.95 mL·min·mm Hg).

Conclusions: As PLM predominantly reflects NO-mediated vasodilation, these findings support the idea that augmenting physical activity and fitness can protect NO bioavailability, attenuating the deleterious effects of advancing age on vascular function.


image of Soybean Meal Quality and Analytical Techniques | IntechOpen

Soybean Meal Quality and Analytical Techniques | IntechOpen

Sep 12, 2011 · Essential amino acid composition (%) of soybean meal obtained from various regions of the United States. 1 Values are expressed on a dry matter basis as average ± SD and were determined from samples analyzed in 2009 at Ajinomoto Heartland LLC’s amino acid laboratory. 2 Values are expressed on a “as-is basis” as average ± SD and were determined from samples …Open access peer-reviewed chapter.
From: www.intechopen.com

2. Soybean meal in poultry and swine feeds

Soybean meal is the most commonly-used source of protein for poultry and swine feeds in the world, with 67% of the animal feed market (Pettigrew et al., 2002). In order for a feed ingredient to be considered an important component of an industry feeding program, it must have several fundamental qualities. First, it must provide one or more important nutrients. Second, it must be available in amounts that allow it to be used regularly and on a large scale. Third, it must be cost effective to use. Soybean meal abundantly fits into this category as a high-protein product with good amino acid balance that is highly digestible. It is available in large quantities year round and has had most of the associated antinutritional compounds inactivated. Interestingly, antinutritional factors in soybeans are relatively easy to inactivate and are reduced substantially by normal soybean processing. This is in contrast to many of the other commonly-used plant proteins that have non-labile antinutritional factors (Pettigrew et al., 2002).

In the early years of compound feed production, grain products were paired with animal protein meals that provided a natural balance of vitamins and minerals in addition to protein. As animal protein products such as fishmeal became more expensive, and synthetic sources of vitamins (particularly vitamin B12) were developed, soybean meal captured a larger portion of the animal feed protein market. Modern feed formulation programs further increased the demand for soybean meal as the principle protein source as least cost diet formulation became more common.

Worldwide, nearly 2/3 of the protein sources used in animal feeds come from soybean meal, with canola meal, cottonseed meal and sunflower meal providing additional plant protein sources. In the United States, plant protein source usage in animal feeds is primarily (92%) soybean meal. Over half of the soybean meal produced in the United States is fed to poultry (Waldroup and Smith, 1999). Approximately 66% of protein in broiler feeds comes from soybean meal. With the development of reasonably-priced synthetic methionine sources, feed manufacturers are now able to produce relatively simple feeds based on a combination of corn and soybean meal with supplementation of minerals, vitamins and methionine. Swine account for 27% of the soybean meal used in animal feeds in the United States. Soy protein’s digestibility, combined with a relative abundance of lysine, which is the first limiting amino acid in swine feeds, make soybean meal an excellent protein source for swine.

Most areas of swine and poultry production have economical access to soybean meal for compounding animal feeds. In some places, however, local access to soybeans has led to interest in the processing of full fat soybeans meals for local usage. Full fat soybean meal, often an extruded product, has the advantage of higher energy values due to the full complement of oil in the native seeds as compared to commercial soybean meal, which has had most of the oil extracted for sale (Reese and Bitney, 2000). Other advantages include: 1) the addition of fat to a feed in a more easily-handled granular form and 2) the addition of fat to a feed in a form that is less likely to reduce pellet quality (Waldroup, 1985).

Performance results indicated that there was significant variation in the nutrient content from various batches of extruded soybean meals (Reese and Bitney, 2000). The authors concluded that it would be difficult to compare extruded soybean meal to regularly-processed soybean meal for this reason. It would be wise if considering these products to do extra nutrient analysis. Numerous research groups have explored the use of full fat soybean meals in poultry feeds as well (Waldroup, 1985). Extruded full fat soybean meals have seen limited use, although dry roasting, followed by grinding, has also been tested. Waldroup and Cotton (1974) determined the levels of full fat soybean meal that could be included in mash broiler feeds before performance suffered (less than 25%). Higher levels could be utilized in pelleted broiler feeds because the pelleting process causes more cell wall disruption and increases the digestibility of full fat soybean meal products (Waldroup and Cotton, 1974).

Soybean geneticists are continually improving productivity characteristics of soybeans for crop production. Additionally, efforts have been underway for some time to enhance the quality of soybeans in relation to animal feeding of soybean meal (Bajjaleih, 2002). Areas of interest include increasing levels of sulfur containing amino acids, increasing the proportion of soybean meal phosphorus that is available for digestion (reducing phytate-bound phosphorus) and increasing energy availability through selection away from carbohydrate fractions of low availability to monogastrics.

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1. Introduction

Many authors have noted that physical exercise induces an increase in production of free radicals and other reactive oxygen species (ROS) [1]. Current evidence indicates that ROS are the primary reason of exercise-induced disturbances in muscle redox balance, and it was observed that severe disturbances in redox balance have been shown to promote oxidative injury and muscle fatigue impairing the exercise performance [2, 3].

During the physical exercise practice, it is possible for the activation of some biological processes, such as the macrophages infiltration, the movement of electrons that occurs at the level of the transport chain on the mitochondrial ridges, the catabolism pathway of the purines, or the reaction catalyzed by the enzyme xanthine oxidase, which all may lead to the release of ROS. On the basis of the above-mentioned information, sportsmen have to improve their antioxidant defense systems to overcome the exercise-induced oxidative damage. It is well established that the increase in reactive oxygen species and free radical production during exercise has both positive and negative physiological effects. In 2008, for the first time, moderate exercise has been defined as an antioxidant, explaining that the mild burst of ROS, generated by training, acts as a signal responsible for the activation of signaling pathways that lead to the induction of antioxidant enzymes in human tissue [4]. To prevent these hypothetically negative or side effects of physical exercise, supplementation with different types of antioxidants has been used in a great number of studies [2].

The term “antioxidant” in general indicates the molecules capable of preventing, delaying or, in some cases, completely canceling oxidative damage to specific target molecules. For example, the superoxide dismutase enzyme, the catalase enzyme, and the glutathione peroxidase enzyme are endogenous antioxidants; glutathione, vitamins E, C and A, and coenzyme Q10 (CoQ10) are nonenzymatic molecules with antioxidant properties [5].

The antioxidants can also be taken through the “exogenous antioxidant” diet, and this supplementation can improve the ability to protect muscle fiber, during training, from oxidative damage caused by fatigue. In fact, the deficiency of antioxidants could induce an increased predisposition to oxidative damage induced by exercise and therefore compromise the sporting performance [6].

Over the past few decades, many attempts have been made to improve antioxidant potential, and therefore increase physical performance by improving nutrition, training programmers, and other related factors. Recently, the problem of whether or not athletes should use antioxidant supplements is an important and highly debated topic.

In the context of this chapter, information in brief about the well-known and recently used antioxidants in particular the polyphenols is given. This review describes only human trials. The effects of these antioxidants on exercise performance and exercise-induced oxidative stress are also explained.

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2. Oxidative stress and antioxidants

All aerobic organisms constantly synthesize free radicals as part of normal metabolic processes. Free radicals are chemical species with an unpaired electron in their outermost orbital; the free radicals that can be formed precisely by the oxygen molecules are indicated by the acronym ROS, that is, reactive oxygen species [7, 8].

Free radicals and reactive oxygen species are the main oxidizing agents in cellular systems and are involved in aging and the onset of many types of diseases. They are physiologically produced in different cellular biochemical reactions occurring in the body, such as in mitochondria for aerobic oxygen production, in fatty acid metabolism, in drug metabolism, and during activity of the immune system. On the other hand, free radicals can also be produced by exogenous factors such as pollution, bad lifestyle habits, UV rays, ionizing radiation, and psychophysical stress resulting from intense physical activity [9, 10, 11]. Although these free radicals have positive effects on immune reactions and cellular signaling, they are also known to have negative effects, such as oxidative damage of lipids, proteins, and nucleic acids. Organisms are equipped with antioxidant defense systems that protect cells from the toxic effects of free radicals [9, 10, 11].

Antioxidants are molecules able to give an electron to free radicals, neutralizing, diminishing, or eliminating their ability to damage cells and the main biomolecules such as nucleic acids, proteins, and lipids.

As already mentioned, it is possible to divide the antioxidants into two categories: enzymatic antioxidants, such as the enzyme superoxide dismutase (SOD), the enzyme glutathione peroxidase, or the enzyme catalase; nonenzymatic antioxidants, such as glutathione, vitamin E, vitamin C, and bilirubin.

These “endogenous” antioxidants have the function of delaying or preventing the oxidation of extracellular and intracellular biomolecules. We know that even antioxidants taken from the diet, such as vitamins and minerals, can condition the oxidative state of the body. Some mammals, except humans, possess the biochemical mechanism that allows them to synthesize vitamin C. And this information can be useful for the purpose of supplementary integration during a sports performance [9].

Therefore, oxidative stress produces oxidative damage that can influence various physiological functions and can be defined as an imbalance between oxidants and antioxidants in favor of oxidants.

The production of ROS induced by exercise is an important signaling path for inducing biological adaptations to training, but ROS production could also have a deleterious impact on cells and tissues, that is, lipid and protein peroxidation. This concern has led some experts to suggest consuming more dietary supplements and supplements containing antioxidant to mitigate ROS production which can cause excessive oxidative stress during and after exercise [9, 10, 11, 12].

2.1. Oxidative stress and physic activity

We have said that free radicals are normally generated during various physiological mechanisms. But their production increases considerably during a physical activity; in this situation, the skeletal muscles need a greater oxygen supply, resulting in an obvious change in the blood flow between the various organs. Subsequently, muscle damage induced by physical exercise causes infiltration of phagocytes (macrophages and neutrophils) in the area where the lesion occurred. All these physiological changes that occur during acute exercise cause an increase in the production of ROS, with consequent oxidative damage to the biomolecules. Through the use of biochemical and molecular techniques, it is now possible to evaluate events that occur at the cellular level and demonstrate in an increasingly precise manner, as free radicals certainly play a role in the physiological adaptations observed in the athlete after training. But free radicals generated by exercise can have both positive and negative physiological effects [10].

Exercise-induced oxidative stress associated with increased free radical production has been studied for 40 years, since it was first reported in 1978. In the study, subjects perform a 60-min cycle ergometer exercise at 50% VO2 max intensity and reported increased levels of expired pentane, an index of lipid peroxidation [10]. Subsequently, in 1987, a study was carried out on six young men who performed an incremental load exercise on a cycle ergometer until it was exhausted, and it was discovered that the blood levels of reactive substances to thiobarbituric acid (TBARS), another marker of lipid peroxidation, increased [24]. In another study, in 1988, in which eight highly trained young men performed cycle ergometer exercise for 90 min at 65% VO2 peak intensity, the levels of GSH, a nonenzymatic antioxidant, decreased, whereas the GSSG levels conversely increased [10].

The expression of the proteins involved in mitochondrial biogenesis, that is, the receptor gamma-activator receptor activated by the peroxisome alpha proliferator (PGC-1α) is increased by regular resistance training. In fact, ROS stimulates the cascade of mitochondrial biogenesis precisely in response to endurance training, that is, the chronic muscular contractions [12]. The newly formed mitochondria are highly efficient and have the capacity to synthesize less ROS for the same amount of adenosine triphosphate product, that is, they are more functional.

For example, expression of PGC-1α in skeletal muscle was significantly increased following 4 weeks of endurance training [13], indicating a skeletal muscle contraction-stimulated mechanism of mitochondrial biogenesis. During muscle contraction, ROS can also be generated through mechanisms that do not involve the mitochondria. In fact, it has been shown that muscle contraction causes an increase in superoxide ion in the cytosol, before the increase in mitochondria occur. It has been hypothesized that the activity of nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) causes the superoxide ion to increase in the cytosol [14]. Accordingly, ROS production (level of H2O2) was previously shown to increase in isolated mitochondria after acute muscle contraction in comparison with rested skeletal muscle biopsy sample [10].

ROS production leads to muscle fiber damage, which eventually results in muscle fatigue.

ROS production leads to damage to the muscle fiber, which then results in muscle strain. However, increasing evidence suggests that small stimuli, such as a low concentration of ROS, are able to stimulate the transcription of the major genes that encode proteins with antioxidant power. Superoxide dismutase (SOD) and glutathione are the examples of important molecules capable of defending cells from ROS-induced oxidative stress. Being able to deepen the mechanism of correlation between muscle fatigue and oxidative damage could be an important strategy for nutritional interventions aimed at increasing the performance of the exercise. An effective strategy could be antioxidant supplementation, considering the effects of scavenging ROS, which could lead to a decrease in muscle damage caused by prolonged exercise [14].

To date, there has been a plethora of reports on the effects of acute aerobic exercise on oxidative stress markers. Most of these studies have been conducted on young healthy men, and the difficulty of linking the various studies depends on the fact that, in each study, the training status is different. The most common exercises are those in which the athletes analyzed use a cycle ergometer or treadmill, in which the subjects, in an air-conditioned laboratory, generally engage in a maximal or submaximal exercise for 10–90 min.

Other studies have evaluated the effects of eccentric contraction exercises, such as downhill exercises. The most analyzed biological sample is blood. In a limited number of studies, skeletal muscle, exhaled air, and urine were also examined. Oxidation products of lipids, proteins, and DNA (i.e., MDA, PC, and 8-OHdG) have been used as oxidative stress markers; antioxidant levels and the redox balance in tissues were also assessed [3, 8].

Oxidative stress can be induced by aerobic exercise, but it can also be activated by anaerobic exercise. In fact, in addition to studies using sprint exercises, other studies have evaluated the effects of resistance exercises (formation of muscle groups throughout the body through the use of different types of resistance exercises) on oxidative stress markers. In a study in which 12 highly trained youths performed three sets of eight types of resistance exercise at 10 repetition loads, levels of malondialdehyde, a marker of lipid peroxidation, increased in the blood [8, 9]. This is one of the many tests that demonstrate that resistance exercises involving the whole musculature of the body modify the blood levels of oxidative stress markers [8]. But also local resistance exercises (defined as exercises that train a specific muscle group using a single type of resistance exercise) modify the oxidative stress markers of the blood [8]. While all these studies have assessed oxidative stress by measuring the change in blood parameters, other studies have observed muscle biopsies, to demonstrate that local resistance exercises increase oxidative stress in skeletal muscles [8].

On the other hand, other studies have shown that levels of oxidative stress in the blood are not conditioned by resistance exercises. Probably, the discrepancy of this data may have been conditioned by the training status. However, a study of individual changes in oxidative stress responses to eccentric exercise demonstrated high inter-individual variability after exercise of eccentric knee extension, even in subjects with the same training status [8]. Furthermore, this study showed that in about one person in three exercise-induced oxidative stress was unexpected or negligible (response rate of 5% or less). These data reasonably suggest that the inconsistencies between the various results, both for the anaerobic and aerobic exercises, can be caused both by the training status, but also by the great inter-individual variability of the response to the oxidative stress induced by physical activity [3, 8].

2.2. Antioxidants and exercise

An active debate still exists on the effect of antioxidant supplementation on exercise-induced oxidative stress. Typical treatment generally includes vitamins A, C, and E, at various dosages, administered alone or in combination, chronically or acutely [15, 16]. Of these, vitamins C and E have been used more frequently in clinical and experimental studies, mostly because of their safety profile and easy availability [15]. One study showed the administration of vitamin C (500 mg, a moderate dose), reduced exercise-induced lipid peroxidation, and muscle damage in an untrained male group compared to the placebo group; on the contrary, it had no effect on inflammatory markers [17].

Other less-used antioxidants include coenzyme Q10 and N-acetylcysteine [15].

Regarding the endpoints, it is possible to hypothesize that the antioxidant could be effective in particular conditions in terms of training; for example, a specific moment of training (for example, before or after the race) or a type of sport compared to another (e.g., anaerobic versus aerobic).

Therefore, to decide whether to administer an antioxidant supplement, the selection and detailed description of the appropriate training stimulus and/or monitoring of the athlete during the training phases is necessary [15].

However, it is important to underline that numerous studies report negative effects of antioxidants. It is hypothesized that one of the motivations for the controversy is the different population analyzed in the studies.

In most of the studies in which a benefit of antioxidant supplementation was demonstrated in attenuating muscle damage and oxidative stress following endurance exercise, data on samples of sedentary and nonresistant subjects were analyzed. The endogenous antioxidant defenses of trained subjects could be over regulated and therefore these subjects may not benefit greatly from the use of exogenous antioxidants [15]. Furthermore, another big difference is represented by the different types of exercise; in fact, we move from the exercise of short-term resistance to the exercise of long-term resistance. In fact, aerobic endurance exercise will surely induce, due to the massive use of oxygen, a different flow of radicals with respect to the exercise of anaerobic resistance [15].

Recently, a large body of literature has highlighted a potential relationship between oxidative stress and the bioactive compounds present in plant foods. In particular, the researchers’ attention has been shifted to the effects of a peculiar class of bioactive nutraceutical compounds, that is, polyphenols.

The study of phenolic compounds present in food has attracted great interest since the 1990s due to the growing evidence of their beneficial effect on human health. One of the first studies that stimulated the interest of scientists is the epidemiological study of Zutphen. In this research, an inverse association was proposed between the intake of foods rich in polyphenols and the incidence of diseases, such as diabetes mellitus, cardiovascular diseases, and cancer [18] and in particular of those pathologies associated with an evident oxidative stress.

Therefore, efforts to develop dietary strategies against oxidative stress caused by physical activity are being made and recently, there has been a growing interest in investigating the potential of polyphenols to modulate physical performance and prevent oxidative stress.

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3. Polyphenols

Human diets are rich in polyphenols; western populations consume an estimated 1–2 g/day polyphenols, mainly from fruits, vegetables, and beverages such as tea, coffee, wine, and fruit juices. Polyphenols exert a range of biological activities, and various epidemiological studies and clinical trials have linked their intake with a reduced risk of chronic diseases, such as coronary heart disease, stroke, type II diabetes, and some cancers. There has recently been growing interest, supported by a number of epidemiological and experimental studies, on the possible beneficial effects of polyphenols on brain health.

For this reason, these phytochemicals are currently considered important components of a healthy diet, and it is believed that the health benefits of a diet rich in fruit and vegetables are to be attributed to these molecules. For example, the protective effects of tea against cardiovascular disease or coffee against type II diabetes could be explained by the large concentration of catechins present in these drinks.

As a consequence, the scientific and commercial interest in these phytochemicals has increased considerably in recent years; in particular, there are numerous works in which topics concerning their bioavailability, bioactivity, metabolism, and health effects have been addressed [19, 20, 21].

3.1. Nomenclature, classifications, and occurrence in foods

Polyphenols are classified into flavonoids and nonflavonoids, according to the number of phenol rings and structural elements bound to these rings.

Flavonoids represent the largest group of polyphenols. The chemical structure is characterized by 15 carbon atoms, derived from the flavone and all share certain properties. They are mainly soluble in water; usually, they are present in the plant as glycosides and in the same plant, there can be a flavonoid aglycone in combination with different sugars. Their name derives from flavus (=yellow) and refers to the role they play as plant pigments. The coloring that they give to the tissues depends on the pH. A specific group of flavonoids, the anthocyanins, is responsible for the red, blue, and violet colors of flowers and fruit and is therefore very important as a mediator of pollination. It is therefore not surprising that the variety of shades of color associated with anthocyanins has been increasing through the evolutionary process.

There are six dietary groups of flavonoids:

  • flavones (luteolin and apigenin), which are found in parsley, capsicum pepper, and celery;

  • flavonols (kaempferol, quercetin, and myricetin), which are found in onions, leeks and broccoli, cherry tomato, apple, berries, beans, tea and red wine;

  • flavanones (hesperetin, naringenin, and eriodictyol), mainly present in orange, lemon juice, grapefruit, and herbs (oregano);

  • isoflavones (genistein and daidzein), which are mainly found in soybeans;

  • flavanols (catechin, epicatechin, and gallocatechin), abundant in green tea, apple, red wine, cocoa, chocolate and may be present as monomers or as oligomers; in particular flavan-3,4-diol polymerization produces so-called “condensed tannins”: they are also the origin of the catechins and probably polymerize with them to give the proanthocyanidins;

  • anthocyanidins or anthocyanins (delphinidin, pelargonidin, cyanidin, malvidin, and petunidin), whose sources include red wine, berries, blackcurrant, and cherry [22, 23, 24, 25].

The nonflavonoid group can be separated into three different classes: phenolic acids, stilbenes, and lignans.

Phenolic acids can be found in many plant species, in dried fruit. The most common phenolic acid are:

  • caffeic acid is generally the most abundant phenolic acid and is mainly found as a quinic ester; present in many fruits and vegetables; it is a major phenolic compound in coffee;

  • chlorogenic acid is the ester of caffeic acid and quinic acid; it is present in blueberries, kiwis, prunes, and apples;

  • ferulic acid present in cereals, which is esterified to hemicellulose in the cell wall.

The best studied stilbene is resveratrol, and it can be found in cis or trans, or glucosylate, or in lower concentrations as the parent molecule of a family of polymers such as the food sources of viniferine, pallidol, or ampelopsin A. The resveratrol is found in particular in the grape skin and in the wine, to a greater extent in the red one.

Lignans (secoisolariciresinol, matairesinol, medioresinol, pinoresinol, and lariciresinol) are found in high concentration in linseed and in minor concentration in algae, leguminous plants, cereals, vegetables, and fruits [22, 23, 24].

To the large group of polyphenols are also added some molecules that form a separate category, compared to the four high. These include tyrosol and curcumin, which have long been discussed for potential health benefits.

The main classes of polyphenols present in the common diet are the flavanols, in particular the catechins and tannins of tea; the flavanones, mostly hesperidin present in citrus fruits; flavonols, such as quercetin in tea, apples, and onions; hydroxycinnamic acids, phenolic acids, abundant in coffee and many fruits and vegetables; anthocyanins, polyphenols responsible for the color of fruit and vegetables.

Among others, fruits like apples, grapes, pears, and berries typically contain high amounts of polyphenols (200–300 mg/100 g). Other polyphenol compound is curcumin (1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), a member of the curcuminoid family. It is found in turmeric, a spice produced from the rhizome of Curcuma long. Moreover, olive oil is a source of at least 30 phenolic compounds; the three phenolic compounds found in the highest concentration in olive oil are oleuropein, hydroxytyrosol, and tyrosol [21, 23].

Since agriculture was developed in 10,000 bc, humans have been modifying plant secondary metabolite profiles. By selecting fruit, flower, and vegetable colors, farmers involuntarily elected higher anthocyanin content, whereas in selecting for scents, they modified volatile phenolics. Anyway, as regards the content of polyphenols present in foods, it seems impossible to classify basic foods in terms of “how many polyphenols they provide annually”. However, the most important food products, consumed in large quantities, which are the main source of polyphenols, are fruits and vegetables, green and black tea, red wine, coffee, chocolate, and extra virgin olive oil.

Even herbs and spices, nuts and algae are possible sources of food polyphenols; this depends on the culinary traditions and habits.

In 2010, a website was created (www.phenol-explorer.eu) containing over 35,000 content values for 500 different polyphenols in over 400 foods [16, 26].

Numerous factors can affect the content of polyphenols in food, may be environmental factors, such as exposure to the sun, precipitation, different types of crops, different types of soil, yield in fruits for the tree, degree of ripeness, but also conservation and methods of culinary preparation [27, 28].

3.2. Bioavailability of polyphenols

Bioavailability is defined as the fraction of a nutrient that the body is able to absorb and use for its physiological functions. Bioavailability may vary in relation to numerous factors, depending in part on the nature of the food and partly on the characteristics of the organism that assumes it. It is evident that bioavailability is very important in the nutritional field, but often neglected. A compound could have strong antioxidant activities or other biological activities in vitro, but if it were not bioavailable, if only a small amount of this type reached the target tissues, the molecule would have little biological activity in vivo. It is therefore essential to estimate the bioavailability of the polyphenols in order to set up effective nutritional protocols.

There are numerous studies carried out in vitro, then performed using as experimental models cultured cells or tissue slices, which provided fundamental information to understand the beneficial effects of polyphenols.

Despite the encouraging results, it is advisable to be very cautious in interpreting and extracting the data obtained in these experiments. Indeed, aglycons are often tested instead of active metabolites. Many researchers, when trying to unravel the physiological mechanisms involved in the health effects of polyphenols, often analyze the properties of a compound of little biological relevance. The dose used is also important, which should, in reality, be approximated to real life conditions. In vitro concentrations commonly range from low μmol/L to mmol/L, while plasma metabolite concentrations, after a normal dietary intake, rarely exceed nmol/L. Using excessive doses in experiments performed in vitro could “force” positive outcomes; therefore, the results obtained must be extrapolated with great care in in vivo situations [23, 29].

3.3. Biological effects

Historically, polyphenols were mostly of interest to botanists, as they play many roles in plants. In the 1990s, polyphenols were classified as general antioxidants [30], and it was thought that it was easy to explain their activity. The reality of polyphenols is much more complex: biological effects involve detailed biochemical interactions with pathways at the molecular level. Much progress has been made in the last few decades.

Although the chemical structure gives polyphenols primarily an antioxidant activity, this property does not necessarily represent their biological effect, since any action on the organism depends on both bioavailability and molecular targets.

The overall effect of these phytochemicals on the reduction of disease risk is supported by epidemiology, where foods and beverages rich in polyphenols are protective against the development of certain chronic diseases, in particular cardiovascular diseases, type 2 diabetes, and cancer [21, 31, 32, 33, 34, 35].

In recent years, revisions have been published supporting a new effect of polyphenols, that is, their role as supplements in athletic performance [11, 12].

However, despite these reviews, the overall effect of polyphenols on performance is inconclusive as most studies involve a small sample size.

Polyphenols are natural antioxidants present in the human diet in which they can reduce the damage due to the production of ROS. The chemical characteristics of the polyphenols allow them to act as direct scavengers of free radicals, such as the catechol group on the B ring, the presence of hydroxyl groups on the 3 and 5 position, and the 2,3-double bond in conjugation with a 4-oxofunction of a carbonyl group in the C-ring [9]. However, polyphenols can also behave as pro-oxidants at high doses or in the presence of metal ions, leading to DNA degradation. There is no evidence of systemic pro-oxidant effect of polyphenols in humans [21, 36]. Because of the low bioavailability and the kinetic constraints, the direct antioxidant activity of the polyphenols appears to be ineffective in vivo. Therefore, it has been hypothesized that the beneficial effects are not due to the direct scavenger properties on ROS, but to an indirect antioxidant action. In fact, polyphenols can modulate gene expression by inducing the endogenous antioxidant enzyme defense system.

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4. Polyphenols action on athletic performance

As of today, a lot of studies are on polyphenols and physical exercise and in particular the polyphenolic compounds that have been demonstrated both to exert a significant effect in exercise-induced muscle damage and to play a biological/physiological role in improving physical performance. The effects of different polyphenols have been investigated in a wide range of exercise conditions, using a variety of supplementation strategies, timing, and dosage. Until a few years ago, despite the active search for “natural,” polyphenol-rich extracts that might enhance physical performance and decrease oxidative damage because they are antioxidants, the information we had was very limited and in some cases, they suggested the converse [37]. But in recent years, studies have increased considerably, and more information is now available on the effect of polyphenols on sports performance [14, 38, 39, 40, 41, 42].

4.1. Quercetin

Among nutraceutical compounds, flavonoids are the mainly studied ones for their positive effects on human health, and some of them have been proposed to be beneficial in exercise and exercise performance. Among flavonols, quercetin accounts for about 13.82 mg/day, resulting in being one of the most abundant flavonols in Western diet. Quercetin (3,4,5,7-pentahydroxylflavone) is a natural bioactive flavonoid, mainly present as quercetin glycosides (rutin, spiraeoside, troxerutin, quercitrin, isoquercetin, and hyperoside). It is distributed in a wide variety of natural foods, such as nuts, grapes, broccoli, and black tea; it is found in apples, berries, onions, grapes, and tomatoes as well as in some medicinal plants as Hypericum perforatum and Gingko biloba [42].

Antioxidant properties of quercetin are attributed to its chemical structure, particularly the presence and location of the hydroxyl (–OH) substitutions. Quercetin supplementation studies in athletes have focused on the potential effects of exercise-induced inflammation, oxidative stress, immune dysfunction, and exercise performance [42]. The first human exercise study investigating quercetin supplementation was published in 2006, with many more published in the past few years and continuing to be published. When athletes are studied, most of the researches have failed to find an ergogenic effect, in contrast to that of a study of elite cyclists, who exhibited an improvement of their aerobic performance, and another study indicated that administration of quercetin (1200 mg) for 6 weeks resulted in performance improvement in cyclists [43].

The effects of quercetin supplementation in cycling athletes have been investigated [44]. Forty athletes were recruited and randomized to quercetin or placebo. Subjects consumed 1000 mg quercetin or placebo each day for 6 weeks before and during 3 days of cycling at 57% work maximum for 3 h. Despite previous data demonstrating potent antioxidant actions of quercetin in in vitro and animal models, long-term quercetin supplementation was not able to exert any preventive effect on exercise-induced oxidative stress and inflammation biomarkers. In another study, the influence of 1000 mg quercetin with or without 120 mg of epigallocatechin 3-gallate, 400 mg of isoquercetin and 400 mg of eicosapentaenoic acid and docosahexaenoic acid was evaluated on sports performance, biogenesis of muscle mitochondria and changes of markers of immunity and inflammation before and after a 3-day period of heavy effort. Two-week supplementation with polyphenols was effective in augmenting inflammation after 3 days of heavy exertion in trained cyclists. The feeding of untrained healthy men and women was supplemented with 1000 mg quercetin for 7 days, and the effect on VO2 max and fatigue time was evaluated using a bicycle ergometer. Both fatigue (13.2%) and VO2 max (3.9%) increases were found [42].

Other studies have analyzed the effect of quercetin on exercise performance, some reporting positive effects, while others do not, but to our knowledge, an increase in mitochondrial biogenesis has not been reported in human even though it has been shown a modest and insignificant increase in relative mitochondrial DNA copy number following quercetin supplementation [45].

A meta-analysis results have demonstrated that polyphenol supplementation for at least 7 days increases performance by 1.90%. Sub-analysis of seven studies using quercetin identified a performance increase of 2.82% [41]. There were no adverse effects reported in the studies in relation to the intervention. Polyphenol supplementation for at least 7 days has a clear moderate benefit on performance in healthy individuals. The performance benefits caused by quercetin supplementation are higher than those of other polyphenols. Further research is needed to confirm the optimal dose, even if a major intake could improve performance response.

Overall, the pooled results show that quercetin is viable supplement to improve performance in healthy individuals.

4.2. Catechins: green tea extract

Although quercetin is the most studied flavonoid in relation to exercise, other molecules are under investigation for their ability to prevent exercise-induced muscle damage and to affect physical performance. As of today, many studies on polyphenols and physical exercise concerned in supplementation with antioxidants like the green tea extract (GTE) from Camellia sinensis. GTE extract is rich in polyphenols, with flavonoid structure, including epigallocatechin gallate, epicatechin, epigallocatechin, and epicatechin gallate, which result in a powerful antioxidant activity [22, 23, 24, 25]. Green tea supplementation has been advocated as a strategy to improve exercise recovery due to the activity of its catechins with high antioxidant and anti-inflammatory potential [46, 47, 48].

Although most studies on green tea have been performed in animals, a considerable amount of data is now available in humans. A green tea extract rich in catechins and caffeine increases the daily energy expenditure in humans. More recently, an acute dose of green tea extract has been evaluated on healthy untrained men in a 30 min cycling test at 60% VO2 max [46, 47, 48].

Other studies showed that GTE supplementation might reduce oxidative stress and promote improvement in the maximal oxygen uptake during cycling to exhaustion. Furthermore, GTE can reduce muscle soreness resultant of eccentric exercise and decrease markers of muscle damage after eccentric exercise, intense aerobic exercise, and strength exercises. Similar effects were not found when a single-dose of GTE was intake before intense muscle-endurance. The effects described for GTE supplementation suggest that GTE supplementation could be a valuable strategy for preserving performance during repeated periods of exercise that cause cumulative fatigue [47, 48].

Jowko et al. have tested the activities of green tea catechins in healthy individuals and soccer players and have been found to be very modest protection from oxidative damage in the first and no effect in the second [47].

Furthermore, it should be understood whether the supply of catechins increases or decreases the performance, in addition to the alleged cellular antioxidant activities. It has been tested a combination of epigallocatechin-gallate and N-acetylcysteine in healthy volunteers who performed eccentric exercise bouts [49]. In another study, the 4-week green tea extract supplement in previously untrained men increased the total plasma antioxidant potential and prevented oxidative damage. In another study, the protective effect of green tea drinks on oxidative stress and muscle damage parameters was also observed in weight-trained men [47, 48].

GTE supplementation protected against oxidative stress is induced by acute muscular endurance test, as well as against muscular damage induced by the training alone. Similar observations were reported in a study [50] about a group of resistance-trained men. In both cited studies, significant decrease in post-exercise plasma creatine kinase activity was noted as a result of supplementation.

However, GTE supplementation provided no protection from exercise-induced muscle damage. On the other hand, a number of previous studies revealed intensified muscle damage and hindered recovery as a result of antioxidant supplementation [47, 48].

Supplementation with GTE prevents oxidative stress induced by high-intensity repeated sprint test in male sprinters. On the other hand, neither protection from exercise-induced muscle damage, nor an improvement in sprint performance was noted after GTE intake. The use of GTE as a supplement is probably not useful in the case of sprinters, at least during the preparatory phase of their annual training cycle. Instead, the effects of taking GTE during the competition phase of the annual training cycle, being associated with a considerably greater exercise load, should be the subject of other research. Supplementation with green tea extract prevents oxidative stress induced by two repeated cycle sprint tests in sprinters. Furthermore, GTE supplementation does not seem to hinder training adaptation in antioxidant enzyme system. On the other hand, neither prevention of exercise-induced muscle damage, nor an improvement in sprint performance is noted after GTE administration [46].

Taken together, data from available studies seem to suggest that catechins can improve physical performance particularly in term of endurance capacity and VO2 max in untrained subjects, and the same results could be reached in physically active people and well-trained athletes.

In conclusion, it is possible to state that supplementation of green tea extracts before a cumulative fatigue event minimizes muscle damage and oxidative stress in trained athletes. It also has positive effects on neuromuscular parameters related to muscle activation and muscle fatigue. Therefore, the use of GTE as a supplement can be considered a valid strategy in the context of competitive sport of resistance, which aims at the performance of athletes and the recovery of the exercises [48].

4.3. Resveratrol

At the beginning of the 90s, the idea was born that resveratrol, a compound present in red wine, could contribute in part to the “French paradox,” the presumed phenomenon for which in France, despite the relatively high consumption of foods rich in acids saturated fat, the incidence of mortality from cardiovascular disease was relatively low, lower than other dietetically comparable countries [51]. Resveratrol (3,4′,5-trihydroxystilbene, RES) is a small polyphenol compound freely available in food supplements, and it is found in various berries, nuts, in the seeds and skins of grapes, red wine, mulberries, peanuts and rhubarb and other plants sources, including traditional Asian medicines [22, 23].

RES is an important activator of the sirtuin proteins and genes (SIRT, silent information regulators), causing an increase in the use of energy, and therefore, reinforcing the mitochondrial function. Sirtuins are silent, but significant regulators of metabolism, cancer, aging, and longevity; they are enzymes associated with the signal transduction pathways connected to stress [52].

Only few studies have investigated resveratrol ability in humans to modulate exercise performance, and some evidence suggests that it could play a role improving endurance capacity. There is a growing interest in the association between RES and exercise, because it has been hypothesized that the administration of RES can produce favorable effects on the rejuvenation of the liver cells, preserves the liver glycogen stores decreased during physical activity, and exercises a regulatory effect on glucose metabolism. To date, most of the studies that have investigated the effect of resveratrol administration on patient outcomes have been limited by their sample sizes.

In a study involving 14 athletes, RES supplementation was shown to inhibit the lipid peroxidation caused by exercise. In a study, it has been demonstrated that a combination of resveratrol and exercise training increased time to exhaustion compared to exercise training. The authors suggested that resveratrol optimizes fatty acid metabolism, which may contribute to the increased contractile force response of skeletal muscles [53]. Despite the inconsistency among reports regarding the topic, it has been suggested that RES delays fatigue by hindering lipid peroxidation, and recently there has been an interest in the capability of resveratrol to modulate physical performance and prevent oxidative stress. Currently, most clinical trials have been conducted with small samples, a wide range of dose levels and groups studied. As a result, it is difficult to establish a specific safety/efficacy range for the RES assay. Many conflicting discrepancies and information must be resolved before recommending the use of resveratrol as a supplement in sports performance [54].

4.4. Polyphenols mixtures

In recent years, the research has focused on studying not only the action of individual polyphenols but also the biological effects of polyphenols mixtures.

In muscular myotubes incubated with polyphenolic extracts of blueberry fruits (Vaccinium corymbosum cv. Reka), a dose-dependent protective effect on oxidative stress was observed [55].

The dark chocolate polyphenols were held responsible for some positive effects of dark chocolate consumption during the year. The effects of regular dark chocolate consumption (80 g/day for 2 weeks), rich in cocoa polyphenols, were analyzed on a sample of 20 active men. Plasma metabolites, hormones, and oxidative stress markers were evaluated after prolonged exercise. It has been observed that dark chocolate intake is associated with reduction of oxidative stress markers and increased mobilization of free fatty acids after exercise, but has no observed effect on exercise performance [56].

It has been found that Ecklonia cava (a species of brown alga present in the ocean of Japan and Korea) polyphenols acute preexercise supplementation induces a slight but significant increase in time to exhaustion in healthy human subjects [57].

Anthocyanins represent a class of polyphenols whose use is spreading among sportsmen. They are easy to find in berries and other colorful fruits and vegetables.

They can act as antioxidants and anti-inflammatory and therefore can improve recovery from exercise. In vitro observations showed anthocyanin-induced activation and endothelial nitric hormone metabolite metabolism and human vascular cell migration. The mechanisms by which anthocyanin intake can improve exercise performance may include effects on metabolic pathways, blood flow, and peripheral muscle fatigue, or a combination of all three. However, in general, the effects of these polyphenols on physical performance are less clear. For example, the use of black currant showed effects on the performance of the exercise; less noticeable effects have instead been analyzed after a cherry intake. Therefore, probably, the benefits could be due to specific food-dependent anthocyanins [12, 14].

Yerba Mate (YM) is a South American plant, rich in polyphenols, saponins, and xanthines, of growing scientific interest because of its metabolic effects. YM has been shown to increase fat utilization during exercise in untrained humans. Its metabolic and physical performance effects were characterized in 11 well-trained male cyclists. YM increased fat utilization during submaximal exercise and improved time trial performance [58].

Montmorency cherry concentrate is used as a supplement by the athletes of the Australian Institute, because it is rich in anthocyanidins. These cherries possess high anti-inflammatory and antioxidant capabilities, can improve sleep and reduce muscle damage and post-exercise pain [59].

Exercise-based studies evaluated the effects of cherry juice supplementation on recovery from maximum strength or resistance (duration>60 min), demonstrating the attenuation of markers related to both inflammation and oxidative stress [60].

Any response linked to accelerated recovery would appear beneficial when considering the large training load experienced by high performance athletes. In reverse, cherry juice (CJ) supplementation had no significant effect on the recovery of Water Polo specific athletic performance. Probably, CJ supplementation may not be necessary for water-based nonweight bearing intermittent sports such as Water Polo [61].

Fourteen male students drank 12 fl oz. of a cherry juice blend or a placebo twice a day for eight consecutive days. A bout of eccentric elbow flexion contractions was performed on the fourth day of supplementation. Isometric elbow flexion strength, pain, muscle tenderness, and relaxed elbow angle were recorded before and for 4 days after the eccentric exercise. Strength loss and pain were significantly less in the cherry juice trial versus placebo. These results show efficacy of the cherry juice in decreasing some of the symptoms of exercise-induced muscle damage [62]. Another study has demonstrated that Montmorency cherry juice consumption improved the recovery of isometric muscle strength after intensive exercise [63].

Regardless, future research should examine the use of CJ in other team sports before CJ can be recommended or excluded as an integrator to improve recovery after sport performance.

Blackcurrant (Ribes nigrum) fruits are a real mine of polyphenols, in fact they are rich in anthocyanins delphinidin-3-rutinoside, delphinidine-3-glucoside, cyanidin-3-rutinoside, and cyanidin-3-glucoside. The health benefits are thought to be mediated by the effect of anthocyanins on inflammatory responses, antioxidant activity, and endothelial function [64]. Moreover, blackcurrant intake increases forearm blood flow at rest, potentially mediated by anthocyanin-induced vasodilation and vaso-relaxation which may affect substrate delivery and exercise performance. It is important to emphasize that the blackcurrants properties are common to all berries (raspberry, blueberry, blackberry, currants, and gooseberries).

Recent studies have revealed a potential ergogenic effect of New Zealand blackcurrant (NZBC) extract intake on physiological and metabolic exercise responses and performance outcomes. In one study, the effect of New Zealand’s blackcurrant extract on performance during anaerobic sprint test running in youthful and recreational male soccer players was evaluated. A clear benefit of NZBC’s short-term intake on fat oxidation and physical performance has been demonstrated, and the extract seems to benefit the repeated sprint performance only in trained players [65]. Moreover, 7 day NZBC intake augments fat oxidation during 120 min moderate-intensity exercise in endurance-trained females [66].

Another polyphenols-rich fruit is pomegranate; in fact, pomegranate juice (POMj) is rich in flavonols, flavonoids, gallic acid, ellagic acid, quercetin, and ellagitannins, with numerous health benefits during stressful situations [67].

Its antioxidant potential has proven to be superior even to green tea and red wine. According to recent studies, in fact, the pomegranate reduces oxidative stress of macrophages, free radicals, lipid peroxidation, and oxidation of low-density lipoproteins; the inflammatory processes seem to be blocked by the action of ellagitannins. Pomegranate juice is an excellent post-workout because the antioxidants present in the juice of the arils help the muscles to restore their functionality facilitating the supercompensation of exercise; it has a significant impact on acute post-exercise lipid peroxidation and on enzymatic and nonenzymatic antioxidant responses.

Pomegranate extract has been suggested as an ergogenic aid due to its rich concentration of polyphenols, which are proposed to enhance nitric oxide bioavailability, thereby improving the efficiency of oxygen usage, and consequently, endurance exercise performance. Supplementation with pomegranate juice has the potential to attenuate oxidative stress by enhancing antioxidant responses assessed acutely and up to 48 h following an intensive weightlifting training session [68, 69].

The polyphenol curcumin, derived from the rhizome Curcuma longa L., is a natural antioxidant that exhibits various pharmacological activities and therapeutic properties and has been used to treat a variety of inflammatory conditions and chronic diseases. It has been demonstrated that curcumin can reduce the accumulation of advanced glycation end-products in vitro and in animal models, suggesting that this anti-glycation mechanism may relate to the antioxidant effect of the compound. It has been suggested a positive effect of curcumin and Boswellia serrata gum resin supplementation for 3 months on glycoxidation and lipid peroxidation in athletes chronically exercising intensively and further studies will test whether treatment with curcumin can result in a reduction of the accumulation of advanced glycation end-products in muscle tissue, possibly improving muscle performance in the long term [70]. It has been demonstrated that consumption of curcumin reduced biological inflammation, but not quadriceps muscle soreness, during recovery after exercise-induced muscle damage. The observed improvements in biological inflammation may translate to faster recovery and improved functional capacity during subsequent exercise sessions [71].

Honey, natural food produced by the nectar of flowers from bees, is widely used for its precious nutritional and therapeutic values that provide phytotherapeutic properties, with powerful antioxidant, anti-inflammatory, and antimicrobial effects. So far, around 300 types of honey have been recognized with different taste, color, and odor according to the different types of nectar harvested by bees. Honey is an ancient nutraceutical, which owes its properties to the richness of polyphenols, which vary according to the floral variety from which it derives, but in general it is made up of flavonoids, between 50 and 500 mg/kg, including galangina, quercetin, kaempferol, and luteolin, which represent the bioactive molecules with a strong antioxidant action.

Honey is an energizing substance useful for sportsmen, and it provides up to 17 g of carbohydrates for every spoon consumed and provides the much needed energy, serving as an economic substitute for the enhancers of sporting activities available on the market. A beneficial effect of honey has been shown in athletes, where if a moderate and regular exercise is able to counteract oxidative stress [20]. In one study, 32 healthy volunteers underwent a short but intense exercise on the ergometer. A significant decrease in serum malondialdehyde levels was observed in subjects who had consumed honey before making a physical effort, with a greater difference for those volunteers who had used it for 3 weeks.

In another study, the effects of honey in 39 road cyclists were examined. In the group that received honey supplementation (70 g), the increase in oxidative stress markers was much lower than placebo, and the antioxidant levels were significantly higher. Ahmad and others examined the effect of different doses of Tualang honey in 20 athletes involved in different competitive sports. The results showed that there was no significant difference between the two different doses and that the maximum antioxidant capacity was observed in both cases 2 h after the honey intake [20].

\n
5. Polyphenols supplementation in exercise: limits and considerations

The use of polyphenols has been designed to improve performance by increasing mitochondrial biogenesis in two ways: polyphenols stimulate stress-related cell signaling pathways that increase the expression of genes encoding cytoprotective proteins such as nuclear respiratory factor; the selected polyphenols (i.e., resveratrol, curcumin, and quercetin) have been reported to modulate muscle function and mitochondrial biogenesis by activating the sirtuins and increasing the activity of the c-receptor co-activator activated by the peroxisome proliferator. Furthermore, some polyphenols improve flow-mediated dilation and endothelial function in humans by increasing the synthesis of endothelial nitric oxide. Polyphenols could help overall athletic performance in sports where the rate of blood flow and maximum cardiac output are important determinants of cardiovascular performance, acting on endothelial function.

Polyphenol supplementation is currently controversial, and at the moment, the use of different exercise protocols, different outcomes, in various physically trained subjects, and the use of a variety of laboratory parameters to demonstrate these effects make it still difficult to assess the effects of polyphenols on physical activity. Therefore, in any case, a detailed description of the type of exercise (e.g., aerobic or anaerobic), the oxidative stress biomarkers used, the characteristics of the subject and the training endpoints examined to allow data interpretation is always necessary.

The evidence is not sufficient to make recommendations for or against the use of polyphenol supplements for recreational, competitive, or elite athletes. Polyphenols have multiple biological effects, and future exercise studies must be studied in an appropriate and specific way to determine the physiological interactions between the exercise and the selected supplement, rather than considering only performance.

Those with higher levels of oxidative stress can clearly benefit more from the antioxidant treatment. An initial screening of the state of oxidative stress is therefore essential. Clearly, individual susceptibility related to the presence of specific genetic variants in key enzymes for ROS detoxification may be another important parameter.

It would be useful to consider the integrated effect of exogenous diet and antioxidant supplementation.

\n
6. Conclusion

The relationship between oxidative stress and sport is really very complex; in fact, the release of free radicals is necessary to stimulate the up-regulation of endogenous antioxidant defenses. In recent years, the consumption of supplements rich in antioxidant compounds by athletes has greatly increased, but a natural intake through the diet is more recommended.

For future research conducted on the performance effects of dietary polyphenols, it should provide adequate detail on the method of blinding and participant follow-up to ascertain whether the study was in fact blinded and report performance data in raw values. These designs would enable researchers to optimize both type and dose of polyphenol supplementation to achieve performance benefit. In addition to the general notes on research reporting, very few studies outlined comprehensive dietary control measures.

Researchers should attempt to quantify the participants’ dietary intake of polyphenols, as those with low intakes are likely to respond more favorably to dietary intervention.

Polyphenol supplementation for at least 7 days has a clear moderate benefit on performance in healthy individuals. More research is needed on optimal dose; however, greater intakes could improve the performance response.

The present review summarized the results of studies on the effects of polyphenols intake on exercise-induced oxidative stress obtained in human trials.

The conflicting findings of previous research have brought into question the usefulness of antioxidant supplementation during resistance training. As polyphenolic antioxidants have shown promise as recovery strategies from fatiguing and damaging bouts of exercise, supplementation with polyphenols may be an appealing option to recover from an intense resistance exercise bout. However, it is important to determine whether polyphenol supplementation during a resistance training program will augment or diminish adaptations in muscular strength. Clearly, there is much more to be learned in the exciting field of exercise, oxidative stress, and polyphenols.

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A lot of studies are about how effective dietary intervention and oral antioxidant supplementation may be in reducing oxidative stress in athletes who exercise intensively. Commonly used nonenzymatic supplements have been proposed as ways to prevent exercise-induced oxidative stress and hence improve adaptation responses to endurance training. Plant-derived bioactive compounds can repress inflammation by inhibiting oxidative damage and interacting with the immune system. This review focuses on polyphenols and phytochemicals present in the plant kingdom that have been recently suggested to exert some positive effects on exercise-induced muscle damage and oxidative stress. This review will summarize some of the actual knowledge on polyphenolic compounds that have been demonstrated both to exert a significant effect in exercise-induced muscle damage and to play a biological/physiological role in improving physical performance. 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Introduction",level:"1"},{id:"sec_2",title:"2. Oxidative stress and antioxidants",level:"1"},{id:"sec_2_2",title:"2.1. Oxidative stress and physic activity",level:"2"},{id:"sec_3_2",title:"2.2. Antioxidants and exercise",level:"2"},{id:"sec_5",title:"3. Polyphenols",level:"1"},{id:"sec_5_2",title:"3.1. Nomenclature, classifications, and occurrence in foods",level:"2"},{id:"sec_6_2",title:"3.2. Bioavailability of polyphenols",level:"2"},{id:"sec_7_2",title:"3.3. Biological effects",level:"2"},{id:"sec_9",title:"4. Polyphenols action on athletic performance",level:"1"},{id:"sec_9_2",title:"4.1. Quercetin",level:"2"},{id:"sec_10_2",title:"4.2. Catechins: green tea extract",level:"2"},{id:"sec_11_2",title:"4.3. Resveratrol",level:"2"},{id:"sec_12_2",title:"4.4. Polyphenols mixtures",level:"2"},{id:"sec_14",title:"5. Polyphenols supplementation in exercise: limits and considerations",level:"1"},{id:"sec_15",title:"6. 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His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null},{id:"18",title:"Proteomics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",isOpenForSubmission:!0,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. 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Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartlomiej",middleName:null,surname:"Placzek",slug:"bartlomiej-placzek",fullName:"Bartlomiej Placzek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartlomiej Placzek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about aE˜Optoelectronic PackagingaE™ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrichaE™s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charite",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University, Kuwait. His research interests include optimization, computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, and intelligent systems. Prof. Sarfraz has been a keynote/invited speaker at various platforms around the globe. He has advised/supervised more than 110 students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He has authored and/or edited around seventy books. Prof. Sarfraz is a member of various professional societies. He is a chair and member of international advisory committees and organizing committees of numerous international conferences. He is also an editor and editor in chief for various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Canakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elzbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:"Beijing University of Technology",institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Lakhno Igor Victorovich was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPhD – 1999, Kharkiv National Medical Univesity.\nDSc – 2019, PL Shupik National Academy of Postgraduate Education \nLakhno Igor has been graduated from an international training courses on reproductive medicine and family planning held in Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor of the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s a professor of the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education . He’s an author of about 200 printed works and there are 17 of them in Scopus or Web of Science databases. Lakhno Igor is a rewiever of Journal of Obstetrics and Gynaecology (Taylor and Francis), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for DSc degree \\'Pre-eclampsia: prediction, prevention and treatment”. Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: obstetrics, women’s health, fetal medicine, cardiovascular medicine.",institutionString:"V.N. Karazin Kharkiv National University",institution:{name:"Kharkiv Medical Academy of Postgraduate Education",country:{name:"Ukraine"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"243698",title:"M.D.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:"Shanxi Eye Hospital",institution:{name:"Shanxi Eye Hospital",country:{name:"China"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruna (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruna. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruna",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clinico Universitario Valladolid\nAvda Ramon y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\[email protected]\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clinico multicentrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la prediccion de los resultados funcionales de la cirugia del desprendimiento de retina regmatogeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y Leon.\n' Estudio multicentrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duracion para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneracion macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicentrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneracion macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluacion de la seguridad y bioactividad de anillos de tension capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiologico, prospectivo, multicentrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovirica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clinico en fase IV para evaluar las variantes geneticas de la via del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneracion macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clinico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticcentrico y de 12 meses de duracion, para evaluar la eficacia y seguridad de un regimen de PRN flexible individualizado de 'esperar y extender' versus un regimen PRN segun criterios de estabilizacion mediante evaluaciones mensuales de inyecciones intravitreas de ranibizumab 0,5 mg en pacientes naive con neovascularizacion coriodea secunaria a la degeneracion macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicentrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un regimen de tratar y extender comparado con un regimen mensual, en pacientes con degeneracion macular neovascular asociada a la edad. CP: CRFB002A2411 Codigo Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; Garcia-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolome S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodriguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vitreos en una mujer joven. Problemas diagnosticos en patologia retinocoroidea. Sociedad Espanola de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugia del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (Espana): 2021.\n\n' Multiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' Gonzalez-Buendia L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatia proliferante (VRP) e inflamacion: LA INFLAMACION in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MAS ALLA DE LOS CORTICOIDES. RELACION DE PONENCIAS DE LA SOCIEDAD ESPANOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:null},{id:"318905",title:"Prof.",name:"Elvis",middleName:"Kwason",surname:"Tiburu",slug:"elvis-tiburu",fullName:"Elvis Tiburu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"336193",title:"Dr.",name:"Abdullah",middleName:null,surname:"Alamoudi",slug:"abdullah-alamoudi",fullName:"Abdullah Alamoudi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"318657",title:"MSc.",name:"Isabell",middleName:null,surname:"Steuding",slug:"isabell-steuding",fullName:"Isabell Steuding",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"318656",title:"BSc.",name:"Peter",middleName:null,surname:"Kusmann",slug:"peter-kussmann",fullName:"Peter Kusmann",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"338222",title:"Mrs.",name:"Maria Jose",middleName:null,surname:"Lucia Mudas",slug:"maria-jose-lucia-mudas",fullName:"Maria Jose Lucia Mudas",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Carlos III University of Madrid",country:{name:"Spain"}}},{id:"147824",title:"Mr.",name:"Pablo",middleName:null,surname:"Revuelta Sanz",slug:"pablo-revuelta-sanz",fullName:"Pablo Revuelta Sanz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Carlos III University of Madrid",country:{name:"Spain"}}},{id:"338224",title:"Prof.",name:"Tomas",middleName:null,surname:"Ortiz",slug:"tomas-ortiz",fullName:"Tomas Ortiz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Complutense University of Madrid",country:{name:"Spain"}}}]}},subseries:{item:{id:"4",type:"subseries",title:"Fungal Infectious Diseases",keywords:"Emerging Fungal Pathogens, Invasive Infections, Epidemiology, Cell Membrane, Fungal Virulence, Diagnosis, Treatment",scope:"Fungi are ubiquitous and there are almost no non-pathogenic fungi. Fungal infectious illness prevalence and prognosis are determined by the exposure between fungi and host, host immunological state, fungal virulence, and early and accurate diagnosis and treatment. \r\nPatients with both congenital and acquired immunodeficiency are more likely to be infected with opportunistic mycosis. Fungal infectious disease outbreaks are common during the post- disaster rebuilding era, which is characterised by high population density, migration, and poor health and medical conditions.\r\nSystemic or local fungal infection is mainly associated with the fungi directly inhaled or inoculated in the environment during the disaster. The most common fungal infection pathways are human to human (anthropophilic), animal to human (zoophilic), and environment to human (soilophile). Diseases are common as a result of widespread exposure to pathogenic fungus dispersed into the environment. \r\nFungi that are both common and emerging are intertwined. In Southeast Asia, for example, Talaromyces marneffei is an important pathogenic thermally dimorphic fungus that causes systemic mycosis. Widespread fungal infections with complicated and variable clinical manifestations, such as Candida auris infection resistant to several antifungal medicines, Covid-19 associated with Trichoderma, and terbinafine resistant dermatophytosis in India, are among the most serious disorders. \r\nInappropriate local or systemic use of glucocorticoids, as well as their immunosuppressive effects, may lead to changes in fungal infection spectrum and clinical characteristics. Hematogenous candidiasis is a worrisome issue that affects people all over the world, particularly ICU patients. CARD9 deficiency and fungal infection have been major issues in recent years. Invasive aspergillosis is associated with a significant death rate. Special attention should be given to endemic fungal infections, identification of important clinical fungal infections advanced in yeasts, filamentous fungal infections, skin mycobiome and fungal genomes, and immunity to fungal infections.\r\nIn addition, endemic fungal diseases or uncommon fungal infections caused by Mucor irregularis, dermatophytosis, Malassezia, cryptococcosis, chromoblastomycosis, coccidiosis, blastomycosis, histoplasmosis, sporotrichosis, and other fungi, should be monitored. \r\nThis topic includes the research progress on the etiology and pathogenesis of fungal infections, new methods of isolation and identification, rapid detection, drug sensitivity testing, new antifungal drugs, schemes and case series reports. It will provide significant opportunities and support for scientists, clinical doctors, mycologists, antifungal drug researchers, public health practitioners, and epidemiologists from all over the world to share new research, ideas and solutions to promote the development and progress of medical mycology.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",hasOnlineFirst:!1,hasPublishedBooks:!1,annualVolume:11400,editor:{id:"174134",title:"Dr.",name:"Yuping",middleName:null,surname:"Ran",slug:"yuping-ran",fullName:"Yuping Ran",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9d6QAC/Profile_Picture_1630330675373",biography:"Dr. Yuping Ran, Professor, Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China. Completed the Course Medical Mycology, the Centraalbureau voor Schimmelcultures (CBS), Fungal Biodiversity Centre, Netherlands (2006). International Union of Microbiological Societies (IUMS) Fellow, and International Emerging Infectious Diseases (IEID) Fellow, Centers for Diseases Control and Prevention (CDC), Atlanta, USA. Diploma of Dermatological Scientist, Japanese Society for Investigative Dermatology. Ph.D. of Juntendo University, Japan. Bachelor’s and Master’s degree, Medicine, West China University of Medical Sciences. Chair of Sichuan Medical Association Dermatology Committee. General Secretary of The 19th Annual Meeting of Chinese Society of Dermatology and the Asia Pacific Society for Medical Mycology (2013). In charge of the Annual Medical Mycology Course over 20-years authorized by National Continue Medical Education Committee of China. Member of the board of directors of the Asia-Pacific Society for Medical Mycology (APSMM). Associate editor of Mycopathologia. Vice-chief of the editorial board of Chinses Journal of Mycology, China. Board Member and Chair of Mycology Group of Chinese Society of Dermatology.",institutionString:null,institution:{name:"Sichuan University",institutionURL:null,country:{name:"China"}}},editorTwo:null,editorThree:null,series:{id:"6",title:"Infectious Diseases",doi:"10.5772/intechopen.71852",issn:"2631-6188"},editorialBoard:[{id:"302145",title:"Dr.",name:"Felix",middleName:null,surname:"Bongomin",slug:"felix-bongomin",fullName:"Felix Bongomin",profilePictureURL:"https://mts.intechopen.com/storage/users/302145/images/system/302145.jpg",institutionString:"Gulu University",institution:{name:"Gulu University",institutionURL:null,country:{name:"Uganda"}}},{id:"45803",title:"Ph.D.",name:"Payam",middleName:null,surname:"Behzadi",slug:"payam-behzadi",fullName:"Payam Behzadi",profilePictureURL:"https://mts.intechopen.com/storage/users/45803/images/system/45803.jpg",institutionString:"Shahr-e-Qods Branch, Islamic Azad University",institution:{name:"Islamic Azad University, Tehran",institutionURL:null,country:{name:"Iran"}}}]},onlineFirstChapters:{paginationCount:26,paginationItems:[{id:"80484",title:"The Use of Stable Isotope Labeling with Amino Acids in Cell Culture (SILAC) to Study Ivermectin-Mediated Molecular Pathway Changes in Human Ovarian Cancer Cells",doi:"10.5772/intechopen.102092",signatures:"Na Li and Xianquan Zhan",slug:"the-use-of-stable-isotope-labeling-with-amino-acids-in-cell-culture-silac-to-study-ivermectin-mediat",totalDownloads:28,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Cell Culture: Advanced Technology and Applications in Medical and Life Sciences",coverURL:"https://cdn.intechopen.com/books/images_new/10797.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}},{id:"79751",title:"Reactive Oxygen Species (ROS) in the Pathophysiology of Rheumatoid Arthritis (RA)",doi:"10.5772/intechopen.101333",signatures:"Haseeb Ahsan, Mohammad Yusuf Hasan and Rizwan Ahmad",slug:"reactive-oxygen-species-ros-in-the-pathophysiology-of-rheumatoid-arthritis-ra",totalDownloads:35,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Reactive Oxygen Species",coverURL:"https://cdn.intechopen.com/books/images_new/10803.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}},{id:"80157",title:"Structural Determinants for Ligand Accommodation in Voltage Sensors",doi:"10.5772/intechopen.102094",signatures:"Abigail Garcia-Morales, Aylin Lopez-Palestino and Daniel Balleza",slug:"structural-determinants-for-ligand-accommodation-in-voltage-sensors",totalDownloads:50,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Ion Channels - From Basic Properties to Medical Treatment",coverURL:"https://cdn.intechopen.com/books/images_new/10838.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}},{id:"80024",title:"Perturbation of Cellular Redox Status: Role of Nrf2, a Master Regulator of Cellular Redox",doi:"10.5772/intechopen.102319",signatures:"Lokesh Gambhir, Garima Tyagi, Richa Bhardwaj, Neha Kapoor and Gaurav Sharma",slug:"perturbation-of-cellular-redox-status-role-of-nrf2-a-master-regulator-of-cellular-redox",totalDownloads:47,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Reactive Oxygen Species",coverURL:"https://cdn.intechopen.com/books/images_new/10803.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}},{id:"79690",title:"Mitochondrial Channels and their Role in Cardioprotection",doi:"10.5772/intechopen.101127",signatures:"Keerti Mishra and Min Luo",slug:"mitochondrial-channels-and-their-role-in-cardioprotection",totalDownloads:54,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Ion Channels - From Basic Properties to Medical Treatment",coverURL:"https://cdn.intechopen.com/books/images_new/10838.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}},{id:"79570",title:"Environmental Particulate Air Pollution Exposure and the Oxidative Stress Responses: A Brief Review of the Impact on the Organism and Animal Models of Research",doi:"10.5772/intechopen.101394",signatures:"Pauline Brendler Goettems Fiorin, Mirna Stela Ludwig, Matias Nunes Frizzo and Thiago Gomes Heck",slug:"environmental-particulate-air-pollution-exposure-and-the-oxidative-stress-responses-a-brief-review-o",totalDownloads:66,totalCrossrefCites:0,totalDimensionsCites:0,authors:[{name:"Thiago",surname:"Heck"},{name:"Mirna",surname:"Ludwig"},{name:"Pauline",surname:"Goettems-Fiorin"},{name:"Matias",surname:"Frizzo"}],book:{title:"Reactive Oxygen Species",coverURL:"https://cdn.intechopen.com/books/images_new/10803.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}},{id:"78462",title:"Reactive Oxygen Species in the Development and Resolution of Autoimmune and Inflammatory Disease",doi:"10.5772/intechopen.99988",signatures:"Joshua Banda and Allan K. 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Analysis",editors:[{id:"50150",title:"Prof.",name:"Robert",middleName:null,surname:"Koprowski",slug:"robert-koprowski",fullName:"Robert Koprowski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTYNQA4/Profile_Picture_1630478535317",institutionString:"University of Silesia",institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},testimonialsList:[{id:"27",text:"The opportunity to work with a prestigious publisher allows for the possibility to collaborate with more research groups interested in animal nutrition, leading to the development of new feeding strategies and food valuation while being more sustainable with the environment, allowing more readers to learn about the subject.",author:{id:"175967",name:"Manuel",surname:"Gonzalez Ronquillo",institutionString:"Universidad Autonoma del Estado de 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ipsj.ixsq.nii.ac.jp

Componentization of Operating System Feature Using a TECS Plugin Kawada Tomoaki 1 Azumi Takuya 2 Hiroshi Oyama 3 Hiroaki Takada 4 Abstract: In this study, we componentized the TOPPERS/ASP3 (a real-time operating system) time event notiÞcation using the plugin feature of TECS (TOPPERS Embedded Component System). With the in-情報学広場 情報処理学会電子図書館.
Keyword: 情報学広場, 情報処理学会, 電子図書館
From: ipsj.ixsq.nii.ac.jp

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SOC (Ret) SEAL Eddie Gallagher on Instagram: “Finally got ...

Dec 22, 2019 · SOC (Ret) SEAL Eddie Gallagher shared a photo on Instagram: “Finally got to thank the President and his amazing wife by giving them a little gift from Eddie’s…” • See 5,410 photos and videos on their profile..
From: www.instagram.com


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A New Three‐Dimensional Classification of Proximal ...

Oct 20, 2021 · The length of line CD were 7.25 ± 0.79 cm in X-ray and 7.26 ± 0.83 cm in CT, and there was no statistical difference between the two measurements (t = 0.259, P = 0.899). And similarly, there was no statistical difference in the length of line OA between 2.56 ± 0.31 cm in X-ray measurement and 2.58 ± 0.29 cm in CT measurement ( t = 0.452, P ....
From: onlinelibrary.wiley.com


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XZ = 26 ft ; OX = (±44 x PREVIEW

A) Find the value of x in each parallelogram. B) Find the value of x and y in each parallelogram. 1) OA = (x + 23) in ; OC = 31 in2) XZ = 26 ft ; OX = (±44 + x) ft x = x = x = 1) 2) 3) PR = (7 x) yd ; OP = 35 yd 4) x = 8 10 57 98 A O B D C Z O W X Y S O P R Q O E F H G M O J K L S O.
From: www.mathworksheets4kids.com


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image of GitHub - micro-os-plus/utils-lists-xpack: A source xPack ...

GitHub - micro-os-plus/utils-lists-xpack: A source xPack ...

Branches. Apart from the unused master branch, there are two active branches:. xpack, with the latest stable version; xpack-develop, with the current development version; All development is done in the xpack-develop branch, and contributions via Pull Requests should be directed to this branch.. When new releases are published, the xpack-develop branch is merged into xpack.A source xPack with C++ lists support. Contribute to micro-os-plus/utils-lists-xpack development by creating an account on GitHub..
From: github.com


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