Can we regenerate heart muscle with stem cells? | Chuck Murry

Translator: Marta Suárez Reviewer: Servizo de Normalización Lingüística

I'd like to tell you about a patient named Donna.

Gustaríame falarvos dunha paciente chamada Donna.

In this photograph, Donna was in her mid-70s,

Nesta fotografía Donna tiña uns 70 anos.

a vigorous, healthy woman,

Era unha muller vigorosa e sa, a matriarca dunha gran familia.

the matriarch of a large clan.

She had a family history of heart disease, however,

Porén, tiña antecedentes familiares de cardiopatía

and one day, she had the sudden onset of crushing chest pain.

e, un día, tivo unha dor repentina e opresiva no peito.

Now unfortunately, rather than seeking medical attention,

Desgraciadamente, en lugar de buscar atención médica,

Donna took to her bed for about 12 hours until the pain passed.

Donna deitouse durante 12 horas ata que a dor cesou.

The next time she went to see her physician,

A próxima vez que foi ver o seu médico,

he performed an electrocardiogram,

este fíxolle un electrocardiograma,

que mostrou que padecera un grave ataque ao corazón,

and this showed that she'd had a large heart attack,

or a "myocardial infarction" in medical parlance.

ou “infarto de miocardio”, falando en termos médicos.

After this heart attack, Donna was never quite the same.

Logo dese ataque ao corazón, Donna nunca foi a mesma.

Her energy levels progressively waned,

A súa enerxía diminuíu progresivamente;

she couldn't do a lot of the physical activities she'd previously enjoyed.

xa non podía realizar actividades físicas das que antes gozaba.

It got to the point where she couldn't keep up with her grandkids,

Chegou a un punto onde non podía xogar cos seus netos

e se volveu aínda máis complicado saír á rúa a coller o correo.

and it was even too much work to go out to the end of the driveway

to pick up the mail.

One day, her granddaughter came by to walk the dog,

Un día, a súa neta veu para pasear o can

and she found her grandmother dead in the chair.

e atopou a súa avoa falecida na cadeira.

Doctors said it was a cardiac arrhythmia that was secondary to heart failure.

Os doutores diagnosticaron unha arritmia derivada do fallo cardíaco.

But the last thing that I should tell you

A última cousa que debería contarvos

is that Donna was not just an ordinary patient.

é que Donna non foi só unha paciente.

Donna was my mother.

Donna era a miña nai.

Stories like ours are, unfortunately, far too common.

As historias coma esta, desgraciadamente, son moi comúns.

Heart disease is the number one killer in the entire world.

As cardiopatías son a primeira causa de morte no mundo.

In the United States,

Nos Estados Unidos,

son a razón máis común de ingreso nos hospitais

it's the most common reason patients are admitted to the hospital,

e o noso maior gasto en atención médica.

and it's our number one health care expense.

Gastamos sobre 100 mil millóns de dólares

We spend over a 100 billion dollars -- billion with a "B" --

in this country every year

neste país, cada ano,

on the treatment of heart disease.

no tratamento de enfermidades cardíacas.

Just for reference, that's more than twice the annual budget

Como referencia, é dúas veces máis que o presuposto anual

of the state of Washington.

do estado de Washington.

What makes this disease so deadly?

Que fai tan mortal esta enfermidade?

Well, it all starts with the fact that the heart is the least regenerative organ

Todo comeza co feito de que o corazón é o órgano menos rexenerativo

in the human body.

do corpo humano.

Now, a heart attack happens when a blood clot forms in a coronary artery

Un ataque ao corazón ocorre cando se forma un coágulo de sangue

nunha arteria coronaria que leva sangue ao corazón.

that feeds blood to the wall of the heart.

Isto bloquea o fluxo sanguíneo

This plugs the blood flow,

and the heart muscle is very metabolically active,

e como o músculo cardíaco é moi activo metabolicamente,

and so it dies very quickly,

morre moi rápido,

within just a few hours of having its blood flow interrupted.

unhas poucas horas despois do bloqueo.

Since the heart can't grow back new muscle,

Dado que o corazón non pode rexenerar músculo,

it heals by scar formation.

cura formando cicatrices.

This leaves the patient with a deficit

Isto deixa o paciente cun déficit de músculo cardíaco.

in the amount of heart muscle that they have.

And in too many people, their illness progresses to the point

En moitas persoas, a enfermidade evoluciona ata o punto en que

where the heart can no longer keep up with the body's demand for blood flow.

o corazón non pode facer fronte á demanda de sangue do corpo.

This imbalance between supply and demand is the crux of heart failure.

Este desequilibrio entre a oferta e a demanda é a base do fallo cardíaco.

So when I talk to people about this problem,

Cando falo coa xente sobre este problema,

I often get a shrug and a statement to the effect of,

a miúdo encollen os ombreiros e fan comentarios do tipo:

"Well, you know, Chuck, we've got to die of something."

“Mira, Chuck, de algo hai que morrer.”

(Laughter)

(Risas)

And yeah, but what this also tells me

Si, pero isto tamén me di

is that we've resigned ourselves to this as the status quo because we have to.

que aceptamos isto como o statu quo porque non queda outra.

Or do we?

Ou si?

I think there's a better way,

Penso que hai unha maneira mellor,

and this better way involves the use of stem cells as medicines.

e esta outra forma inclúe o uso de células nai como medicamentos.

So what, exactly, are stem cells?

Pero que son exactamente as células nai?

If you look at them under the microscope, there's not much going on.

Se as vemos a través do microscopio, non hai moito que ver.

Son células redondas, pequenas e simples.

They're just simple little round cells.

But that belies two remarkable attributes.

Pero isto oculta dous atributos notables.

The first is they can divide like crazy.

O primeiro é que se dividen coma tolas.

Podo coller unha única célula e, nun mes,

So I can take a single cell, and in a month's time,

facer que se divida en miles de millóns de células.

I can grow this up to billions of cells.

The second is they can differentiate or become more specialized,

O segundo é que se poden diferenciar ou chegar a estar máis especializadas,

so these simple little round cells can turn into skin, can turn into brain,

así que estas pequenas células redondas poden converterse en pel,

en cerebro, nun ril e demais.

can turn into kidney and so forth.

Now, some tissues in our bodies are chock-full of stem cells.

Agora ben, algúns tecidos corporais están repletos de células nai.

Our bone marrow, for example, cranks out billions of blood cells every day.

A nosa medula ósea, por exemplo, produce miles de millóns de células cada día.

Other tissues like the heart are quite stable,

Outros tecidos, coma o corazón, son bastante estables,

and as far as we can tell, the heart lacks stem cells entirely.

e polo que podemos saber ata agora, este carece totalmente de células nai.

So for the heart, we're going to have to bring stem cells in from the outside,

Entón, para o corazón imos ter que traer células nai do exterior,

and for this, we turn to the most potent stem cell type,

e para isto recorremos ao tipo de célula nai máis potente,

the pluripotent stem cell.

a célula nai pluripotente.

As células nai pluripotentes denomínanse así

Pluripotent stem cells are so named

because they can turn into any of the 240-some cell types

porque poden converterse en calquera dos 240 tipos de células

that make up the human body.

que compoñen o corpo humano.

So this is my big idea:

Esta é a miña gran idea:

I want to take human pluripotent stem cells,

quero tomar células nai pluripotentes humanas,

grow them up in large numbers,

crialas en grandes cantidades,

differentiate them into cardiac muscle cells

facer que se convertan en células do músculo cardíaco

and then take them out of the dish

e logo sacalas do medio de cultivo

and transplant them into the hearts of patients who have had heart attacks.

e transplantalas aos corazóns de persoas que sufriron ataques cardíacos.

I think this is going to reseed the wall with new muscle tissue,

Penso que isto vai reconstruír a parede con novo tecido muscular

and this will restore contractile function to the heart.

e restaurará a función contráctil do corazón.

(Applause)

(Aplausos)

Now, before you applaud too much, this was my idea 20 years ago.

Antes de que aplaudades demasiado, esta foi a miña idea hai 20 anos.

(Laughter)

(Risas)

And I was young, I was full of it, and I thought,

Era novo, estaba cheo de entusiasmo e pensaba:

five years in the lab, and we'll crank this out,

“en cinco anos no laboratorio arranxamos isto e témolo na clínica.”

and we'll have this into the clinic.

Let me tell you what really happened.

Deixádeme contarvos que ocorreu realmente.

(Laughter)

(Risas)

We began with the quest to turn these pluripotent stem cells into heart muscle.

Comezamos coa misión de trocar células nai pluripotentes en músculo cardíaco.

And our first experiments worked, sort of.

Os nosos primeiros experimentos funcionaron, ou algo así.

We got these little clumps of beating human heart muscle in the dish,

Obtivemos pequenos grupos de músculo cardíaco que batía no cultivo,

e iso estaba ben porque significaba, en principio,

and that was cool, because it said, in principle,

this should be able to be done.

que era posible facelo.

But when we got around to doing the cell counts,

Pero cando fixemos o reconto de células,

descubrimos que só unha entre 1000 células nai

we found that only one out of 1,000 of our stem cells

were actually turning into heart muscle.

estaba a converterse realmente en músculo cardíaco.

The rest was just a gemisch of brain and skin and cartilage

As demais eran só unha mestura de células cerebrais, da pel, da cartilaxe

and intestine.

e do intestino.

So how do you coax a cell that can become anything

Como se convence unha célula que pode converterse en calquera cousa

into becoming just a heart muscle cell?

para que torne nunha célula muscular cardíaca?

Well, for this we turned to the world of embryology.

Para isto acudimos ao mundo da embrioloxía.

For over a century, the embryologists had been pondering

Durante máis dun século, os embriólogos pensaron

the mysteries of heart development.

nos misterios do desenvolvemento do corazón

And they had given us what was essentially a Google Map

e déronnos o que era esencialmente un mapa de Google

for how to go from a single fertilized egg

sobre como pasar dun só óvulo fecundado

all the way over to a human cardiovascular system.

a todo un sistema cardiovascular humano.

So we shamelessly absconded all of this information

Así que usamos descaradamente toda esa información

and tried to make human cardiovascular development happen in a dish.

e tratamos de facer que o desenvolvemento cardiovascular ocorrese nun cultivo.

It took us about five years, but nowadays,

Levounos cinco anos, pero, hoxe,

we can get 90 percent of our stem cells to turn into cardiac muscle --

logramos que o 90 % das nosas células nai se convertan en músculo cardíaco,

a 900-fold improvement.

unha mellora 900 veces maior.

So this was quite exciting.

Isto foi bastante emocionante.

This slide shows you our current cellular product.

Esta diapositiva mostra o noso produto celular actual.

We grow our heart muscle cells in little three-dimensional clumps

Facemos crecer as nosas células musculares cardíacas en grupos tridimensionais

called cardiac organoids.

chamados organoides cardíacos.

Each of them has 500 to 1,000 heart muscle cells in it.

Cada un deles ten de 500 a 1000 células de músculo cardíaco.

Se miramos de cerca, veremos como eses organoides se contraen;

If you look closely, you can see these little organoids are actually twitching;

each one is beating independently.

cada un latexa de forma independente.

Pero teñen outro truco baixo a manga.

But they've got another trick up their sleeve.

We took a gene from jellyfish that live in the Pacific Northwest,

Collemos un xene dunha medusa que vive no noroeste do Pacífico

and we used a technique called genome editing

e empregamos unha técnica chamada edición do xenoma

to splice this gene into the stem cells.

para empalmar este xene nas células nai.

And this makes our heart muscle cells flash green every time they beat.

Isto fai que as células emitan un brillo verde cada vez que latexan.

OK, so now we were finally ready to begin animal experiments.

Ben, agora xa estabamos listos para comezar os experimentos en animais.

We took our cardiac muscle cells

Collemos as células musculares cardíacas

and we transplanted them into the hearts of rats

e transplantámolas nos corazóns das ratas

that had been given experimental heart attacks.

que recibiran ataques cardíacos experimentais.

A month later, I peered anxiously down through my microscope

Un mes máis tarde, mirei ansioso a través do meu microscopio

to see what we had grown,

para ver o que crearamos

e vin...

and I saw ...

nothing.

nada.

Everything had died.

Todo morrera.

But we persevered on this, and we came up with a biochemical cocktail

Porén, perseveramos e elaboramos un cóctel bioquímico

that we called our "pro-survival cocktail,"

ao que lle demos o nome de “cóctel prosupervivencia”,

and this was enough to allow our cells to survive

que foi suficiente para que as nosas células sobrevivisen

through the stressful process of transplantation.

ao estresante proceso do transplante.

And now when I looked through the microscope,

Esta vez, cando mirei polo microscopio,

I could see this fresh, young, human heart muscle

vin un músculo do corazón humano novo e fresco

growing back in the injured wall of this rat's heart.

medrar na parede lesionada do corazón da rata.

So this was getting quite exciting.

A cousa íase poñendo emocionante.

The next question was:

A seguinte pregunta era:

Will this new muscle beat in synchrony with the rest of the heart?

latexará este novo músculo en sincronía co resto do corazón?

So to answer that,

Para responder a isto,

we returned to the cells that had that jellyfish gene in them.

volvemos ás células co xene da medusa.

We used these cells essentially like a space probe

Esencialmente, usamos estas células como unha sonda espacial

that we could launch into a foreign environment

que poderiamos lanzar nun ambiente estraño

and then have that flashing report back to us

e nos informaría con eses flashes

about their biological activity.

da súa actividade biolóxica.

What you're seeing here is a zoomed-in view,

O que vedes aquí é unha vista ampliada,

a black-and-white image of a guinea pig's heart

unha imaxe en branco e negro do corazón dunha cobaia

that was injured and then received three grafts of our human cardiac muscle.

que foi ferida e recibiu tres enxertos do noso músculo cardíaco humano.

¿Vedes esas liñas brancas en diagonal?

So you see those sort of diagonally running white lines.

Each of those is a needle track

Cada unha delas é unha marca de agulla

that contains a couple of million human cardiac muscle cells in it.

que contén un par de millóns de células musculares cardíacas humanas.

And when I start the video, you can see what we saw

Cando empece o vídeo, veredes o que observamos

when we looked through the microscope.

cando miramos a través do microscopio.

As nosas células brillan,

Our cells are flashing,

and they're flashing in synchrony,

e fano en sincronía,

back through the walls of the injured heart.

a través das paredes do corazón lesionado.

What does this mean?

Que significa isto?

It means the cells are alive,

Quere dicir que as células están vivas,

they're well, they're beating,

que están ben, que latexan

and they've managed to connect with one another

e conseguiron conectarse entre elas

so that they're beating in synchrony.

para latexar en sincronía.

But it gets even more interesting than this.

Pero é aínda máis interesante ca isto.

If you look at that tracing that's along the bottom,

Se mirades este trazo da parte inferior,

that's the electrocardiogram from the guinea pig's own heart.

ese é o electrocardiograma do corazón da cobaia.

And if you line up the flashing with the heartbeat

E se aliñades o flash co latexo do corazón

que se mostra na parte inferior,

that's shown on the bottom,

what you can see is there's a perfect one-to-one correspondence.

veredes unha correspondencia perfecta un a un.

Noutras palabras, o marcapasos natural da cobaia leva o mando

In other words, the guinea pig's natural pacemaker is calling the shots,

and the human heart muscle cells are following in lockstep

e as células do músculo cardíaco humano seguen o seu paso seguro

like good soldiers.

coma bos soldados.

(Applause)

(Aplausos)

Os nosos estudos actuais trasladáronse ao que penso que será

Our current studies have moved into what I think is going to be

o mellor indicador posible para un paciente humano:

the best possible predictor of a human patient,

and that's into macaque monkeys.

falamos dos macacos.

This next slide shows you a microscopic image

Esta seguinte diapositiva amosa unha imaxe microscópica

from the heart of a macaque that was given an experimental heart attack

do corazón dun macaco que recibiu un ataque cardíaco experimental

and then treated with a saline injection.

e logo un tratamento de solución salina.

Isto é como un tratamento con placebo

This is essentially like a placebo treatment

to show the natural history of the disease.

para amosar o curso natural da enfermidade.

The macaque heart muscle is shown in red,

O músculo cardíaco do macaco móstrase en vermello

and in blue, you see the scar tissue that results from the heart attack.

e en azul vedes o tecido cicatrizante que resulta do ataque cardíaco.

So as you look as this, you can see how there's a big deficiency in the muscle

Como vedes, hai unha gran deficiencia no músculo

in part of the wall of the heart.

en parte da parede do corazón.

And it's not hard to imagine how this heart would have a tough time

Non é difícil de imaxinar o traballo que lle dará a este corazón

generating much force.

xerar forza abondo.

En cambio, este é un corazón tratado con células nai.

Now in contrast, this is one of the stem-cell-treated hearts.

Again, you can see the monkey's heart muscle in red,

Vemos de novo o músculo cardíaco do mono en vermello,

but it's very hard to even see the blue scar tissue,

pero é moi difícil ver o tecido azul cicatrizante,

and that's because we've been able to repopulate it

e iso é porque puidemos repoboalo

with the human heart muscle,

co músculo do corazón humano

and so we've got this nice, plump wall.

e así obtemos esta parede boa e gordiña.

OK, let's just take a second and recap.

Ben, recapitulemos un segundo.

I've showed you that we can take our stem cells

Mostreivos que podemos tomar as nosas células nai

and differentiate them into cardiac muscle.

e transformalas en músculo cardíaco.

We've learned how to keep them alive after transplantation,

Aprendemos a mantelas vivas logo do transplante,

we've showed that they beat in synchrony with the rest of the heart,

demostramos que latexan en sincronía co resto do corazón

and we've shown that we can scale them up

e que podemos aumentalas a escala

into an animal that is the best possible predictor of a human's response.

para un animal que é o mellor indicador posible da resposta en humanos.

You'd think that we hit all the roadblocks that lay in our path, right?

Pensaredes que superamos todos os obstáculos do camiño, non?

Turns out, not.

Pois resulta que non.

These macaque studies also taught us

Estes estudos sobre macacos tamén nos ensinaron

that our human heart muscle cells created a period of electrical instability.

que as nosas células cardíacas creaban un período

de inestabilidade eléctrica.

They caused ventricular arrhythmias, or irregular heartbeats,

Causaron arritmias ventriculares ou latidos irregulares do corazón

for several weeks after we transplanted them.

durante varias semanas despois de que as transplantásemos.

Isto foi bastante inesperado, porque non o viramos en animais máis pequenos.

This was quite unexpected, because we hadn't seen this in smaller animals.

We've studied it extensively,

Estudiámolas en detalle

e descubrimos que isto ocorre porque os nosos enxertos celulares

and it turns out that it results from the fact that our cellular graphs

are quite immature,

son bastante inmaturos,

and immature heart muscle cells all act like pacemakers.

e todas as células cardíacas inmaturas actúan como marcapasos.

So what happens is, we put them into the heart,

O que pasa é que, ao metelas no corazón,

and there starts to be a competition with the heart's natural pacemaker

comeza a haber unha competición co marcapasos natural do corazón

over who gets to call the shots.

sobre quen leva a voz cantante.

It would be sort of like

Sería algo así coma

if you brought a whole gaggle of teenagers into your orderly household all at once,

se trouxésedes unha manda de adolescentes á vosa casa ordenada, todos á vez,

and they don't want to follow the rules and the rhythms of the way you run things,

e non quixesen seguir as normas nin os vosos ritmos de facer as cousas.

and it takes a while to rein everybody in

Levaríavos un tempo controlar a todos

and get people working in a coordinated fashion.

e conseguir que traballasen de forma coordinada.

Polo tanto, os nosos plans neste momento

So our plans at the moment

are to make the cells go through this troubled adolescence period

son facer que as células pasen ese convulso período de adolescencia

while they're still in the dish,

mentres aínda están no cultivo

and then we'll transplant them in in the post-adolescent phase,

e despois transplantalas na fase postadolescente,

where they should be much more orderly

cando deberían ser moito máis ordenadas

and be ready to listen to their marching orders.

e estar preparadas para obedecer as ordes.

In the meantime, it turns out we can actually do quite well

Mentres tanto, resulta que nos vai bastante ben

by treating with anti-arrhythmia drugs as well.

tratando con fármacos contra as arritmias.

So one big question still remains,

Aínda queda unha gran pregunta,

and that is, of course, the whole purpose that we set out to do this:

que é, por suposto, o propósito co que empezamos a facer isto:

Can we actually restore function to the injured heart?

podemos realmente restaurar a función dun corazón ferido?

Para responder a esta cuestión,

To answer this question,

we went to something that's called "left ventricular ejection fraction."

pasamos a algo chamado “fracción de expulsión ventricular esquerda”.

A fracción de expulsión é simplemente a cantidade de sangue

Ejection fraction is simply the amount of blood

that is squeezed out of the chamber of the heart

que se expulsa fóra da cámara do corazón con cada latexo.

with each beat.

Now, in healthy macaques, like in healthy people,

En macacos sans, como en persoas sas,

ejection fractions are about 65 percent.

as fraccións de expulsión son dun 65 %.

After a heart attack, ejection fraction drops down to about 40 percent,

Despois dun ataque ao corazón, a fracción de expulsión cae ata un 40 %,

so these animals are well on their way to heart failure.

polo que estes animais están camiño da insuficiencia cardíaca.

In the animals that receive a placebo injection,

Nos animais que reciben unha inxección de placebo,

when we scan them a month later,

cando os escaneamos un mes despois,

we see that ejection fraction is unchanged,

vemos que a fracción de expulsión non cambia,

because the heart, of course, doesn't spontaneously recover.

porque o corazón, por suposto, non se recupera espontaneamente.

But in every one of the animals that received a graft

Pero en todos os animais que recibiron un enxerto

of human cardiac muscle cells,

de células do músculo cardíaco humano,

we see a substantial improvement in cardiac function.

observamos unha mellora substancial da función cardíaca,

This averaged eight points, so from 40 to 48 percent.

cunha media de oito puntos, do 40 ao 48 %.

What I can tell you is that eight points is better

O que vos podo dicir é que oito puntos é mellor

than anything that's on the market right now

que calquera cousa que haxa no mercado agora mesmo

for treating patients with heart attacks.

para tratar pacientes con infartos.

It's better than everything we have put together.

É mellor que todo o que fixemos ata agora.

So if we could do eight points in the clinic,

Se puidésemos facer oito puntos na clínica,

I think this would be a big deal that would make a large impact

sería un grande avance cun enorme impacto na saúde humana.

on human health.

But it gets more exciting.

Pero a cousa ponse máis emocionante.

That was just four weeks after transplantation.

Iso foi só catro semanas despois do transplante.

If we extend these studies out to three months,

Se ampliamos estes estudos a tres meses,

we get a full 22-point gain in ejection fraction.

obtemos unha mellora de 22 puntos na fracción de expulsión.

(Applause)

(Aplausos)

Function in these treated hearts is so good

A función destes corazóns tratados é tan boa

that if we didn't know up front that these animals had had a heart attack,

que se non soubésemos de antemán que estes animais sufriran un infarto,

we would never be able to tell from their functional studies.

nunca seriamos capaces de dicilo a partir dos seus estudos funcionais.

Going forward, our plan is to start phase one,

No futuro, o noso plan é comezar a fase un,

first in human trials here at the University of Washington in 2020 --

primeiro en ensaios con humanos aquí, na Universidade de Washington, en 2020,

two short years from now.

dentro de só dous anos.

Presuming these studies are safe and effective,

Asumindo que estes estudos sexan seguros e eficaces,

which I think they're going to be,

e eu penso que o van ser,

our plan is to scale this up and ship these cells all around the world

o noso plan é ampliar isto e enviar estas células a todo o mundo

for the treatment of patients with heart disease.

para tratar pacientes con enfermidades cardíacas.

Given the global burden of this illness,

Dada a carga global desta enfermidade,

I could easily imagine this treating a million or more patients a year.

poderiamos tratar facilmente un millón de pacientes, ou máis, ao ano.

So I envision a time, maybe a decade from now,

Imaxino un momento, tal vez dentro dunha década,

where a patient like my mother will have actual treatments

no que un paciente coma a miña nai terá tratamentos

that can address the root cause and not just manage her symptoms.

que poidan abordar a raíz do problema en lugar de manexar os seus síntomas.

This all comes from the fact that stem cells give us the ability

Todo isto débese a que as células nai nos dan a capacidade

to repair the human body

de reparar o corpo humano

from its component parts.

a partir dos seus compoñentes.

In the not-too-distant future,

Nun futuro non moi afastado,

repairing humans is going to go

reparar humanos vai pasar de ser

from something that is far-fetched science fiction

unha idea tola de ciencia ficción

into common medical practice.

a unha práctica médica común.

And when this happens,

E cando isto suceda,

it's going to have a transformational effect

vai ter un efecto transformador

that rivals the development of vaccinations and antibiotics.

que rivalizará co desenvolvemento das vacinas e antibióticos.

Grazas pola vosa atención.

Thank you for your attention.

(Applause)

(Aplausos)