ñoños

CrA³nica de Una Meada AnunciadaaE¦

Poco 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!

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.»

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.

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.

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.").

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.)

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.

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.

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].

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".

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.

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.

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.

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.

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]

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.

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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.

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.

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.

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.

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.

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.

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].

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].

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].

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.

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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