0:08
Hello, I'm a Jim Ausman, and I like to introduce you to the next lecture. Which is a lecture on major advances in the CNS.
0:20
This talk is going to be at spout software in the brain. It'll be given by Itzhak Fried who is a professor of neurosurgery and psychiatry at U. C L A, and has worked in this area for for many years.
0:36
With him on the panel is Antonio de Salas, whose founder and chief of Neuro Sapiens and Sao Paulo, Brazil, ather, M, professor and head of neurosurgery at Aga Khan University, and one Jorge
0:50
later have also from the U. Cla formerly had pediatrics,
0:58
I like to give you some background to it. Cites a lecture. It's an excellent lecture covering a lot of ground.
1:06
But we have to go back one hundred and twenty years.
1:10
By that time, in the nineteen hundreds of neurons, the structure of neurons were known, physiology was being
1:19
studied and elucidated and and so a, and knew how electrical impulses were generated and regenerated signal,
1:30
so we knew the physiology of the nurse Raimondi Kahan. Was able through excellent to histology and histopathology to delineate shows the neural networks in the brain imaging at the time wasn't really
1:46
very good in the twenties. There was of in Turkey, a lot graphy and authorities, and it gets more needs developed and geography, and also in the late thirties and forties, was a neurosurgeon and
1:58
Canada, by the name of Wilder Penfield, Wilder, Penfield was the. First person really to open the skull in patients who are awake, and then stimulates the cortex, revolutionary studies, showing
2:13
where the motor strip was sensory strip, Hearing could be located. Stimulation could produce visual experiences and he was able to elicit bait elicit memories. He could share memories, and
2:26
patients
2:28
in the this word continue do with more. Evaluation of people with epilepsy, identifying the fossa and being able to surgically treat them, but also in the fifties and sixties, movement disorders
2:45
began to be treated with surgery, stereotactic neurosurgery where lesions in the basal ganglia would be made in order to the road to diminish the the tremors from Parkinson's disease with some
2:59
success. In the early sixties a biochemical treatments were developed using L dopa to treat Parkinson's disease in the brain with a high degree of success. This was revolutionary in its own way,
3:14
because what it showed is that neuro problems, neuro problems in the brain could be treated chemically and with excellent results, so not only way of surgical treatments, we had chemical treatments
3:29
for awhile. The chemical treatments overshadowed the shortage, surgical treatments, Eg and conflict complex monitoring was developed, the seventies and eighties and the nineties That was the time
3:42
when we first began to have Cts in at Mars, and the technological revolution came, and with it we had more complex analysis of Egypt, Gs and signals from the brain which enables more refined
3:55
epilepsy surgery. We could see the structure of the brain on M, R and C T in more detail, which led to more detailed placing of electrodes in the brain of a recording, which would also be from not
4:10
only multiple cells, but single cells, and also stimulation, which could be used in various portions of the basal ganglia to treat Parkinson's disease, so now, hour, and they, the early two
4:24
thousands, two thousand and ten. And people began to wonder what can be done to treat patients who had depression, major depression, and that was that failed any kind of known treatment, and so
4:40
it was thought that. Making lesions in the brain using a Dbs as deep brain stimulation could be used and the first patients were treated in Toronto, Ontario,
4:57
it with good results to treat people with untreatable
5:02
basically untreatable depression. Now these people could be helped with certain forms of functional neurosurgery.
5:12
Rather then more diseases rented like obsessive compulsive disease, and is Tony De Salad gave him his lecture in the past, present and future of functional neurosurgery obesity, addiction, and
5:25
others are now on the list of things that can be treated. It Suck, has been working in epilepsy for some years and worked on a new technique that was developed, That was also revolutionary.
5:39
Recordings could make Dayton may be made from a series. Your focus in the brain transmitted to a a modulator stimulators sensor under the skin, which had a computer program in it would analyze the
5:55
signals. See if an epileptic seizure was coming, and then send a stimulus to the brain to stop the seizures of closed loop system. It was a revolutionary idea because it meant maybe that could be
6:09
used for other disorders of the brain. And and so it's like his continued his work that by the way was called responsive neuro stimulation, responsive neuro stimulation, R.
6:25
N. S. You'll see that in an abbreviation in its to talk, that sorta beats response of nervous relation, so it's actually began to work further in the memory. I would begin to be localized to the
6:41
hippocampus. Know cortex. He did some work. He'll share with you. The show that you stimulate the internal cortex in animals. You're able to improve their memories of things they had seen before,
6:55
and they would go localized those things immediately because it was obviously prominent in their memory.
7:02
The the potential for this to be used in a human disease is very attractive and encircled tell you more about is up. Groundbreaking work in these areas, obviously one of the areas that Alzheimer's
7:17
disease. Over one hundred million cases
7:21
of Alzheimer's disease will be a president in the world by two thousand and fifty, and these are people who suffer from early memory disorders. I can't remember what they had for breakfast. I
7:37
bought by perhaps spice, stimulation the into rhino cortex. I can remember that earlier, which would help a large category of patients with a very disabling feature their disease. It's act
7:51
believes this could be done by something similar to a hearing aid, hearing aid for for hearing loss, which can either go to the directly to the ear canal or can be directly transmitted to the brain,
8:06
and so this could be done in in memory disorders and other disorders that are waiting. Be discovered, so this is the future you're gonna see in your lifetime by two thousand and fifty. Now we're at
8:21
a very primitive stage. Two thousand and twenty one, and the next thirty years of research is going to advance in these areas, and these are things that are neurosurgeons are going to be involved
8:32
in
8:34
neurosurgeons in preference to anyone else because they can operate on the brain. They can stimulate the brain. They can enter the brain And. this is one of the future areas of growth of
8:45
neurosurgery Tony, As mentioned this, in his talk, Functional neurosurgery is a huge area of neurosurgery expansion.
8:55
After it's that gives us lecture. I'll give a summary of of what I thought about the meeting.
9:03
In the various talks were given him what that really means to us, so we hope you'll enjoy all this. We appreciate your being here and.
9:13
Check, please proceed
9:16
with the welcome. Everybody. It's a real pleasure to be in this session. In this great the education that legs experience, and I really appreciate the opportunity to talk to people in so many
9:27
geographical region, so we're gonna take a little leap, or perhaps the day into the future part of which is naturally present and the will. Talk about maybe changes in in in our profession,
9:45
and essentially I, I like tool to look at it as hardware and software, and I sing, you know will obviously very accustomed to dealing with the hardware of of the of the of the brain, and I think
9:59
in the future the future no neurosurgeons are will have to true, become an expert in the software and the language of the. Never system so, with application to memory, in particular,
10:15
I guess I'd like to look at it as as a challenges offer, perhaps enhancement fist as as a general goal of enhancement a of a neurological function, but perhaps say a further in the future,
10:30
inception and deletions of particular memories, particular thoughts. In all this you're at the surface of a neurological problem stood out will become more and more severe, and in the future,
10:48
though, if we are actually looking at what is awaiting us, we are only have to look at real present or even in in the last ten years and see the prevalence of neurological disorder by by cause them.
11:03
Of course we know about epilepsy, we know about Parkinson's disease, but right there are also Alzheimer's disease and other dementias, and of course the neuro psychiatric, A disorders that to
11:21
okay idea that we can see the older effective they did the disorder anxiety disorder, depression, alcohol and addiction. Drugs and drug abuse, bipolar disorders, eating disorders, and such these
11:39
older, that are already a already a topic of fair, Nora neurosurgical interest, so in a way, I think that we are facing a cognitive tsunami, meaning that if you just look at the picture of her
11:57
outside to the disease, you realize. That by the mid section of the century, we're going to have over one hundred million of people affected wizards. Probably every one of us or every one of our
12:13
and our children will recognize a some somebody in the vicinity who is affected with Alzheimer disease, and right now, of course, there is no pharmacological and options. I think we have looking
12:30
at the at the brain as an electro chemical machine. We have to consider what can can be done by neurosurgeons in this setting,
12:41
so I think I'm in over the last decade. There was really sort of opening up of brain surgery. Not in this article in nature In over ten years ago. There are already seeing the trend of opening up
12:55
our field. And being really critical in the transition of a basic neuroscience into it was, Because translational neuroscience here we see know Darpa wants to fix broken brains and the Dapa and and
13:13
obviously Nih and the Nsf and and the Eu, European Aid agencies and the agencies all over the the world are now turning increasing attention. To this issue of direct translation of brain scientists
13:30
and scientists into into practical application, now I think we can look at it at odds as a challenge is really a fixing, fixing brain circuits, and is now fashionable to talk about brain circuits,
13:44
and we, as as a little neurosurgeon have to really think about it. We already doing it. Obviously we're doing it in in Pakistan, disease and movement disorder. We're doing it in epilepsy, but
13:56
we're slowly venturing into the door, psychiatry as you know, when it mainly was deep depression, pain, ptsd obesity addiction, and right you know behind the corner is one of the most difficult
14:13
challenges of really interfering in the community demand in general and in memory in particular. Let me take on this challenge just talking about. It's a. I think the challenges that we faced have
14:29
really several aspects. One is a science challenge. Know we need to understand the neural code for what we do know is neurosurgeons. We had to deal with situation. Where obviously neither we know
14:43
other people knew exactly what we were The weird. We you know we we are treating effectively Pakistan and dystonia. And then the understanding of those circuits is only gradually emerged, and
14:57
certainly treatment was available before we completely understand it, so we're kind of in a grey zone of On the one hand, you know we want to understand what we are doing On the other hand our
15:10
patients you know need to have some solution to a pressing issue, so the other challenges the engineering challenge. As as you, you know, and then there's obviously is a medical challenge. You
15:23
know who should get the treatment, and under what clinical circumstances and the overseas, a societal issue of what we can do from an ethical standpoint other remedies that we envision fundamental
15:37
logic of patients. Are they going to be embrace you know by the general public, and then who is going to set the rules and and the criteria for this situation? So this is what we are facing Now we
15:51
go back, you know, and we owe a lottery to Penfield. Who was already. I think, thinking in this functional terms already in the middle. This section of the twentieth century. You can see him
16:05
obviously in the in the classical situation of local anaesthesia. You see the components of the team, Right, You see the patient obviously under local anesthesia with the red arrow at the bottom.
16:17
You see Penfield and his assistant operating? You see Jasper in the in the At at galleries, Are you looking at the electoral physiology and that was really the beginning. I sing offer of an era and
16:33
the okay, Let's see after, and of course we all know that even this situation really yielded a lot in terms of understanding the molecules all the language areas. Just by using this method which we
16:48
are still using today and penfield, you know as he, he was really looking and applying stimulation to the brain patient really expressed all of these experiences. Suddenly flashbacks came back.
17:02
Memories came back, but it was just you know incidentally in and the other just a million pairs of current were channeled into their brain and suddenly a memory appeal. It was very special and
17:16
offers you can imagine the excitement that type of getting such a complex function out of just applying electrical stimulation to the brain that is pith the penfield already said at this time because
17:28
there is a permanent record of the stream of consciousness within the brain and hidden in the interpretive areas of the temporal lobe. There is a mechanism that unlocks the past is and fifty eight.
17:44
Was principled was a great pioneer, and you know had a really a sort of finish, philosophical and and also practical approaches combine, and you know I liked the statement, as the brain is the
17:58
organ of destiny, he told within its humming mechanism secrets that will determine the future of the human race, and this is the true.
18:07
Even at that time, you know he was able through which to really envision that we are using the same type of situation today. You know patients are being updated their local anesthesia years ago,
18:19
fourteen year old, and they're looking at Stg, are talking a storm during an operation on on the language area, the top and bottom, and here you can see a violin which I operate on for essential
18:32
tremor, and wanted to really find the ultimate point where she could play the violin was no tremor which we did. So the situation is already available for us, but there are also a great source for
18:44
understanding the brain, and in the extra operative situation, you all know that we have in the subdural electrodes on the surface of of the the brain, and we have those that depth electrode now
18:58
called Se Gi, where we can, in our hands, We attached to a tweet, Michael, Why in this bank free electrode? That we have been using over the last two decades for try to decipher the neural code
19:12
for memory in humans and trying to see how we can translate this new code, perhaps into something that we can do for our patients, and this was the challenge, so if we look at what we can extract
19:27
from the brain itself, you know what we can learn because I remember the first challenge is to decode. Meaning what you know, if you understand the neural code, can we translate it as his firing
19:39
of neurons, which is really the languages and our system can be translated into function, and then we need to know that the transformation how it can be done, so we can measure at etching, put
19:52
potential, which is at ten K Harris, essentially, and going down to local field potentials, this we can measure from the brain and as draw surgeon, who have? Electrodes in the brain. This is
20:05
really the only opportunity to really look at this in humans.
20:11
So, and the only thing that we here are really the firing of then of the neurons, really that we can essentially look at with those micro wires at the end of our electrodes, which replacing
20:26
epilepsy patients of posts for monitoring of seizures, but we can only. It can also come there and present them with all kinds of memory task and see what the dunes are doing so,
20:40
and you. Of course deep brain stimulation. I just don't want to. In you all know is being used of course as another measure of stimulating the brain, but also now in the more advanced debate, Dbs
20:54
Si situations, we can all also extract information at the same time. This is not the the topic of our talk, but there is great work being done by by many people don't eat film star and other people
21:06
about closing the loop here in in deep brain stimulation. As well. You know this. We don't need to go over this, but this has been figured out more or less you know interests of the circuits.
21:19
He's probably easy to truly look at at a at a function such as in motor function, but what about the cognitive function? You cannot just stimulate. Then the patient is dominant. Tell you. I feel
21:32
smarter. Or suddenly. I remember, so the challenge. It is a bit more in of measuring what you can achieve a great advance. In the last a few years. It is only available in North America. At
21:46
this stage is responsive neurostimulation which is a first closed loop system approved by by the F, F, D, A to use for epilepsy, and this is a system. Well, we implant the neuro stimulator in
22:01
this column itself as you can see here and then it can. We can attach to a two electrodes at this point and each one has for contacting cause, he's a digital code or subdural electrode, and
22:14
actually we can measure and then see seizure activity and then you can apply stimulation to stop it. So here's this is a closed loop system you can see here electrodes in the hippocampus itself.
22:27
Right here, you can see the unit in planning the skull, not in the chest, as in most, and you know Dbs procedure, and what's happening here is that this information can be downloaded by the
22:40
patient, says by a one that truly it can be transmitted over there. The Internet is essentially eat your way to a center which can process the information so you can already see that a lot of
22:53
challenges here What we? We're trying to transmit a lot of information in these kinds of situations from patients, and we will need you to deal in the future. Already. The President was issue of
23:06
privacy and patients, right, etc, which I won't get into this point and bugs may be appointed for discussion, U C L A just between two thousand and fourteen, when he was a cruel to a two thousand
23:17
and eighteen will blended for forty patient. Now we are over a one hundred and The the study a patients for epilepsy. Essentially have a twenty two with medial temporal placement, fifteen bilateral,
23:31
Because you can apply this in the case where you have more than one focus. You have median reduction of seizure frequency of seventy five percent, and we have a select group. About thirty percent
23:42
of the patient was super rich responders. This. You know what we. We. We call them Super responded because they have greater than ninety percent reduction in seizures. At least is a work by
23:53
daughter. Il, area achievement in at U, C. L. A. In our in our group, but of course these.
32:34
Yep, now, but in the animal domain, there's already optogenetic tick, tick, nice, where you could identify for instance a certain places in rodents, brain, and then had the rodent remember
32:51
that place better or go back the next day into that same place that you wanted to go, or to quote, Remember, Okay, it's a paper in science in two thousand and thirteen. If there is a you know an
33:05
array of papers which are talking, essentially, I tried to use this, you know and movie inception to kind of put you in the right mood, but know you from a theoretical standpoint we can find the
33:21
machinery in the brain which code you know this particular actress, Oh, which encodes you know Leonardo Dicaprio, which and we can ewing sleep. We can in principle really promote the memory for
33:38
this particular concept or this particular mental construct. Now. Of course, we're not doing it at this point, but already in the animal literature is already away, Because what happens you in
33:52
your sleep in in the road is a brain. The places of the rodents visited can be seen as sequences of firing of cells. And if you identified online line, you can actually enhance those and the rodent
34:09
in these studies, which up the next day, and he goes to that particular place, if you reinforce it, or avoid that particular place. If you were a, attached me to a negative stimuli, so this has
34:24
to do with the ability to identify neuronal sequences which are specific to specific memories or specific thoughts. And this is done by book genetic techniques, which obviously at this stage are
34:38
only starting to get into the human domain is very special instances like blindness, and it is thus been a recent paper about it, but I'm just posing this sort of as a challenge, so coming back you
34:55
to
34:57
who what are the challenges are here is a diagram by by then Michael Richards, Cla. In any noticeable engineering, now looking at such a system, which I would call this a memory aid, and I will
35:09
post you the basic question. If you accept the hearing aid. Why would you accept a memory aid If I could give you a memory aid or cochlear implant, like divide, which will enhance memory. What
35:25
would you say about him and he is this where the future is really leaving us. It was the limitation, as I've said, we're partly an engineer in Asian. Know this is a nerve pixel, The which is now
35:38
used in rodents, and in none, he nonhuman primates, which can record from a thousand neurons at the same time, in many of yours, Some of you have heard about New Orleans. You know they're
35:53
They're the relatively new enterprise of it en masse were. A a robot is looking at the surface of the brain, and like a sewing machine, places thread like electrodes into the brain, avoiding
36:07
vessels, and putting hundreds of those in in and all of these a small, their whole, okay which you can plug you know with with this device, which is health, and you know by the finger, and
36:21
essentially can communicate wirelessly. He's not a dream, I already. We all we have seen this re little pig show that he had about six months ago. This is Robyn by the way, and recently having a
36:35
monkey playing pong, and right now this these kind of technologies year the toward a toward patients, you know who acquired crudup, probably Egypt, and and by thought will be able to move perhaps
36:49
a robotic arm, but if you have a thousand channels will be doing much better than what you are doing now. With you to erase, you know which have only hundred channels, so by one order of magnitude
37:02
or more technology can bring us forward, but of course we need the science, and mostly we need that neurosurgeons right who beat this fall challenges, you know which I, I sort of place to the
37:15
beginning of the story, the science, engineering medicine and the society to change, and I think the most important thing you know for for us, really. Is your surgeon to realize that we are
37:28
important players at this table of the future and I will leave you with with this statement which I guess leaves us for a few minutes or for questions and discussion to thank you very much for your
37:43
attention, So if I, if I might say thank you, it's a fantastic little, but I mean. We have friends from many many years, so you didn't have spent the major to say offend you inside for about
37:56
religion, but is thinned you inside for a fantasy little bit. Then at the point is I think, but and when you are, but as an wouldn't be a law that says that the pro -level if an assignment or with
38:10
memory, I, I think that also addresses, and we spoke about that addresses the issue of consciousness because it's not only memory. Yeah, I'd say I mean, am I able to recite the entire boy that I
38:27
learned when I was in fifth grade. Yeah, Okay, but these that the only thing that counts it together with the boy. I mean when I look at and to Tony the silence I not seen since the nineteen
38:39
ninety three, Okay, I recognize his face. Yeah, That's the daunting, but with that theme comes a whole world of of things that make. Why yeah, so I think they're fantastic challenge that your
38:56
work on another people like you and Estonia talk about that yesterday We've got a Sandra she is, Is that as a challenge that we will finally neurosurgeons will unravel the problem of consciousness?
39:11
I mean this is the the Holy grail that that are addressing. Find that you. Not only that you remember the face of your grandchildren is a genre of who your grandchildren walk out before you.
39:25
Yeah, I absolutely agree with is of course consciousness, the B b C O the odd problem you know is is that how this problem, but I think from a practical standpoint. You know when you look at it,
39:39
it Alzheimer patient. It's a very early stage, and maybe even at the minimum cognitive impairment stage, you know the problem is not true. We remember you know Tony. The the dishonest twenty
39:54
years ago. Their problem is I remember what they ate for breakfast. Their problem is ready to deal with the challenges of making new memories. Okay, that is really what enables them to function in
40:07
society, so from a practical standpoint it is it's a real issue. How to help the believe that early stage. It the same way that we are helping pockets of patient. It A relatively, as you said,
40:19
If we can help them, It's a very latest that the system is all over the ruling, okay, but I think our goal is to give them some quality of life at a relatively early stage. We're not gonna make
40:31
them conscious or unconscious. This is obviously a very difficult problem in a separate left. I think. What attracted today. I watch again, sure of June twenty first century,
40:48
and we started the meeting with the Tonys talk, and Alison was push again about how neurosurgery will change before twenty one hundred.
41:02
Is this whole concept of the meeting is pioneering in terms of education of the world is getting smaller and we think everybody around the world has ideas, and we want to get everybody together to
41:15
share the idea. Ideas In many ways. Technology is not up to that to to that challenge
41:24
Because technology has trouble with her people have trouble with technology, but that's the world we're emerging into. Removing moving from the twentieth century into the twenty first century, and
41:38
if you look around the world, every country in the world is having trouble with that transition are having trouble politically economically socially intellectually, and we are no different.
41:53
This meeting in itself was an experiment. It was an experiment in education. Can we get people together and discuss ideas openly? Do we need launched? It was proved this morning when the
42:06
technology fail that we went on anyway, and we had a discussion with people.
42:14
It was proved yesterday. How we've seen at the fact that you can present ideas and get multiple different inputs and find that even the experts cabinet can descend to disagree. We've had everybody
42:28
pay attention to the low and middle income countries the Samurai showed in the year Neuro intensive care session. The problems they face in Baghdad are far different than what we fake pace in Los
42:40
Angeles or New York, And how do you? How do you solve those problems? You do the best you can with what you've got everywhere in the world
42:50
In no answer is no one right answer for everybody.
42:55
Which then goes back to some of the politics of today have tracking, trying to have everybody ruled by one philosophy. It won't work. It'll trip.
43:05
So anyway I wanted to fake. I want to thank all the people who came as of yesterday. We over a thousand people who came from over one hundred and fifty countries. They didn't all stay today.
43:20
We've had a majority of the people came from to middle income countries. We're very excited from the poll yesterday. I, eighty five percent of the people in each session said that there was either
43:34
good to excellent, and when asked if they want to have more of these ninety five percents said yes,
43:41
so that tells us where we're warrior warrior, Coming from what happened,
43:48
We're meeting a world of the twenty first century. Neurosurgery has to move into the twenty first century. In Africa, it's it's It's moving from the twentieth century into the twenty first century.
44:02
It's painful. They need help when he doubt
44:07
we see our colleagues in in China with enormous advances at where we had a talk yesterday about how you can repair the spinal cord. Something we were then taught. For decades. You cannot do. You
44:21
cannot do that. Then we saw a dog walking yesterday after spinal cord was cut on. What can you possibly say about her? Except that it worked. We need to add more understanding of the science.
44:35
We've just heard it. Succeed. He and I have a hearing aid. I have glasses.
44:41
Not Why not him something from memory. We have people, and I don't think he had a chance to talk about it, but they're working on it where you can take people who are blind and get them to see at
44:52
least something. These are emerging advances we've seen and aneurysms which are prominent, and Tony mentioned this yesterday in the twentieth century are being replaced by intervention on surgery.
45:06
You have mentioned that this morning, but there are some places where it's too costly, so you have to steal no one hundred and two traditional things, so neurosurgeons need to be prepared for the
45:18
twenty first century, and that's what we're trying to do. That's what this is. What this was an experiment? I particularly want to thank author Jorge Jib List. Who's a young resident who is
45:34
phenomenal. Help my cheer anywhere sir in, or it was R. I T person who owe a. You can imagine where it is worth working with a few neurosurgeon Alert is working with one hundred hob. So I think
45:50
that. These wrote, everybody tried extremely hard work Done this for sixteen months to bring this new venture. This new experiment to you. We hope that it was valuable. We help you learn
46:03
something I did. Ah. I want to thank. It's not a xiaoping Ren Tony out for for just introducing very revolutionary concepts, Langston Holly for doing a wonderful spine session along with
46:19
instrumentalist. And call for taking on what was a very controversial issue of intracranial hematoma and traumatic brain injury, and seeing how this is solved around the world. There is no one
46:32
right answer. They can afford intracranial pressure monitors in Baghdad. It doesn't matter. We have to go on,
46:41
so we appreciated or has been a great friend for a long time. I appreciate his rise console. And I appreciate everybody who's contributed the fifty seven speakers who spent a lotta time. We can all
46:54
do better. We wish you the best we want to evaluate what all the all the polling is. We're probably going to ask you some more questions independently so we can decide what to do in the future. Do
47:08
we have more of these meetings? How frequently we have them. If we have them. What should be their content, We experimented with thanks.
47:18
And we've got to have to experiment with more things, because education is going to be different than it was in the twentieth century. It isn't lectures. It's communicating information and
47:31
experience. That's the twenty first century and the technology we have to harness to do what we want. Not the other way around, so thank you very much, we hope you enjoyed her thanks to all my
47:46
friends who helped. We really appreciate. I have a good day. Have a good weekend.
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