Scientists can now manipulate brain cells using smartphone

A team of scientists in Korea and the United States have invented a device that can control neural circuits using a tiny brain implant controlled by a smartphone.

Researchers, publishing in Nature Biomedical Engineering, believe the device can speed up efforts to uncover brain diseases such as Parkinson's, Alzheimer's, addiction, depression, and pain.

The device, using Lego-like replaceable drug cartridges and powerful bluetooth low-energy, can target specific neurons of interest using drug and light for prolonged periods.

"The wireless neural device enables chronic chemical and optical neuromodulation that has never been achieved before," said lead author Raza Qazi, a researcher with the Korea Advanced Institute of Science and Technology (KAIST) and University of Colorado Boulder.

Qazi said this technology significantly overshadows conventional methods used by neuroscientists, which usually involve rigid metal tubes and optical fibers to deliver drugs and light. Apart from limiting the subject's movement due to the physical connections with bulky equipment, their relatively rigid structure causes lesion in soft brain tissue over time, therefore making them not suitable for long-term implantation. Though some efforts have been put to partly mitigate adverse tissue response by incorporating soft probes and wireless platforms, the previous solutions were limited by their inability to deliver drugs for long periods of time as well as their bulky and complex control setups.

To achieve chronic wireless drug delivery, scientists had to solve the critical challenge of exhaustion and evaporation of drugs. Researchers from the Korea Advanced Institute of Science and Technology and the University of Washington in Seattle collaborated to invent a neural device with a replaceable drug cartridge, which could allow neuroscientists to study the same brain circuits for several months without worrying about running out of drugs.

These 'plug-n-play' drug cartridges were assembled into a brain implant for mice with a soft and ultrathin probe (thickness of a human hair), which consisted of microfluidic channels and tiny LEDs (smaller than a grain of salt), for unlimited drug doses and light delivery.

Controlled with an elegant and simple user interface on a smartphone, neuroscientists can easily trigger any specific combination or precise sequencing of light and drug deliveries in any implanted target animal without need to be physically inside the laboratory. Using these wireless neural devices, researchers could also easily setup fully automated animal studies where behaviour of one animal could positively or negatively affect behaviour in other animals by conditional triggering of light and/or drug delivery.

"This revolutionary device is the fruit of advanced electronics design and powerful micro and nanoscale engineering," said Jae-Woong Jeong, a professor of electrical engineering at KAIST. "We are interested in further developing this technology to make a brain implant for clinical applications."

Michael Bruchas, a professor of anesthesiology and pain medicine and pharmacology at the University of Washington School of Medicine, said this technology will help researchers in many ways.

"It allows us to better dissect the neural circuit basis of behaviour, and how specific neuromodulators in the brain tune behaviour in various ways," he said. "We are also eager to use the device for complex pharmacological studies, which could help us develop new therapeutics for pain, addiction, and emotional disorders."

The researchers at the Jeong group at KAIST develop soft electronics for wearable and implantable devices, and the neuroscientists at the Bruchas lab at the University of Washington study brain circuits that control stress, depression, addiction, pain and other neuropsychiatric disorders. This global collaborative effort among engineers and neuroscientists over a period of three consecutive years and tens of design iterations led to the successful validation of this powerful brain implant in freely moving mice, which researchers believe can truly speed up the uncovering of brain and its diseases.

Euthanasia in Cuba: To Die with Dignity?

Most interviewees are in favor of euthanasia, provided it’s regulated and the means to exert strict control.

"Euthanasia, what’s that? ", told me - incredibly! - a recently graduated doctor. With that answer I never knew for sure if he ignored the term or he simply didn't want to take part in this respect.

Searching for approaches on euthanasia I certain positions, although from these first lines I’d rather established that most interviewees are in favor of its practice, provided it’s regulated and the means to exert strict control.

A neighbor in her early 80’s pointed out sharply: “That’s not my case, but an old man, for example who doesn't have a quality of life and becomes a burden for the family, what’s the point on go on surviving under such conditions? "  

"I agree provided is beyond saving, and every medical and scientific resources have been tried, expressed Carmen Ibañez, specialist in Information and Documents Management.

The worker at Granma newspaper considered that the euthanasia should be practice also when a baby comes with a congenital malformation and the parents don't want to have the child.

"It’s very sad to bring to a human being to life with a defect. Take a look at myself, I have negative Rh factor and always - in my permanent concern - I told the doctor that, if any test were outside the standard, I’d rather act ahead of time! ".

Not all opinions were favorable, and some of them denied the euthanasia flatly. Inés and Heriberto are married and both are evangelical religion followers. In that, perhaps, resides their total disagreement with this practice which, according to them could bring about other inconveniences.

"The euthanasia, for example could be used as a shield to carry out unscrupulous actions, related to the acquisition of assets, inheritances, or other negative attitudes and bad behaviors", they stressed.

Two Doctors, One Opinion

Accustomed to work with patients whose lives "hang by a thread", to put it in a way, Doctor Tania Fernández Sordo, first degree specialist in Intensive and Emergency Care, already coincides with approaches related to the topic which are also complex for her.

Master in Medical Emergencies she considers that the euthanasia should be applied in those patients who – on their own request – desire with a terminal or incurable illness, like cancer.

"Besides, in critical patients, like those we take care of in our ward (intensive care unit), where their vital parameters are kept with the use of medication or apparatuses to prolong life, without real chances at recovery."

The doctor affirmed that in our country such practice is not regulated. Nevertheless, she believes that it could be analyzed by professionals of health, mainly doctors working in the ICU wards, oncologists, and other specialists. "Our job is to save lives (those that are possible), and not those that cause suffering and stretch agony."

On the other hand, the medical resident in Geriatrics Diana Rosa Graverán González explained: "taking into account the concepts handled through centuries, we must not overlook the importance of euthanasia regarding the cultural, religious traditions and habits of each country in correspondence with its environment as for socio-cultural development.

"As a doctor I think that one of our missions - and the most important one- is to alleviate the pain of human beings. However, the euthanasia could be carried out keeping in mind the patient's decision, of their relatives, whenever they are aware of the suffering and the irreversibility of the disease; not applicable to coma patients and who have not put in written in their last will their expressed desire.

"In Cuba is forbidden, there are no laws on this regard. But the law can be passed, hence patients (conscious) with irreversible illnesses they can put an end to sufferings, on well grounded legal terms.

"Human beings can’t choose when or how to be born, if only we could have the chance to - in great pain and discomfort - be able to make the call of ending with a difficult situation. The saying that goes there’s still hope while you can breathe it is not always that simple. There are coma episodes, long and irreversible, that prove otherwise."

A vote in favor from his position as lawyer

The young Cuban lawyer Malena Pérez Rodríguez thrilled with a matter on which her schoolmates at law school didn't want to go deep – due to its own content and the ignorance about it - the young lawyer Malena Pérez Rodríguez decided to go further (she even wrote a thesis) on euthanasia, which supports completetly, although she explains that before its approval some conditions must be established.

Some human beings - Malena explained - suffer from pains, regardless the drugs they are given. They are those who fight against cancer, for example, but others feel they aren’t strong enough to join this battle. And the relatives are within arm’s length, watching them suffer without any solution in sight. Therefore I say Yes to euthanasia, because there are people who don't want to live, mainly those at an advanced phase of the disease.

"How many phrases are heard in the street that go: 'I don't want to get old like that! '; 'well (…) he finally rested in peace'; 'he died and didn't suffer! '. Nobody wants to die with anguish and pain. Then, why not speed up death? Euthanasia could be included in the Civil Law; to pass a law.

"When I was studying law I found information explaining that the State cannot regulate euthanasia if the medical community and society were in agreement. In this regard, the last saying falls completely in the hands of health professionals, but I think there’s phobia with this practice.

“It’s true that the State cannot force society to accept it, but it can regulate it, for those who wish to undergo assisted death. It’s not passing a compulsory ordinance, but knowing that the chance is at hand, and that at a given time you can use it.

The possibility should exist of deciding whether / or not I want or abstain. It is important to know that proceeding is regulated and if I want to undergo that procedure I’d be committing no crime.

"Those suffering from Alzheimer, suffer a degenerative illness, but they are in no pain. However, a patient with terminal cancer suffers, it suffers an irreversible disease. That’s why I don't see euthanasia as a general alternative, but for those who want to finish with a life of suffering.

"Brakes in the current Cuban society? Mainly, I see it in the field of medicine, starting from the so-called Hippocratic oath – first do not harm, you will help to prolong life -. It is indispensable to widen the idea in this regard, and reflect on up to what point carrying euthanasia is effective to help a sick person. That is the goal. Before being doctors, first we are human beings, and we have the responsibility to aid patients and avoid traumatic processes".

According your approach, how to regulate it in order to avoid windows to wickedness?

As everything else in this world it also has negatives aspects. The Achilles heel is that euthanasia could be used to malpractice, but even so in Cuba medical mistakes have happened and as there were not aggravating rights everything has stayed just there. Anyway, I think that its approval would bring more benefits than disadvantages."

The first-in-human clinical trial targeting Alzheimer's tau protein

So far, many of the antibody drugs proposed to treat Alzheimer's disease target only the amyloid plaques. Despite the latest clinical trial that is hailed as our best chance in the quest for treating AD, all later phase trials have failed with many causing severe side effects in the patients, such as abnormal accumulation of fluid and inflammation in the brain. One of the reasons for side effects, many speculate, is due to the antibody directing a reaction towards normal amyloid present in blood vessels or simply releasing beta-amyloid caught in the vessel wall.

The authors of the study have developed a vaccine that stimulates the production of an antibody that specifically targets pathological tau, discovering its "Achilles' heel." It is able to do this because healthy tau undergoes a series of changes to its structure forming a new region that the antibody attacks. This new region (the "Achilles' heel"), while not present in healthy tau, is present in diseased tau early on. Therefore, the antibody tackles all the different varieties of pathological tau. In addition to this important specificity, the antibody is coupled to a carrier molecule that generates a considerable immune response with the added benefit that it is not present in humans, thus avoiding the development of an immune reaction towards the body itself.

Side effects have included a local reaction at the site of injection. This skin reaction is thought to occur due to the aluminum hydroxide, an adjuvant used in vaccines to enhance the body's own antibody production. No other serious secondary effects were directly related to the vaccine. Overall, the safety of the drug and its ability to elicit an immune response were remarkable.

While many trials against Alzheimer's disease stubbornly continue to target amyloid, our study dares to attack the disease from another standpoint. This is the first active vaccination to harness the body's ability to produce antibodies against pathological tau. Even though this study is only a phase 1 trial, its success so far gives the authors confidence that it may be the answer they are looking for to halt the progress of this devastating disease.

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